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CD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ versus CD38−CD49d− CLL cells, we showed overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also up-regulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38−CD49d− cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors for CCL3 and CCL4, were found in CLL-derived monocyte-macrophages. Consistently, CCL3 increased monocyte migration, and CD68+ macrophage infiltration was particularly high in BMB from CD38+CD49d+ CLL. Conditioned media from CCL3-stimulated macrophages induced endothelial cells to express vascular cell adhesion molecule-1 (VCAM-1), the CD49d ligand, likely through tumor necrosis factor α overproduction. These effects were apparent in BMB from CD38+CD49d+ CLL, where lymphoid infiltrates were characterized by a prominent meshwork of VCAM-1+ stromal/endothelial cells. Lastly, CD49d engagement by VCAM-1 transfectants increased viability of CD38+CD49d+ CLL cells. Altogether, CD38 and CD49d can be thought of as parts of a consecutive chain of events ultimately leading to improved survival of CLL cells. [Cancer Res 2009;69(9):4001–9]
- integrins
- chemokines
- CD49d
- prognosis
The life and death economy of cells is mediated by a balanced net of events ruled by surface receptors, adhesion molecules, and soluble factors, among other parameters. This holds true for chronic lymphocytic leukemia (CLL) cells, which derive a relevant part of their proliferative drive from positive interactions with the neighboring nonneoplastic environment ( 1). Out of the panoply of surface molecules examined in CLL, attention has been recently given to CD49d, a member of the integrin superfamily ( 2). CD49d regulates adhesion to extracellular matrix by binding fibronectin and to other cells by interacting with vascular cell adhesion molecule-1 (VCAM-1)/CD106 ( 2). CD49d-dependent interactions have a role in preventing both spontaneous and drug-induced apoptosis of normal or neoplastic B cells ( 3– 5). Moreover, chemokine-induced transmigration of CLL cells across endothelia depends on CD49d expression by CLL cells and is favored by the production of the matrix metalloproteinase-9 as the result of CD49d engagement ( 6).
CD49d marks a subset of CLL patients characterized by aggressive and accelerated clinical course ( 7– 10), and its expression is strongly associated with CD38 ( 11– 13), a type II transmembrane glycoprotein acting both as ectoenzyme (EC 22.214.171.124) and receptor for CD31 (reviewed in ref. 14). CD38 also represents a dependable negative prognosticator in CLL ( 15– 18); due to its receptorial features, CD38 is part of a network sustaining growth and survival of CLL cells ( 19). Interactions of CD38+ CLL cells with surrounding nonneoplastic CD31+ cells is more likely to occur, although not exclusively ( 20), in peripheral lymphoid organs and/or bone marrow (BM) for several reasons. First, CD38 expression is usually higher in residential as opposed to circulating CLL cells ( 21– 23). Second, both BM and peripheral lymphoid organs can provide accessibility to CD31, as endothelial, stromal, and the so-called nurse-like cells (NLC) all express high-CD31 levels ( 1, 24, 25).
Although both CD38 and CD49d may be regarded as molecules deeply involved in the continuous interactions taking place between CLL cells and their environment, a functional link between CD49d and CD38 is still missing. By defining the global gene profile of CLL cells coexpressing CD38 and CD49d, we selected the genes for the chemokines CCL3 and CCL4 as overexpressed by CD38+CD49d+ CLL cells. Given this starting point, we provided evidence showing a novel prosurvival circuitry operating in CD38+CD49d+ CLL, sequentially involving the CD38/CD31 pair, CCL3 and CCL4 with their receptors, and eventually the CD49d/VCAM-1 axes.
Materials and Methods
CLL patients, healthy donors, and cell lines. Peripheral blood (PB) samples from 101 typical CLL ( 26) entered this study. The main clinical and biological features of CLL, the experiments for which each sample has been used, are listed in Supplementary Table S1. In 11 cases, matched PB and BM samples were available (Supplementary Table S1). IGHV mutational status and cytogenetic abnormalities were detected as described ( 7, 27). Patients provided informed consent in accordance with the local institutional review board requirements and the declaration of Helsinki.
PB samples and buffy coats of healthy donors were kindly provided by the blood bank of Centro di Riferimento Oncologico. Purified CLL cells, monocytes from CLL samples, and normal B cells were obtained by immunomagnetic selection using fresh PB samples as starting material ( 27, 28). Macrophages were obtained by allowing monocytes to adhere in the presence of 0.5 μg/mL lipopolysaccharide (LPS; Sigma).
