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Current Immunology Reviews (v.7, #1)
Editorial [Hot Topic: Protective or Damaging Immunity in Infection (Guest Editors: Jose Gutierrez and Antonio Sorlozano)] by Antonio Sorlozano, Jose Gutierrez (1-2).
Within immunology, it is especially important to know the basic mechanisms of innate and adaptive immunity in the defence against infectious agents, the most important physiologic function of the immune system. The development of an infectious disease in a person involves complex interactions between the agents and the host. It starts with the entry of the microorganism, the colonization of the tissues and the invasion, after overcoming the host's defences, and the organic lesion or functional alteration of the tissues. Then some agents start spreading the disease through multiplication, liberation of toxins or events of hypersensitivity [1]. The immune system usually responds specifically against the infectious agents present and fights them with the highest efficiency possible, on the principle of all or nothing. The pathogenic capacity of the agents is linked to their capacity to elude or resist the effectors mechanisms of immunity, which are mainly adaptive, humoral or cellular. However, in many infections the disease can be the consequence of the host's response to the infection rather than the direct effect of the agent itself, through the hypersensitivity phenomena, which involve a more or less significant molecular mimetism. Some strains of Streptococcus pyogenes show similarity of capsular epitopes to the host connective tissue, its wall M protein shares epitopes with cardiac myosin; and streptolysin O binds to the erythrocyte membrane cholesterol altering its antigenic configuration. It may also form streptolysin O immunocomplexes and antibodies deposited on tissues, or the anti-streptolysin O may directly injure the cellular membranes [2]. On the contrary, and excluding molecular mimetism, other bacterian agents, such as mycobacteria, may cause granulomatous inflammation and histic destruction [3]. Finally, agents such as Mycoplasma pneumoniae may share mechanisms through the modification of the host antigens and direct tissular destruction [4]. Over the past years it has been stated that some diseases deriving from unknown causes, such as atherosclerosis [5], schizophrenia [6], multiple sclerosis [7] and periodontal disease [8], at least in a subgroup of patients, may be caused by sustained chronic infections, together with a genetic component, and perpetuated by the immune system. This hypothesis is based on epidemiologic and biologic evidence proving that these patients were exposed to infection risk factors during the pre- or post-natal period, such as Toxoplasma gondii, chlamydias, all the human herpesvirus, parvovirus B19, parotiditis virus or flu viruses. This list of microorganisms has increased with time and it will doubtlessly continue to grow, since there would only be the need to study agents with prevalences that are high enough to be significant risk factors. It is more complex to relate the infection with the clinical process because it first requires epidemiologic studies and then experimental animal studies. Some works have been done in relation to this. The belief is that the infection may distort the synthesis of neurotrophins by immune cells, with significant subsequent repercussions. On other occasions it is believed that maternal antibodies which are directed against infectious agents leave secondary injuries on foetal neuron tissues, which are the part of the anatomy affected by the subsequent lesion in subjects with the disease [9]. In any case, whether the infection is pre- or post-natal, the disease is immune-mediated: it generates an irreversible lesion, of greater or lower level which, with time, leads to the appearance of the disease. The hypothesis that foetal infections during gestation or during the first moments of post-partum may trigger the subsequent appearance of the disease, like an organic sequel, is based on the above. Nevertheless, it is also probable that a possibly unsolved very early chronic infection may exist through an agent able to perpetuate itself (such as DNA viruses, chlamydias or T. gondii), which facilitates the appearance or exacerbation of the disease by interacting with other factors. Thus, the subjects may be susceptible to symptomatic treatment of the disease, such as is currently done, but, in addition, in this last case, the subjects may also be susceptible to antimicrobial treatment that may improve their progress. One of the markers to show chronic infection status is the presence of the agent's DNA in leukocytes and an important synthesis of specific IgG and IgA. In principle, herpesviruses are important candidates, since they are cytotropic, they produce latent infection with exacerbations, they may block neuronal function and cause diseases that behave as if they are post-acute. The main criticism received by these studies centers on the fact that the infection and the antibodies against viruses of the Herpesviridae family, C. pneumoniae and T. gondii families are very frequent in the general population, and that most of the carriers are asymptomatic. Doubtlessly, the field of influence of different infectious agents related to diseases of unknown cause is in the midst of development, and, although conclusive results have still not been found, it is necessary to replicate the studies, start new ones and relate these factors with the different manifestations of the disease. As a result of all the above, it would be extremely interesting to show or to rule out whether there is a differential replication of the infectious agent, at least in some of the subjects studied. Thus a dynamic would be set in motion to detect a population that could be susceptible to treatment with specific antimicrobial agents, a better definition of the differential phenotype of the disease, and the possibility of prevention. With the foregoing facts and under the title and#x201C;Immune-Infectology Principlesand#x201D; we deem it opportune to run a monographic volume of the Current Immunology Reviews journal studying the relationship between infectious agents, human immunity mechanisms and disease, from different points of view.
Immunity to Bacterial Infections by Maria Jimenez-Valera, Alfonso Ruiz-Bravo (3-12).
Co-evolution of pathogenic bacteria and hosts has led to the development of an array of virulence genes (the virulome) and a set of mechanisms of defense which constitute the immune system. Mechanisms of innate or non-specific immunity involve mucosal epithelial surface barriers, antibacterial peptides and enzymes, defensive molecules (collectins, complement), and cells (macrophages, dendritic cells, polymorphonuclear neutrophil leukocytes, natural killer cells). The presence of bacterial products in host tissues induces a complex series of non-specific responses which constitute the inflammatory reaction. Inflammation is critical to the resolution of infection, the key process being the ingestion and killing of bacteria by phagocytes, but inflammation also causes tissue damage and contributes to the pathology. The innate immunity is the initial step in the host defense against pathogens, but some pathogenic bacteria with appropriate virulence factors can overcome the innate immunity mechanisms. In these cases, the goal of innate immunity is to contain the infectious process until specific immunity is developed. The specific immune responses are performed by lymphocytes: B cells, T helper (TH) cells, and cytotoxic T lymphocytes (CTL). Specific antibodies are produced by B cells, usually with the cooperation of TH2 cells. In general terms, extracellular bacteria can be killed by antibodies and complement proteins, or cleared by phagocytosis after opsonization by antibodies, and bacterial exotoxins are neutralized by their specific antibodies. In contrast, resistance to intracellular bacteria requires the induction of TH1 and CTL responses. In this review, we will focus on current knowledge about the defensive mechanisms against bacterial infections. We will discuss the innate immunity mechanisms, connections between innate and specific immunity, the key role of T helper 1 (TH1) and TH2 cells, and the antibody and cell-mediated responses.
Immune Response to Mycobacteria by Maria del Mar Casal, Manuel Casal (13-18).
The immune response to mycobacteria is a complex process, varying according to the infection or disease involved and to its acute or chronic nature; it is not yet fully understood. A better understanding is essential for definitive diagnosis and the development of new vaccines. The immune response involves a wide range of molecular and Th1- model cellular components: antigen-presenting cells (macrophages and dendritic cells); T lymphocytes (CD4, CD8, NK and and#x3B3;and#x3B4;); cytokines such as IL-2, IFN-and#x3B3;, IL-18 and TNF-and#x3B1;; and the chemokines RANTES, MCP-1, MIP-1and#x3B1; and IL-8, which play a key role in granuloma formation in M. tuberculosis and atypical mycobacterial infection. The immune response also involves epithelial and natural killer (NK) cells, several signaling proteins (costimulatory molecules and transcription factors) that participate in regulating T-cell activation, toll-like receptors and major histocompatibility complex Class 1 molecules. M. tuberculosis-secreted antigens that reportedly induce the secretion of mediators associated with protection against M. tuberculosis infection include CPF-10, ESAT-6, 27kDa and 38 kDa, which induce production of IFN-and#x3B3;, TNF-and#x3B1; and nitric oxide. The immune response to M. leprae infection involves the Th-1 model in tuberculoid leprosy and the Th-2 model in lepromatous leprosy, with the production of IL-4, IL-5 and IL-13 or IL-10 (Th-3 response).
Antiviral Immunity by Jose Maria Navarro, Mercedes Perez-Ruiz (19-24).
Viruses are obligate intracellular parasites that cause infection by invading cells of the body. Their life cycle comprises a relatively short extracellular period, and a longer intracellular period during which they undergo replication. The immune system has non-specific and specific mechanisms that attack the virus in both phases of its life cycle. Nonspecific immune response is mainly mediated by interferons and natural killer cells (NK). Type I interferons are produced by many cell types and lead to both inhibition of viral replication and cell proliferation; they also enhance the ability of NK to lyse infected cells. NK represent a different lineage of lymphocytes that recognize and lyse virally infected cells. They are mainly effective during an early stage of viral infection, since there is no lag phase of clonal expansion for NK as occurs with T and B lymphocytes. Specific immune antiviral mechanisms are both humoral and cellular. Specific antibodies protect against viral infections and play an important role in antiviral immunity, mainly during the early stage of the infection. The most effective antiviral antibodies are neutralizing antibodies which bind to the viral envelope or capsid proteins, and block the virus from entering into host cell. The main effectors involved in specific antiviral immunity are CD8+ cytotoxic T lymphocytes (CTL). These cells recognize viral antigens presented at the cell surface associated with class I MHC molecules. CTL response is not always beneficial, since the tissue destruction caused by CTL is sometimes greater than the damage done by the virus.
Immunity to Parasites by Nuria Tormo, Maria del Remedio Guna, Maria Teresa Fraile, Maria Dolores Ocete, Africa Garcia, David Navalpotro, Mercedes Chanza, Jose Luis Ramos, Concepcion Gimeno (25-43).
Parasites such as protozoa or helminths currently account for greater morbidity and mortality than any other class of infectious organisms, particularly in developing countries. The structural and antigenic diversity of pathogenic parasites is reflected in the heterogeneity of the adaptive immune responses that they elicit. Protozoa that live within host cells are destroyed by cell-mediated immunity, whereas helminths are eliminated by IgE antibody and eosinophil mediated killing as well as by other leukocytes. The principal innate immune response to protozoa is phagocytosis, but many of these parasites are resistant to phagocytic killing and may even replicate within macrophages. Phagocytes also attack helminthic parasites and secrete microbicidal substances to kill organisms that are too large to be phagocytosed. Some helminths may also activate the alternative pathway of complement. The principal defense mechanism against protozoa that survive within macrophages (e.g. Leishmania spp., Toxoplasma gondii) is cell-mediated immunity, particularly macrophage activation by TH1 cell-derived cytokines. Protozoa that replicate inside various host cells and lyse these cells stimulate specific antibody and cytotoxic T lymphocytes (CTL) responses (e.g. Plasmodium spp.). Defense against many helminthic infections is mediated by the activation of TH2 cells, which results in production of IgE antibodies and activation of eosinophils and mast cells. The combined actions of mast cells and eosinophils lead to expulsion and destruction of the parasites. Most parasitic infections are chronic because of weak innate immunity and the ability of parasites to evade or resist elimination by adaptive immune responses Parasites evade the immune system by varying their antigens during residence in vertebrate hosts, by acquiring resistance to immune effector mechanisms, and by masking and shedding their surface antigens.
New Vaccines and Delivery Strategies for Adult Immunization by Elisa Prieto-Lara, Manuel Carnero, Joaquin Fernandez-Crehuet (44-49).
A series of new vaccines have recently been licensed or are at advanced stages of development. Among the illnesses targeted are herpes zoster, meningococcal meningitis serogroup B and pneumococcal disease, which represent an important cause of morbidity and mortality in adults. Zoster is a localized, painful cutaneous eruption caused by reactivation of latent varicella zoster virus (VZV). Approximately one in three persons will develop zoster during their lifetime, occurring most frequently among older adults and immunocompromised persons. Possible complications of zoster are postherpetic neuralgia, facial scarring, and loss of vision. Licensed zoster vaccine is a lyophilized preparation of a live, attenuated strain of VZV recommended for all persons aged 60 years or more who have no contraindications. Serogroup B meningococci represent the main cause of meningococcal disease in developed countries. Previous efforts for the production of an effective and safe vaccine have focused on outer membrane vesicle vaccines, which have been implemented successfully during clonal outbreaks. Nevertheless, ongoing research is being directed towards a universal vaccine against endemic polyclonal serogroup B meningococcal disease. Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia in adults. The use of an adult 13-valent pneumococcal conjugate vaccine could optimize protection against pneumococcal disease over the lifetime of the individual overcoming some of the limitations of the 23-valent polysaccharide. In addition to these efforts, progress is being made on dose sparing strategies that use intradermal delivery with microneedles in order to simplify administration and face possible shortages of vaccines. Despite the established benefit of intramuscular influenza vaccination, intradermal administration with comparable or improved immunogenicity is being explored.
Population Diversity and its Relationship with Infectious and Tumor Diseases by Rosario Sabariegos, Antonio Mas, Pilar Clemente-Casares (50-56).
Evolution is based on mutation processes and the subsequent selection of the best-adapted individuals, i.e., and#x201C;survival of the fittestand#x201D;. Thus, diversity is a common feature in living things. Pathogens and their hosts, as well as tumoral processes are no exception. Changes in the genetic material of microorganisms allow them to colonize new ecological niches while hosts try to adapt to the new residents by either eliminating them or by establishing mutualistic interactions. The permanent coexistence of microorganisms and their hosts leads to continuous evolvement necessary for their survival, following a strategy that was initially proposed for coevolution models in predator-prey interactions known as the and#x201C;Red Queen Hypothesisand#x201D;. Similar conclusions can be established for tumoral processes. Thus, in general, tumors, microorganisms, and hosts can be considered at the population level as complex distributions of related although not identical individuals. Initially, these complex systems were described in a theoretical model that tried to explain the functioning of populations of primitive replicons during the origin of life. This theory was later experimentally confirmed by analyzing populations of positive-strand RNA viruses or RNA(+). In both cases, for replicons and RNA(+) viruses, the populations are described as quasispecies. Here, we will review the most recent discoveries regarding interactions between population diversity and pathogenicity, both in microorganisms and tumors.
The Role of Microbial Agents in the Etiology of Schizophrenia: An Infectious Hypothesis for Psychosis? by Blanca Gutierrez, Gabriel Heiber, Francisco Torres-Gonzalez, Jorge A. Cervilla (57-63).
