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Product DescriptionUse our 1 ounce colorful plastic mini mugs for a novelty shot glass or to hold a party favor. Our 1 ounce novelty mugs are packed in assorted colors in a poly bag. Please order in increments of 1 dozen.
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- Was really looking for clear ones. Review by Chairmain
Just what I was wanting, just wrong color. Great Price, best I could find.
(Posted on 2/18/13)
- Perfect little glasses for "Mini Beers" Review by JoJo
I use these little glasses in my bar. We fill it almost to the rim with Liqueur 43 and top it off with just a splash of heavy cream. It looks like a little mug of beer! And it's delicious!
(Posted on 12/25/12)
- Great for invitation trinkets Review by Johnding
Used for out Oktoberfest party invitation. Tied them to a German beer coaster with invite glued to coaster. I wish they could provide just blue glasses howver
(Posted on 9/26/11)
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Used for many things especially toy making! Fun for foraging animals!
(Posted on 7/29/11)
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We used these mugs for an Octoberfest celebration. They were perfect for sampling the different German beers at the Beer Tasting.
(Posted on 1/5/11)
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DIY Halloween Door Decorations
You can quickly get into the Halloween spirit by decorating your front door! Just follow these easy steps.
Oktoberfest Recipes
Use these recipe ideas for delicious snacks and beverages to serve at your Oktoberfest party!
Party Tips for Hosting a Kid-Friendly Halloween Party
Teachers and moms, use these Halloween decorating and party planning tips in order to throw a faBOOlous Halloween party this year that won't give the kids nightmares!


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Just the other day I was thinking back on my cloth diapering journey of almost 4 years continuously and simultaneously diapering two babies. I thought to myself: what part of reusing diapers has made the most difference in my day-to-day life? The answer might surprise you. It's actually cloth wipes! My washing routine for cloth diapers has changed slightly over the years by moving houses and going from top-loading machine to high efficiency front-loader. My preferences in cloth diapers has changed too — at first I was a hook-and-loop girl, and now I'm definitely a fan of snaps. But I
Tag Archive: diaper changing
It's not too late to get your entry in for The CAN Challenge. Only a few weeks remain in our competition to see which man is the fastest diaper changer! Videos of the current leaders are beginning to roll in and we wanted to share them with you. Maybe you can improve your technique and trim a few seconds off your time. Remember, practice makes perfect! Joseph Hall is currently in the top 5. He entered at Fluff 'n Stuff in Knoxville, TN. Check out his awesome diaper changing skills: This epic showdown between man vs. diaper only lasts until
Our last post featured the contents of Jill's diaper bag, so I thought I'd show you mine, too! My favorite diaper bag was always the Petunia Picklebottom touring tote, but when we added a second child in cloth diapers to our family, it was suddenly too small! Instead of upgrading to the Sashay Satchel (which would have been my first choice but wasn't in the budget at the time), I decided to go to Etsy and find an artisan that could make me a bag from cloth. Mine was custom-made, but here's the design it is based on from The
After toting diaper bags for over 4 years, I think I finally have the contents paired down to the right amount of helpful stuff without over-stuffing it with half the medicine cabinet and 2/3 of the nursery. Come on, admit it. As a new mom you walk around with so much stuff for your baby, you should be dragging a rolling luggage bag behind you, right? Granted, we are beyond the newborn stage, and I have one who's potty trained, so I don't need to carry quite as much stuff as is needed with tiny babies. So here's a little
Editor's note: This blog post was written and intended to be published in time for Father's Day. However, the newest addition to Jessica's family had other plans in mind, which required some last minute edits. We're happy to announce the arrival of another little one into the Cotton Babies family and hope you enjoy this piece, despite it's slightly late arrival. The first baby my husband ever held was my nephew, for probably 3 minutes before handing him back to me. Fast forward 19 months, and the next baby he held was our daughter. I remember him asking me when
LET'S GET READY TO RUMBLE! DING, DING, DING! To celebrate Father's Day, bumGenius, Flip, and Econobum are launching The CAN Challenge, a chance for the man in your life to compete for the ultimate title – The Fastest Diaper Changer! This epic showdown between man vs. diaper will take place from June 16 to August 4 at a participating retailer near you. All classes are eligible! Whether it's a proud papa, grandpa, friend, or brother, we want to put his diaper-changing skills to the test! All you need to do is get your man into a participating retailer and have
Be sure to stop by your local Cotton Babies this weekend and join us as we celebrate Earth Day! Stop by any of our St. Louis, MO or Vancouver, WA locations tomorrow to learn how you could win six bumGenius Freetime diapers through our Change3Things Challenge. We have great sales planned for all day including, buy 5 get 1 FREE on bumGenius 4.0, Freetime, Elemental, and Newborn cloth diapers and other amazing deals on FuzziBunz, Thirsties, GroVia, and more!* We look forward to seeing you! Stores are open until 8 p.m. Be Green. Save Green. *Online sale ends Monday, April
So you've gotten over the learning curve of cloth diapering, and you're loving the fuzzy bum on your new bundle of joy. It's easy for you, because you've got your washing routine down and all your supplies where you need them! But what about when it comes time to hand off your little one to a different caretaker? Whether it is a family member, a babysitter, a Mother's Day Out program once a week, or even regular daycare – talking to someone who isn't familiar with cloth diapers can be daunting! After my son was born, I went back to
It's spring break for many of us here in St. Louis, which means only one thing… time to get out and enjoy the great outdoors. Whether you're staying home or traveling to the beach, spring break is a time to relax. And what better way to relax than to save yourself a load or two of laundry? Flip Travel Packs are just the answer! Each pack has two Flip one-size covers and a pack of disposable inserts. If you are leaving home, with Cotton Babies free economy shipping, you can even save some room in your luggage by shipping them
Cloth diapering a newborn can seem intimidating, especially if it's your first child that you'll be diapering. But then again, everything about newborns can seem a little intimidating, right? It's because it's new, not because it's hard. Now that I have the diapering of three kids (and the potty training of two of them, more or less) under my belt, I'm going to go ahead and say it: diapering newborns is the easiest part. Newborns don't move around that much. Not that they can't wriggle and squirm but at least they can't get up and run away laughing in the

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Recently, new complexities in cell fate decision for helper T cells have emerged. One new lineage, which has come to be called Th17 cells, selectively produces proinflammatory cytokines including interleukin-17 (IL-17, A and F), IL-21, and IL-22. In conjunction with transforming growth factor β-1 (TGFβ-1), IL-6, IL-21, and IL-23, which activate the transcription factor, signal transducer, and activator of transcription 3 (Stat3), the expression of another transcription factor, retinoic acid-related orphan receptor-γt (RORγt) leads to the differentiation of Th17 cells in mice. Other cytokines including IL-2, IL-4, interferon-γ (IFN-γ) and IL-27 inhibit Th17 differentiation. However, IL-2 acting with TGFβ-1 induces differentiation of naïve CD4+ T cells to become regulatory T cells (Tregs). Th17 cells are now known to play an important role not only in the pathogenesis of inflammation and autoimmune diseases, but also host defense against extracellular bacteria. Conversely, extensive data substantiate the role of Tregs as essential in maintenance of peripheral tolerance. Selectively targeting Tregs and Th17 cells are likely to be important strategies in the treatment of inflammatory and autoimmune diseases in humans.
It is well-established that the innate immune response leads to activation of adaptive immunity, shaping the proper response, depending upon the pathogen eliciting the reaction. Conversely, though, it is also clear that adaptive immune response, especially, CD4+ or helper T cells orchestrate responses to effectively eliminate pathogens. Classically, helper T cells were considered to differentiate into two lineages, T helper 1 (Th1) cells or Th2 cells (1). In addition to ligation of the T-cell receptor (TCR) and co-stimulatory receptors, a suitable cytokine milieu is required for fate decision of helper T cells (1). In particular, interleukin-12 (IL-12), which is produced by activated antigen-presenting cells (APCs), promotes Th1 differentiation (2), whereas IL-4, produced by activated T cells and some innate immune cells, drives Th2 differentiation (1).
