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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 478429, 8 pages
Modulatory Function of Invariant Natural Killer T Cells in Systemic Lupus Erythematosus
1Department of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan
2Department of Otolaryngology-Head & Neck Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
3Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei 114, Taiwan
4Department of Internal Medicine, Tri-Service General Hospital, Taipei 114, Taiwan
Received 2 January 2012; Accepted 10 April 2012
Academic Editor: Harris Perlman
Copyright © 2012 Yi-Ping Chuang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with complex immunological and clinical manifestations. Multiple organ failure in SLE can be caused by immune dysfunction and deposition of autoantibodies. Studies of SLE-susceptible loci and the cellular and humoral immune responses reveal variable aberrations associated with this systemic disease. Invariant natural killer T (iNKT) cells are a unique subset of lymphocytes that control peripheral tolerance. Mounting evidence showing reductions in the proportion and activity of iNKT cells in SLE patients suggests the suppressive role of iNKT cells. Studies using murine lupus models demonstrate that iNKT cells participate in SLE progression by sensing apoptotic cells, regulating immunoglobulin production, and altering the cytokine profile upon activation. However, the dichotomy of iNKT cell actions in murine models implies complicated interactions within the body's milieu. Therefore, application of potential therapy for SLE using glycolipids to regulate iNKT cells should be undertaken cautiously.
1. Introduction
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with complex immunological and clinical manifestations. Reduced immune tolerance and abnormal activation of T and B cells lead to autoantibody production mainly against protein-nucleic acid complexes, such as chromatin, and small ribonucleoprotein particles. These autoantibodies complexed with their cognate self-antigens deposit within capillaries of various organs and subsequently mediate systemic disorders. The commonly affected organs include the skin, heart, kidneys, lungs, joints, and central nervous system. This disease usually begins in the 20–45-year age range, although it can occur at nearly any age. SLE is more common in women than in men (>8 : 1). Studies using animal models suggest a role of estrogens in the disease development. The induction of SLE depends on hereditary factors and environmental agents, and inherited genes, infections, ultraviolet light, and some medications are all involved. In general, triggers causing cell death, inefficient clearance of apoptotic cells, and improper exposure of intranuclear antigens to an uncontrolled immune system are potential causes of SLE [1].
Reduced immune tolerance leading to an overt immune response normally precludes various autoimmune disorders. Regulatory T-cells play important roles in mediating peripheral tolerance and immune cell homeostasis. Among them, the natural killer T (NKT) cells are a unique subset of T lymphocytes. NKT cells, which express both NK1.1 and the T cell receptor (TCR) in humans and most murine models, are heterogenous containing both CD1d-restricted and CD1d-nonrestricted populations. CD1d-restricted NKT cells might recognize glycolipids presented by CD1d for development and activation. Type I NKT cells within the CD1d-restricted population express an invariant TCR in the mouse (Vα14Jα18) and human (Vα24Jα18) combined with a limited but not invariant TCRβ chain repertoire (preferentially V8.2, Vβ7, or Vβ2 in the mouse and V11 in human) [2]. These cells are thus classified as invariant NKT (iNKT) cells that account for more than 80% of CD1d restricted NKT cells in mice. Type II NKT cells are also CD1d-restricted; however, they express variable TCRαβ chain combination and are difficult to identify. The most potent agonist of CD1d-restricted NKT cells, α-galactosylceramide (α-GalCer), a synthetic glycolipid similar to that from an extract of marine sponges, is used widely to define the number and function of type I NKT cells [3]. In this paper, we use the term "iNKT cells" to describe CD1d-restricted NKT cells; however, methods used to identify these cells are described in the text when relevant to avoid confusion.
iNKT cells are innate-like lymphocytes. Immediately upon activation through TCR engagement, iNKT cells secrete a wide array of cytokines and chemokines. These cells also exert cytolytic activity through granzyme B and FasL-induced apoptosis. iNKT cells can upregulate CD80, CD86, and CD40 on antigen-presenting cells (APCs) to mediate downstream immune responses. Therefore, iNKT cells are considered effector cells that bridge the innate and adaptive immune response [4]. iNKT cells are associated with various autoimmune diseases, including type I diabetes experimental autoimmune encephalomyelitis, and arthritis [5]. Studies also indicate that the number and function of circulating iNKT cells decrease in SLE patients although the immunophysiological role of iNKT cells in SLE is unclear.
Various murine lupus models have been used to investigate the effects of the aberrant number and function of iNKT cells on disease activity. MRL/lpr mice, which have a defective point mutation in Fas, spontaneously develop inflammatory lesions affecting the skin and kidneys with marked lymphoproliferation and autoantibody production. CD1d-deficient MRL/lpr mice show exacerbated skin lesions [6]. The other widely used murine model, NZB/W F1 (BWF1) mice show an increase in activated iNKT cells with age; however, CD1d deficiency accelerates the onset and progression of nephritis [7]. A chemical-induced lupus model showed that exposure to hydrocarbon oils, such as pristane, facilitates SLE progression through an unknown mechanism. CD1d deficiency exacerbated lupus nephritis in this model, suggesting a regulatory role of iNKT cells [8].
In this paper, we discuss recent studies using different murine models to identify the possible roles of iNKT cells in SLE.
2. Numerical Deficiency of iNKT Cells in Human SLE
Changes in the number of iNKT cells are associated with many autoimmune disorders in humans, such as SLE, psoriasis, rheumatoid arthritis, and myasthenia gravis. In human SLE, iNKT cell number is measured using various methods.
Measurement of the expression of TCR Vα24Jα18 mRNA level indicates that the numbers of invariant TCR Vα24Jα18+ CD4 CD8 double negative (DN) T cells are reduced in peripheral blood lymphocytes and in the rheumatoid synovium of patients with SLE [9, 10]. Flow cytometry shows that the number of DN NKT cells expressing TCR Vα24/Vβ11 is lower in the blood of SLE patients than in healthy controls [11]. Because SLE patients develop progressive lymphopenia, the absolute cell number is affected by the reduction in total lymphocyte number. The proportion of iNKT cells can be calculated to determine the level. The frequency of NKT cells (percentages of CD56+CD3+ T cells among all lymphocytes) is lower in patients with SLE than in controls [12]. Studies using 6B11 monoclonal antibody, which binds specifically to the conserved CDR3 region of the Vα24Jα18 TCR [13, 14], have shown that both the percentage and absolute number of iNKT cells are lower in SLE patients than in healthy controls [15]. Another subpopulation of human Vα24+CD8+ iNKT cells express mainly CD161 (NK1.1) and recognize CD1d molecule [16], and the cell number of this population is lower in patients with SLE than in healthy controls [17].
iNKT cell deficiency correlates with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [15, 18], suggesting that iNKT cells are involved in the control of disease activity. Although immunosuppressive drugs correlated significantly with log-transformed absolute iNKT cell numbers in one study [15], the direct effect of medication on iNKT cell numbers was excluded because SLE patients without drug exposure had consistently lower iNKT cell numbers than did healthy controls. Another study found no correlation between drug therapy and the proportion of NKT cells [19]. Thus, the reduction in NKT cells in SLE patients does not appear to be a secondary response to drug therapy.
3. Functional Deficiency in iNKT Cells in Human SLE
In addition to the reduction in iNKT cells in human SLE, the poor response of iNKT cells to α-GalCer has also been demonstrated in SLE patients [11], whose proliferative response of PBMCs was measured in cells cocultured with α-GalCer. The magnitude of the responses varied between subjects, and both good and poor responders were prevalent among both patients and healthy controls. However, the proliferation indices were significantly lower in patients than in healthy controls (median 7.5 versus 28.7, ) [20]. α-GalCer potently activated iNKT cells to produce IFN-γ and IL-4. The levels of both mRNA and cytokines in the supernatant of α-GalCer-induced PBMCs were lower in SLE patients than in healthy controls.