The ultimate cause of schizophrenia remains to be found, but it clearly includes a significant genetic component with an estimated heritability up to 85and#x25;. This suggests that genes may act as a predisposing factor upon which a variety of environmental risk factors can exert their deleterious effects, determining the emergence of psychotic symptoms. A recently growing interest has re-arisen on perinatal brain infections, which may increase the risk for schizophrenia that can, in turn, be modified by hazardous genetic loading. This hypothesis is based on epidemiological evidence, which has shown a significant exposure of affected individuals to infections with different pathogens. Such results are supported by tests carried out on animals. Another possibility is that there may be a link between a primary maternal infection and the subsequent development of schizophrenia in offspring. It is also been hypothesized that maternal antibodies against microorganisms may damage the fetal neural tissue, the area which is later found to be affected by the lesion occurring in patients with schizophrenia. In the present chapter, we review recent evidence on the potential role of infectious agents in the etiology of schizophrenia and discuss possible implications on the future of diagnostic, preventive and therapeutic issues.
Microbial Agents, Immune Function and Atheromatosis: The Chlamydophila pneumoniae Role by Jose P. Linares-Palomino, Gonzalo Piedrola, Cristina Lopez-Espada, Eduardo Ros-Die (64-74).
Some pathogens have been associated with the pathogenesis of atherosclerosis. The best studied and characterized has been Chlamydophila pneumoniae. Over the last years, several reports in the literature have suggested that infection with C. pneumoniae may contribute to the pathogenesis of atherosclerosis. C. pneumoniae would need to persist within infected tissue for extended periods of time, thereby stimulating a chronic inflammatory response. C. pneumoniae has been shown to disseminate systemically from the lungs and alveolar macrophages through infected peripheral blood mononuclear cells and to localize in arteries where it may infect incipient atheromatous lesions and their cellular compounds (endothelial cells, vascular smooth muscle cells (SMC), monocytes/macrophages). This situation promotes inflammatory atherogenous process. The involvement of C. pneumoniae in atherosclerosis was investigated by seroepidemiological and pathological studies, in vivo and in vitro studies, and in clinical antibiotic treatment trials. C. pneumoniae has been demonstrate in atheromas by inmunohistochemical techniques, DNA isolation and even has been cultured from arterial walls. The immune system may interplay between C. pneumoniae infection and coronary artery disease. Major histocompatibility complex genes regulate innate and adaptive immunity. A recent analysis showed the HLA-B35 allele to be the strongest-risk gene for C. pneumoniae infection.
Microbes, Immunity and Multiple Sclerosis by Ana Maria Fernandez, Marcos Papais-Alvarenga, Victoria Fernandez, Miguel Guerrero, Oscar Fernandez (75-82).
Multiple sclerosis (MS) can be considered a disease that appears in genetically predisposed persons who, by chance, are also affected by some unknown environmental factor, probably infectious, that sets in motion an abnormal immune response leading to an autoimmune disease. Infectious agents are involved in the appearance of autoreactive T cells against myelin via various mechanisms, such as molecular mimetism or acting as superantigens. Numerous possible microorganisms have been suggested, including bacteria like Chlamydophila pneumoniae and many viruses, e.g., canine distemper virus, measles, varicella zoster, human herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV). The association with EBV is the best studied over recent years. The frequency (incidence and prevalence) of MS seems to be increasing, which is better explained by the effect of some environmental factor. In this study we analyze some of the infectious agents that have been associated with the disease and discuss the hygiene hypothesis, which is one of the possible explanations for the epidemiological changes reported over recent decades.
Oral Pathogens, Immunity, and Periodontal Diseases by Francisco Mesa, Jose Liebana, Pablo Galindo-Moreno, Francisco J. O'Valle (83-91).
The pathogenesis of periodontal disease is not fully understood. Subgingival bacterial pathogens are essential for the initiation and development of the disease, but it is the resulting host reaction that primarily mediates tissue damage. Complex inflammatory and immune responses are involved in the progression of periodontitis. Activated monocytes, macrophages, and fibroblasts all produce cytokines that orchestrate the cascade of destructive events in periodontal tissues. Cells from individuals with immune-mediated diseases exhibit different cytokine profiles, which may be due to genetic differences among individuals, causing hyper-responsiveness in some patients. Adaptive immunity, involving Bcells and subsets (B1, B2), plasma cells, and T-cell subsets, can be estimated by their cytokine profiles (Th1, Th2, Th17). Based on these data, it may be feasible to distinguish a protective from a destructive host response in periodontitis. Gene polymorphisms of inflammatory markers are also associated with the presence of viable periodontopathogenic bacteria. Lipopolysaccharides of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are considered key factors in the development of chronic periodontitis. Lipopolysaccharides utilize toll-like receptor-2 and increase osteoblastic expression of RANKL, interleukin-1, interleukin-8, prostaglandin E2, and tumor necrosis factor-and#945;, which are all known to induce osteoclastic activity. The aforementioned findings support the hypothesis that complex interactions among microbiota, immune system, and host genome may underlie susceptibility to aggressive periodontitis. This article reviews research on periodontopathogens and provides an update on immunity paradigms in the pathogenesis of periodontal diseases.
Editorial [Hot Topic: Aging and Immune-Mediated Diseases (Guest Editors: Christian Dejaco, Christina Duftner and Michael Schirmer)] by Christian Dejaco, Christina Duftner, Michael Schirmer (92-93).
Due to the and#x2018;baby boomersand#x2019; and health care advances, the aged population of Western countries is continuously growing [1]. Thus diagnosis and treatment of age-related diseases becomes an ever greater priority, for immune-mediated diseases translating into a need to better understand immunological dysfunction and its contribution to disease. The aging immune system, collectively termed immunosenescence, demonstrates a reduced capacity to mount a robust immune response and differentiate between self and foreign antigens. Immunosenescence manifests itself at several levels, from the whole organism to individual cells [2]: At the organism level, immunosenescence results in an increased susceptibility to age-related diseases including infections, cancer and autoimmune diseases. Besides, immunosenescence is associated with an impaired humoral response to vaccines, with suboptimal vaccination protection [3]. Biomarkers predicting the success of vaccination in aged individuals would improve current vaccination practice but such biomarkers have not been introduced into clinical routine yet. In this journal D. Herndler- Brandstetter et al. report that the presence of end-stage differentiated CD8+CD28- T-cells is associated with a reduced antibody production, whereas high levels of CD45RO+CD28+IL-2Rand#945;dimCD8+ T-cells may indicate preserved immuno-competence. As infectious diseases cause high morbidity and mortality in the elderly, this topic has to be considered as a major public health burden for the future [4]. At the cell population level, immune-aging is characterized by decreased function of progenitor and early differentiated cells as well as by the accumulation of highly specialized, senescent immune cells [5-7]. The involution of primary lymphoid organs and defects in the production of early lymphoid precursors contribute to these changes [8]. Other mechanisms such as lifelong encounter of the immune cells with acute and chronic pathogens further accelerate the progression of immunosenescence [4]. Age-associated thymic involution for example results in a significant loss of its capacity to generate and export new T-cells. Homeostatic equilibrium is then maintained by self-replication of T-cells in the periphery [8]. These peripheral mechanisms, however, are not unlimited: Telomere lengths decrease with each cell division and proliferative capacity of T-cells exhausts when telomere lengths are reduced to a critical level known as the and#x201C;Hayflick limitand#x201D; [9]. Chronic virus infections such as Human Immunodeficiency Virus (HIV) or Cytomegalovirus (CMV) accelerate peripheral proliferation of T-cells, and affected patients exhibit an aged T-cell population very early in life [4, 10]. M. Prelog and C. Duftner et al. discuss the role of early thymic failure for the development of autoimmune diseases, including juvenile idiopathic arthritis and rheumatoid arthritis [8, 11]. It is still a matter of debate, whether premature thymus dysfunction and T-cell senescence are the cause or consequence of autoimmunity. The observation that premature immune-aging also occurs in healthy individuals bearing the HLA-DR4 gene, the strongest genetic risk factor for rheumatoid arthritis, strongly supports the concept that immunosenescence precedes the onset of disease [12]. On this background immune-aging leads to phenotypical and functional changes of both, innate and adaptive immune cells. T-cell senescence for example is characterized by the down-regulation of the costimulatory molecule CD28, de-novo expression of innate immune receptors and gain of new effector functions [8]. Clinically, CD8+CD28- T-cells predict a low vaccine response (as outlined above) and are associated with an increased 2-year mortality in aged Swedish individuals [4]. Besides, higher prevalences of CD4+CD28- T-cells in the peripheral blood are linked with a worse outcome of autoimmune diseases and contribute to plaque instability in patients with coronary artery disease [8]. Concerning age-associated changes of innate immune cells, S. Mahbub et al. discuss functional changes of macrophages, neutrophils, dendritic cells, NK- and NKT-cells in aged compared to young individuals [13]. They report that aged innate immune cells have a lower capacity to clear invading pathogens as a result of lower chemotactic and phagocytosis activity. Besides, aged innate immune cells sub-optimally stimulate adaptive immune responses because of a decreased production of pro-inflammatory cytokines and defects in antigen presentation. Innate immune cells from aged individuals additionally show a lower activity after stimulation compared to young people, even though basal activation seems to be higher. The high basal activation of these cells possibly explains the common observation of high systemic levels of pro-inflammatory cytokines in the elderly. Depletion of CD28- T-cells in autoimmune diseases in order to interrupt chronic inflammation and increase homeostatic space for naive T-cells is proposed by C. Duftner et al. [8]. Such an approach, however, is critical and should be paralleled by increment of thymic output and survival of peripheral T-cells, as depletion of circulating aged T-cells drive into excessive autoproliferation aimed at re-filling-up peripheral niches. In summary, immunosenescence affects the innate and the adaptive immune system and manifests at different levels of the organism. Individuals with an aged immune system have a higher susceptibility to infections and autoimmune diseases and show a reduced immune response to vaccines. More detailed understanding of the underlying age-related alterations of the immune system should now pave the way to develop therapeutic strategies to delay, prevent or reverse immunosenescence; thereby improving quality of life in old age and new treatment regimens for patients with autoimmune diseases.
The Aging of the Adaptive Immune System by Dietmar Herndler-Brandstetter, Birgit Weinberger, Gerald Pfister, Daniela Weiskopf, Beatrix Grubeck-Loebenstein (94-103).
Adaptive immune responses are severely affected by the aging process as reflected by an increased morbidity and mortality from infectious diseases and a low efficacy of vaccination in elderly persons. Age-related changes within the bone marrow and thymus lead to an impaired generation of new T and B cells severely compromising the maintenance of a diverse and balanced T and B cell repertoire in old age. The maintenance of a balanced T cell repertoire is further challenged by latent persistent infections, such as Cytomegalovirus. Understanding the mechanisms of age-related alterations of the adaptive immune response may help to facilitate the development of more efficient vaccines for elderly persons and to envisage strategies to overcome immunosenescence.
Aging of the Innate Immune System: An Update by Shegufta Mahbub, Aleah L. Brubaker, Elizabeth J. Kovacs (104-115).
The relationship between advanced age and immunologic deficits is becoming an area of rapidly advancing research. Many of the clinical hurdles in the elderly population result from dysregulation of the immune system leading to the inability of the elderly to swiftly combat infection and to the increased incidence of chronic disease states and autoimmune conditions. Herein, we address the crucial alterations in the innate immune system that occur with advancing age. Specifically, we discuss how the effects of advanced age may lead to functional changes in the neutrophil, macrophage, dendritic cell, natural killer cell, and natural killer T cell populations in human and murine models that translate into aberrant innate immune responses. Furthermore, we elucidate how these changes may contribute to documented deficits in adaptive immunity as well as the pathological conditions and the increased morbidity and mortality seen in the elderly population.
Immune Aging and Autoimmune Diseases in Children by Martina Prelog (116-123).
Several lines of evidence suggest that premature aging of the immune system may cause alterations in the peripheral T cell homeostasis making individuals vulnerable to triggers of autoimmunity. Childhood-onset autoimmunity may offer the investigation of these aspects in the setting of a young, relatively inexperienced immune system which is affected by an imbalance in thymic output, altered proportions of peripheral T cell subpopulations and proinflammatory cytokines. One hypothesis favors the idea that premature immunosenscence in childhood-onset autoimmunity is the primary defect causing breakdown of self-tolerance; another hypothesis postulates that premature immunosenescence in children with autoimmune disorders is secondary to chronic stimulation and activation of the immune system by inflammatory processes. Population-based longitudinal studies on risk factors for development of autoimmunity beginning at infancy are required to understand the pathogenetic factors, which lead to the breakdown of self-tolerance and perpetuation of inflammation, to allow the design of targeted therapy and preventive strategies.
Early Aged T-Cells in Immune-Mediated Diseases by Christina Duftner, Christian Dejaco, Michael Schirmer (124-132).
Early loss of thymic function may be crucial for the development of immune-mediated diseases. According to this concept premature collapse of thymic output is compensated by homeostatic proliferation of peripheral T-cells, driven by recognition of self antigens and finally resulting in the expansion of autoreactive, senescent T-cell clones. Such senescent T-cells are characterized by the loss of the co-stimulatory receptor CD28 and the gain of new immunomodulatory molecules such as natural killer cell receptors and toll-like receptors. The immune system may compensate for these changes by regulatory mechanisms, including the evolvement of regulatory T-cells. However, the aging process may also affect these regulatory T-cells leading to a second and#x201C;hitand#x201D; of the immune system. Current therapeutic approaches in patients with immune-mediated diseases target common end pathways of inflammation, driven by proinflammatory cytokines and effector cells. Future directions will include the aim to reset the immune system, by restoring the ability to repopulate the immune system with young and adaptable lymphocytes as well as by strengthening the effect of regulatory T-cells.
A Role for Glucocorticoids in Thymic Involution? by G. Jan Wiegers, Denise Tischner (133-134).
Aging of the immune system is characterized by a decline in adaptive immunity that leads to immune dysfunction in the elderly. The striking involution of the thymus with age is thought to be mainly responsible for the loss of immunocompetence. This involution process has been attributed not only to changes in the production of sex hormones but also to intrinsic defects in aged progenitor T-cells. Counteracting thymic involution is expected to contribute to restoration of immune function in the elderly. Here, we focus on recent evidence that glucocorticoid hormones might fulfil such a role.