While the Th1/Th2 paradigm provided invaluable insights for immunologists, its limitations were also clear. What was the most obvious was the inability of this dichotomy to explain autoimmune diseases. More recent studies have shown the existence of the additional subpopulations of T helper cells that are also important in immunoregulation and host defense. One important subset is CD4+CD25+, regulatory T cells (Tregs) (3, 4). Tregs suppress the proliferation and function of effector T cells, and attenuate immune responses against self or nonself-antigens (3, 4).
Another recently identified new fate of T cells is Th17 cells that selectively produce IL-17 (A and F) (5, 6). In the past three years, discoveries pertaining to this newly identified T helper subset in humans and mice have accumulated with tremendous speed (7-10). It is also clear that the notion of a single type of Th17 cell may not be correct, as there seems to be further complexity in terms of the cytokines produced by these cells. In this review, we will discuss the historical developments that led to a new understanding of the role of T cells in autoimmune diseases and recent advances that have led to even newer insights into T cell biology.
Until a few years ago we thought we knew which subset of helper T cells was responsible for host defense or exacerbation of autoimmune diseases and we thought that answer fit well with the standard Th1/Th2 cells paradigm (11). Th1 cells produce interferon-γ (IFN-γ) and lymphotoxin, and are responsible for protection against intracellular pathogens such as viruses, mycobacteria, and protozoa (11). Produced by activated APCs, IL-12 activates the transcription factor, signal transducer, and activator of transcription 4 (Stat4) (2). Stat4-dependent signaling in conjunction with TCR-dependent signals induces the expression of T-box-expressed-in-T-cells (T-bet), the so-called master regulator of Th1 differentiation (2). Recently, in humans, it has been shown that STAT4 polymorphisms are associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (12). IFN-γ also activates Stat1 which further induces T-bet to form an autocrine feedback loop for IFN-γ production (2). T-bet promotes not only IFN-γ production but also suppression of Th2 cytokines production by T cells (2). On the other hand, Th2 cells produce IL-4, IL-5, and IL-13 (1). IL-4 activates Stat6, which up-regulates the expression of GATA-binding protein 3 (GATA-3) (1). Th2 cytokines are potent activators of B-cell Immunoglobulin E production, eosinophil recruitment, and mucosal expulsion mechanisms, and are essential for promoting host defense against helminths and other parasites (1). In addition, Th2 cells have been shown to mediate allergic diseases such as asthma, rhinitis, and atopic dermatitis (11).
Traditionally, autoimmune diseases had been assumed to be associated with dysregulated Th1 responses (13). Because the treatment with anti-IL-12p40 antibody was effective in Crohn's disease (CD) and psoriasis (14, 15), it was further assumed that IL-12-mediated IFN-γ production and Th1 response were involved in the pathogenesis of autoimmunity. However, it was shown that IFN-γ deficiency exacerbated rather than ameliorated mouse models of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) (16). Subsequently, a new cytokine, which consists of IL-23p19 and IL-12p40, was identified and termed IL-23 (17). Interestingly, the IL-23 receptor (IL-23R) forms dimers with the IL-12Rβ1 chain shared by IL-12 and IL-23 (18). IL-23R is predominantly expressed on T and natural killer (NK) cells (18, 19). IL-23 activates Janus kinase 2 (Jak2) and tyrosine kinase 2 (Tyk2), which in turn leads to activation of Stat1, Stat3, Stat4, and Stat5, among which Stat3 is the predominant factor phosphorylated by this cytokine (17, 18).
Of note, IL-23p19-deficient mice or IL-12p40-deficient (IL-12/IL-23-deficient) mice were resistant to collagen-induced arthritis (CIA) and EAE (20, 21). However, IL-12p35-deficient mice had increased susceptibility to CIA and EAE (20, 21). These studies directly negated the pathogenic role of the IL-12/IFN-γ axis in autoimmunity. This was an important piece of information that led to the unraveling of the Th1/Th2 paradigm as an explanation of autoimmunity. Accordingly, additional studies on IL-23p19-deficient mice and the anti-IL-23p19 antibody revealed that IL-23, but not IL-12, was the culprit in autoimmunity, at least in mouse disease models (21-23). The pathogenic role of IL-23 was also confirmed by the phenotype of IL-23p19 transgenic mice, in which premature death, systemic inflammation, anemia, and elevated serum levels of inflammatory cytokines and acute phase proteins were observed (22). In human disease, the mRNA levels of both IL-23p19 and IL-12p40 were shown to be increased in skin lesions of psoriatic patients (24), suggesting that elevated IL-23 contributed to the pathogenesis of psoriasis. Therefore, IL-23 began to attract attention as a factor crucial to inflammation and autoimmune diseases.
While it was becoming clear that IL-23 was the culprit in autoimmune and inflammatory diseases, the question remained, how was it acting? Another inflammatory cytokine, IL-17, was noted to be produced by activated purified T cells in the presence of LPS-stimulated dendritic cells (DCs) (5). It was also found that IL-23 promoted IL-17 production from memory T cells and this production was suppressed by treatment with anti-IL-12p40 antibody (5).
Now IL-17 is recognized as the founding member of a family of proinflammatory cytokines: IL-17 (IL-17A), IL-17B, IL-17C, IL-17D, IL-17E (known as IL-25), and IL-17F (6). IL-17A and IL-17F induce the production of various proinflammatory cytokines such as tumor necrosis factor-α (TNF- α), IL-1β, and IL-6, and CXC chemokines from monocytes, airway epithelial cells, vein endothelial cells, and fibroblasts to mount defense against extracellular bacteria such as Klebsiella pneumonia, Bacteroides fragilis, and Mycobacterium tuberculosis (6, 25, 26). These responses result in the recruitment, activation and migration of neutrophils to the sites of inflammation and infection (6). CD4+ T cells are major producers of IL-17, but in addition CD8+ T cells, neutrophils, γδ T cells, and invariant natural killer T (NKT) cells also produce this cytokine (26-28).
Various reports associated IL-23 with IL-17 production with the onset or exacerbation of inflammation (20-23, 29). For instance, IL-23p19-deficient mice showed reduced incidence of CIA, with fewer IL-17-producing CD4+ T cells (20). Consistent with this report, treatment with anti-IL-23p19 antibody reduced serum levels of IL-17 and inhibited development of EAE (29). Moreover, IL-23 was found to be essential for production of IL-17 and IL-6 in colitis mouse models (22, 23). Regardless of exactly how IL-23 works, these reports supported the idea that an IL-23/IL-17 axis, but not IL-12/IFN-γ axis, was a crucial pathway in the pathogenesis of various autoimmune diseases (21, 30).
Although many results linked IL-23 with IL-17 production in CD4+ T cells, less was known about how Th17 cells arose from naïve CD4+ T cells. It was very clear that development of IL-17-producing T cells was not dependent on the cytokines and the transcription factors required for Th1 or Th2 differentiation and then it was proposed that IL-17-producing CD4+ T cells represented a new subset of helper T cells (Th17 cells), which were crucial in mediating inflammatory responses (30-32). While there was evidence that IL-23 stimulated CD4+ T cells to express various genes, including IL-17, and that IL-23-stimulated T cells were important in the pathogenesis of EAE (30), it was less clear whether IL-23 was the factor that drove naïve CD4+ T cells to become IL-17 producers.
It was especially puzzling that naïve CD4+ T cells did not express IL-23R (18). In a search for optinum culture condition for Th17 differentiation it was recognized that naïve CD4+ T cells cultured with activated DCs produced IL-17 (16). It was then recognized that the combination of IL-6 and transforming growth factor β-1 (TGFβ-1), with appropriate stimulation of TCR, were the optinum stimuli inducing Th17 differentiation (Fig. 1a) (16). Accordingly, TGFβ-1-deficient mice showed impaired Th17 development, whereas addition of TGFβ-1 rescued the number of Th17 cells (7, 33). Thus it became clear that IL-23 was not the direct initiator of Th17 production (16), but rather was an important factor for expanding and maintaining Th17 cells in vivo (34).