Human umbilical vascular endothelial cell (HUVEC), microvascular endothelial cells from subcutaneous adipose tissue (ADMEC), and murine L-fibroblast cells transfected with full-length human CD31 (L-CD31), VCAM-1 (L-VCAM-1; courtesy of Pablo Engel, University of Barcelona, Barcelona, Spain), or vector alone (L-mock) were obtained as described ( 29– 31).
Flow cytometry. Sources, specificities, and fluorochrome combinations of monoclonal antibodies (mAb) used for CLL diagnosis and CD38 or CD49d determination were reported elsewhere ( 7, 10). A CLL sample was defined CD38+ or CD49d+ when the molecule was found in at least 20% of CD5+/CD19+ cells. CD38 and CD49d expression was also investigated in matched PB and BM samples from six CD38+CD49d+ and five CD38−CD49d− cases (Supplementary Table S1). Although CD38 expression was slightly higher in BM samples of five of six CD38+CD49d+ cases, average expression levels of CD38 and CD49d were comparable between BM and PB samples (not shown). CCR1/CD191 and CCR5/CD195 expression by CLL and healthy donor PB cell subpopulations was evaluated on fresh samples combining CCR5-FITC, CCR1-PE (R&D Systems) with CD3-PerCP, CD19-APC, and CD14-Pe-Cy7 (Becton Dickinson). Data were acquired on a FACSCanto flow cytometer and analyzed by Diva or CellQuest softwares (Becton Dickinson).
Apoptosis was evaluated by sequentially staining CLL cells with Syto16 (Molecular Probes, Invitrogen), anti–CD19-APC mAbs, and 7-amino-actinomycin-D (7-AAD, Becton Dickinson; ref. 32). Viable cells (Syto16bright/7-AAD−) are distinguished from apoptotic (Syto16dim/7-AAD−) or necrotic (Syto16−/7-AAD+) cells in flow cytometry plots ( 32).
Immunohistochemical and immunocytochemical analyses. BM biopsies (BMB) sections from 20 CLL cases were tested for the expression of CD10, CD20, CD34, CD49d, CD68, VCAM-1, CCR1, CCL3. CCL3 expression was also tested on cytospin preparations of purified CLL cells treated in vitro with anti-CD38 mAbs. Staining procedures are reported in Supplementary Materials and Methods.
Two different semiquantitative four-tier grading systems were used for the immunohistochemical evaluation of CD68 and VCAM-1 staining within CLL-infiltrated areas. Both systems relied on the analysis of positive cells on five randomly selected high-power microscopic fields (magnification, 400×) showing the highest degree of lymphoid infiltration. CD68 was graded as follows: grade 0, absence of CD68+ cells; grade 1, up to 20 CD68+ cells; grade 2, 21 to 40 CD68+ cells; grade 3, >40 CD68+ cells. VCAM-1 grading system was as follows: grade 0, absence of VCAM-1+ cells; grade 1, one or more scattered VCAM-1+ cells forming an incomplete meshwork; grade 2, detection of a diffuse but meager meshwork of VCAM-1+ cells; grade 3, detection of a diffuse and dense meshwork of VCAM-1+ cells.
CCL3 assessment on BMB was similarly performed in CLL-infiltrated areas. CCL3+ cases showed a clear cytoplasmic reactivity to anti-CCL3 antibodies in most CLL cells. Scattered CCL3+ cells (e.g., infiltrating T cells) could be present also in CCL3− cases.
CD38 and CD49d engagement. Purified CD38+CD49d+ CLL cells were incubated with either the agonist IB4 or the nonagonist IB6 (5 μg/106 cells) anti-CD38 mAbs or plated onto mytomicin-C–treated L-CD31, L-VCAM-1, and L-mock cells (2.5 × 105 per well). Both CLL cells and supernatants were collected after 14 and 24 h. For spontaneous apoptosis evaluation, cells were collected after 1 to 3 wk of coculture with L-VCAM-1 or L-mock cells.
ELISA. The amounts of CCL3 and CCL4 proteins in CLL cell culture supernatants and tumor necrosis factor α (TNFα) in macrophage-derived conditioned media (CM) were determined by ELISA (Bender Medsystems GmbH). Expression of CCR1 and CCR5 by adherent macrophages and VCAM-1 by endothelial cells was evaluated by an ad hoc ELISA ( 30) using unconjugated anti-CCR1, anti-CCR5 (R&D Systems), or anti–VCAM-1 (Chemicon) mAbs.