The lower response of iNKT cells results mainly from their impaired function rather than a defect in the presentation ability of CD1d-bearing cells. In one study, the percentages of CD1d+ PBMCs and monocytes were similar in SLE patients and healthy controls, and the expression level of CD1d on PBMCs and monocytes was also indistinguishable between SLE patients and healthy controls [20]. To define further the defective function of iNKT cells, sorted antigen-presenting cells (APCs) from patients or controls were cocultured with patients' iNKT cells. CD3+6B11+ iNKT cells from an SLE patient failed to proliferate upon α-GalCer activation in the presence of monocytes from a healthy control, but iNKT cells from a healthy control were expanded successfully in the presence of monocytes from a healthy control [20]. Another study confirmed that Vα24+ DN iNKT cells from nonresponders fail to proliferate in the presence of APCs from responders, whereas APCs from nonresponders could expand iNKT cells from responders [11]. Another study observed an increase in apoptosis of iNKT cells from patients after 7 days of incubation with α-GalCer [15], suggesting that the poor response of iNKT cells might partly result from the susceptibility to activation signaling-induced cell death.
Although the CD1d expression level on B cells and CD1d+ B cells is significantly lower in patients than in controls, in vitro coculture experiments indicate that monocytes, but not B cells, are effective APCs for iNKT cells [15].
These data show that iNKT cells in SLE patients are dysfunctional and suggest that activating this population may have therapeutic potential.
4. Function of iNKT Cells Associated with SLE Disease
Various murine models have shown the importance of iNKT cells in SLE progression and systemic disorders. These models have been analyzed and described in detail [21, 22]. In this paper, we focus on recent studies that clarify the functions of iNKT cells and their associations with SLE.
4.1. Detection of Apoptotic Cells and Triggering of the Immune Response
SLE can cause severe multiple organs failure resulting from autoantibodies induction. These autoantibodies target nuclear antigens that are theoretically inaccessible. It is hypothesized that the inefficient clearance of apoptotic cells is the source of the antigen pool and that secondary necrotic bodies fuel the inflammation [23–25]. Several genetic studies have identified SLE-susceptible loci, such as CRP [26], and C1q [27], which is involved in clearance of dead cells, and these data support the concept that impaired apoptotic cell clearance is involved in SLE. Recent data suggest that cleavage of autoantigens by granzyme B during cytotoxic-T-lymphocytes- (CTL)-induced apoptosis is involved in human systemic autoimmune diseases [28]. Because CTL-induced targets are often pathogen-infected cells, the molecular mimicry between microbial antigens and autoantigens is not the only explanation for the initiation of autoimmunity after infection.
In one study of C57BL/6 mice, injection with irradiated apoptotic cells induced autoantibody production [29]. In this mouse model, deficiency in iNKT cells exacerbated the effects of the disease by increasing the production of autoantibodies and glomerular deposition of IgG immune complex [30]. Injection of apoptotic cells rapidly upregulated the expression of CD69 in splenic iNKT cells; the number of IFN-γ-producing iNKT cells decreased and the number of IL-10-producing iNKT cells increased in the injected mice. Syngenic apoptotic cell transfer into mice induced iNKT cells to limit the activation of wild-type B but not B cells that were adoptive-transferred, respectively, into recipient. The production of both IgM and IgG3 anti-DNA antibodies was reduced. These data suggest that autoreactive B cells can be regulated by iNKT cells triggered by apoptotic cells in a CD1d-dependent manner.
Increased levels of lysophosphatidylcholine and other oxidized lipids are exposed on the outer leaflet of apoptotic cells [31]. Immunization with these apoptotic cells induces the production of IgM that recognizes oxidized lipids. NKT cells may survey the lipid derivatives on apoptotic cells presented by APCs and then mediate immune tolerance. It was shown recently that apoptotic cells with phosphatidylserine exposed on the outer membrane leaflet can rapidly activate iNKT cells through recognition by T-cell Ig-like mucin-like-1 (Tim-1) on iNKT cells [32]. However, airway hyperactivity was observed rather than improved outcome in this model.
4.2. Modulation of Antibody Production
The fact that SLE progression can be caused by various abnormal stimuli of lymphocyte activation suggests the presence of high immunoglobulin levels in the plasma of SLE patients. However, as expected for a heritable trait, such as SLE, analysis of the blood from relatives of SLE patients with subclinical phenotypes should more precisely reflect the pathogenic mechanism and the relationships with genetic and cellular aberrations.
High plasma IgG levels have been noted in both patients with SLE and their relatives [12, 19]. The levels of total IgG and anti-dsDNA IgG in patients with SLE and their relatives are associated with a low frequency of Vα24+ iNKT cells. This result suggests that iNKT cells play an important role in the regulation of IgG production.
Although an inverse relationship between iNKT cells and IgG production has been observed in humans, murine models reveal a dichotomy in the regulation of IgG production by iNKT cells. One study showed that CD1d-reactive iNKT cells contribute to the development of lupus in BWF1 mice by promoting autoantibody production by B cells [7]. Another study showed that purified iNKT cells but not conventional T cells augment the in vitro secretion of IgM, IgG, and anti-dsDNA antibodies by BWF1 B cells [33] and that CD1d and CD40 are indispensable for this interaction. In addition, adoptive transfer into irradiated nu/nu BALB/c mice of T cells from the spleen of transgenic BALB/c mice expressing the TCR Vα4.4Jα24 and Vβ9 chain recognizing CD1d on syngenic B cells induced lupus and severe immune complex glomerulonephritis, including the production of anti-dsDNA antibodies, in the host mice [34].
Another view suggests that iNKT cells have a suppressive role in the regulation of IgG production. In a model using heterozygous mice, which show similar pathophysiology to human SLE by having a reduced rather than complete absence of iNKT cells, the mice had a significantly higher anti-dsDNA IgG level and increased activation of autoreactive B cells [30]. Pristane-injected BALB/c mice showed increased autoantibody production and exacerbated nephritis [35, 36]. Further studies of mice with chemically induced diseases examine that the deficiencies in CD1d-restricted cells contribute to the disease.
In lipopolysaccharide-activated mouse models, reconstitution of active Vα14+ iNKT cells in BALB/c mice downregulated anti-dsDNA antibody and rheumatoid factors production but did not change total IgG levels [37]. iNKT cells increased total IgG production and the appearance of activation markers on B cells through soluble mediators and helper T cells, whereas autoreactive B cells were impaired in a contact- and CD1d-dependent manner. This highlights the ability of iNKT cells to distinguish autoreactive from nonautoreactive B cells. Differences in CD1d expression on autoreactive and nonautoreactive B cells suggest differences in regulation between these cells because CD1d expression is higher on dsDNA-responsive autoreactive B cells.
The potent agonist of iNKT cells, α-GalCer, is used widely to study the effect of iNKT cells in various disease models. With the administration of C8-α-GalCer (with an 8-carbon acyl chain), which skews the serum cytokine secretion toward a Th2 pattern, 50% of BWF1 mice developed lupus nephritis by 30 weeks. And 50% of control BWF1 mice developed proteinuria by about 36 weeks [38]. In contrast to α-GalCer, injection of β-galactosylceramide, a 12-carbon acyl chain containing glycolipid which rapidly reduced the ratio of iNKT cells in the liver and spleen [39], ameliorated lupus and reduced anti-dsDNA IgG2a production. This implies a complicated role of iNKT cells during the progression of autoimmunity and that alternative agonists of iNKT cells produce different outcomes in murine SLE models.
4.3. Modulation of the Cytokine Profile
Abnormal cytokine profiles have been implicated in the loss of immune tolerance and in a variety of autoimmune diseases. Type I NKT cells produce variety of proinflammatory cytokines, including Th1-, Th2-, and Th17-related cytokines. However, the pathophysiology of human SLE is contradictory to be related to the cytokine alteration by NKT cells in patients. Although early reports demonstrated defective Th1 and excessive Th2 responses in lupus [40], recent data suggest that the levels of both Th1 (IFN-γ, IL-12, and IL-18) and Th2 (IL-4, and IL-10) cytokines are increased in the sera of lupus patients [41, 42]. Intracellular cytokine staining reveals comparable IL-4- and IFN-γ-expressing lymphocytes in PBMCs from SLE patients without nephritis and healthy donors [43, 44]. However, in a subgroup of patients with severe lupus nephritis, the intracellular cytokine ratio shifts to a Th1 phenotype [44, 45]. In disease-alleviated SLE patients, decreased IFN-γ-producing cells and increased IL-4-producing CD4+ T cells were observed after corticoid treatment [43] and low-dose UV phototherapy [46], respectively. Although Th1/2-related cytokines might contribute to SLE progression and severity, the cytokine profiles of activated iNKT cells from SLE patients are yet to be determined.