In the classic Th1/Th2 paradigm, T cell subsets produce factors that promote their differentiation and constrain the differentiation of the opposing lineage. It was of interest in this regard that the Th17 cells were found to selectively produce IL-21 (35-38). IL-21 has structural homology with IL-2 and IL-15, and the initial report showed the effects of IL-21 produced by CD4+ T cells and NKT cells on the proliferation and function of NK cells, B cells, and T cells (39, 40). Recently though, it has also been found that the autocrine production of IL-21 by Th17 cells promotes Th17 differentiation while inhibiting IFN-γ production (35-38). Accordingly, the deficiency of IL-21 (or its receptor), or blocking of IL-21, attenuates the generation of Th17 cells (35-37).
To precisely understand the molecular mechanisms of Th17 differentiation, it is important to define the transcription factors that directly regulate IL-17 production. All of IL-6, IL-21, and IL-23 activate the transcription factor Stat3 in T cells (38, 41, 42); accordingly, Th17 differentiation is abrogated in Stat3-deficient T cells (38, 42-45). Moreover, conditional deletion of Stat3 in T cells also abrogates the development of autoimmune diseases such as EAE and autoimmune pneumonitis in mice (43). The role of Stat3 in Th17 differentiation seems to be remarkably direct – i.e. Stat3 binds to the Il17 and Il21 loci, as detected by using chromatin immunoprecipitation (ChiP) assays (38, 41). In addition, IL-6 and IL-23 promote IL-23R expression and this also is Stat3-dependent (10, 36, 37). Recently, the importance of Stat3 in human Th17 differentiation has been documented (46).
Like other T cell subsets, Th17 cells also have a lineage-specific transcription factor, namely the retinoic acid-related orphan receptor-γt (RORγt) (8). Interestingly, RORγt-deficient T cells produce fewer Th17 cells, whereas overexpression of RORγt in T cells promotes IL-17 expression (8). Furthermore, RORγt-deficient mice are less susceptible to EAE, suggesting that RORγt is a key regulator of Th17 differentiation (8). Recent studies have shown that RORγt expression is significantly reduced in Stat3-deficient T cells (43-45). However, the precise molecular mechanisms of Stat3-mediated expression of RORγt are still unclear. Even so, RORγt could be a good candidate to target in treating inflammatory diseases (discussed in further detail below). Also, it has been shown that expression of another retinoic acid related nuclear receptor, RORα also induces Th17 differentiation (47). RORα seems to synergize with RORγt to promote development of Th17 lineage (47).
Because of their potential for inducing immune-mediated damage to the host, it is perhaps not surprising that multiple mechanisms exist to inhibit the production of Th17 cells (Fig. 1b). Indeed, it has been recognized that the Th1-related cytokine IFN-γ inhibits Th17 differentiation (31, 32). Consistent with this concept, T-bet-deficient mice show enhanced Th17 differentiation (48). Similarly, the Th2-related IL-4 is also shown to down-regulate Th17 differentiation (49). However, how IFN-γ and IL-4 inhibit IL-17 production is not yet known. Interestingly, IL-27, an IL-12-related heterodimeric cytokine, also has anti-inflammatory effect by inhibiting the generation of Th17 lineage and leads to limitation of EAE (50). Like IFN-γ, IL-27 suppresses Th17 differentiation through a STAT1-dependent manner (51, 52).
IL-25 (IL-17E) was also shown to inhibit IL-17 production by promoting Th2 differentiation (53). These reports suggest a cross-regulatory relationship among Th1, Th2, and Th17 differentiation. However, it still remains to be determined how Th1-related and Th2-related transcription factors negatively regulate IL-17 production.
Another new subset of helper T cells that provides considerable insight into the pathogenesis of autoimmunity is the CD4+CD25+ regulatory T cells (Tregs) (3, 4, 54). Tregs suppress proliferation of effector T cells and maintain self tolerance by down-regulating immune responses against self or nonself-antigens (3, 4, 54). The mechanism by which Tregs preserve peripheral tolerance is still not entirely clear; however, they preferentially express cytotoxic T-lymphocyte antigen 4 (CTLA-4), and immunosuppressive cytokines including TGFβ-1 and IL-10 (55-57). Naturally arising Tregs (nTregs) are generated in the thymus, whereas inducible Tregs (iTregs) arise from naive T cells after antigen exposure and cytokine stimulation in the periphery, especially in the gut (58). Recently, it has been shown that CD4+CD25+ T cells express the transcription factor, forkhead box protein 3 (Foxp3), which is necessary and sufficient for Tregs to develop and function (59, 60).
In mice, IL-2 and TGFβ-1 were able to differentiate CD4+CD25- naïve T cells into CD4+ CD25+ Foxp3+ Tregs (61, 62). Therefore, the importance of TGFβ-1 for both Tregs and Th17 lineage led to the speculation that these lineages were related. This putative relationship also led to investigation of the importance of IL-2 in Th17 differentiation (44). In fact, IL-2 was found to inhibit the expression of RORγt while the enhancing expression of Foxp3 (44). Furthermore, blockade of IL-2 or deletion of Stat5 promoted Th17 differentiation, suggesting that IL-2 inhibited Th17 lineage by affecting the RORγt-Foxp3 balance (44). Therefore, helper T cells seem to have a unique way of achieving a balance between Tregs and Th17 cells during ongoing immune responses. Recently, it has been reported that TGFβ-1 can promote either Th17 or Tregs lineage differentiation, depending on its local concentration (63). Interestingly, Foxp3 may inhibit RORγt activity on its target genes, at least in par,t through direct interaction with RORγt (63).
The roles of Th17 cells are complicated by the fact that these cells also have the ability to produce anti-inflammatory cytokines such as IL-10 (34). This cytokine has anti-inflammatory properties that suppress functions of DCs and macrophages (64). IL-10 can be produced by many cell types such as B cells, macrophages, DCs, Th2 cells, and distinct populations of Tregs (64). Recently, it has been reported that de-novo generation of Th17 cells in the presence of IL-6 and TGFβ-1 leads to the production of IL-10 with up-regulation of RORγt and IL-17 (34). Furthermore, IL-1β, but not IL-23, potentiates IL-10 production in Th17 cells along with IL-6 and TGFβ-1 (34). Paradoxically, IL-6 and TGFβ-1 seem to drive initial Th17 lineage commitment but also restrain the pathogenic potential of Th17 cells by producing IL-10 also (34).
Another cytokine produced by Th17 cells is IL-22 (25, 65, 66). IL-22 belongs to the IL-10 family of cytokines which include IL-19, IL-20, IL-24, and IL-26. Expressed in activated T cells, Th1 cells and NK cells (67), IL-22 induces expression of various antimicrobial peptides such as β-defensins in skin, respiratory, and digestive tissues, which express IL-22R (68). In fact, expression of IL-22 and β-defensins is higher in skin from patients with psoriasis and atopic dermatitis than in that from healthy individuals (69).
While it is clear that IL-22 and IL-17 can contribute to host defense and to pathogenesis of various autoimmune diseases (25), it is also notable that IL-22 also has important anti-inflammatory effects (70). Specifically, IL-22-expressing Th17 cells provided protection in models of hepatitis (70). Recently, IL-22 also has been shown not to be required for the development of EAE in mice (71). These facts indicate the complexity of Th17 cells, which produce multiple cytokines and have diverse functions during inflammation. As such, their relevance may vary among different autoimmune diseases.