Macrophage-derived CM and monocyte chemotaxis assay. To obtain macrophage-derived CM, macrophages were cultured for 24 to 48 h with either 50 ng/mL of recombinant human CCL3 (R&D Systems; CCL3-CM), 0.5 μg/mL LPS (LPS-CM), or medium alone (CNT-CM). Subconfluent HUVEC and ADMEC were incubated for 12 h with 100 μL/well of CM and evaluated for VCAM-1 expression. In selected experiments, CM were preincubated with an antihuman TNFα neutralizing mAb (R&D Systems; 20 ng antibody/1 mL CM for 30 min at 37°C).
Responsiveness of purified monocytes to CCL3 and CCL4 (3 ng/mL) was investigated by a 2-h chemotaxis assay, carried out in 24-well 5-μm pore size Transwell plates (Costar), as reported ( 28). Results were expressed as migration index (MI), i.e., transmigrating cells in the presence of chemokine divided by transmigrating cells in the absence of chemokine.
CCL3 and CCL4 are overexpressed in CD38+CD49d+ CLL cells. A gene expression profile of purified CLL cells from 26 cases (11 CD38+CD49d+ and 15 CD38−CD49d−; Supplementary Table S1) was performed (see Supplementary Materials and Methods). Results indicated 294 differentially expressed genes: 89 down-regulated and 205 up-regulated in the CD38+CD49d+ group. A hierarchical clustering, generated using these 294 best-correlated genes, clearly split the 11 CD38+CD49d+ from the 15 CD38−CD49d− CLL (Supplementary Fig. S1A and Supplementary Table S2). Among the genes up-regulated in CD38+CD49d+ CLL, we found the CD38 and CD49d genes and several genes previously identified as related either to the CD38+ phenotype and/or poor prognosis, such as lipoprotein lipase, Septin-10, activation-induced cytidine deaminase, and spastic paraplegia 20 (Supplementary Table S2; refs. 33, 34).
To further elucidate the biological functions of genes representing the expression signature of CD38+CD49d+ CLL, the identifiers for the 294 best-correlated genes were linked to the "Onto-Express" bioinformatics tool ( 35). Biological processes showing the highest significant enrichment for genes found to be differentially expressed between CD38+CD49d+ and CD38−CD49d− CLL are listed in Supplementary Table S3. Of note, the genes for the chemokines CCL3 and CCL4 were constantly selected as overexpressed by the CD38+CD49d+ CLL group (CCL3 mean fold change, 3.47; CCL4 mean fold change, 4.36; Supplementary Table S3). Quantitative real time–PCR (QRT-PCR) experiments, carried out in 37 CLL samples (22 CD38+CD49d+ and 15 CD38−CD49d−; Supplementary Table S1), confirmed the constitutive higher expression of both CCL3 and CCL4 transcripts in CD38+CD49d+ CLL (Supplementary Fig. S1B). Such a higher expression was also confirmed by comparing CCL3 and CCL4 transcript levels in BM samples from six CD38+CD49d+ and five CD38−CD49d− cases, without significant differences with the corresponding PB samples (Supplementary Fig. S1C). These data, along with the notion of a role played by chemokines in favoring microenvironmental interactions of CLL cells ( 28, 36, 37), suggested to investigate in detail the function of CCL3 and CCL4 in the pathophysiology of CD38+CD49d+ CLL.
CCL3 and CCL4 are up-regulated by CD38 engagement in CD38+CD49d+ CLL cells. The next step was the analysis of CCL3 and CCL4 mRNA and protein modulation upon CD38 ligation in CD38+CD49d+ CLL cells. Purified CLL cells from 11 CD38+CD49d+ CLL cases (Supplementary Table S1) were cultured either with the agonist IB4 mAb or the nonagonist IB6 anti-CD38 mAb as comparative control. After 14 (t14) and 24 (t24) hours, CLL cells and culture supernatants were collected for evaluation of CCL3 and CCL4 at the mRNA and protein levels. As compared with controls, higher levels of transcripts for CCL3 (mean fold increase, 18.0 ± 8.1; P = 0.041) and CCL4 (mean fold increase, 13.8 ± 5.2; P = 0.005), both peaking at t14, were detected by QRT-PCR upon CD38 ligation (not shown). A parallel increase was observed at the protein level ( Fig. 1A ), although with a later (t24) peak (mean CCL3 protein, 0.9 ± 0.1 ng/mL; mean fold increase, 14.0 ± 4.4; P = 0.003/mean CCL4 protein, 1.7 ± 0.5 ng/mL; mean fold increase, 49.0 ± 29.0; P = 0.01). Consistently, a clear increase of CCL3-specific staining of CLL cell cytoplasm was observed upon a 24-hour CD38 engagement by agonist mAbs ( Fig. 1B). Notably, a direct correlation was found between CD38 expression levels by flow cytometry and the levels of CCL3 protein released in culture supernatants both at control conditions (P = 0.03; Spearman's ρ rank correlation) and upon CD38 engagement (P = 0.02).