In addition to Th1- and Th2-related cytokines, iNKT cells can also express IL-17 and IL-21 [47, 48]. IL-17 has recently been implicated in the pathogenesis of SLE [49]. Evidence indicates that production of IL-17 is abnormally high in sera of SLE patients [42] and is correlated with SLE disease severity [49, 50]. When activated by IL-17, the PBMC of patients with lupus nephritis produced higher level of total IgG, anti-dsDNA IgG, and IL-6 [51]. IL-17 production is also high in murine models affected by lupus nephritis [52–55]. It shows spontaneously developed germinal centers in the spleen where IL-17+ T cells colocalize with IL-17R+ B cells [55] providing the suggestion that IL-17+ T cells impact B cells in lupus disease. The main source of IL-17 in SLE patients derives from double negative (DN) TCRαβ+CD4−CD8−T cells [56]. DN T cells are scarce in healthy individuals, but they expand in peripheral blood of SLE patients and infiltrate into kidney with lupus nephritis where they produce proinflammatory cytokines, including IL-17, IL-1β, and IFN-γ [56–58]. Also in lupus murine models, DN T cells are important IL-17 producer [52]. It also demonstrates elevated plasma levels of IL-21 as well as percentages of IL-21 expressing T cells in SLE patients compared with healthy controls [59, 60]; nevertheless, there is no correlation between IL-21 and disease severity or anti-ds DNA titers [59].
The study of CD1-lipid reactive T cells is much more complicated in humans than in mice. In addition to CD1d, CD1a-, b-, and c-restricted T cells in humans are relatively diverse with CD4+, CD8+, or double negative (DN) populations. Although Vα24 DN NKT cells are numerically decreased in SLE patients, the influence of the subsets of other CD1-lipid reactive T cells on SLE pathogenesis in humans should be further investigated.
In murine models, treatment of adult BWF1 mice (age 8–12 weeks) with α-GalCer exacerbated the disease activity, whereas treatment of young BWF1 mice (age 4 weeks) ameliorated SLE symptoms [61]. Moreover, transfer of NK1.1+ T cells from aged SLE mice to young BWF1 mice (before the onset of renal failure) induced proteinuria and swelling of the glomeruli. It has been indicated that iNKT cells expand in aged BWF1 mice and the authors reported that α-GalCer administration induced predominant IFN-γ production in old mice [7]. Use of a blocking anti-CD1d monoclonal antibody to treat BWF1 mice augmented the Th2 responses and ameliorated lupus [61]. These results suggest that the impact of α-GalCer treatment on disease in BWF1 mice varies with age and imply that the cytokine profile of iNKT cells influences the progression of SLE.
In pristane-induced nephritis models, the effect of α-GalCer differs between mouse strains. In BALB/c mice, Th2 responses are induced by treatment with α-GalCer, which protects mice against nephritis. Conversely, in SJL/J mice, treatment with α-GalCer increases the Th1 responses and exacerbates disease [62]. The differences in the effect of α-GalCer seem to correlate with the cytokine profile produced by activated iNKT cells. It is the common regulatory mechanism in several autoimmune diseases, such as experimental autoimmune encephalomyelitis, and type 1 diabetes.
iNKT cells mediate various immune responses, including maintenance of self-tolerance, tumor surveillance, and the response to microbial pathogens. Given the limited TCR diversity, attention has focused on the mechanisms underlying the activation of iNKT cells [63]. In addition to the microbial glycolipid antigens engaging directly with the invariant TCR on iNKT cells [3], indirect activation of iNKT cells by cytokines or endogenous antigen presentation through microbial-stimulated dendritic cells (DCs) is also possible [64–66]. This may explain the ability of various stimuli to activate iNKT cells in the body and implies that iNKT cells might mediate both beneficial and detrimental outcomes depending on the milieu produced by the activated DCs.
The beneficial roles of iNKT cells are involved in immune tolerance and can ameliorate or prevent tissue inflammation [67, 68]. The suppressive effect is mediated globally through tolerogenic DCs, B cells, or regulatory T cells or directly by skewed cytokine production and induction of apoptosis through Fas-FasL engagement of autoreactive lymphocytes [69]. SLE patients have reduced proportions and functions of iNKT cells, which imply that the suppressive effect is mediated by this population. However, a reduced population of iNKT cells cannot be a diagnostic clinical marker of SLE because the frequency of iNKT cells varies markedly between healthy people. Although the suppressive effect was identified recently in a murine lupus model, the function of iNKT cells in humans needs to be clarified.
Long-term anergy of iNKT cells by reactivation can be induced in mice [70]. The unresponsiveness to GalCer includes reduced proliferative activity and failure of IFN- production. This suggests that the aberrant proportion and function of iNKT cells in SLE patients may reflect only the outcome after repeated exposure to cognate self-antigens. By contrast, Green et al. did not exclude the possibility that the reduced level of iNKT cells results from attack by upregulated antibody in SLE patients [12]. Therefore, iNKT cells may be a potential therapeutic target in the treatment of SLE patients, although the complicated interactions between iNKT cells and other immune cells and the exact function of iNKT cells require further consideration.
5. Conclusion
In this paper, we have discussed the association between iNKT cells and SLE in clinical and murine models. In human SLE patients, the reduced proportion and function of iNKT cells correlate with disease activity and iNKT cells correlate inversely with IgG levels. Recent studies indicate that iNKT cells can sense apoptotic cells and mediate immune tolerance and suggest that iNKT cells can distinguish autoreactive B cells from nonautoreactive B cells to suppress autoreactive antibody production in a CD1d-dependent manner. However, other studies have reported that iNKT cells upregulate total IgG and IgM levels (Figure 1). These findings suggest that iNKT cells are involved in suppressive regulation in SLE.
This work was supported by the National Science Council, Taiwan. (NSC100-3112-B-016-001, NSC99-2320-B-016-001-MY3), Tri-service General Hospital foundation (TSGH-C101-009-0S01), National Health Research Institutes (NHRI-100A1-PDCO-0809111), Ministry of Economic Affairs (100-EC-17-A-20-S1-028), and in part by the C. Y. Foundation for Advancement of Education, Sciences and Medicine.
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Do you presently have your own e-store or home business, are you looking to develop your product line with small up-front costs? Our Wholesale or Drop Ship Program is perfect for you. Become an approved partner in the My Goodness Duds' Wholesale or Drop Ship Program and you can add our very original organic baby clothes to your own store's inventory.
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This figure a woman holding a mirror is of a picture type known as an allegory, or symbolic figure. The mirror refers to the fortunes of lov...
Hiroshige's One Hundred Famous Views of Edo
Hiroshige's 118 woodblock landscape and genre scenes of mid-nineteenth-century Tokyo, is one of the greatest achievements of Japanese art.
On View: Plaque of a Female Figure
Many deities in the official Egyptian pantheon can be recognized by their headdresses. The Double Crown of the beneficent goddess Mut, whose...
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Found the same room at a different price? Tell us, and we'll offer to match it.
Marine Hotel - The Hotel Collection
4 | AA Assessed Hotel | Ratings explained |
The Marine Hotel is a grand building that conjures up images of Scotland.
The hotel is only five minutes from Prestwick Airport and the Ferry Terminal to Northern Ireland is only one mile away.
The Hotel overlooks the Royal Troon Golf Course.