While a large body of evidence has documented that the best recipe for generating Th17 cells from murine naïve CD4+ T cells is the combination of TGFβ-1 and IL-6 or IL-21, several groups initially reported that the regulation of human Th17 differentiation was quite distinct (Fig. 1c) (9, 10, 66, 72-74). Specifically, TGFβ-1 was initially considered to have inhibitory effect on human IL-17 production; however, the role of TGFβ-1 in human Th17 differentiation has recently become clearer. While TGFβ-1 alone had an inhibitory effect on production of IL-17 by T cells, culturing human naïve CD4+ T cells from cord blood in serum-free medium revealed a requirement of TGFβ-1 for Th17 differentiation (72). TGFβ-1 seems to have dual effects on human Th17 differentiation in a dose-dependent manner. While TGFβ-1 is required for the expression of RORγt in human naïve CD4+ T cells from cord blood, TGFβ-1 can inhibit the function of RORγt at high doses (72). However, inflammatory cytokines (IL-1β, IL-6, and IL-21 or IL-23) relieve the latter effect of TGFβ-1 (72). By using serum-free medium it has thus been clarified that the optimum conditions for human Th17 differentiation are TGFβ-1, IL-1β, and IL-2 in combination with IL-6, IL-21 or IL-23 (72-74). Of these latter cytokines, IL-23 seems to be the most effective (10, 66, 72, 73). A key aspect of Th17 regulation is the regulation of IL-23R (10). Naïve CD4+ T cells express low levels of this receptor, but the combination of TGFβ-1, IL-1β, and IL-23 can strongly induce this receptor (10, 72). Thus, IL-23 promotes expression of its own receptor, allowing it to be an effective inducer of IL-17.
It is of note is that CCR6+IL-23R+ human memory CD4+ T cells are major producers of IL-17 (75, 76). Because CCR6+CD4+ T cells, but not CCR6-CD4+ T cells, secrete IL-17 and expression of IL-23R, CCR6, and RORγt is up-regulated during Th17 differentiation (72), these factors seem to be essential for development of human Th17 lineage.
Importantly, it has been shown that mutations presumed to underlie hyper-IgE syndrome (HIES, "Job's syndrome") are identified in the STAT3 gene (46). Purified naïve CD4+ T cells from HIES individuals can not differentiate into Th17 cells in vitro and have lower expression of RORγt (46), suggesting that Stat3 signaling is also a crucial factor for the generation of human Th17 cells.
Although Th17 cells are important and essential subsets participating in host defense against extracellular antigens, evidence implicating Th17 cells as a causal factor of autoimmune diseases is also mounting (25). Following extensive analysis of mouse disease models such as EAE, CIA, and IBD, it has also become evident that IL-17 is a contributing factor in human autoimmune diseases. For instance, perivascular IL-17-producing T cells are present in brain lesions of active MS patients and these cells are reduced in quiescent MS patients (77). Moreover, DCs from MS patients secrete more IL-23 than healthy controls, and T cells from MS patients secrete more IL-17 than healthy controls (78). Also, elevated levels of IL-17 have been noted in the sera and in tissues of patients with RA, IBD, and psoriasis (25). We will see more evidence confirming the roles of IL-17 in human diseases and inflammation in the future.
Recent genetic data has linked polymorphisms of the Il23r gene to various human diseases such as ankylosing spondylitis, CD, and psoriasis (79-81). Accordingly treating CD and psoriasis patients with anti-IL-12p40 antibody has resulted in some success (14, 15). These results argue strongly for a role of the IL-23/IL-17 axis in human autoimmune diseases.
It is of particular interest to evaluate the contribution of Th17 cells to the pathogenesis of RA, because targeting pathogenetic Th17 might be a reasonable strategy for treating RA. First, IL-17-deficient mice fail to develop CIA when challenged (82). Consistent with this, treatment with neutralizing IL-17 monoclonal antibody ameliorates joint inflammation in CIA models (83). Furthermore, it has been reported that active immunization using virus-like particles conjugated with recombinant IL-17 leads to high levels of anti-IL-17 antibodies in mice and reduces scores of disease severity in CIA (84). These results highlight the role of IL-17 as an exacerbation factor in rodent arthritis models.
Because the expression of IL-17 and IL-23p19 was observed in the synovial fluid and serum of RA patients, these factors were presumed to be pathogenic (85). In particular, IL-17 up-regulates the production of IL-1β and TNF-α from APCs in arthritic joints (86, 87). Moreover, IL-17 induces IL-6, IL-8, and IL-23 from RA synovial fibroblasts and chemokines such as CCL20/MIP3α from synoviocytes to induce migration of T cells and DCs into inflammatory lesions (86, 87). IL-17 also promotes cartilage breakdown by inducing matrix metalloproteinases-1 (MMP-1) from RA synovium (86, 87). Additionally, IL-17 induces cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) synthesis by osteoblasts and it then induces expression of receptor activator of NF-κB ligand (RANKL) to differentiate osteoclast progenitors into mature osteoclasts (86, 87). Pro-oxidants such as nitric oxide are also produced by chondrocytes and osteoblasts in response to IL-17 (86, 87). Taken together, these multiple factors induced by IL-17 seem to promote bone resorption, extracellular matrix degradation, synovium proliferation, angiogenesis, and recruitment and activation of immune cells for bone erosion and articular destruction in RA joints. This being said, there is little evidence of T cell proliferation in RA and we still do not know for certain the cellular source of IL-17 in RA synovium (88).
For these reasons, IL-17 seems to be a rational target in the treatment of RA, and Phase I/II clinical trials of anti-IL-17 monoclonal antibody (AIN457) have commenced (http://www.clinicaltrials.gov/). It has been reported that combining inhibitors to block TNF-α and IL-17 has the synergistic effect of suppressing IL-6 production and collagen degradation in the synovium and bone of RA patients (89). Therefore, anti-IL-17 therapy may become an alternative for treating patients unresponsive to conventional anti-TNF therapy. It still remains to be seen whether blocking IL-17 will affect other proinflammatory cytokines for example IL-6, IL-1, and IL-22 in RA patients. More studies will shed light on the validity of anti-IL-17 therapy.
While the role of IL-6 in regulating IL-17 production has only recently been appreciated, the role of IL-6 as a proinflammatory cytokine has long been recognized. For this reason, targeting IL-6 in RA has been considered for some time. Indeed the efficacy of humanized anti IL-6R monoclonal antibodies (tocilizumab/atlizumab) in the treatment of adults and children with arthritis has recently been reported (90). Also, in April 2008 tocilizumab was been approved in Japan for treatment of RA in Japan, and Phase III trials have been completed in the US (http://www.clinicaltrials.gov/). To what extent their efficacy relates to inhibition of IL-17 will be important to ascertain. Similarly, in the US, recombinant human anti-IL-1Rα antagonist (anakinra) has been approved for use in the treatment of RA (91). Recently, more IL-1-targeting therapies for RA patients are in Phase II studies including anti-IL-1β monoclonal antibody (ACZ885), human monoclonal antibody to IL-1R (AMG108), and IL-1 Trap/rilonacept (http://www.clinicaltrials.gov/). Although IL-1 has been reported to contribute to Th17 differentiation in mouse and man, it remains to be determined whether therapeutic targeting of IL-1 will substantially affect IL-17 in RA. On the basis of the efficacy of anti-IL-12p40 therapy in human autoimmune diseases (14, 15), a humanized monoclonal anti-IL-12p40 antibody (ABT-874) was tested in RA (92). However this antibody was not shown to be effective because of the trial design (92). Another strategy for targeting IL-12/IL-23 is apilimod mesylate (STA-5326), an oral inhibitor of IL-12p35/p40, which has been tested in a Phase II study for RA (http://www.clinicaltrials.gov/). Whether selectively targeting IL-23p19 will be more efficacious or have a better safety profile remains to be determined.
In principle, targeting IL-21 might also be efficacious in treating RA in which IL-17 is involved in immune-mediated damage. Importantly, the common gamma chain and JAK3 play a pivotal role in the signal transduction of IL-21 (25). In fact, a JAK3 inhibitor (CP-690550) is about to be tested in RA (Phase II trial) (http://www.clinicaltrials.gov/). It will be important to know whether the efficacy of this drug is related to inhibition of IL-17.