A similar up-regulation of CCL3 and CCL4 transcripts was obtained in four representative CD38+CD49d+ cases, in which CD38 engagement was performed using CD31-transfected murine L-fibroblasts instead of agonist anti-CD38 mAbs (not shown). Finally, no additional up-regulation of CCL3 and CCL4 transcript levels was observed upon simultaneous engagement of CD38 and CD49d by agonist anti-CD38 mAbs and L-VCAM-1 transfectants, respectively (not shown).
CCL3 is expressed by BM CLL cells from CD38+CD49d+ CLL. BM can provide the optimal microenvironment for CLL cells to interact with endothelial and stromal cells, e.g. via the CD38/CD31 pair ( 14). We investigated CCL3 expression by BM infiltrating CLL cells from BMB of 10 CD38+CD49d+ and 10 CD38−CD49d− cases (Supplementary Table S1). By CD20 staining, different infiltration patterns and a variable degree of BM involvement were observed, without significant differences between CD38+CD49d+ and CD38−CD49d− CLL ( Table 1 ). By limiting analyses to CLL-involved areas, CCL3 protein was detected in eight CLL cases, all but one belonging to the CD38+CD49d+ CLL group (P = 0.02; Table 1), with a distinct CCL3-specific cytoplasmic staining observed in the vast majority of infiltrating neoplastic cells ( Fig. 1C).
Monocyte macrophages express the CCR1 and CCR5 chemokine receptors and migrate in response to CCL3 and CCL4. Expression of the CCL3-specific and CCL4-specific receptors CCR1 and CCR5 was examined by flow cytometry in PB cell populations from 39 CLL cases (12 CD38+CD49d+, 14 CD38−CD49d−, 10 CD38−CD49d+, and 3 CD38+CD49d−; Supplementary Table S1) and 9 healthy donors. Irrespective of CD38 or CD49d expression by CLL cells, monocytes showed in all cases the highest mean fluorescence intensity levels for CCR1 and CCR5, the latter at a lower intensity (Supplementary Table S4; Fig. 2A ). Similar CCR1 and CCR5 expression levels were detected in adherent macrophages from CLL cases, with an increase upon in vitro activation ( Fig. 2B). Conversely, CLL cells and residual T lymphocytes showed low mean fluorescence intensity levels for both chemokine receptors (Supplementary Table S4; Fig. 2A). Similar expression patterns were observed in PB cell subsets from healthy donors (Supplementary Table S4).
After showing that monocytes express CCR1 and, to a lesser extent, CCR5, we analyzed the effects exerted by CCL3 and CCL4 on migration of purified monocytes from nine CLL cases (five CD38+CD49d+, one CD38−CD49d−, two CD38−CD49d+, and one CD38+CD49d−; Supplementary Table S1). Both chemokines increased monocyte migration; however, the effects were more apparent with CCL3. Indeed, a statistically significant higher number of monocytes migrated in response to CCL3 rather than CCL4 (MI for CCL3, 8.7 ± 1.7; MI for CCL4, 1.7 ± 0.5; Fig. 2C); no significant differences were observed between monocyte preparations purified from CLL cases expressing different CD38 or CD49d levels (not shown).
CD68+ cells infiltrate CLL areas of BMB from CD38+CD49d+ CLL. Based on the expression of CCL3 selectively found in CLL cells from BMB of CD38+CD49d+ cases, along with the capability of this chemokine to attract monocytes, we attempted to quantify the extent of infiltration of CD68-expressing monocytoid cells in the context of CLL-involved areas of BMB from CD38+CD49d+ and CD38−CD49d− CLL ( Fig. 3 ). The number of round-to-spindle–shaped CD68+ cells intermingling with CLL cells was significantly higher in CD38+CD49d+ compared with CD38−CD49d− cases (P = 0.016). In particular, a grade 3 infiltration was solely found in BMB from CD38+CD49d+ CLL (5 of 10 cases); conversely, all five grade 0 (null) or grade 1 (low) infiltrations were observed in the CD38−CD49d− group ( Table 1). Infiltrating CD68+ cells strongly expressed the CCL3-specific receptor CCR1 (Supplementary Fig. S2).
CM from CCL3-treated macrophages up-regulates VCAM-1 by endothelial cells. In our model, we hypothesized a role for the CD68+ macrophage component recruited in the context of BM lymphoid aggregates by CCL3 released by CD38+CD49d+ CLL cells. In particular, we investigated the ability of CCL3-stimulated macrophages to induce endothelial cells to express the CD49d ligand VCAM-1 ( 38).