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There is practically no other place in Switzerland where the sun shines as often as it does in the Val d'Anniviers. Yet, despite this, the valley is snow-sure because the slopes reach an altitude of 3,000 m.a.s.l. Hence, the Lona Piste is the perfect place for an intensive winter experience. You can reach the starting point by gondola, chairlift and ski lift. The difficult descent is mostly above the tree line and affords wonderfully wide turns. Below Bendolla it leads directly onto the FIS Piste to Grimentz.
Starting point: Lona (2920 m a.s.l.)
Starting point: Lona (2920 m a.s.l.)
Accessibility of starting point: chairlift
Destination: Grimentz (1350 m a.s.l.)
Length: 4.3 km
Altitude difference: 1350 Meter
Gradient: 30% (average), 60% (maximum)
Level of difficulty: difficult (normal slope)
Food and beverages: at the end

subset: commoncrawl


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Edwards' annual directory to the inhabitants, institutions, incorporated companies, manufacturing establishments, business, business firms, etc., etc., in the city of St. Louis for ... /
Saint Louis Theater.
Pine Street,
[missing figure]bet.between Third & Fourth.
BenDebar, , - - . Proprietor .
KOoeei, , ... Acting Manager .
Open Ever Night, with a
Full Dramatic Company
Engagements have been made with all the most
Popular Stars,
Who Will Appear In Rapid Succession.
Dress Ciecle, Orchestra Seats and Balcony Circle, 75c.corner Pit And
Gallery, 25c.corner
Box Office open daily from 10 a.m. till 3p m., for the securing of seats.
P.Gleason, , Treas'r .