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- Visit the Acropolis Museum
Ah, one of the finest architectural diamonds and best museums worldwide. You will be impressed, no matter how many times you visit. Over and over again, the feeling one gets is overwhelming – admiration and awe take over. With the exhibition area occupying 14,000 m2 and the exhibits numbering 4,000, it is understandable that one visit cannot cover all this beauty. There are always details waiting to be discovered. The light coming through the glass engages in a playful motion with the surfaces and the night casts a magical veil on the past and the dynamics of the space. You can only be taken aback by its everlasting splendor.
- Ride along the coastline
Athens Riviera: Faliro, Glyfada, Voula, Vouliagmeni, it doesn't matter where to – just climb on the tram or the bus line that takes you there and rush to the calling of the sea. Leave the madness of the city behind and relax by viewing the amazing Saronic Gulf. If the weather is appropriate, take a swim and lay on the beach with company, or with the company of a book. If the water is not yet warm enough, get lost in the endless horizon listening to your favorite mp3 music. Whatever the case, the ideal time to begin your ride is just before sunset.
- Eat 'vromiko' downtown
As the daylight evaporates, the canteens start getting their fast food ingredients ready. The smell of grilled meat takes over the surrounding streets and neighborhoods, capturing the people that move among them. The sandwich is called 'vromiko', which in Greek means 'dirty', because it is generously stuffed with full-fat ingredients that create delightful bites. The canteens are scattered in various downtown spots, but the most popular is in Mavili Square, where, after all-night partying, the night walkers gather to claim a tasteful epilogue to their fun.
To read more, please see blog.visitgreece.gr
By Dionisis Stathakopoulos


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Very Good Recipes of Cooking and Grilled
There are 6 Cooking and Grilled recipes on Very Good Recipes.
Do you like cooking and grilled recipes?
See all cooking recipes or all grilled recipes.
Click on the title of a recipe or the photo of a dish to read the full recipe on its author's blog.
Summertime Cooking with Epicurean Butter: Grilled Caesar Salad with Roasted Garlic and Herb Croutons
By Savoury Table
05/31/14 01:31
Last November I had the pleasure of cooking with and reviewing some of Epicurean Butter's compound butter flavors. I really like using them because of their ability to elevate the simplest of dishes to gourmet status with minimal effort. I can honestly...
Add to my recipe book
Grilled Fish + Sauté Spinach: Easy Healthy Delicious Cooking
By mealitary
10/23/13 00:00
The post Grilled Fish + Sauté Spinach: Easy Healthy Delicious Cooking appeared first on mealitary.
Add to my recipe book
Crab Rangoon Grilled Cheese Sandwich~a Crazy Cooking Challenge
By The Freshman Cook
05/07/12 18:03
It's that time again~Crazy Cooking Challenge time! This month our challenge is Grilled Cheese Sandwiches. I have never been a huge fan of grilled cheese sandwiches, but after making and eating the recipe I found, I have had a change of heart! I found the...
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Jalapeno Popper Grilled Cheese {Crazy Cooking Challenge}
By The Kitchen is My Playground
05/07/12 18:00
Well hello, GRILLED CHEESE Crazy Cooking Challenge! What a fun adventure you have been!! When Tina of Mom's Crazy Cooking announced this month's Crazy Cooking Challenge topic - GRILLED CHEESE - I thought, "Hmmm, how much can we really do with grilled cheese?"...
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Crazzy Cooking Challenge .. Grilled Cheese Sandwich
By culinaryvibes
05/07/12 15:59
I love Cheese.. its just so yummy.. So when I stumbled across this amazing Grilled Cheese Sandwich from Cooking Classy , I knew my search was over and this would my recipe for the Crazy Cooking Challenge.. Though the recipe has ham in it.. I was just so...
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Grilled Cheese for Crazy Cooking Challenge
By BIZZY BAKES
05/07/12 09:48
May is here and that means the Crazy Cooking Challenge, hosted by Tina from Mom's Crazy Kitchen, is HERE. Being a fan of grilled cheese made this month's challenge, even more fun. Who knew all the ways, we can make grilled cheese sandwiches? We will find...
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Brushed Steel 3-Watt LED Mini Eyeball Recessed Light
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This energy efficient LED recessed light is perfect for use as a directional spotlight. The mini eyeball lens has a 42 degree pivot to direct the light source where you want it.
One 700mA constant current LED driver is required for each continuous run. Be sure to select a driver whose wattage rating is equal to or slightly greater than the total wattage of the run being powered. Be sure to note any minimum wattage requirement of the driver you choose.
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Giveaway: Five 1-Year Subscriptions to AceProject
AceProject, a collaboration-oriented project management web application, is giving away five subscriptions to their Standard package for one year (worth $240 each). Read on to see how you can participate in this excellent giveaway.
** Update: Giveaway Period Has Ended **
About AceProject
AceProject is a web-based application that will help you manage and organize your projects and tasks, as well as keep them on track and help you manage your time.
The web app is loaded with amazing features. For example, thanks to the timesheet module, you can precisely (and conveniently) track the time you spend working, allowing you to bill your clients and project areas accurately.
The document management feature of AceProject is strong and powerful, with document sharing, versioning, and file locking so that you don't accidentally delete or edit certain files.
Use AceProject for Free!
Sign up now for a free account, which gives you an account with 5 users, up to 5 projects, 0.25 GB of storage space, and more.
** Update: Giveaway Period Has Ended **
How to Win an AceProject 1-Year Standard Subscription
In order to win one of these excellent prizes, help AceProject tweak and enhance their product by answering the following question (you can sign up for a free account in seconds to review the app):
- Interface and usability wise, how could they improve AceProject?
Giveaway Details
This giveaway ends on Tuesday, February 22, 2011 after which the comments section on this post will be closed and you will no longer be able to leave a comment. Please leave a valid email address when filling out the comment form so that we can contact you if you've won. Please only comment once. The 5 winners will be randomly selected using the same method as previous Six Revisions giveaways. The winners will be announced on a separate post and you're advised to subscribe to our RSS feed so that you can be quickly notified when the winners announcement post has been published. Please note that comments are moderated and so your comment may not show up right away. Please also note that comments that do not follow the instructions on how to participate (mentioned above) may not be published, or may be removed later on.
Related Content
- 7 Tips for Giving Effective Design Project Quotes
- 10 Ways Designers Can Earn More from Projects
- 6 Reasons Why You Should Do Personal Design Projects
- Related categories: Project Management and Productivity
About the Author
29 Comments
They should highlight free sign up on the homepage with call to action button so they can get exposure to convert visitor into customer. ( This link >> https://signup.aceproject.com/ )
Magento Themes
Aceproject sounds really interesting and I appreciate the fact that free trail is provided.
Have heard lot about about AceProject. Would like to use it in my future projects.
Interface is the most important thing in this app, it should be friendly good looking
One of the problems I have with many popular project management solutions is that they are geared around teamwork on a project, sometimes at the cost of ignoring the individual needs. It's often times difficult for me, as an individual on the team, to go and get an overview of the tasks and workload assigned to me for that day.
Mike Jongbloet
Until I saw this article through my RSS subscriptions I'd not heard of AceProject.
Suprising as I work in the industry, Basecamp seems to market a lot more and as such I would suggest getting the name out more.
Its likely a great product but with a lot of people not knowing about it will just go straight to what they know – which seems to be Basecamp at the moment.
Suggestions would be getting more people to post blog reviews of it, giveaways on more blogs etc.
I will likely sign up for a free trial now I know about it!
Felipe Genuino
Gostaria muito de utilizar os serviços de gerenciamento aceproject.
Lee B
I have heard many good things about AceProject. I have a few new projects coming up soon and would be keen to use it on them.
Mike S
Looks impressive, maybe a good alternative to Basecamp.
RE: Interface, a "widget-style," role-based dashboard would be nice for customizable data display, since different project aspects take priority for different roles.
Looks like a great service, the application interface is great and definitely an improvement from what I currently use Intervals Online.
One thing that they should refine is their entire homepage. It has too much text, it's too crowded and looks more enterprise than friendly. Of course they would want enterprise customers, but the overall feel of the most important page of the site feels too stiff.