VCAM-1 expression was determined in two endothelial cell models (HUVEC and ADMEC) after 12 hours of incubation with CM collected from CLL-derived macrophages challenged in vitro with either CCL3 (CCL3-CM) or culture medium alone (CNT-CM) from four different CD38+CD49d+ CLL macrophage preparations (Supplementary Table S1). As shown in Fig. 4A , the mean VCAM-1 expression seemed significantly up-regulated in both cell models upon exposure to CCL3-CM compared with CNT-CM.
It is known that VCAM-1 expression can be up-regulated in different cell types by TNFα ( 38). Accordingly, a significant enrichment of TNFα protein was detected in CCL3-CM compared with CNT-CM ( Fig. 4B). The highest levels of TNFα protein were found in CM from LPS-exposed macrophages (LPS-CM), which was also the most effective CM in inducing VCAM-1 up-regulation by endothelial cells ( Fig. 4A and B).
The specific contribution of TNFα to VCAM-1 expression by HUVEC and ADMEC was confirmed by neutralizing its biological activities in CCL3-CM derived from selected macrophage cultures (CLL cases 90 and 97). As shown in Fig. 4C, TNFα neutralization was followed by a significant reduction of VCAM-1 up-regulation in both cell models.
VCAM-1 is up-regulated in endothelial/stromal cells from BMB of CD38+CD49d+ CLL. These results were validated by analyzing VCAM-1 expression in BM lymphoid aggregates of CLL cases expressing or not CD38 and CD49d. A significantly more prominent meshwork of VCAM-1+ cells was detected in the context of the lymphoid infiltrates of CD38+CD49d+CLL compared with CD38−CD49d− cases (P = 0.002). No cases graded 0 or 1 for VCAM-1 expression were observed in the CD38+CD49d+ group, whereas high (grade 3) VCAM-1 expression levels were only scored in this group ( Table 1; Fig. 3A–D).
Inside the lymphoid aggregates, VCAM-1 marked both the sinusoidal endothelia and the meshwork of interdigitating BM stromal cells, the former identified by CD34 and the latter by CD10 staining in serial sections (Supplementary Fig. S3). Moreover, double immunostaining indicated that the VCAM-1+ endothelial/stromal component generally lacked CD68 expression. In turn, CD68+ macrophages were almost constantly VCAM-1− (Supplementary Fig. S4).
CD49d engagement by VCAM-1 protects CLL cells from apoptosis. Given the high expression of VCAM-1 characterizing BMB of CD38+CD49d+ CLL, and the close proximity in CLL-involved BM microenvironment of CD49d+ CLL cell membranes and VCAM-1+ cellular processes from stromal/endothelial cells (Supplementary Fig. S5), we tested whether engagement of CD49d by VCAM-1 was able to delay the spontaneous apoptosis observed in cultured CLL cells ( 1).
Purified CLL cells from five CD38+CD49d+ cases (Supplementary Table S1) were cultured on murine L-fibroblast cells transfected with full-length human VCAM-1 or vector alone, and cell viability was determined over a time period spanning from 7 to 21 days. Figure 4D shows that CLL cells exposed to VCAM-1 were characterized by a relevant improvement in cell viability. In particular, the effects on protection from apoptosis exerted by CD49d/VCAM-1 interactions became apparent after 7 days of culture and were more evident after 14 and 21 days of culture, reaching 42% mean viable cells compared with 28.5% in nonstimulated conditions (P = 0.001; Fig. 4D).
CCL3 and CCL4 are small (8–10 kDa), structurally related, and secreted proteins, which are inducible and produced by mature hematopoietic cells (reviewed in ref. 39). Biologically, CCL3 and CCL4 have overlapping effects and act as potent chemoattractants for monocyte macrophages, dendritic, T, and natural killer cells ( 39). Despite indirect suggestions of a putative role for CCL3 and CCL4 in CLL ( 13, 40, 41), their involvement in this disease has not been investigated in detail.
Here, we show a distinctive overexpression of transcripts for the CCL3 and CCL4 genes in CD38+CD49d+ CLL cells and a clear-cut transcript up-regulation and increased release of CCL3 and CCL4 by CD38+CD49d+ CLL cells upon CD38 triggering. Of note, a direct correlation between the levels of CD38 and CCL3 protein was shown by considering both the basal CCL3 levels in CD38+CD49d+ CLL, and the increased amount of CCL3 released upon CD38 engagement.