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Amarillo High senior forward Karsten Solano said the Sandies had their "eyes opened" when Palo Duro jumped ahead with a goal seven minutes into their District 5-4A opener Monday, but the reigning district champions soon took control.
Amarillo High tied the match in the eighth minute and scored twice more in the next 13 minutes to beat Palo Duro, 3-1, at Dick Bivins Stadium.
"That's the thing about the group this year, we don't panic very much," Amarillo High head coach David Daily said. "We've gone down a goal, and nobody feels like we're really out of a game."
Pedro Tavarez scored Palo Duro's goal off a rebound from Rajabu Ramadhani's shot that bounced off the goalpost, but Amarillo High's Garrett McMillian responded with a goal in the next trip down the field on an assist from Solano to tie the match.
Solano then added two goals of his own in the 22nd and 29th minutes, respectively, although Amarillo High (7-3, 1-0 in district) had to fend off several second-half scoring chances for Palo Duro (3-6, 0-1).
"We kind of got more laid back, and we needed to pick it up after we scored because it was pretty bad after we got the lead," Solano said.
Palo Duro head coach Irvin Johnson said Amarillo High dictated the play in much of the first half while the Dons battled nervousness, but after halftime he saw his team take a much more aggressive approach against what he said was the best team the Dons have faced this season.
"First district match, everybody's going to be a little nervous, but I talked to them at half and let them know that we're a much better team than this," Johnson said. "We settled down in the second half. I felt like they controlled the first half, and we controlled the second half."
But Amarillo High survived the second-half charge from Palo Duro and will now have a week off before it faces Caprock at 7 p.m. Monday at Dick Bivins Stadium.
The Sandies win also completed a sweep of Palo Duro after the Amarillo High girls team shut out Palo Duro, 3-0, in the preceding match at Dick Bivins Stadium.
Junior forward Jordan Duke put the Lady Sandies (5-3-1, 1-0) ahead with both of the team's goals in the first half. Her first came in the 12th minute on assists from senior defender Hailey Stockton and senior midfielder Aubrey Hanna, while senior midfielder Audra Park assisted on Duke's goal in the 31st minute.
Junior midfielder Sierra Briseno added the third goal in the final minute of play on an assist from junior midfielder Jessica Romo, while senior goalkeeper Darci Duncan held the Lady Dons (7-2-2, 0-1) scoreless in the first half, and freshman goalkeeper Aislinn O'Kelly played the second half to preserve the shutout.
"I think we did very well," Amarillo High head coach Stacey McPherson said. "We were able to maintain possession, spread the field."
The Amarillo High girls team will also have a week off before it faces Caprock at 5 p.m. at Dick Bivins Stadium.
The Palo Duro girls team will host Canyon at 5 p.m. Friday at Dick Bivins Stadium followed by the boys match between those schools at 7 p.m.
Amarillo High 3, Palo Duro 1
Amarillo High 3 0 — 3
Palo Duro 1 0 — 1
First Half — 1, Palo Duro, Pedro Tavarez, 7th minute; 2, Amarillo High, Garrett McMillian (Karsten Solano), 8th minute; 3, Amarillo High, Solano (Max Tatum), 22nd minute; 4, Amarillo High, Solano (Trenton LaFleur), 29th minute. Records: Amarillo High 7-3, 1-0; Palo Duro 3-6, 0-1.
Amarillo High 3, Palo Duro 0
Amarillo High 2 1 — 3
Palo Duro 0 0 — 0
First Half — 1, Amarillo High, Jordan Duke (Hailey Stockton, Aubrey Hanna), 12th minute; 2, Amarillo High, Duke (Audra Park), 31st minute.
Second Half — 3, Amarillo High, Sierra Briseno (Jessica Romo), 79th minute.
Records: Amarillo High 5-3-1, 1-0; Palo Duro 7-2-2, 0-1.
District 5-4A
Canyon 7, Pampa 0
Canyon 4 3 — 7
Pampa 0 0 — 0
First Half — 1, Canyon, Miguel Reyes (penalty kick), 25th minute; 2, Canyon, Brian Ortiz (Reyes), 36th minute; 3, Canyon, Abrham Posadas (Trevor Macklin), 37th minute; 4, Canyon, Posadas (Reyes), 39th minute.
Second Half — 5, Canyon, Posadas (Macklin), 46th minute; 6, Canyon, Reyes (Tanner Macklin), 50th minute; 7, Canyon, Trevor Macklin (unassisted), 55th minute.
Canyon: Miguel Ardate 5 saves.
Records: Canyon 4-4, 1-0; Pampa 0-1 in district.
Caprock 4, Dumas 1
Dumas 1 0 — 1
Caprock 0 4 — 4
First Half — 1, Dumas, Ricardo Robles (Bernardo Lozano), 38th minute.
Second Half — 2, Caprock, Isreal Varela (Raul Tovar) 50th minute; 3, Caprock, Tovar (Roy Garcia) 52nd minute; 4, Caprock, Varela (Javier Rubio), 72nd minute; 5, Caprock, Verela (unassisted), 78th minute.
Records: Dumas 0-1 in district; Caprock 2-3-1, 1-0.
Canyon 5, Pampa 0
Canyon 3 2 — 5
Pampa 0 0 — 0
First Half — 1, Canyon, Aeriel McBride, 6th minute; 2, Canyon, McBride, 18th minute; 3, Canyon, Madi Taylor (pk), 27th minute.
Second Half — 4, Canyon, Brittany Gregory (McBride), 43rd minute; 5, Canyon, Gregory (McBride), 56th minute.
Records: Canyon 4-2, 1-0; Pampa 0-1 in district.
AISD JV Boys Tournament Winners
from Saturday
Gold Division: Palo Duro
Silver Division: Caprock
Bronze Division: Lubbock High
Area soccer schedule
District 2-5A
Tuesday: Tascosa at Lubbock Coronado, 5 p.m.
Saturday: Tascosa at San Angelo Central, 2 p.m.
District 5-4A
Tuesday: Borger at Frenship, 6 p.m.
Friday: Canyon at Palo Duro, 7 p.m.; Amarillo High JV at River Road, 4:30 p.m.
Saturday: Borger at Pampa, noon.; Randall at Caprock, 2 p.m.
District 2-5A
Tuesday: Tascosa at Lubbock Coronado, 7 p.m.
Saturday: Tascosa at San Angelo Central, 4 p.m.
District 5-4A
Tuesday: Dumas at Caprock, 4:30 p.m.; Borger at Frenship, 4 p.m.
Friday: Canyon at Palo Duro, 5 p.m.; Borger at Pampa, 5 p.m.
Saturday: Randall at Caprock, noon.


text:
34 Holiday Ideas for Gifts in a Jar
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Majestic Flower Embossing Board Card
By: Crafter's Companion
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This majestic flower embossing board card is great for spring, but you can use it any season! Add your own personal message inside for a sophisticated card for your next special occasion.
- Majestic Impressions Embossing Board
- 6mm Embossing Tool
- 1 Sheet Of Letter Size Card (Card Main Body)
- Top Score Board (And Scoring tool)
- Drier Sheet Or Candle
- Scrap Pieces Of Card In Various Coloursnts
- Faux Gem Brads
- Adhesive
- Foam Pads
Step 1
Cut a small piece of card large enough to fit over the large central oval, and lay this face down on the board. Hold it in place with low-tack tape.
Rub over the reverse of the card with a dryer sheet or candle wax, and begin with your tool in the central leading channel at the bottom of the design.
Step 2
Push the tool firmly into the channel and push upwards, applying pressure onto the card.
Push the tool until you feel the ball meet some resistance; this usually means the channel has changed direction or shape. Continue around the board until you have embossed the whole design. Carefully cut around the frame on the outside of the embossed lines.
Step 3
Repeat the above process with excess scrap pieces fo card over top of the lily flower. Use various coordinating sheets and on some emboss the outer pattern, others the inner pattern. Cut these out.
Curl the leaves by rolling them over a pencil and then layer the flowers up and secure the centres with brads. Emboss the bow design onto a contrast piece of card in the same way - always remembering to cut around the outside of the embossed line.
Step 4
Take a piece of scrap background paper large enough to cover the solid oval inside the frame. Lay it over the frame and hold it in place with low tack-tape as in stage 1.
Emboss around the paper then cut out on the outside of the embossed design again. Stick this into place over the main frame.
Step 5
Take a piece of Letter Size card and using the Top Score Multiboard, score and fold this into a gatefold shape card. Stick the oval frame to the left hand side of the card only (this allows the card to open) and then position each of the flowers at different angles over the frame to create the look above.
Finish off with the embossed bow at the top centre piece of the card and give this extra dimension using 3D foam squares.
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Feb 24, 2012
I would LOVE to have tried this craft, but there is no accompaning photo as a guide.
Pat P
Jan 31, 2011
This sounds great, but I am one who does better by seeing a photo of the finished product, even if I don't follow it exactly. :)
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text:
To be
a continuously growing world-class paper making company we shall;
attain 35000 MT Tissue production capacity by 2007. By way of
technological up-gradation, operational efficiency and expansion.
To continue to produce tissue of international standards. To meet
the aspirations of the shareholders
Expand plant
capacity to 35000 Mt by 2007.
Be amongst top
three tissue manufacturers in the region by 2007.
Achieve customer
satisfaction levels on par with world class organisations.
Make CPML the
employer of choice by caring for employees.
Ensure zero
effluent discharge and contribute to improving quality of life.
CPML has crossed all the implementation milestones and gained
experience over the few years of successful operation. Through this
robust structure and prodigious manufacturing line, we have been
able to produce delicate yet tenacious tissue paper to cater UAE and
CPML is producing
Tissue Paper grades ranging from 13.5 gsm of delicate Facial Tissue
to 38 gsm of strong Hand Towels. It is supplied to converters in
jumbo reels for onward processing.
CPML has focused
mainly on the local demand, but yet maintained a presence in many
other markets across. CPML is currently exporting Tissue Jumbo Rolls
to countries like India, Pakistan, Sri Lanka, Nigeria, Zambia,
Morocco, Ethiopia, Libya, Singapore, Australia, United Kingdom,
Jordan, Yemen and all GCC countries.
Although paper plants
use almost traditional technology, we are committed to achieve
efficiency of scale by full automation up to the state of art
processes. And buck does not stop here. We are also committed to
improvement of extensive R&D unit, equipped with latest apparatus
committed to the object of quality as well as improvements and
alternatives, not only for the product but also the processes.
When you
deal with CPML, it is not one off business transaction. We believe
in long term relationships. We believe that suppliers or buyers are
our partners. Your first closed deal is a venture into a partnership
with us that grows with every transaction. We have always believed
in growing with our partners to ensure an 'everybody win' situation.
Yes! When we say 'you are welcome', we mean it.
Copyright � 2007
Crown Paper Mill Ltd. FZC, P.O. Box: 4192, Ajman, U.A.E.