The past four years have witnessed major revisions of our views on the lineage commitment of helper T cells. The conventional Th1/Th2 dichotomy has been replaced by more complex multi-lineage models which do a much better job of explaining the pathogenesis of autoimmunity (Fig. 1). It now seems that Th17 cells are one of the more important villains in the pathogenesis of autoimmune diseases. However, it is of note that they are also essential for host defense against extracellular bacteria. Therefore, the challenge will be to keep Th17 function in check to control autoimmunity, while maintaining host defense at the same time. In this regard, we still need to learn what are the most critical factors for Th17 differentiation. We also need to better understand which human autoimmune diseases are truly mediated by IL-17 and, by extension, which diseases will benefit most from anti-IL-17 therapy. With the current pace of investigations on Th17, this field has a great potential for advances. There is no doubt that IL-17 and the other proinflammatory cytokines are likely to be relevant therapeutic targets in the treatment of human autoimmune diseases.
The authors have a Cooperative Research and Development Agreement with Pfizer Inc.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


text:
See Also:
Monday, September 26, 2016
Oliveros Collaborates With Ernesto Perez-Carrillo
Thursday, September 22, 2016
General Cigar and Giannini Part Ways
Thursday, September 22, 2016
La Palina Launches Value-Priced Goldie Called Illumination
Wednesday, September 21, 2016
My Father's The Judge Will Hold Court Soon
Tuesday, September 20, 2016
Two Limited-Edition La Aurora Cigars Coming Soon
- More from News & Features
30 Inches of Snow? Time for a Smoke
Andrew Nagy
Posted: February 9, 2010
Webster's may need to rewrite the definition of determination to include a photograph of Greg Franks, a cigar enthusiast who resides in Baltimore, Maryland.
Franks, pictured, did not let this past weekend's Mid-Atlantic snowstorm, which dumped 30 inches of snow on the area, prevent him from enjoying a cigar.
"That's my backyard," Franks said, explaining the photograph he sent into Cigar Aficionado online. "I can't smoke inside."
A resident of Baltimore for 15 years, Franks works for Merrill Lynch/Bank of America and says he has enjoyed fine smokes for about 20 years.
Franks began smoking Cubans while he was living in Europe, and now he prefers to smoke either a Camacho or La Flor Dominicana cigar. He smokes about two or three cigars a week.
"I picked up the habit when I lived in Europe—in London," Franks said.
Married with three children, Franks has been a loyal subscriber to Cigar Aficionado for "about seven or eight years."
No doubt Franks' backyard retreat will be in use again shortly, as another big snowstorm is expected to hit the region soon.
Check out our Moments to Remember section where you can find out how to submit your own cigar-smoking photographs.
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text:
Trail of Tears (disambiguation)
From Wikipedia, the free encyclopedia
(Redirected from Trail of Tears (album))
Trail of Tears is the forced relocation of many Native Americans groups.
Trail of Tears may also refer to:
- Trail of Tears State Forest in southern Illinois
- Trail of Tears State Park in Missouri
Art, entertainment, and media[edit]
- The Trail of Tears: Cherokee Legacy, a 2006 documentary
- Trail of Tears (band), a Norwegian musical group
- "Trail of Tears", a song composed by Roger Cook, Allen Reynolds and Randy Handley and recorded by John Denver, on his 1985 album, Dreamland Express and by Hal Ketchum on his 1992 album Sure Love
- "Trail of Tears", a song by Eric Johnson, from his 1986 album, Tones
- "Trail of Tears", a song by Nuclear Assault, from their 1989 album, Handle with Care
- "Trail of Tears", a song by Testament, from their 1994 album, Low
- "Trail of Tears" (Strangers with Candy), a Season 3 episode of the television comedy Strangers with Candy
See also[edit]
- "Trial of Tears", a song by Dream Theater, from their 1997 album, Falling into Infinity
|This disambiguation page lists articles associated with the title Trail of Tears.
If an internal link led you here, you may wish to change the link to point directly to the intended article.


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Must Watch
Ali G: Rezurection
- Summary
- Reviews / Ratings
- Photos
- Videos
- Events
"Ali G: Rezurection" is one of those television series which, if we try to explain it, might sound relatively confusing, but we're going to do so anyway. There is, you see, this character played by Sacha Baron Cohen called "Ali G" and there was a television series built around him. Not every episode of the British series aired here in the States, but now, Sacha Baron Cohen is back introducing old episodes of the series, some of which, as stated, never aired here.
More Details
Official Website
TV Network - FXX
TV Network - FXX
- Starring - Sacha Baron Cohen


text:
40 hours left to pledge for Stygmata
We are entering the final stretch in the Stygmata kickstarter and would love for you to join us. Our four main characters come with crossover cards that you can use... Read more
We are funded
Stygmata is now funded. We have reworked our stretch goals so that all four of the minis are now unlocked. But we need your help to unlock more stretch goals.
Last chance at change of address.
We seemed to have gotten a bunch of change of address last minute from our last update. Since we don't want to miss anyone we are giving you till the... Read more
Last day of sale and change of address.
Hello Backers, Last day to take advantage of the 15% off discount and free shipping at the Eden store. Check out the great new releases too. It is also the... Read more
Bots are ready to ship and 15% off at webstore
Dear backers, We have not forgot you. I am ashamed of how long it has taken to get these missing bots to you. I sincerely hope that this failure on... Read more
Missing Bots informations - Informations sur les bots manquants
Don't worry we're not dead, despite what this extended period of silence may suggest!
We have however been extremely busy in the wake of Escape's success!
We are aware of... Read more
Final handling and shipping operations : 16th of March !
The vessel carrying your escape boxes will land in Rotterdam on March the 16th !
"Shanghai Express"
You can track it on : http://www.vesselfinder.com/?imo=9501368
Final trip will be done by truck... Read more
Escape stock sailing to France
Our supplier confirmed that the container has left China and heads toward europe.
We will confirm reception of the products soon !
We got some more sample boxes by airmail... Read more
Production and packing of the game is over - container now boarding in Shanghai
All the boxes have been packed and shrink wrapped.
The container is now boarding in Shanghai. We will keep you informed when the ship reaches "Le Havre" port in France.... Read more
Escape - Production done ! - Now packing the boxes in China
The plastic models are all casted and assembled.
They have been deliverey to the printing plant where our partner Whatzgames, will add the miniatures to the game boxes
Shipping to... Read more
Plastic injection update
As told in late october, all the injection molds have been tooled in november, and the production of the plastic component is going on this month of december, and the... Read more
ESCAPE - Final production and delivery schedule
Hello all dear resistant !
Our Chinese partner finally came up with the final production schedule.
End of tooling assembly: mid October,
end of injection : mid November ... Read more
Meet the Escape Team in Essen and playtest the game !
Most of the Escape design team will attend the international Spiel Tage 2013 in Essen (Germany) : 24-27th of October, Hall 2, booth E127
We will display all the Escape... Read more
Blue Kira !
Hello everyone!
Here is the sculpture of Blue Kira by the young and talented Louis Desbordes a concept Stephane Louis.
We took some of the profiles and the sytem to... Read more
Faction dice - update !
Hi everybody !
We have recieved our faction dices this week from our supplier...
Taking advantage of both our summer sales and your KS support, we ordered all the 8... Read more
Project update - August
Hi everybody !
Even if we have paused the pledge manager process for 2 weeks, most of our team is working hard on the game !
All the miniatures that... Read more
Marvin - Resin prototype
Here is the Resin prototype of Marvin !