These results are in keeping with the known capacity of CD38 engagement to mediate, along with proliferative and/or antiapoptotic signals ( 19, 31), cytokine release in other cellular systems ( 14, 42). Because CD31 is expressed by various cell types, including monocytes, endothelial cells, and CLL cells themselves irrespective of CD38 expression ( 20, 43), it is conceivable that interaction of CD31+ cells with CD38+ CLL cells might frequently occur in vivo, contributing to increased levels of CCL3 and CCL4 in biological fluids. In this regard, a preliminary survey of CCL3 protein concentration in plasma samples from 53 CLL revealed almost 3-fold higher CCL3 levels in CD38+ (25 cases) compared with CD38− (28 cases) CLL (mean values of 43.8 versus 15.1 pg/mL, respectively). 8
These findings raise the issue of the role played by CCL3 and CCL4 in CLL. According to our results, CLL-derived CCL3, more than CCL4, significantly contributes to the recruitment of cells from the monocyte macrophage lineage to BM microenvironmental sites. These conclusions are supported by distinct lines of evidence. First, CCR1 and CCR5 (the receptors for CCL3 and CCL4) are strongly expressed, the former more than the latter, by PB monocytes and macrophages ( 44) from healthy and CLL samples, but not by the majority of T or neoplastic B cells. Second, PB monocytes from CLL samples are uniquely sensitive to CCL3 signals in vitro, in keeping with the strong expression of CCR1 ( 39, 45). A third line of evidence is represented by the in vivo observation of a higher number of infiltrating CD68+ cells in the context of CLL-involved areas of BMB from CD38+CD49d+ CCL3-producing cases compared with CD38−CD49d− CLL. CD68 was shown to mark a heterogeneous population of myeloid cells, including macrophages, dendritic cells, and NLC, a distinctive cell population arising from monocytes cultured in vitro in close contact with CLL cells ( 1, 24, 25). According to costaining studies, this CD68+ component infiltrating the BM stroma of CD38+CD49d+ CLL, in addition to being CCR1+ in keeping with their putative capacity to respond to CCL3, expressed CD14 9 and lacked VCAM-1, a phenotype also reported for NLC ( 1, 24, 25).
The observation of a preferential monocyte macrophage infiltration in CLL-involved BM stroma from CD38+CD49d+ cases raises the additional question regarding the functional role of these cells in the pathophysiology of CD38+CD49d+ CLL. We addressed this issue by considering (a) the parallel increase of CD68+ cells and neovasculature, as detected in lymph nodes of lymphoproliferative disorders ( 46); (b) the association in CLL lymph node sections between high CD38 expression by tumor cells and increased tumor vascularity ( 22); and (c) the known feature of VCAM-1, the CD49d ligand, to be induced on the surface of stromal/endothelial cells upon several stimuli ( 38). This background prompted us to evaluate the expression of VCAM-1 in CLL-involved BM tissues from cases expressing CD38 and CD49d or not. Results indicate a close correlation among the CD38+CD49d+ phenotype by CLL cells, infiltration of CD68+ macrophages, and presence of a stromal/endothelial component strongly expressing VCAM-1. A functional link between CD68 and VCAM-1, as expressed in CLL-involved BMB, was indirectly found by showing the capacity of CM produced by CCL3-stimulated macrophages from CD38+CD49d+ CLL cases to up-regulate VCAM-1 expression in endothelial cell models ( 29, 30). As indicated by our experiments and in keeping with literature data, TNFα turned out to be among the major cytokines released by CCL3-stimulated macrophages likely responsible for VCAM-1 up-regulation by endothelial cells ( 47). However, as suggested by an incomplete reversion of VCAM-1 overexpression upon TNFα blocking, other cytokines allegedly released by CCL3-stimulated macrophages (e.g., interleukin-1) may also contribute to VCAM-1 up-regulation ( 47).
Microenvironmental interactions in marrow or secondary lymphoid organs have been shown to confer growth advantage and extended survival to CLL cells and play a role in disease progression and resistance to therapy ( 1, 48). Operationally, growth and prosurvival signals are delivered through a number of different receptor-ligand pairs. As an example, interactions occur between CLL cells, expressing CD40, and CD40L+ T cells, the latter specifically attracted by CLL-derived CCL22 ( 1, 49). Moreover, NLC interact with CLL cells using the CD38/CD31 axis usually associated with CD100/plexinB1–mediated contacts ( 31) and by producing soluble factors, such as CXCL12 and BAFF/APRIL, which bind CLL cells, in turn expressing their respective receptors ( 50). These interactions are favored by the release by NLC of chemokines (e.g., CCL19, CCL21, and CXCL12) capable of attracting CLL cells, especially if expressing CD38, ZAP-70, and CD49d ( 28, 36, 37).