text:
"Health Equity Needs to be a Part of the Public Health DNA"
Oct 21, 2011, 6:41 PM, Posted by NewPublicHealth
Hispanics are three times as likely to get pregnant as teens. Infants born to black women are up to three times more likely to die than infants born to women of other races and ethnicities. American Indians and Alaska Natives born today have a life expectancy that is 5.2 years less than the U.S. average. And lower income residents report fewer healthy days across all races and ethnicities (according to a Centers for Disease Control and Prevention report). The statistics are striking and disturbing – health disparities persist.
John Auerbach, MBA, outgoing president of ASTHO and commissioner of the Massachusetts Department of Public Health, helped to make health equity a priority for health officials with his year-long President's Challenge to reduce disparities [read a Q&A with John Auerbach on the Challenge here]. Yesterday at the ASTHO Annual Meeting, he led a discussion with Anna Whiting-Sorrell, MPA, director of the Montana Department of Public Health and Human Service and Joshua Sharfstein, MD, MPH, secretary of the Maryland Department of Health and Mental Hygieneon progress in advancing health equity in the last year and challenges still ahead.
"Health equity needs to be part of the public health DNA – a thread that runs through the core activities we pursue in public health," said Auerbach.
Topics in the discussion included how to talk about racism (if you're talking about it at all, you're headed in the right direction), and efforts to make the public health workforce better reflect the people it serves. Another major theme of the discussion was how to measure programs that address health equity.
"We have to decide what is success. Is it just how many people call the quit-line? Or is it broader health?" said Whiting-Sorrell.
The conversation showcased some of the videos and campaigns targeted at reducing health disparities. Sharfstein discussed a video his office created to address infant mortality.
"We tried to understand the striking data in infant mortality. Every year there would be 20-25 preventable deaths per year, almost all African American babies, often because of unsafe sleeping patterns," said Sharfstein. "We decided the mothers who'd lost children were the best conduit to get the message out."
This moving video was the result:
To address high smoking rates among American Indians living in Montana, Whiting-Sorrell and her staff developed a series of public service announcements that were targeted, while still being inclusive of different identities and ways of life within this group. "To try to be inclusive of everyone, you have to walk in both worlds – traditional and mainstream – and we have to acknowledge both, particularly in images." The videos reflect a diverse range of people to help more people identify with the messengers:
There is also an effort to move away from individual health behavior change messages, and move toward changing our communities to make the healthier choice the easier choice. "That's difficult to capture in a PSA," said Auerbach. This video was developed as a training video by the state of Ohio, as an example of how we can begin to think about educational efforts that focus on social determinants:
A video from Massachusetts addresses heart disease, and was developed specifically for the Latin American population – not just translated from English – to ensure it would be culturally appropriate.
"Hopefully we'll be able to see the health outcomes that will be the true test of whether what we're doing is working," said Auerbach.
This commentary originally appeared on the RWJF New Public Health blog.


text:
Alabama High School Athletic Association volleyball play began on Thursday and several tournaments were played over the weekend, including the prestigious Juanita Boddie at Hoover and the Mayor's Cup in Montgomery.
Sparkman lost a key player when Cierra Davis was suspended from the program for violation of team rules.
A 6-foot outside hitter, Davis was selected No. 8 on the AL.com A-List of top senior players in the state. She won't be returning to the team, according to sources close to the program.
Class 7A second-ranked Hoover (8-0) captured the 32nd annual Juanita Boddie title, downing fourth-ranked Grissom (7-2) in the final to pick up its first Boddie championship. The Bucs' front line was dominating in the tournament with A-List No. 3 Kathryn Cather and junior Ali Lowe leading the attack, while Olivia Portera anchored the defense.
Class 6A top-ranked John Carroll (6-2) beat Class 7A fifth-ranked Huntsville to win the Boddie Silver Bracket.
Class 3A second-ranked Montgomery Academy beat Class 6A seventh-ranked Pelham (6-2) to win the Mayor's Cup in Montgomery. Seniors Frances Freeman and Jillian Tinglin paced the Eagles during the weekend.
Class 2A third-ranked Providence Christian downed Class 5A top-ranked St. Paul's to win the Mayor's Cup Silver Division and Class 4A fifth-ranked UMS-Wright beat Leeds to win the Bronze Division.
Class 6A fourth-ranked Walker (6-0) won Briarwood Christian's Serve-Off Tournament, downing the host Lions in the final. Walker's Miranda Bruce led the attack with help from setter Jolee Dobbs while Madison Hood paced the defense.
Class 6A Arab (7-0) beat host Albertville a tournament. Shyan Flack, Shelby Grace Mays, Skylar Holmes and Kate Hammond led the Knights.
Class 4A top-ranked Danville (7-1) won the West Morgan tournament, downing host and Class 3A fourth-ranked West Morgan (6-1). Key for the Danville attack was A-List No. 4 Sydni Shelton along with Kellee Stiles and setter Charlee Anderson.
Class 4A Saks won its tournament by beating Class 3A Pleasant Valley in the championship.
DeQuandra Lyles, Kejuana Lee, Rakeila Anderson and Laurieta Small helped Akron downed host Sipsey Valley to win the tournament.
Class 3A Madison Academy earned its first volleyball win in school history over perennial power Class 7A Huntsville during Juanita Boddie play, downing the Panthers 25-19, 27-25 during Friday pool play.
Outside hitter Jeneva Salter of Bob Jones – A-List No. 5 – was cleared to play on Thursday following knee surgery, but hasn't practiced yet. She'll work her way back into the lineup, maybe this week.
Bob Jones setter Erin Shockey was injured on Thursday and didn't play in the Juanita Boddie tournament. She's day-to-day.
Arab setter Abby Borden (foot) and middle hitter Mattie Putman (knee) are both injured and not expected back for several weeks.
Spanish Fort's Ashley Treace and her family were involved in a car accident during the summer and Treace injured her hand. She won't return until late September.


text:
This weekend our staffers are losing themselves in nonfiction that opens up new worlds.
Let us know what you think of our choices – and what you're reading.
Her Pick: A Moveable Feast by Ernest Hemingway
As an aspiring writer who recently spent time in Paris, I've become enamored with all books related to the City of Light. Allow yourself to fantasize with this classic memoir of Hemingway's days as a young expatriate writer living on Rue du Cardinal Lemoine in the 1920s. "If you're lucky enough to have lived in Paris…" he writes. You'll wish you could go back in time and join him.
Leslie Baldwin, Account Manager
Her Pick: Shucked by Erin Byers Murray
It's the true story of a lifestyle editor in Boston who realizes she wants to explore her passion for food, so she gets a job working as an oyster farmer for a year. The book gives you amazing insights into the hard work that goes into sustainable ocean farming. It also makes you reconsider what you do every day and wonder if you'd ever take a bold step like Murray's to pursue something you love.
Tom Gliatto, TV Critic
His Pick: My Lunches With Orson: Conversations Between Henry Jaglom and Orson Welles edited by Peter Biskind
In the long, inactive autumn of his life, legendary filmmaker Orson Welles allowed his friend, director Henry Jaglom, to tape their conversations over lunch at Los Angeles's Ma Maison. His talk is full of Hollywood history and gossip (Welles was no fan of Woody Allen, whose "particular combination of arrogance and timidity sets my teeth on edge.") But it's also sadly deflating: Welles was constantly brokering – and, perversely, unbrokering – deals for new projects that would all, in the end, amount to nothing more than talk. Fascinating stuff.
Check back every Thursday for another round of staff picks, and see more book reviews each week in PEOPLE magazine, on newsstands now. Plus, check out last week's coming-of-age novels and more great book finds here.