Marvin and all the other plastic models are in the hands of our chinese supplier who is now working on the molding... Read more
Awiya = Alexia
Hi everybody.
in response to your latest questions :
Alexia will be the final name for the miniature created after the concept of Alexandra (whose pledger pseudo was Awiya). It... Read more
Last "mini creator" concept : Alexia
Here is our last mini creator miniature : Alexia, resistance tech, drawn by Stéphane Louis and designed by Alexandra Peigné
Alexia will be available in resin, exclusive to the kickstarter... Read more
Jericho : WIP
Here is the WIP of Jericho, 2 bladed fighter of the resistance !
This dynamic miniature is available either in resin or plastic.
Both versions with Escape profile card
Original... Read more
WIP Green Youkai
Here is the master model of the deadly Green Youkai !
The ISC Sensei and Ultimate survivor pledges will include 3 of these hunting horrors
Available as a goodie coice... Read more
Program of the next 2 weeks !
Dear Backers
What's going on right now ?:
- we have gathered all the backers emails and are building up the survey document. (XLS format)
- we will send... Read more
Thank you ! and see you soon for the campaign follow up !
We will contact all our backers and contest winners this week to gather their name, adress, pledge details etc...
Next step will be to set up a pledge manager for... Read more
New Resin Goodies !!!
Addition of :
Marvin - Resin 15$ / Plastic 10$
Blue Kira - Resin 15$ / Plastic 10$
Jake - Resin 15$ / Plastic 10$
Jericho- Resin 15$ /... Read more
No more Mini creator pledge left !
Awesome, all the 3 Mini creators have been taken !
Thumbs up for Awiya !
We will soon discover the concept this pledger has in mind for us...
Blue Kira unlocked !
I don't know if we will have enough time to update the Escape goodies list, but you can already ask for the resin versions of Jack and the blue Kira... Read more
The Doors.... full resin packages
Here is a render of the doors 3D models
We know that most of you want a full set of doors, and that many crazy backers have bought enough packs to... Read more
WIP Blue Fusetsu !
Here is the work in progress of the big ISC drone "Blues Fusetsu"
The same at an earlier stage of sculpting, with a 36mm for scale reference :
New Escape goodies : Resin Oshoku and Plastic lipped bases
We have just added 2 new Escape goodies :
- Resin Yellow Oshoku (15$)
- Bag of round plastic bases with lip. Including 10 x 30mm diameter bases and 4... Read more
Blue Fusetsu concept !
Here is the concept of the Blue Fusetsu
Now you know where the swarm-bots come from !
Let's unlock this mechanical horror until the end of the campaign
Alice (in... Read more
Yellow Oshoku unlocked !
The summer will be very hot in the corridors of L.A.B 03 ;-)
We have unlocked the Yellow Oshoku !
Additionally, all the "Resistance leader" and "Escape Master" pledges will... Read more
Mise à jour de la page en Français ! (French KS page update)
Nous avons réalisé une mise à jour de la page en français, avec le rajout des derniers stretch goals, et surtout d'une FAQ qui réponds à vos messages les plus... Read more
Last chance to step in the world of Escape !
Here is our second mini creator ; Jeremy !
Jeremy as designed this Resistance pilot with Stephane Louis, and we wil start sculpting the actual master model in the next... Read more
We gonna' call Jack !
It seems that the Resistance will soon be outnumbered by the spooky ISC drones :-\
Let's call Jack to take care of the problem ;-)
A special gift fot our Resistance leaders and Escape masters...
As we're closing in to our Yello Oshoku stretch, here is our new offer.
If we unlock the Yellow Oshoku, we will also reward the Resistance Leader and Escape Master... Read more
Youkai - Youkai -Youkai !
3 lovely Youkais now haunt LAB 03 corridors !
Huge thanks to all our backers ...
But an even deadlier ISC Drone comes behind them !
Puppet WIP - Clot01
Here is the first one of the 3 puppets (unlocked this morning)
She pretends to be Clot01 ;-)
We should ask Mohand, the "Father" of this 3 sisters
New Stretch Goal : Plastic Doors !
We heard the request to replace all the door tokens with an actual 3D door.
Here is a stretch goal to answer :
The Narrow door pack will include 15... Read more
Puppets Unlocked ! New concept art unveiled
The Puppets have been unlocked and will be added to the ISC Sensei and Ultimate survivor pledges (3 different models)
You can also select them at the other pledge levels... Read more
Our First Mini Creator - WIP !
Here is the work in progress for "Lawrence"
Laurent has worked with our Design Studio, submiting his vision of a Resistance fighter and providing personal pictures.
Based on both Laurent... Read more
Escape Video : Co-operative and Solo Gameplay
This video presents the gameplay for 1 to 6 players VS the ISC.
In case of solo game, the player will manage all the resistance fighters.
If played with... Read more
Here comes the Master !
The original sculpt of the Puppet Master is finished.
This huge model has required many hours of work, we hope that you will enjoy the result !
Sculpture by Mohand
New Stretch Goal : Blue Fusetsu
Blue Fusetsu : You though that escaping LAB 03 would be easy with the help of the Puppet Master ?
Maybe not !
Let's unlock the Blue Fusetsu to tame... Read more
New Escape goodies : Abby and Carmin Samourai
2 additions to the Escape goodies pool today !
Abby for the Resistance, and the Carmin Samourai for the ISC
Both can be selected as Escape goodies for 15$
These... Read more
Wormbots Unlocked !
Your KS version Escape boxe is now infested by Wormbots :
All the Escape boxes will be upgraded to a total of 21 swarmbots (instead of the 16 originally planned)... Read more
Last week of Campaign ! A word from the game creator ....
Dear Visitors and Pledgers
Our main objective is to develop a boardgame with highly detailed minis wich will bring more depth to the Eden world and will give to all... Read more
Oshoku WIP !
We have recieved the Oshoku master today...
Original model by Patrick "Artik Toys" Masson
Enjoy !
Lots of new things coming your way
Dear backers !
So many things are coming our way in this final week of our Kickstarter Campaign.
First, Kate arrives as a resin goodie.
But not alone, as the... Read more
Puppet Master unlocked ! Oshoku unveiled !
The Big one is in the box... huge thanks to all the pledgers who are supporting us from the start of the campaign !
Now, here is the true face... Read more
Outbreaking news : Master moves one step forward !
We have got hundreds of post, e-mails and PM asking for the puppet master !
We know that many pledgers feared that this model wouldn't be released or are waiting... Read more
Règles Escape V1 en Français
Voici la version Française des règles 1 contre 1 du jeu escape.
N'oubliez pas que la version définitive contiendra un mode solo et un mode coopératif jusqu'à 6 joueurs !... Read more
New Escape Facebook contest !
Last week of our funding campaign... let's celebrate with a new Facebook contest.
This time you have an opportubnity to win a resin copy of Miss Pamela !
Rules of... Read more
Resin doors : WIP
Here is the WIP of the resin doors included in the ISC Sensei and Ultimate survivor pledges.
The master models will soon be 3D printed !
New Escape goodies added : resin bases and Escape miniatures !
We have added 2 new miniatures to the Escape goodies list :
Courtney from the resistance (35mm tall) and the Grey kitsune, ISC drone (54mm tall)
These models will be... Read more
Boardgame Geek contest results !
Our Escape contest on Boardgame Geek ended today...
Congratulations to the winners !
The blue Kira is back
Let's raise another automated horror of the ISC
The Blue Kira will be back to L.A.B 03 if we reach 105K !
New Resistance miniature to unlock !
You might have noticed that there was a gap between Jack and the Yellow Oshoku...
Let's fill it up with Marvin... a new resitance fighter who will toast those nasty... Read more
New stretch concept unveiled !
Here comes Pamela !
Thanks to all our backers, this babe will join the Resistance...
But we don't want the ISC players to be frustrated...
The drones too have their... Read more
Pamela master, for your eyes only
Hello dear backers !
Pamela is really close to be unlocked, so we asked our sculpting team to show us what they got...
Here you have it as a WIP... Read more
Painting the flybot !
An update for our fellow painters ! : Learn how to paint the ISC drones tabletop+ level !
On this tutorial, we will explain how our studio staff achieved great... Read more
New stretch goal : textured bases !