Here we showed that CD68+ NLC or monocyte macrophage cells can also be attracted by specific chemokines (e.g., CCL3) produced by CLL cells when expressing high levels of surface CD38 to allow efficient CD38/CD31 interactions. These attracted CD68+ cells, in addition to directly interact with CLL cells, can be active in determining, through the release of TNFα and other cytokines, the overexpression of VCAM-1 by the stromal/endothelial component of BM microenvironment. Specific VCAM-1/CD49d interactions can efficiently increase survival of CD49d-expressing CLL cells ( Fig. 5 ). The proposed circuitry may represent the cellular basis explaining the aggressive clinical course of CLL coexpressing CD38 and CD49d.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Grant support: Ministero della Salute (Ricerca Finalizzata IRCCS, "Alleanza Contro il Cancro," and Rete Nazionale Bio-Informatica Oncologica/RN-BIO), Rome (V. Gattei); Associazione Italiana contro le Leucemie, linfomi e mielomi (AIL), Venezia Section, Pramaggiore Group (V. Gattei); Ricerca Scientifica Applicata, Regione Friuli-Venezia-Giulia, Trieste ("Linfonet" Project) (V. Gattei); Ricerca Sanitaria Finalizzata, Regione Piemonte (G. Gaidano); AIL-Novara (G. Gaidano); the Chronic Lymphocytic Leukemia Global Research Foundation (S. Deaglio); the Associazione Italiana Ricerca Cancro (S. Deaglio); Programmi di ricerca di Rilevante Interesse Nazionale (F. Malavasi); Fondi di Ateneo, University of Turin and Regione Piemonte (F. Malavasi); Fondazione Internazionale Ricerca Medicina Sperimentale (F. Malavasi); and Fondazione Guido Berlucchi, Brescia (F. Malavasi).
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U S.C. Section 1734 solely to indicate this fact.
We thank Emilio Iannitto and Rossana Porcasi (University of Palermo), Antonio Ramponi (Division of Pathology, Novara), Lucia Rizzi (University of Trieste), and Renato Campanini (University of Bologna).
Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
↵8 D. Benedetti, unpublished observation, March 2008.
↵9 C. Tripodo, personal observation, June 2008.
- Received November 7, 2008.
- Revision received January 30, 2009.
- Accepted February 10, 2009.
- ©2009 American Association for Cancer Research.


text:
Aderezo para ensalada César
Un condimento clásico con sabores fuertes y una consistencia cremosa sin conservadores.
- 6 yemas de un huevo grande pasteurizadas
- 3 cucharadas de vinagre de vino tinto
- 3 dientes de ajo
- 1/3 de taza de jugo de limón amarillo
- 4 filetes de anchoas
- 1 cucharadita de mostaza en polvo
- 1 taza (120 g) de queso parmesano rallado
- 1 taza (240 ml) de aceite de oliva
- 1 cucharadita (3 g) de sal (opcional)
- ¼ de cucharadita de pimienta negra molida
- Vierta todos los ingredientes en el vaso de la Vitamix en el orden indicado y cierre bien la tapa.
- Seleccione la velocidad 1.
- Encienda la licuadora e incremente poco a poco la velocidad hasta 10.
- Licúe durante 25-30 segundos o hasta obtener una mezcla sin grumos.
Refrigere dentro de un recipiente hermético de tres a cuatro días.
Información nutricional
|Tamaño de la porción
|2 cucharadas (30 ml)
|Cantidad por porción
|Grasas saturadas
|Fibra dietética
Caesar Salad Dressing is rated out of 5 by 9.
Rated 5 out of 5 by anya24060 from Great recipe! This recipe is delicious. The key to making it work is SLOW addition of the oil. I make this all the time and my family/guests rave about it. I use my Vitamix scale to measure all the ingredients and it is super easy.
Date published: 2017-09-03
Rated 3 out of 5 by Pojo28 from Does not emulsify I've made this twice, once as directed and once by adding oil in slowly. While the flavor is bright fresh and wonderful it's runny.
Date published: 2018-02-04
Rated 2 out of 5 by Justink from Recipe conversions make no sense Be careful with this recipe - it appears that the 64 oz.versions do not properly scale the flavoring ingredients against the structuring ingredients, so the flavor will be diluted and structure will be runny in the 64 oz.versions.