For example, look at Mail Chimp's website design: http://www.mailchimp.com/. They offer a service for anyone that need to send a lot of emails including enterprise customers, but their site is simple and doesn't throw everything in your face all at once.
Other than that, I like the application interface, nice and smooth, easy on the eyes too.
its already near to its perfection, but don't stop updating your software. :) nice software..!
I think the use of a font which doesn't hurt the eyes so much would be appreciated.
DeNae Leverentz
I would suggest providing notification of the length restriction on the domain during sign-up. I had to alter my preferred domain.
Vladislavs Judins
User interface should guide user, not making user think what and where to do things
Brian Rowdy
50 item limit on free account makes me think of ActionMethod. Allow more items than they do and promote hooks into other systems like Freshbooks >> http://www.aceproject.com/time-tracking/
I think what be nice a very complete sample proyect because i like see how can be a gantt and a project very complex.


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Is the royal baby finally on the way? The Queen abruptly left a cricket match on July 18 at Lord's, prompting many spectators to believe that Kate had gone into labor!
Kate Middleton is days past her reported July 13 due date, and the world is feverishly on royal baby watch. So when her grandmother-in-law Queen Elizabeth II quickly left a scheduled appearance on July 18 without warning, all signs pointed to the heir to the throne's arrival.
Queen Elizabeth Leaves Cricket Match — Royal Baby On The Way?
The Queen arrived to the match at Lords about 15 minutes late, according to E! News. Her Majesty met with the Australian and English teams before the Ashes test match, the Intertantional Business Times is reporting.
The 87-year-old stayed for about an hour, but left without warning. Her abrupt exit sparked rumors that she had to leave early to be there for the birth of her grandson Prince William and wife Kate's first baby.
However, she also could have wanted to beat the intense London heatwave, and had to leave early to look out for her own health. There is no sign of a royal baby just yet, but we are all keeping a watchful eye and ear for the good news!
Queen Elizabeth 'Would Very Much Like' Baby To Arrive
Although it looks like the Queen didn't have to attend to the news of the royal baby's arrival just yet, she would like the little bundle of joy to come sooner rather than later — she has a vacation she needs to get to! She told a group of kids at an an appearance in Lake Windermere in Cumbria on July 17:
I would very much like it to arrive. I'm going on holiday. No sign yet.
Meanwhile, we are all on the great #KateWait. What do YOU think of the Queen leaving the cricket match, HollyMoms? Do you think the royal baby is coming soon?
WATCH: Kate Middleton To Announce Baby's Birth On Twitter
– Christina Stiehl
More Kate Middleton Baby News:
- Kate Middleton & Prince William 'Relaxed' Before Baby
- Prince William 'Torn' Over Leaving Pregnant Kate Middleton's Side
- Kate Middleton: Car On Standby At Parents' Home 1 Hour From Hospital
View Comment
Posted at 4:11 PM on July 19, 2013
The Queen was joking! lol far too many people reading too much into her comment. The world will not know Kate is in labour, the hospital has many entrances and exits unknown to the press where royals can enter and leave.The Royal family don't make a habit of telling everyone when a member of their family goes into labour!!!. The Queen would never attend a royal birth – if she has left because of the baby it's because it has already been born. If this is the case, the birth announcement will be placed onto the gates of buckingham palace within hours of the birth – perhaps tonight. That's the only traditional way the Royals tell the world of the birth. It is impossible to know anything about the situation, until Kate gives birth to the future King or Queen we won't know a thing.
Carole Falsone
Posted at 6:32 PM on July 20, 2013
Posted at 6:47 AM on July 19, 2013
Sarah Lund
Posted at 1:57 AM on July 19, 2013
Posted at 12:49 AM on July 19, 2013
So the queen cares more about her damn vacation holiday, whatever. Maybe she belong with the damn filthy Kardashians. Any grandmother and great grandmother would wait and be very excited over the birth of a baby, wheather royal or not. This proves the queen has always been a beeyatch, specially when princess Diana was alive. What makes me sick also, is Camila the witch and idiot Charles for cheating with Camila on Diana.
Posted at 1:02 AM on July 19, 2013
Lord Byron
Posted at 2:02 PM on July 19, 2013
sharifah syed-mohammad
Posted at 9:57 AM on July 19, 2013
What the Queen meant was she will be in Balmoral, Scotland for her annual vacation, thus it would be harder for her to visit if Kate gives birth while in Scotland, you moron. The Queen NEVER takes a vacation just like everyone else. Even when on vacation, she still has to do her Constitutional duties as the Monarch and have her weekly meetings with the Prime Minister. Clearly you didn't understand her wit in that comment.
I soooooooooooo agree w/ you. Karma could set them all straight by Kate delivering on the 29th (Charles & Diana's Wedding Date) and a Girl would do the trick on that day. Hope big ears Charles looks in his grand daughters eyes and sees Diana! And Camilla? Shut the hell up!! No one asked you horseface!! Just keep riding Charles and be happy w/ that……………….Ugh..
Posted at 10:05 PM on July 18, 2013
Posted at 7:18 PM on July 18, 2013


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Great for roof rack
Reviewed By Amy L (MONROVIA, CA) Reviewed for a 2014 Subaru Outback —1/12/2015 2:05 PM
Easy to use for a roof rack. Downside is that some mtn bikes need additional adapter.
Reviewed By Betsy M (ISSAQUAH, WA) —12/21/2014 8:39 AM
100% pleased with this bike rack. I have an older version of this rack and gave this one as a Christma present. Installation was easy, all the parts were there, and the upgrades to the rack look and work great. Now I want to get the newer rack!! Also very pleased with the service and delivery from this company. Rack arrived within a couple of days, just like promised, and the price was the best I found, by a significant amount.


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Description: Insight into the always fascinating world of Alabama elections. Most information is from 2006.
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text: If you take a minute to read my bio, many of you will know that I am also a professional camera operator for CNN and FOX. The one thing about shooting and production is that it always takes a tremendous amount of planning. What you see on the television looks magical, but the amount of behind the scenes work that goes into the most simple of scenes would shock most. I did a shoot this past weekend and it was not planned properly at all and boy did it show. I knew the dangers of not planning going into it, but never the less proceeded anyway. To no surprise, the finished product was no where what it could have been. And so it is with real estate, plan, plan, plan, if not, the end results will be ugly. As in production, the planning is paramount for your end result to be up to par. Lack of planning will always show in the end. To avoid this, we at Redfin have supplied you with some great information to help you plan. We do all the work, so you don't have to.


text:
The old tires on my brother's vehicle have surface cracks on them. He told me that it's something called "ozone cracking" that happens when rubber is exposed to the elements and direct sunlight for a long time.
He said that newer tires are treated with something to keep this from happening. However, his old car has the old kind of tires, and it sits out in the sun instead of inside a shed.
It doesn't help that he rarely drives it. If he would have given the tires a regular workout, they probably could have held up better to stress and wouldn't have cracked as soon as they did.


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This is more "inside baseball" but I continue to be surprised by the amount of interest in the subject. Today, the exploration focuses on the financial cost.
« August 2012 | Main | October 2012 »
This is more "inside baseball" but I continue to be surprised by the amount of interest in the subject. Today, the exploration focuses on the financial cost.
Posted by Laughing_Wolf on Sunday, September 30, 2012 in Travel | Permalink | Comments (0) | TrackBack (0)
I'd just like to draw your attention to one slide from that military report card, the one on Enemy Initiated Attacks.
What I want to draw your attention to is the "ISAF Observations" portion of the slide, but first let me explain how I read the chart. The important thing about this slide is that it shows that the Surge was a failure. Why does it show that? Because the Surge was intended to collapse the opposition, so that Afghan forces could stand up and take control. Instead of those recurrent peaks, representing the annual fighting seasons, you should see a peak and then a decline. Compare the same chart from the Iraq war:
Here you see a sharp drop from the peak until the tail is more than 90% lower than the peak, beginning just as the Surge really takes effect in the summer and fall of 2007. With a few blips, the general trend is to tail off.