Nice and easy stretchgoal today !
If we beat this one, we will order a complete set of sculpted bases. LAB 03 themed !
We will swap the initial plain... Read more
2-players rules online !
As promised, you'll find in that link the rules for the 1vs1 mode, in an English PDF.
This is not the final booklet, and the rules will get some fine tuning... Read more
New Escape goodie : Cryogenic Tank
A new goodie has been crafted by our studio : a big cryogenic tank that will be useful to identify your mission objectives !
Available individually, or per 3 pack... Read more
Painted Scarabot and Flybot
Some have noticed on Coolminiornot the post made by Mohand...
For the others, here is the painted version of the small ISC critters !
New pic reveal : the puppets !
As Martin was unlocked, we felt like you wanted to see more...
Here are the puppets, unlockable at 80k.
Enjoy !
PS : did we tell you that Pamela was... Read more
Stretch goal reached = concept unveiled !
Escape Facebook winner announced
Hello dear Post-Apocalyptic fans !
As promised, the name of the winner is finally known to all : Geoffrey Briggs was amongst those who shared, commented and liked our post... Read more
Martin and Dr Ito prototypes up
They are both eagerly waiting for Pamela to be unlocked...
Here are some pics of their prototypes for you.
New graphs to show the content of the pledges and Martin around the corner...
Hello, dear Backers,
We are updating right now the descriptions of each pledge to make them clearer and allow each baker to know what they are pledging for.
also, a... Read more
New gameplay video - Resistance Vs ISC
Let'us unfold a round of the 1 VS 1 gameplay mode with this video !
New pledge level : Basic supporter
A new pledge level was created to allow people who want the goodies but not the Escape : the game.
For $10.00 Basic Supporteris equivalent to a minimum price... Read more
New stretch goal !
This one comes from the dark corners of the lab and feels like even the walls are brought to life to prevent you from escaping !
The Green Youkaïsare... Read more
New Background videos (and glimpse to some gameplay tricks !)
Hello dear Escapists !
Following popular demand, here are our first short video about the Resistance chief commander, Alice ! You will know more about her past but also what... Read more
Doors unlocked and new stretch goal !
First and foremost, thanks so much for your support. We're happy to add the doors to all ISC Sensei and Ultimate survivor pledges for free. They are also unlocked... Read more
Escape Contest on facebook !
Win a resin copy of the Puppet Master !
We want to celebrate this way the first week of our Escape crowfunding campaign !
The game is funded and we... Read more
Creeping closer !
Here are the prototypes of the ISC critters : the Swarmbots...
This mechanical vermin will try to outnumber your Resistants as they fight their way out of L.A.B 03 !... Read more
One more survivor joins the Resistance !
While working on the layout of our injection molds we found an empty spot next to the Yellow Oshoku !
We will take advantage of it to introduce an extra... Read more
D-DAY anniversary outbreaking News !
New limited pledge (50 units)
To acknowledge all who are supporting us since the beginning of our campaign and in tribute to others who fought for freedom on a 6th... Read more
New stretch goals, New goodies !
New goodies !
We have added 3 Escape goodies to the existing pool. All avaialble right now for the pledges "Resistance Leader" and above :
Dr Ito Kureiji - Resin... Read more
Resistance prototypes and Dr Ito Kumeiji WIP !
Product sneak peek
Here are the prototype of the resistance miniatures included in your Escape gamebox !
As those who are allready familiar with the Eden universe will notice, Ashton,... Read more
New Escape goodies and stretch goal details !
New selection of Escape Goodies :
Escape 2in1deluxe : Eden universe and rulebook (152 pages, full color, Hardcover) + a deck of profile, missions and tactical cards that will allow... Read more
Big thumb up and new visuals !
First of all, thanks everybody for your fantastic support : the game box has been funded in less than 60h ! We will inform our plastic supplier and start working on... Read more
Pledges and Stretch goals pathfinder !
Dear Backers !
Following the many messages asking for a clearer view of the Pledge contents and a follow-up of the stretch goals, we have designed the following arrays.
Check... Read more
Page Kickstarter Escape en Français - French Escape KS page
Nous avons créé une page web en version Français, à l'attention des internautes souhaitant obtenir le jeu dans cette langue
Vous pouvez la visionner ici
Nous vous recommandons en... Read more


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Below are top resources on SparkPeople for Caffeine Amounts.
Caffeine: Most of us can't get through the day without it. Whether brewing a fresh pot of coffee in the morning, enjoying lunch with a refreshing can of cola, or recharging in the afternoon with an energy drink, we have many routines and food rit... Read more
We've all seen the flashy cans of energy drinks crowding the shelves at gas stations and grocery stores. From students to sports stars, it seems like everyone has used an energy supplement to up their game at some point. But what exactly puts the... Read more
Whether you drink it as a hot beverage to ward off Old Man Winter or iced to cool off on a hot summer day, tea is an invigorating drink that people around the world consume in copious amounts. In America alone, each person drinks approximately 155 cu... Read more
Headaches can be frustrating, popping up when you're tense, stressed, dehydrated or otherwise unbalanced. It's easy to blame them on the obvious culprits: a late night, a skipped meal or an insane work schedule. But some of your healthiest ha... Read more
Often described as an intense throbbing or pulsing in one specific area of the head, a migraine headache is a condition that can't--and shouldn't--be ignored. This severe headache can last for a few hours or up to several days. People who suf... Read more
It says my least amount of calories I should eat is 1200. That seems like a lot for someone trying to loose weight. I was thinking I should eat 900. Like 300 for each meal.... Read more
What's the amount of fiber you eat every day?... Read more
Went to the gym today and lost a couple amount of calories, i' m starting a meal a day diet to lose some weight, is it good??... Read more
I enjoy making the recipes on Spark. There is only one thing that I find a problem with and that most of the ones that I use/want to use, does not say how much of a portion for each person. Can this be corrected in some way?... Read more
I heard that a healthy amount of carbs is about 98 mg./day.
Sparkpeople has it listed starting at 198 for my weight loss goals. Who's right?... Read more
Woman Smiling With a Tiny Cup of CoffeeCoffee is actually very healthy.It is loaded with antioxidants and beneficial nutrients that can improve your health.The studies show that coffee drinkers have a much lower risk of several serious diseases.Here... Read more
Coffee isnt just warm and energizing, it may also be extremely good for you.In recent years and decades, scientists have studied the effects of coffee on various aspects of health and their results have been nothing short of amazing.Here are 7 reaso... Read more
Caffeine need not be a dirty word when dieting. Our team is for all Sparkers hopelessly in love with their coffee. Drop by the cafe, we're open 24/7 and the coffee is always great!!... Read more
A few years ago you could pick up almost any running or fitness magazine and read about the benefits of consuming caffeine prior to running or exercising. Runners, just like many of you, like to take a swig of their favorite caffeinated beverage befo... Read more
Recently my teenage son and I found ourselves killing time at the grocery store while waiting for the pharmacy to fill a prescription. Surrounded by an array of protein supplements and energy drinks, my typical "tell mom only what is absol... Read more
I have stuck to 1 mug of coffee, 3 mugs of tea, a peppermint tea and a Twinings Digestif Tea today. I have matched each one, volume for volume, with water and drunk at least 8 glasses of water in total.
Last night I fell asleep quickly, got up o... Read more


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Copywriting for social media marketing tool
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wife meets stranger from internet ad for NSA cocksucking
Met from internet personals NSA as at storage facility in utility trailer so I could drain his cock without husband finding out. I have a few different online strangers that I will meet as often as I can for cock-sucking and swallow.
- Runtime:
- 2:15
- Views:
- 31690
- Date:
- 3 years ago
- Rating:
- (22 votes) 95%


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Custom Promotional Chairs
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From beach days to tailgate parties, custom chairs are one of the most useful and efficient promotional products you can provide your customers. These custom chairs are convenient and easy to carry, guaranteeing your brand will be making its way to picnics, soccer games and other outdoor events alike! Get your logo custom printed onto a promotional chair for a brand that's always on the go!