text:
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What's Next for NAFTA?
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Removal of the last transitional trade restrictions established by the North American Free Trade Agreement (NAFTA) presents a new challenge to the agreement's signatories—Canada, Mexico, and the United States. Because the architects of NAFTA deliberately avoided creating strong supranational institutions that could have deepened the economic relationship fostered by the agreement, the member countries will have to exercise their national autonomy, either individually or in concert, in order to take additional actions that advance regional economic integration. Actions that would build upon NAFTA are sometimes referred to as "NAFTA Plus."
One possible approach to NAFTA Plus, analyzed by ERS and Canadian researchers, is for the member countries to move in the direction of a customs union, a free-trade area with a common set of external tariffs. A customs union would eliminate the possibility that differences in external tariffs would distort decisionmaking by the private sector. However, reaching consensus on these tariffs may be difficult. Each member country has preferential trade agreements other than NAFTA, and there are some substantial differences in the most-favored-nation (MFN) tariffs applied by individual NAFTA countries. As members of the World Trade Organization (WTO), each NAFTA country is generally required to apply its MFN tariffs to all other WTO members. Important exceptions to the MFN obligation include preferential trade agreements, such as NAFTA, and special access for developing countries.
Common external tariffs would enable the NAFTA countries to eliminate the agreement's rules of origin. In a preferential trade agreement, rules of origin determine whether a product originated from the area covered by the agreement and thus qualifies for its preferential tariff, which in NAFTA's case is usually duty-free status. NAFTA's rules of origin are not a major impediment to regional agricultural trade since most of the goods traded are produced using inputs originating from the NAFTA countries. Nevertheless, compliance with these rules imposes an administrative cost on firms participating in NAFTA trade. Those firms must complete NAFTA Certificates of Origin and ensure that they seek preferential tariff treatment only for qualified products.
Since 2003, the NAFTA Working Group on Rules of Origin has crafted multiple incremental changes to the agreement's rules of origin that have been implemented by the NAFTA governments. A handful of these changes directly apply to agriculture. For instance, one provision allows the regional content of certain cranberry juice mixtures to be determined on the basis of transaction value or net cost, rather than volume. Whether these steps eventually lead to a North American customs union remains to be seen, however, since they do not involve the establishment of common external tariffs.
Is NAFTA Plus an Option in the North American Agrifood Sector?, by Karl D. Meilke, James Rude, and Steven Zahniser, The World Economy, July 2008, 31(7):925-46.
NAFTA at 13: Implementation Nears Completion, by Steven Zahniser, USDA, Economic Research Service, March 2007
NAFTA, Canada & Mexico, by Steven Zahniser, USDA, Economic Research Service, April 2016
On the go? Stay connected with our Amber Waves app for tablets. Subscribe to the monthly magazine on iTunes or Google Play.


text:
For learning: Thai
Base language: English
DescriptionHello everyone,
I hope this file would be useful to whom that is interested in learning Thai and English. If there's any suspects, please inform me so that I could enhance my weak points. Thanks for your attention.
Merci! Thanks so much for every comments! I feel like I have a lot of power and energy inside my body and brain. CheersPleyley
i like it very much, i learn from that alot.i would like to be your friend, that we can chat in english and thai.i am sure that i can study from you alot.
pls chat with me on skype or msn my name is yoram_sasson. from israel.
This is great. If you have the time and energy, please post more like it! Thanks


text:
Microprocessor Controlled Induction Heaters Datasheets
EASYHEAT Induction Heating System -- 0112
from Ambrell
from Ambrell
Equipped to operate over a broad frequency range from 150 to 400kHz the EASYHEAT-0112 is a compact and efficient heating solution for applications requiring up to 1.2kW of power. EASYHEAT-0112 is frequency –agile, continuously optimizing the power delivered to the load for accurate, repeatable... [See More]
- Features: Dynamic Power Regulation; Grounding Wire Available; Microprocessor Controlled; Multiple / Independent Timing Controls; Overheat Protection; Portable
- AC Voltage Required: 117 to 220
- Phase: Single Phase AC Voltage
- Output Power: 1.20
Dyna-Flux -- Dyna-Flux V
from L.C. Miller Company
from L.C. Miller Company
Water cooled, high-frequency matching transformer with a 4:1 turns ratio [See More]
- Features: Microprocessor Controlled; Multiple / Independent Timing Controls (optional feature)
- AC Voltage Required: 230 to 460
- Phase: Three Phase AC Voltage
- Output Power: 5.00
from Ludeca, Inc.
from Ludeca, Inc.
EDDYTHERM microprocessor controlled Induction Heater for bearings and other objects allows precise setting of time or temperature to prevent premature bearing failures due to overheating. Temperature probe continuously measures and screen displays actual temperature. "Stand by" feature permits... [See More]
- Features: Microprocessor Controlled
- AC Voltage Required: 220 to 480
- Phase: Single Phase AC Voltage
- Applications: Bearings


text:
Episode Description:
Ken Wilber coined the terms "ascending" and "descending" to describe two possible orientations to spiritual practice. The ascending path has to do with transcending the world, leaving samsara behind, and fusing with the infinite. The descending path has to do with finding spirit in the world–in the midst of everyday life. Both approaches are important, and both have been clearly highlighted in Stuart Davis's journey as a Zen practitioner.
Listen in to hear Davis's radical flip-flop between these two approaches. Where Davis once found himself sitting up in his "Zen tree fort in the sky" he now finds that "the mystery" is most intimately connected with being a father & husband. Lastly, Davis shares with us a very strange and powerful connection he has with crows (yes, the animals), who apparently are an important symbol in the Zen tradition.
This is part 2 of a two-part series. Listen to part 1, Stuart Davis: Bodhisattva Rocker.


text:
On October 1, 2009, the People's Republic of China (PRC) will be 60 years old. What a turbulent jiazi (60 years)! To mark this significant occasion, Bucknell University will be hosting an international conference to reflect upon the past and explore the future of the PRC in October 2009. We are planning to have three panels: two on China's domestic challenges, one on China's foreign relations.
We encourage established and promising scholars on China to submit paper proposals on political, economic, social, environmental, technological, and diplomatic challenges that China faces today from a historical perspective. Proposals that are theoretically grounded and empirically informed are most welcome.
Bucknell University will provide accommodation and offer honoraria to the selected panelists for their contribution to the conference. Papers of the highest quality will also be published in an edited volume by a reputable publisher.
The conference is coordinated by the MacArthur Chair in East Asian Politics at Bucknell University and co-sponsored by the University's Office of the Provost and relevant programs. Located in central Pennsylvania's beautiful Susquehanna Valley, Bucknell University is ranked among the top liberal arts institutions in the United States.
Please submit a paper proposal of no more than 300 words and a short bio as a word document to email@example.com before March 15, 2009. Please put "PRC at 60 Conference" as the subject.
Deadline for Paper Proposal: March 15, 2009
Notification of Paper Acceptance and Invitation to Conference: April 15, 2009
Completed Paper Due: September 15, 2009
Conference: October 2, 2009 (arriving on Oct. 1, leaving on Oct. 3)
Revision of Paper Due: November 15, 2009
Publication of Book: Early 2010


text:
- Text Size:
- ASmall Text
- AMedium Text
- ALarge Text
A hit ABC reality show will have a new co-host when its 18th season debuts next month.
In a news release, ABC Entertainment announced that Erin Andrews, a sports correspondent for FOX Sports and previous contestant on "Dancing with the Stars," would co-host the dance competition.
Andrews, 35, replaces Brooke Burke-Charvet, who according to the release will not be returning to the program.
Andrews, who will continue to work for FOX Sports, competed on season 10 of "Dancing," where she made it to the finals. She will join co-host Tom Bergeron.
The show's new season premieres 8 p.m. on March 17. The cast will be revealed on "Good Morning America" on March 4.


text:
Leo Oknefski is a hands on guy.
"I gotta get up here like this so it's steady," says Leo Oknefski, has tremors.
Nothing is as easy as it once was. Take a look at Oknefski's hands.
"It's more on than it usually is," says Oknefski.
"If I get nervous it can be a little worse," says Oknefski.
He's one of an estimated 10-million people who suffer from a tremor disorder.
"As far as I know it's hereditary because my mother had it," says Oknefski.
Doctors find many times there is a genetic link to this neurological disorder.
"It's a movement disorder and actually the most common movement disorder. In other words shaking up and down of ones hand usually, but it can involve the head, it can involve the trunk or the voice as well. It usually is hereditary," says Dr. Amanda Avila, neurologist on Lee Memorial Health System's medical staff.
Tremors in themselves are harmless, but they can be troubling. Think of getting dressed, eating, driving a car, even signing your name-without a steady hand. For many it's reason enough to seek help.
"If the tremor is very mild we usually suggest occupational therapy. They have some adaptive devices that can be helpful; heavier pens, heavier forks and knives. Then there are medications that we use to treat tremors," says Dr. Avila.
Sedatives, blood pressure meds and those used in seizure disorders have been shown to help. A newer technique is deep brain stimulation. A surgical treatment that implants a pacemaker, like device into the brain.
"This surgery actually interrupts the abnormal circuitry in the brain that's sending those incorrect signals to the hands," says Dr. Avila.
Okneski rethinks his every move.
"Handwriting, I have to put one hand against the other," says Okneski.
But modern medicine is helping many others get a grip on their tremors.


text:
Rupert Eibauer
> Hello,
> I am getting this message occasionally. How big is the chance that it is
> really a man-in-the-middle attack?
Non zero.
> The first time I got this error, I have deleted the offending line in
> the $HOME/.ssh/known_hosts file, and just retried. The authentication
> using the authorized_keys file was also not working, so I entered the
> root password.
> After the same happened again a few minutes later, I became suspicious
> and created a new ssh key and root password.
> But now the same happens again: I get the following message, but not
> always. It happens to work ~10 times or minutes in a row, and then I get
> the error message a few times, without any recognizable pattern, and
> from the same shell.
> It seems to start working again after I try the same from a different
> user on my local machine.
Is www a single box, or a load balanced IP of some sort?
If it's a round robin dns or some other load balanced address, your
ssh client will be confused as it may be getting a different sshd
every it hits the www address.
The antidote in that case is to pick a single static ip to login to
and not ssh to a load balanced address.
The right thing to do when a key changes is to find out why, have the
admin verify the right keys for you by telling you the output of them
ssh-keygen -l -f /etc/ssh/ssh_host_dsa_key.pub
ssh-keygen -l -f /etc/ssh/ssh_host_rsa_key.pub
from a trusted console.
The key shouldn't legitimately change frequently. If you are the
admin for the box, it shouldn't ever change without your knowledge.
Sometimes updates to ssh cause a new key to be generated, or naturally
when the system is wiped and reinstalled.
Best Regards,
Todd H.