What the Afghan slide shows instead is that the surge did nothing to break the enemy's capacity to initiate violence. In the beginning, we see an insurgency built around a fighting season, but showing robust capacity to return year after year and strongly contest government control through violence. At the end of the chart, we see the same thing. We can't even say that enemy capacity was decreased by the surge, because although the peaks are slightly lower at the end of the surge than in its first year, they are about the same level as pre-surge. In other words, the surge increased the level of enemy initiated violence, which is only now returning to the pre-surge levels.
Remember that the majority of Americans who have died in Afghanistan died during these 'surge' years, under this, President Obama's plan. What have they given their lives to achieve?
Now, what I said I wanted to talk about was the "ISAF Observations" portion of the slide. Read it over. There's no acknowledgement of anything we just discussed. Some staff officers at ISAF are trying to help their boss put a happy face on this: hey, a 5% drop if we look at it just this way! 9% here! None of them dare to tell their boss to brief that the surge has left EIA levels almost exactly where they were before the surge, and accomplished only raising those levels during the surge.
Staff officers in Afghanistan: Odds are your boss already knows what you don't want to tell him, and just like you he doesn't want to have to be the one to brief his commander. Nevertheless, you must encourage in each other the same courage we ask of the infantryman who has to advance into enemy fire. It's time to speak the truth. Nobody wants to hear it, but here it is.
Posted by Grim on Saturday, September 29, 2012 in Current Affairs, Military | Permalink | Comments (15) | TrackBack (0)
-- According to Danger Room, even the military's own assessment of the Afghan surge gives it an "F". Of course it's not particularly hard to get an "F" when you announce that you're really not serious about victory by setting a pull out date at the same time as the surge.
--Looks like the F-35 will be getting a new engine in the 2020 timeframe. This is the first new engine we've develped in 50 years. More thrust (power) and better fuel economy. That will extend its combat radius.
--Okay, this is just cool. How about skydiving from a B-17. Some soldiers recently did that.
--The Army is under fire for its camouflage patterns:
Critics allege that the Army has wasted $5 billion on uniforms and equipment all printed in the inadequate UCP. The GAO estimates that the Army will have to spend another $4 billion on uniforms and equipment over the next five years when it selects its new family of camouflage patterns.
--Skidmarks on a Chinese carrier deck (yeah, not those kind of skidmarks, although there's no report about the pilot's unmentionables)? A picture has analysts wondering if the Chinese may actually be further ahead in their employment of Naval air than previously thought.
--If this sort of info is important to you, the Ranger Medic's Handbook has been updated:
The book is written by the 75th Ranger Regiment and includes 70 additional pages of updates since the 3rd Edition, which was published in 2007.
"This is an extremely popular book," Matt Westra, vice president of sales for North American Rescue, said at Modern Day Marine 2012. "This has got everything in it from their medical protocols to drug doses. They use it for sick call and for treating trauma. There's new packing lists for how they pack up their kit."
NAR is the sole distributor of the Ranger Medic Handbook. It retails for $40 and all proceeds go to the Sentinels of Freedom, a non-profit, wounded-warrior foundation chosen by the Ranger Regiment, Westra said.
--Meanwhile, in Iraq, you likely never heard a word about this:
Prisoners seized weapons and set off hours-long clashes with security guards at a prison in Saddam Hussein's hometown that left 12 dead, including 10 guards, before dozens of inmates managed to escape from the facility, Iraqi officials said Friday.
The escaped prisoners included al-Qaida suspects, said a provincial spokesman, though he could not say whether the terror group was behind the jailbreak in Tikrit, 130 kilometers (80 miles) north of Baghdad.
It was the latest embarrassing security lapse in Iraq, raising questions about the Shiite-led government's ability to ensure the country's security in the wake of the U.S. troop withdrawal last December.
Things are just going along ... swimmingly, aren't they?
--Finally, over at SpouseBuzz, they give advice on what NOT to wear to a military ball. Looking at the picture heading the post, I'm going to be a respectful dissenter here.
Enjoy the weekend.
Posted by McQ on Saturday, September 29, 2012 in Current Affairs | Permalink | Comments (4) | TrackBack (0)
I had to do something besides doom-and-gloom research and analysis - before the rest of my hair turns grey and falls out. My political cartoons are appearing each weekend at The US Report. Blackfive readers should get a kick out of President Obama's National Security Responsinator from last week.
Posted by Crush on Friday, September 28, 2012 | Permalink | Comments (0) | TrackBack (0)
"When you say 'he ran through enemy fire' it makes it sound dramatic, but it's not so much something that you do, but something that you have to do in order to make space for yourself and others around you. If you are running through enemy fire you are doing it for a reason – you are either leaving, or making space for somebody else to have an effect on the enemy." - Captain Nick Garland about his MiD
The MoD announced the latest batch of awards for bravey. There's more than a few citations for bravery including one that bears some explaining: "Mention in Despatches" or MiD.
The Mention in Despatches is one of the oldest forms of recognition for gallantry within the UK Armed Forces. Since 1993 the Mention in Despatches has been reserved for gallantry during active operations.
You can go to the following links to read about:
MiD: Platoon Sergeant Tony Branham's charge across 100 meters of deadly ground in order to give one of his elements the ability to move out from under fire (because the enemy was now trying to kill Branham).
Military Cross: Corporal Sean Jones ordered his men, pinned down, to fix bayonets and charge across 80 meters of enemy fire to save his platoon from a deadly ambush.
MiD: Wounded a few years ago and returned to the fight, Captain Nick Garland fought off ten near ambushers and led his company through to victory (and brought all of his soldiers home).
Queen's Gallantry Medal: Sapper Matthew Garey disposed of IEDs and received the QGM which is for heroism while not under fire. Garey, having lost another Sapper leader the week before (lost both legs to an IED), found a daisy chained IED field and spent 5 hours negotiating the area and clearing it.
Military Cross: Rifelman Matthew Wilson, shot in the head during an ambush on his recon unit, continued to fight and show his team where the enemy was, directing fire and eliminating the threat. Video of award ceremony at the link above.
MiD: Private Morales Matthews vaults from behind cover to save a fellow soldier that was knocked unconcious by an ambush.
MiD (2nd award): Captain Mark Cripps changed the game during an ambush by maneuvering his ANA soldiers against the enemy and leading by example.
and last, but not least (and definitely my favorite citation)...
MiD: Sergeant Mark Moffitt, who stayed in the line of fire for half
an hour to foil an enemy ambush after promising his wife he wouldn't do
anything brave in Afghanistan.
Posted by Blackfive on Friday, September 28, 2012 in Military | Permalink | Comments (0) | TrackBack (0)
RE: Daniel Rodriguez - from COP Keating to NCAA Football - Someone You Should Know (January 2012)
RE: This Ain't Hell: Combat Vet to Play at Clemson (August 2012)
Over at This Ain't Hell, Jonn posts a request that we should all get on with and, for those of you on Facebook, vote for Daniel as the 2012 USAA Athletic Inspiration Award for Courage in Sports here.
Posted by Blackfive on Friday, September 28, 2012 in Caring For The Defenders, Current Affairs, Military, Someone You Should Know, Sports | Permalink | Comments (0) | TrackBack (0)
[Note: Like all charities that we post about, we believe in BOOTSTRAP and made a donation to the program. Please help if you can.]
Background: A few years ago, Uncle Jimbo posted about a new concept of how Yoga can help those with Post Traumatic Stress. Jimbo sent readers over to the Kitchen Dispatch to learn more. Now, BOOTSTRAP is launched and needs your help in supporting our troops.
What is BOOTSTRAP?
BOOTSTRAP has been created by Eric Walrabenstein, himself a former U.S. Army Infantry Officer and now, a nationally-recognized expert in yoga and mind/body health.
To create this one-of-a-kind program, Eric has combined his years of experience in the military with his track record of using mind/body wisdom to heal thousands who have been exposed to severe psychological traumas.
Much more than the physical exercise that many associate with yoga, BOOTSTRAP combines yoga's lesser-known mental disciplines with proven practices from modern stress-management techniques to deliver a powerful healing experience—all customized for our troops and veterans.