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BUMP ! i have the same problem, only i don't have the answer. Would appreciate if someone (if not author) could explain what he/she did ? Thanks !
BUMP ! i have the same problem, only i don't have the answer. Would appreciate if someone (if not author) could explain what he/she did ? Thanks !
Well my solution was not pretty.
Basically I opted to upgrade my VPN to 30mbit, that satisfied most of my needs.
But for certain services I simply added their IP range as a separate route, and set the gateway of that route to use my home router, this way the traffic to those services use my main Internet connection, and all other traffic use the VPN.
so there would be no way for my server to be accessible to all queries made at xxx.dyndns.com ? Can't apache listen specifically to the non-vpn ip ?
Well, the VPN connection is only grabbing outbound traffic by setting itself as the default route.
Unless you specify Apache to only listen to the VPN interface, it should also server traffic coming in on other interfaces.
If you do not want Apache to listen on the VPN, then you need to specify what interface it should listen to, I think by default it listens to all.
I should not that I no longer run a webserver, nor do I have the VPN anymore. I do still have my server, but it is only used for outbound traffic, so I have no need for the VPN anymore.
You can specify which interface a virtual server binds to in the <VirtualHost> directive.
Code:NameVirtualHost 10.10.10.10:80 <VirtualHost 10.10.10.10:80> ServerName ... </VirtualHost>
If you ask for help, please have the courtesy to check for responses and thank the people who helped you.
Blog · Linode System Administration Guides · Android Apps for Ubuntu Users
What I've understood so far, and i am sure to be wrong so please correct me, is I could create a "virtual interface" connected straight to internet, and have an another one, I suppose default eth0 that would be connected to the vpn, and map apache to the new virtual interface, thus bypassing the vpn.
How could I do that ?
Only when I am connected to the VPN I cannot connect to my server. Maybe this is due to the VPN's falt, but going having my hostname point to the vpn's address isn't really an option as I would be seriously damaging connection times to the webserver.Originally Posted by eldaria
Last edited by SASDOE2; March 28th, 2013 at 07:59 PM.
Moved to own thread! Please do not post in a thread that has been a year or so without a reply.


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CLARK – Clark Recreation's summer day camp program is entertaining approximately 500 children daily.
Middlesex Superior Court Seeks Youth Volunteers
by staff report •
NEW BRUNSWICK — The Superior Court of New Jersey, Middlesex Vicinage, seeks youth volunteers between the ages of 14 and 17 from Highland Park, Monroe, New Brunswick, North Brunswick and South Plainfield in Middlesex County to serve on the Juvenile Conference Committees (JCC) in their communities.
Union Catholic Plans "Race To The Gold" 5K Run
by staff report •
SCOTCH PLAINS – As part of the celebration of Union Catholic High School's 50th anniversary, the school will host a 5K run event to raise money for its athletic program.
Charity Car Show Celebrates Decade Of Helping Families Of Children With Cancer
by staff report •
WHIPPANY – From devoted automobile enthusiasts to casual onlookers and families, there will be something for everyone at the 10th annual Two Kids Foundation Charity Car Show, which once again will draw hundreds of classic and custom cars to Morris County to raise money for families of pediatric cancer patients, on Sunday, Aug. 7.
Bowling Industry Organization Tries For World Record
by staff report •
STATE – The Bowling Proprietors' Association of America is trying to set a record with one million games bowled on Saturday, Aug. 6. Last year, there were 923,948 games bowled on the association's World Record Day.
Remembering The Past: Elizabeth Businesses
by Diane Harrison •
"I remember Burry Buscuits, there was a Ford car dealership on Newark Avenue, a Mercury car dealership on North Broad Street, a Buick car dealership on N. Broad Street, and a Dodge car dealership on Newark Avenue.
"Cowboys & Aliens" – Way Out West
by staff report •
Ever since we were little, my best friend Bob has loved films where worlds collided…especially those sword and sandal epics intermeshed with dinosaurs and a healthy peppering of mythical monsters. So I figure I'll call and tell him that he'll probably like director Jon Favreau's similarly anachronistic "Cowboys & Aliens."
Community Calendar
by staff report •
Blood Drive • Aug. 5 from 2 – 8 p.m. – Woodbridge Center Mall, 250 Woodbridge Center Drive, Woodbridge, will host a blood drive. Info: 1-800-933-2566.
Sunday Is Iselin Day 2011
by staff report •
ISELIN – The Woodbridge Wellness Committee is sponsoring Iselin Day 2011 on Sunday, Aug. 7 from noon – 3 p.m. at Kennedy Park on Goodrich Street.


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PLAY EPISODEGame Fnatic: Search for a Legend
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PLAY EPISODEAOL Build
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PLAY EPISODENext Level Living
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PLAY EPISODEFatherhood
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text: The medical imaging market is in a period of significant change driven by the adoption of Electronic Medical Records (EMR), teleradiology, and commoditization of the imaging industry. It is clear that medical imaging companies must innovate to accommodate these changes in the marketplace but can they actually capitalize on them to spur revenue growth? Listen to this podcast to hear Tim Hansen, long-time diagnostic imaging industry insider, describe how successful medical imaging companies are propelling forward during this tumultuous time.


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dosing system Companies in United Arab Emirates
Current filtering criteriaYou can remove a filter by clicking on the x
Business type: Technology ×
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Avista Technologies
Distributor in UNITED ARAB EMIRATES
Avista Technologies is a speciality chemical company with a singular focus of providing products and services for water treatment membrane separation systems and associated pretreatment equipment. Our goal is to help customers operate their membrane systems as efficiently and cost effectively as possible through the effective application of specialty chemicals. These ...
Intercare Limited
based in Sharjah, UNITED ARAB EMIRATES
Came in to this world over 25 years ago, and has now grown into a mature entity. Never forgotten are the creative days of the early 1970`s where the infrastructure which Intercare modestly helped to build, is today in place, however, the excitement of those consummated moments can never be replaced, and leaves us with fond memories of the past. It is the pride of being ...


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Suites Marne
AddressRio Marne Numero 12 Colonia Cuauhtemoc Mexico CitySee nearby area
For rates, enter dates/guests
Description provided by property
Located just 1 block from the crossroads of Reforma Avenue and Insurgentes Avenue, Suites Marne offers free private parking and functional accommodation with free Wi-Fi. Reforma Metrobus Station is a 5-minute walk away.
Each simple room at Suites Marne has classic-style décor and carpeted floors. All rooms include cable TV and a private bathroom. Apartments also have a well-equipped kitchenette.
Suites Marne is situated in the Colonia Cuauhtemoc neighbourhood, surrounded by bars, restaurants, shops and embassies. Chapultepec Park and the historic city centre are both within 2 km.
Staff at Suites Marne's 24-hour reception are happy to provide information about the city. At an extra cost, you can also book transfers to Mexico City International Airport.
Services & facilities
Guest services
- Tour desk
- 24-hour front desk
- Airport shuttle (surcharge)
Wi-Fi/internet access
- Free WiFi
Nearby places
Monumento a la Madre
Just off Reforma, this monument and open plaza dedicated to mothers features a statue of a woman and child. The first brick was laid on...
Monumento a Cuauhtémoc
Reforma's busy intersection with Avenida Insurgentes is marked by the Monumento a Cuauhtémoc, memorializing the last Aztec emperor.
Centro Bursátil
An angular tower and mirror-ball ensemble housing the nation's Bolsa (stock exchange) marks the southern edge of the Colonia Cuauhtémoc.
A welcome sight in a nation where two breweries control about 98% of the market, Crisanta makes its own porter and sells Mexican and...
De Mar a Mar
One of the Zona Rosa's best restaurants, the menu here was designed by chef Eduardo Garcia, a rising star on the Mexico City culinary...


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