text:
"According to Pennsylvania's boating accident reports, almost 80 percent of all boating fatalities happen to boaters not wearing a life jacket," said Laurel Anders, PFBC Director of Boating and Outreach, "During late spring and early summer, boaters can expect to encounter high and cold water due to frequent rain events. These factors can be a recipe for disaster for boaters who underestimate the power of water."
Sudden cold water immersion is one of the main reasons people drown. When a person is unexpectedly plunged into cold water below 70ºF, the body's first response is usually an involuntary gasp. This is something no one can control and ruins the ability to swim because the person hyperventilates.
"There is a wealth of new research on cold water survival which states that wearing a life jacket significantly increases a person's chance of survival," Anders said. "Without a life jacket, a victim may inhale while under water and drown without coming back to the surface. This can only be prevented by wearing a life jacket at all times while on the water."
So far this year, six people have died in recreational boating incidents, several of which occurred in high water following rain events. At least two of the victims were not wearing life jackets.
Many boaters don't wear life jackets because they claim they can swim. However, a recent American Red Cross survey found that most Americans overestimate their swimming ability. Overall, the survey found that more than half of all Americans (54 percent) either can't swim or don't have all of the basic swimming skills.
"Cold, fast waters can make treading water very difficult even for those with moderate or better swimming abilities," said Anders. "Make a personal commitment to boating safety by always wearing your life jacket and insisting that your passengers do as well."
Water survival safety tips include:
To learn more about life jacket wear and cold water survival, visit the PFBC website: http://fishandboat.com/safety.htm.
Media Contact
Eric Levis, Press Secretary


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Caffeine-producing plants use three different biochemical pathways and two different enzyme families to make the same molecule.
Top 10 Innovations 2015
December 1, 2015|
The newest life-science products making waves in labs and clinics
December 1, 2015|
The newest life-science products making waves in labs and clinics
January 20, 2015|
To improve the reach of optical microscopy, researchers are enlarging the biological features they wish to view.
January 1, 2015|
Whole-animal, light-based imaging of infected small mammals
December 23, 2014|
A new microscope attachment can allow smartphone users to take a closer look at fluorescently labeled DNA.
October 13, 2014|
The Scientist speaks with W.E. Moerner, who last week shared the Nobel Prize in Chemistry for his work on super-resolution molecular imaging.
May 27, 2014|
Technique allows researchers to see the inner workings of cellular scaffolding molecules actin and tubulin.
April 1, 2014|
Three approaches for isolating and characterizing rare tumor cells circulating in the bloodstream
January 1, 2014|
A guide for doing in vivo microscopy on neurons in the mammalian brain
December 1, 2013|
Meet some of the products that didn't break into the Top 10 in 2013, but recieved praise from our expert judges nonetheless.
December 1, 2013|
The Scientist's annual competition uncovered a bonanza of interesting technologies that made their way onto the market and into labs this year.


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2005 Layton
|Research another park model
Special NotesPrint
Manufacturer note:
PARK MODELS - 1995-current prices include microwave, awning, water heater and air conditioner are standard equipment in the Deluxe models.
Year note:
Values include LP bottles, FS dinette with 4 chairs, hide-a-bed, swivel chair(2) and a queen bed with bedding.
RVs for Sale
RV Insurance
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New trucks and SUVs for your consideration
Searching for the best deal...
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Over/Under 35-18Sides 13-7Team Totals 6-8
looking at the card...
gl guys !
Originally Posted by Bruins455: I'm fairly sure that the Giants have won 11 straight over the A's at home... seems like it could be a good pick tomorrow, but who knows which Lincecum will show up
Too lazy to research any furthe, but, the home team has won the LAST 12 in this series!
Copyright © 1995-


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New YoYoFactory 888.11 is available in two splash colours and one special edition "Eight O Eight" colourway in addition to all new logos and laser engravings!
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The 888 marks the beginning of a revolution. Until very recently, full metal yo-yos were more of a novelty than high skill competition yo-yos. In 2007, YoYoFactory's design team decided to change the way metal yo-yos were viewed.
The goal was to create a metal yo-yo that offered such drastic performance improvements over all other yo-yos on the market that it would become the new benchmark in modern yo-yo performance.
It's machined with the same accuracy that is used in the aerospace industry and spins so smooth, you can barely feel it spinning! The undersized shape and tumbled 6061 aluminum create a comfortable, smooth shape & surface. The large Central Bearing Co. SPEC Bearing and silicone response system enable the yo-yo to spin longer than most ever imagined.
To top it off, the 888 features YoYoFactory's patented triple bearing "Hubstack" technology, which enables the user to hold the yo-yo in their fingertips while it's spinning.
Made in the USA.
|Butterfly / Wing.
|65.50 gr.
|50.30 mm.
|41.30 mm.
|4.90 mm.
|Size C (.250 x .500 x .187) YYF SPEC
|Gap Type:
|System Response:
|Pads Standard, 19 mm.


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They call him the Lovebird Killer, a merciless fiend unleashing a flood of unspeakable cruelty upon Sacramento's most loving couples, young and old. This real-life monster's reign of terror has left the city's residents paralyzed with fear.
All but Lizzy Gardner. Because hiding from monsters isn't Lizzy's style, not since she faced the madman who kidnapped and terrorized her as a teenager. So when a routine workers' compensation case suddenly leads her and her two young assistants onto the killer's trail, Lizzy revels in the chase. She is determined to bring this psychopath to justice before he has the chance to claim another victim. She never imagines he could be two steps ahead, watching her every move and plotting his bloodiest, most triumphant conquest of all. He knows Lizzy won't go down without a fight. And that's just the way he likes it.…
©2013 T. R. Ragan (P)2013 Brilliance Audio, Inc.
"Good Thriller"
Yes. Very good and plausible suspense thriller.
I thought Kate Rudd did a great job narrating all.
Very good 3rd book in the series. I don't see any more and certainly hope that Ragan will continue with these. Although there is quite a bit of jumping from past to present it is done in a coherent way that is easy to follow. I also really liked that at the beginning of each chapter there were quotes from real life well known serial murderers. I thought this added to the credibility of this book.
"Great Book! Did not want to put it down"
Amazing, Thriller, Action
It was a book I did not want to stop.
After readying the other reviews I almost didnt download it. There is nothing I hate more in a book that does not wrap everything up. For the person that made the comment about the couple being attacked by those guys. Please go back they did tell what happened to them and it was resolved. I'm not sure if you missed it or did not realize what happened.
the book does jump timelines quite a bit which was some times a little hard to follow but i would def recommend this book!
I love espionage, legal, and detective thrillers but listen to most genres. Very frequent reviews. No plot spoilers! Please excuse my typos!
"Another great Lizzy Gardner thriller!"
A Dark Mind is Book 3 in T. R. Ragen's six book Lizzy Gardner thriller series.It completes my listening to the series. It is a superb thriller as are the other 5 novels in the series. Kate Rudd does an great job of narration of all six novels.
I highly recommend this entire series.
Thrillers are my genre of choice for fiction while romance novels are just the opposite. I remain impressed that romance writers such as Theresa (T. R.) Ragen, Jessica Ann (J.A.) Redmerski, and Lisa Gardner (who writes romance novels as Alicia Scott) also write great thrillers. I suppose I should also mention Nora Roberts who writes thrillers as J. D Robb. and Sandra Brown who writes romance novels using several pen names, but neither of them write thriller novels of the quality of those of Ragen, Redmerski, or Gardner.
"too many characters..."
Too many characters stuggle to finish. Half way through I lost track of who was who. Why did the serial killer need three names? Well really 4 or 5? Then the extra story about the adoption could have been left out. Way too much going on in this book. I enjoy her novels so I will keep going in the series. But good grief the last time I took notes while reading I was in college studying for finals. Reading should be entertaining not work.
"What a Mess!"
This book has so many plots going, that she forgets to tie up all the loose ends, leaving part of a kidnapped couple taken by 4 men instead of the main villain, half resolved. I don't understand why she even included their kidnap/torture because it didn't fit in with the rest of the book in anyway. The reader does a good job of keeping your interest, as she stops short of a monotone, but she can do nothing to this pile of sorted plots make sense.
"I'm in love "
I'm in love with this story!! Lizzie is a real life bad ass! Jessica is on her way I feel to becoming more then what she thinks she is! sadly I think we may lose value Hayley to the dark for good! 😞 but we shall are in the next book!
"It's the Story..."
Book 1 was very good. Book 2 was ok. But book 3 has been difficult. A well known and thought of (?) woman PI catches lucky breaks without demonstrating any skill. She will manage to fall deadly prey because of poor choices!? I'm unable to finish the book knowing the end is only because the author will ignor common sense and use extravagant exaggerations to turn the story to establish the conflict and miraculously "solve" the confict.
"Suspense as always!!!"
I couldn't stop listening. Good story. But each story keeps getting sad. Narrator was good
"Favorite of the series!"
My favorite of the series so far! Can't wait to read the next one! Love that it dove deeper into Hailey's story.
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Global NewsStay informed, sign up
Below are recent news items from WFA's network of advertiser associations and the wider advertising industry. Stay informed by signing up to our monthly global newsletter.
Australia refreshes its branding ahead of Global Marketer Conference 2014The Australian Association of National Advertisers (AANA) has refreshed its brand ahead of the AANA/WFA Global Marketer Conference 2014 to be held on 26th March in Sydney, Australia.
Over 1300 entries in 2013 Golden Drum Awards1395 entries from 26 countries are competing for Golden Drum Awards 2013 organised by the Slovenian Advertising Chamber. The Golden Drum Awards, is part of the International Advertising Festival of New Europe, is one of the biggest advertising festivals in Europe.