Over three years in development, BOOTSTRAP is a home-based, curriculum-driven program melding modern stress-management strategies with the wisdom of yoga (no mumbo-jumbo, beads, or incense; just proven, practical techniques that get results). The ten-week program is specifically designed for the military audience and has been proven effective in less than one hour a day.
Because BOOTSTRAP will be deployed online, many of the obstacles to getting effective help through more traditional means are no longer an issue: long application processes, bureaucratic red tape, travel, appointments, waiting lines—and the fear of judgment and criticism…gone.
How can you help?
1. Please spread the word about BOOTSTRAP.
2. The team at BOOTSTRAP funded the development and launch, but putting the program into the hands of the hundreds of thousands in need is a colossal task.
Because our pledge is to never charge a fee to a troop or veteran in need, we are turning to all Americans to give back through Operation BOOTSTRAP.
So please visit www.bootstrapUSA.com/give and:
Funds raised will put the entire ten-week interactive program online and allow us to provide live ongoing support to those engaged in the healing process.
Last, as the online BOOTSTRAP Life Restore portal will be fully operational in the next few months, they are also accepting advanced requests for the program. Send troops in need of free help here: www.bootstrapUSA.com/request.
Posted by Blackfive on Friday, September 28, 2012 in Caring For The Defenders, Military | Permalink | Comments (0) | TrackBack (0)
NRA Life of Duty Frontlines Episode 3: Kosovo
NRA Life of Duty presented by Brownells and FNH USA have teamed up to bring you the third episode from the brand new Frontlines series with LtCol Oliver North. This month, Chuck Holton and the NRA LOD team report from Kosovo – where more than 1,000 U.S. troops are deployed for a peace keeping mission. Watch more episodes from this series on the NRA Life of Duty Frontlines channel sponsored by FNH USA at www.nralifeofduty.tv/north .
Posted by Blackfive on Friday, September 28, 2012 in Military, Video Channels | Permalink | Comments (0) | TrackBack (0)
The following review is a special from Elise Cooper for BlackFive readers. You can read all of our book reviews by clicking here or on our Books category:
Mike Gallagher's latest book, 50 Things Liberals Love To Hate, is everything you wanted to know about Liberals but were afraid to ask. Gallagher is the host of a national radio show, The Mike Gallagher Show, and a conservative political commentator. Since only 20% of those polled call themselves liberal,
both Democrats and Republicans will like this book. It brings humor to todays politically charged environment.
This book is both humorous and informative. The theme is that Liberals want to take away what Americans enjoy. Included in his rundown are Walmart, Steakhouses, McDonalds, Flag Pins, Football, the V-8 Engine, Success, the Second Amendment, Freeways, the Military, and The Founding Fathers. The book starts off with Gallagher's insightful description, "I learned that they spend a whole lot of time thinking about America's faults, and how to correct them. About America's ills, and how to cure them. Liberals love to hate things most Americans love, and spend the rest of their lives endlessly trying to take those things away from us."
Right off the bat he lists McDonalds, but any fast food chain could be substituted. Maybe New York Mayor Bloomberg should be given a copy of this book since he convinced the New York City Board of Health to ban sugary drinks (sodas, teas, and sport drinks) over sixteen ounces in fast-food restaurants, stadiums, movie theaters, and other eateries. An excerpt from the book where his humor comes out loud and clear, "Conservatives see a fat person and think: 'Lay off the bread. Take the stairs. Would it kill you to have a salad once in awhile?' Liberals see a fat person and think: 'We should immediately pass laws forbidding this kind of obesity…'" He commented to BlackFive about this quote, "You would think New Yorkers would be absolutely outraged and in the streets that Mayor Bloomberg thinks that it's the governments role to tell somebody what size container they can buy from a private establishment."
He does not see McDonalds as bad but as "representing American ingenuity." Furthermore, it's personal for him since his single mom and he had a tradition where every Christmas Eve they would go to McDonalds and have a Big Mac.
He is disgusted by their claim of supporting the soldier, not the mission. In the book he discusses how "From the tribal wastelands of Afghanistan and Pakistan to the pirate havens of East Africa, the military of the United States is on a classic civil mission, daring to impose Western values upon indigenous cultures. And keep Americans safe at the same time." He directly noted, "What the American soldier lives by is peace through America's fighting power. Instead of the liberal credo, 'Give peace a chance,' which is a really bad song by a guy who also imagined no heaven, and no countries. Liberals have the same contempt for today's soldier as they did for the Vietnam veteran."
Anyone who enjoyed these few tidbits will enjoy the whole book. In 50 Things Liberals Love to Hate, Gallagher gets his point across, about liberal's absurd ideas, with cutting irony and biting wit. For the humor alone people should read this book.
Posted by Blackfive on Friday, September 28, 2012 in Books | Permalink | Comments (7) | TrackBack (0)
Haven't we heard that before?
Paul Sperry over at the NY Post has an article that shows evidently, over at the Puzzle Palace, the solution to the "Green on Blue" Ad Hoc Unfriendly Bullet Exchange Program is not for us to double down on our Force Protection measures and examine how we are going to keep our savage allies from shooting us; it is to stop by the clearing barrel on the way into a classroom to be Powerpointed to Death on how it is that blowing your nose in front of a Muslim is such a blood libel that the only answer to it is for the person who witnessed it to immediately murder the nose blower.
If you don't want to be shot in the back by your Afghan training partners, the Pentagon advises, don't offend their religious sensibilities. Don't kick your feet up on a table, for instance, and never ask to see a picture of their wives and kids. "There's a percentage [of attacks] which are cultural affronts," Joint Chiefs Chairman Gen. Martin Dempsey said in a recent interview.
I probably don't need to say that the fact that General Dempsey ordered this safety standown makes him a world class tool. Responding to incidents and widespread operational issues like this with our troops with solutions like this further confirms for me the exact consistency of the chewy center of this poopy flavored lollipop; and evidently, I am not the only one who has had to lick this thing...
"I would like to see a public affairs officer explain to the press where showing the bottom of your shoe to a Muslim or shaking with your left hand was legitimate grounds for murder," growled one US Army official.
"The cultural affronts excuse is a bunch of garbage," a senior US Army intelligence official told me. "The Afghans that know we're doing all this PC cultural sensitivity crap are laughing their asses off at our stupidity."
I am speaking from a point of expertise on this; as someone who has been part of having an extremely angry Afghan soldier attempt to murder Captain Jack because he didn't want to pull security and felt offended enough to reach for his AK-47 and teach Captain Jack a thing or two about offending him. For his troubles, he got his ass kicked by Captain Jack and nearly got his head blown off when he turned to come at me. So let me say that the proper response is not to look deep inside our souls and reflect on how it is that we could have done something to not offend these savages.
Posted by Deebow on Tuesday, September 25, 2012 in Bust Their Chops, Caring For The Defenders, Current Affairs | Permalink | Comments (25) | TrackBack (0)


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A personal, guided tour to the best scoops and stories every day in The Wall Street Journal.
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Mylan Named As Gilead's Exclusive Branded Medicines Business Partner For India
PITTSBURGH and MUMBAI, India, Jan. 31, 2014 /PRNewswire/ -- Mylan Inc. (Nasdaq: MYL) today announced that its India-based subsidiary Mylan Pharmaceuticals Private Limited has been named Gilead Sciences, Inc.'s (Nasdaq: GILD) exclusive branded medicines business partner for India.
Under the agreement, Mylan will market and distribute in India Gilead's:
- HIV therapies Viread ® (tenofovir disoproxil fumarate), Truvada ® (emtricitabine/tenofovir disoproxil fumarate) and the newer single tablet regimen Stribild ® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg)
- AmBisome ® (amphotericin B liposome for injection), a treatment for life-threatening, systemic fungal infections, which is also used to treat the parasitic disease visceral leishmaniasis
- Viread ® for its indication as a treatment for chronic hepatitis B virus (HBV) infection.