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The Germany Company, Smartbook AG has released a new tablet device, the Smartbook Surfer360 MR7U. Newly Android tablet is packs a 7-inch multitouch display with resolution of 480 x 800 pixels. Smartbook Surfer 360 MR7U...Read More →
The Germany Company, Smartbook AG has recently introduced a new Android tablet, the Surfer 360 MN10U. The new tablet is based on the nVidia Tegra 2 SoC platform and running on Android 2.2 Froyo OS....Read More →
Smartbook AG has recently launched new Android tablet in Germany, namely the Smartbook Surfer. The new tablet is looks an awful lot like the Augen GenTouch78 tablet. The Smartbook Surfer is powered by a Telechips...Read More →
The German company, Smartbook AG is continues to assert their rights to the term of "Smartbook", they will release product under this name, the Smartbook Logo. Basically, "Smartbook" is a cross between smartphone and netbook/notebook....Read More →
Netbook is more modest versions of laptops, however, the price of a netbook can be increase considerably when it is plated with precious materials. SmartBook AG, German company has proved it, their netbook with Swarovski...Read More →


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In the latest blog entry, Drew Stanton gives an update on his offseason is going and comments on the hiring of Jim Schwartz as Detroit Lions head coach.
From what he can tell in such a short time, he's a fan of Schwartz. He also said that when he tried contacting Schwartz on Wednesday, the coach was interviewing someone.
Who was he interviewing? Stanton wouldn't say. But he did say it was someone he'd "love to get here in Detroit." Wonder if he's referring to new offensive coordinator Scott Linehan?!
DrewStanton, January 21: I really do not have much to report about Coach Schwartz. He called me yesterday and left a message from the Senior Bowl. I do not know how much you can take from a voicemail, but I was very excited after getting the message. I called him back, but his phone went to voicemail right away, which meant he was probably on the plane back to Detroit. I then went in today to introduce myself in person, but he was in an interview with someone who I would love to get here in Detroit, but will remain nameless at this point. His secretary informed me that it would probably last the rest of the day, so I will attempt again tomorrow.
Thanks, Jason, for letting me know Drew updated his blog!


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My stupid x-box wont connect to x-box live!!!!. I recently went to a hotel and connected there, but when i got home I haven't been able to connect back to online. i reset my modem and router, I've even ran a ethernet cable to the router. Nothing. It keeps telling me Error Code 80151901. Xbox apparently doesn't have a solution under there Error Code lists. Can anyone help a girl out? I'm going thru game with drawls!!!!!
Huge Xbox LIVE fan and former Community Ambassador
Always open for questions
YESS!!!!!! SanxBroski Ur the man! All i had to do was reset my network to factory settings and then re-connect! fantastic =^-^=


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The former owner of a West Allis strip club appeared in court Wednesday, three years after two women accused him of sexual assault. Recently discovered video of the incident brought life to the three-year-old case.
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text: Kenneth L. Stewart Chair, United States vCard (+Outlook) Dallas T:+1 214 855 8060 F:+1 214 855 8200 Houston T:+1 713 651 5236 F:+1 713 651 5246 Email: Practices Corporate, M&A and securities Securities Mergers and acquisitions Key industries Energy Life sciences and healthcare Financial institutions Ken Stewart is Chair of Norton Rose Fulbright US LLP. With more than 30 years of legal practice, Ken's experience encompasses almost every aspect of corporate law. A certified public accountant as well as a seasoned counselor, he offers his clients solid negotiation skills and a deep understanding of the law as it relates to corporate business transactions. Ken has handled mergers and acquisitions, partnership arrangements, securities transactions, business financings, and general corporate transactions and operations. Ken has worked with clients in several significant transactions, including the representation of a NYSE-listed MLP pipeline company in a merger with another MLP pipeline company, the special committee of directors of a NASDAQ health care company in connection with a management buyout and a NYSE-listed specialty steel manufacturer in an acquisition by merger. [+Open all] Education 1979 - JD, Vanderbilt University 1976 - BSBA, Accounting, University of Arkansas While in law school, Ken was honored as a member of the Order of the Coif and was an editor of the Vanderbilt Law Review. He was admitted to practice law in Texas in 1979. Memberships & Activities American Bar Association - Business Law Section State Bar of Texas - Corporate Counsel Section Dallas Bar Association - Corporate Counsel Section, Chair (2000) Center for American and International Law - Board and Executive Committee (2006 - 2012), Secretary (2010-2012) Rankings and recognitions Texas Super Lawyers, mergers & acquisitions, Thomson Reuters, 2003 - 2011 Texas Top Rated Lawyer, LexisNexis Martindale-Hubbell, 2012 - 2014 The Best Lawyers in America, Best Lawyers, 2006 - 2017 Memberships and activities Dallas Regional Chamber, Board Member (2005 - 2011) Executive Committee (2010 - 2011) Finance Committee (2005, 2006) Water Resource Committee (2007 - 2010), Chair (2010 - 2011) China Task Force (2006, 2007) Trinity Task Force (2007) Dallas Breakfast Group, Board Member (2010 - 2012) Dallas Citizens Council Trinity Commons Foundation Junior Achievement Dallas, Inc., Chair of the Board (2002, 2003) Dallas Business Hall of Fame, Chair (2001) Admissions Texas State Bar License Interests Ken has three daughters and enjoys hunting and golfing. [+Open all] Publications Interview with Kenneth L. StewartKenneth Stewart, our Chair of Norton Rose Fulbright US LLP in Dallas and Houston, has also acted as Global Chair since May 2015.. February 08, 2016 News Stephen Parish named global chair of Norton Rose FulbrightGlobal law firm Norton Rose Fulbright today announced that Stephen Parish, became global chair effective May 1, 2016.. May 03, 2016Lawyers Weekly – Ken StewartProfile of our new global chairman, Ken Stewart.. May 04, 2015 All related news


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I wasn't sure whether or not I wanted to jump on the bandwagon with this bee series. I live in Atlanta and I've spent a lot of time in Boston, but I wouldn't really consider either my hometown. I grew up in South Florida, but I wouldn't know what to write about because I haven't lived there in years! So, I decided to focus on a place where I've spent a lot of time in my life: Walt Disney World. Here's the catch: we're not gonna set foot inside the parks!
Obviously, I love the parks. But one of the great things about Disney is that the magic doesn't end at Space Mountain and ice cream bars. Resort-hopping is one of my favorite things to do at Disney because it allows you to be immersed in the magic without having to deal with the crowds. Best of all, the resorts are all about the details falling into place under a broader theme…sound familiar? 😉 Let's start with my personal favorite, shall we?
Disney's BoardWalk
The moment you walk through the hotel's doors, you'll feel as though you've stepped back in time. The Boardwalk is designed to look like something out of early 1900s Atlantic City or Coney Island. The resort includes the main hotel and several small villas set on a lake. And yes, there is an actual boardwalk! Give in to nostalgia as you play carnival games and take pictures in an old fashioned photo booth. Grab some tasty hummus at Spoodles, or if you're looking for something a little more gourmet, try the Flying Fish Cafe. One of the things that separates Boardwalk from other resorts is the nightlife. Catch the game at ESPN, grab some beer at Big River Grille and Brewing Works or…
…hit up the Atlantic Dance Hall for some clubbing! If you do feel like going to the parks, EPCOT is within walking distance.
Disney's Animal Kingdom Lodge
This is not your typical Disney resort. Imagine waking up in a rustic, wood-framed bed. You glance above at the African masks that line the walls. You get up, walk over to the window to greet the day, and OH HI GIRAFFE! Yep, the Animal Kingdom Lodge sits on about 30 acres of savanna. It depends on the time and the weather, but you're likely to see all sorts of beautiful animals just outside your window. If you're looking for a better guarantee for wildlife sightings, you can cozy up with your fellow newlywed aboard the Sunset Safari. This tour is pretty much the closest thing you can get to an actual safari without going to Africa. You'll tour the savanna for 1.5 hours and learn all about the vegetation, the landscape, and animals like these guys:
The dining experience is also quite unique. We have a pretty good mix of international cuisine in Atlanta, but even then, a good African restaurant is hard to come by! For exotic and intimate dining, check out Jiko. Or, if you're feeling adventurous and want to try a variety of smoky and spicy dishes, check out the buffet at Boma. Even though it's a family-friendly place, even the tables for two fill up fast so recommendations are highly recommended! Finish up your night with some live music at the Sunset Lounge.
Disney's Grand Floridian Resort & Spa
From unconventional Disney, to Disney at its most traditional form. Oh. My. Goodness. This place is just STUNNING. If you're looking for a fancy, upscale, absolutely luxurious honeymoon, this is it. The Grand comes with tennis courts, its own beach, monorail service to and from Magic Kingdom, and yes, there is a spa. Bonus points if you're honeymooning during the holiday season because guess what? There's a life-sized gingerbread house in the lobby:
You can walk over to the Wedding Pavilion and reminisce about your recent nuptials, or relax in your Honeymoon Suite's jacuzzi. For romantic dining at its finest, check out Victoria and Albert's.
Disney's Contemporary Resort
This one isn't really my style, but I wanted to share it with you because of a few fabulous highlights. First of all, the actual hotel rooms are among the largest of all the Disney resorts. Secondly, you could not pick a better location. The monorail will take you to Magic Kingdom and EPCOT, but it also goes by the Polynesian Resort and The Grand. Additionally, you can take a boat to Fort Wilderness Lodge. With all of these hot spots at your fingertips, it's easy to participate in something my cousins call "The Monorail Pub Crawl!" But that's another post for another day.
Since the Contemporary Resort sits on the lagoon, it offers lots of recreational options such as parasailing and fishing. My favorite thing to do at The Contemporary is eat at the California Grille. Why? The view is unparalleled.
Disney's Fort Wilderness
Fort Wilderness just screams Classic Disney to me. It's Disney at its roots…think Davey Crockett! The lodge (shown above) is beautiful, but the resort doesn't stop there. Fort Wilderness also offers cabins, tents, and sites for RV parking, making it perfect for honeymooners who are willing to rough it!
My favorite part of Fort Wilderness is Hoop Dee Doo, the musical revue held at Pioneer Hall. Sure, it's a little touristy, but it makes for good people-watching and the show is fun! Plus it's all you can eat…and all you can drink. Mmm sangria…
Mr. Lion hoop-dee-doo-ing after some serious sangria
That concludes the romantic and resort-y Disney tour! Are any of you planning on honeymooning at Disney?
Mrs. Lioness
- Location:
- Atlanta
- Occupation:
- Physical Therapist
- Wedding Date:
- April 2011
- Venue:
- Anthony's Fine Dining


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Top Definition
A person who is intentionally acting silly (like a silly banana) in order to impress or attract attention from their more generic fruit friends (ringing their bell on purpose).
Banana: Do whales have four legs? *hehe Im so witty and different*
Normal person: Bananabell.
Other normal person: Totally.
Normal person: Bananabell.
Other normal person: Totally.
af The wise blonde. 10. april 2013
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