Gilead has partnered with Mylan since 2006, granting the company rights to manufacture and sell their own generic versions of licensed Gilead HIV therapies in India and up to 111 developing world countries where the HIV epidemic affects millions of individuals. Mylan will continue to maintain these rights, in addition to those in this new agreement.
Mylan CEO Heather Bresch commented, "This further extension of our collaboration with Gilead builds off of our existing successful partnership manufacturing and supplying high-quality, cost-effective generic antiretroviral therapy for those in resource challenged countries, delivering on our mission of providing access to high quality medicine to the world's seven billion people."
Gilead's executive vice president of Corporate and Medical Affairs, Gregg H. Alton said, "The appointment of Mylan as our branded medicine business partner in India is a result of their strong knowledge of the Indian healthcare system and demonstrated capabilities of supporting and distributing antiretroviral therapies. We have established an excellent working relationship with Mylan over the past few years, and believe that their operations in India will allow the company to best serve the needs of patients in that country." In addition to distributing branded Gilead medicines, Mylan will manage regulatory and pharmacovigilance activity, such as adverse event reporting, as well as broader medical education initiatives.Check Out Our Best Services for Investors
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I wanted to pop up a little post to let you know that I have not abandoned my blog and that I will most definitely be getting back into the blogging groove imminently. However, I have had the small (large) matter of a burgeoning business to attend to, and it has been taking up rather a lot of my time recently. I have been living, breathing, and sleeping TheVeganKind and my hard work is paying off (as the picture above attests to; this is just a portion of the boxes we shipped on Wednesday!)
For those of you who don't know, I am a long term vegetarian who became vegan last year, and who struggled greatly when I initially became vegan trying to find support and an easy way to discover new vegan brands. I noticed that although there was a subscription box for just about anything in the UK, there wasn't one solely for vegans and thus, TheVeganKind was born.
We send out a monthly box of cruelty free, vegan products from household, to food, to personal care and beauty, for just £10 per month plus p&p. I can't quite believe it, but we are already working on putting together our SIXTH box and have featured a whole host of amazing vegan brands to wonderful acclaim from our absolutely AMAZING subscribers.
It really is a huge amount of work and effort to pull together a great box every month, which is why blogging has kind of taken a back seat for a while, but I have a backlog of products that I am desperate to share with you so I aim to start posting again very very soon.
Let me know if you would like to see reviews of any of the boxes we have shipped so far!
In the meantime, if you want to keep up to speed with what I am up to, you can follow me on Twitter, Instagram or Youtube where I post semi regularly! Hope to see you over there soon xx
Where you can find TheVeganKind:


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Give us your best shot
What we are looking for
We are gathering amazing photographs by members of the La Sierra University family, including alumni; to be displayed in the La Sierra University Dining Commons. We are seeking high-impact pictures of many subjects – travel, landscapes, people, hobbies, and more.
Technical requirements
- Up to 10 of your best images
- Image size of 5 megapixels or larger
- Good (high) image quality to be reproduced in large format.
- RAW, TIFF, PSD, or JPG
- Edited to your satisfaction
Please email full resolution files via wetransfer.com (free service up to 2 GB) to firstname.lastname@example.com. Please include a short description of the shot (location, date (if known), picture story (what story were you trying to tell when you took the picture/why where you there taking pictures, etc.), and picture credit information (name, email, and phone number of photographer).
All photos MUST be submitted by July 23.
By submitting your image(s), you acknowledge that you own the copyrights to the images or that you are the photographer. Furthermore, you grant permission to La Sierra University to:
- Print and display the photograph in the La Sierra University Dining Commons or other locations as appropriate.
- Display your name, shot location, and story of the photograph in conjunction with your displayed art.
- Edit the file to match the dimensions, style, and colors desired for framing and display (if needed).
If you have any questions about this project, please contact:
Natan Vigna - firstname.lastname@example.com
Nick Norton - firstname.lastname@example.com


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Walid Shoebat has published a video of the Libyan attack in which he reports that some of the gunmen can be heard telling others, "Don't shoot, we were sent by Morsi".
Morsi is the Muslim Brotherhood's President of Egypt.
It's certainly an intriguing development, though it could of course be a local Jihadist leader named Morsi.
The Prophet 'is a red line nobody can touch', Egyptian President Mohamed Morsi was quoted as saying by Egypt's Mena news agency comments on protests across Egypt and Libya and a film on the Prophet slammed as blasphemous. The Prophet 'is a red line for all Muslims and we refuse any attack', said the president. "We will sacrifice with our soul and heart" Morsi also said


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Blogging Pro Job Board Highlights (September 26-30)
Can you believe it's the end of the month already? Time really does seem to fly by so much faster these days! How has your job search been going?
I apologize for the dearth of job listings in the past week, as I have been away for a while. We still have a handful of jobs for you, though, so let's take a look at them now. Read More


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Laugh Detroit's Dave Moroz
Dave Moroz from Aspen Talent is the founder of the Laugh Detroit Comedy Festival. This is the fourth year of the festival that brings talent to the Comedy Castle from all across the country. This year features ten nights of live comedy from all across the country. I had a chance to talk to Dave after the Monday night showcase featuring the great Auggie Smith.
So we just got done with the second night of the Laugh Detroit Comedy Festival.
Yes. Kind of the third day, because we had an unofficial start with Michael McDaniel's One Man Show at the Charles H. Wright Museum on Friday. Over 300 people attended that. He had an amazing performance. He recorded it for his live DVD. He did 90 minutes and it was fabulous. Back here now Sunday night we had David Alan Grier and this was our first showcase with these amazing comics from across the country.
Tonight was pretty successful. It looked like the show was sold to near capacity.
I think we were over 300, which was just wonderful.
Unlike years in the past where you had theme nights, each night this year is a variety of acts.
Yeah, what we found is that when we were doing themes it sounded good on paper, but audiences were looking at their particular tastes and being directed towards certain themes. Ultimately we want people to come and enjoy a night of comedy regardless and this sort of mixed it up. I think the performances we've seen tonight, tomorrow and Wednesday are very different styles of comedy and personalities and a little something for everyone.
Are you doing the same thing where the best of the Fest goes on to the weekend?
Well, we don't call it Best of the Fest because I don't want comics competing with each other, but there are a group of people who are at every show who determine who really stands out and will be with us for the weekend. One person is identified from each of the three showcases. Two of them will open for Lynne Koplitz and the third will open for Bob Saget.
And Mike Baldwin was the person who stood out tonight.
Yeah, Mike Baldwin was the one tonight highlight of the evening.
He was pretty awesome. What's nice about the Festival is it gives Mark Ridley an opportunity to see people live versus on tape. I just worked with Tim Nutt who came to the Castle from the Festival.
He watches every performance and he takes notes. Again, it's not something we promise everyone that if you come in you have a chance to work at the Comedy Castle, but the reality instead of having Mark watch a demo he has a chance to see someone on stage and maybe bring them back.
Who are you looking forward to seeing this week?
Everyone. It's such a treat for me to see folks live. Every night is a treat. It's like eleven little gifts!
Thanks Dave.
Thank you, Mike.
Brian McKim and Traci Skene from Shecky Magazine host the showcase tonight, then on Wednesday one of my favorites Karen Rontowski is taking over hosting duties. This weekend will feature my buddy Lynne Koplitz from the Joan Rivers show Joan Knows Best and then Sunday night is Bob Saget!
Jeff Singer, the Executive Consultant for the Montreal Just For Laughs Comedy Festival is hosting a third comedy workshop after the first two have sold out. Classes are limited to nine people, so try and jump on that third one while you can!
Go to www.laughdetroit.com for more info! Tickets can be purchased in advance by eTix at www.comedycastle.com.
Posted on March 29, 2011, in Interviews and tagged Comedian, comedy, comedy castle, dave moroz, laugh detroit, mike bobbitt, off the mike. Bookmark the permalink. 1 Comment.
So nice to read such a positive article about comedy and to hear that Laugh Detroit is doing so well. From what I hear the first ever Grand Rapids comedy festival was also a huge success. We have a great thing going here with Michigan comedy.