Date published: 2018-12-02
Rated 1 out of 5 by Gigahoo from Didn't work for me Failed to make a smooth, creamy dressing. In my opinion either the recommended power is too low, or the olive should be poured in slowly while the blender is running as in most other blender recipes.
Date published: 2016-08-29
Rated 1 out of 5 by nutrinancy from Not thick or tasty This recipe makes a full quart of runny, flavorless dressing. The ratio of eggs to oil is too low and the seasonings are not in proportion to the liquid.
Date published: 2017-12-31
Rated 1 out of 5 by Meranda from Vitamix doesn't live up to my Oster Beehive I have tried using my vitamix to make this dressing twice. Neither time has it blended properly. I much prefer my old blender for Caesar dressing. Vita leaves chunks of ingredients blasted all over the walls of the blender, and does not smoothly blend.
Date published: 2016-06-25
Rated 4 out of 5 by GoFlo from Caesar salad dressing Very easy to make, a little bit tangy but not to much. Since it was only for two people, i cut the recipe in half and it did not compensate on the taste.
Date published: 2020-07-06
Rated 5 out of 5 by katsc from Not vegetarian, although excellent Quick and tasty, but with an anchovy it is not vegetarian.
Date published: 2015-12-16

subset: commoncrawl


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Export 7 results:Author Title [ Type] Year
Filters: Keyword is energy analysis and environmental impacts department and Author is Kevin Porter [Clear All Filters]
Case Study
"Using Bulk Purchase Commitments to Foster Sustained Orderly Development and Commercialization of PV." Case Studies of State Support for Renewable Energy 2002: 8..
2009 Wind Technologies Market Report. Berkeley: LBNL, 2010. LBNL-3716E..
2010 Wind Technologies Market Report. . Berkeley: LBNL, 2011. LBNL-4820E..
2011 Wind Technologies Market Report. . 2012. LBNL-5559E..
Clean Energy Funds: An Overview of State Support for Renewable Energy. Berkeley: LBNL, 2001. LBNL-47705..
Does It Have To Be This Hard? Implementing the Nation's Most Aggressive Renewables Portfolio Standard in California. Berkeley: LBNL, 2005. LBNL-58728..
Evaluating Experience with Renewables Portfolio Standards in the United States. Berkeley: LBNL, 2004. LBNL-54439..


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Event Date:
Location name:
Law And Sports: Current And Future Perspectives (International Conference)
Call For Papers
19th and 20th February, 2017, Ibn Khaldoun Hall, Qatar University
An International Conference - Call For Proposals Now Open
Proposals Deadline: October 15th, 2016
BACKGROUND OF THE COLLEGE OF LAW IN CONFERENCES ORGANIZATION: The College of Law, Qatar University is committed to the advancement of law within the State of Qatar. To this end, the college has placed a special emphasis on embracing the values and mission of the University in order to boost the education and development of Qatar, thereby leading to fostering the development of both research capabilities and intellectual capital at the University. Accordingly, organizing conferences, workshops and seminars stands as an important mean to achieve the aforementioned vital goals.
In line with this commitment, the College of Law built a record of successful international conferences including: the Comparative Law Conference in 2012, the Syrian Crisis and International Law on 24th 25th February 2014, the Qatari Civil Code Conference marking the tenth anniversary of the enactment of the Qatari Civil Law on 23rd and 24th November 2014 and the Law and Medicine conference on 28th and 29th February, 2016.
IMPORTANCE OF THE CONFERENCE: The regulation of sports activities has been a subject of high importance for various legal systems due to its social context and impact on economy. People generally show interest in sports by either performing a number of sports activities or through following Television sports channels. In addition, the sports sector has become an important economic sector which attracts investment in various aspects. Governments tend to place this sector on top of their economic development priorities. This fact is clearly revealed in Contracts of Sport Sponsorship where the biggest international companies and organizations vigorously compete to win sponsorship contracts for major sport events.
Moreover, this economic emphasis has been also shown in international competitions between states to win the exclusive right to organize major sport activities at international and continental levels, which also contribute in governmental economic revitalization.
In line with the above, the State of Qatar placed high importance on sports and consequently issued a number of laws to regulate this sector in its various aspects whether physical, social or economic. This serves the fulfillment of Qatar National Vision 2030 that is based on four main pillars: economic, social, human and environment development.
More importantly, the fact that Qatar succeeded in winning the right to organize a number of regional, continental and international sport events, particularly the world cup 2022, places it in confrontation of numerous challenges that should be studied and researched.
Finally, this proposed conference predominantly aims to shed the light on various legal aspects related to the exercise of sports activities in the State of Qatar comparatively to other jurisdictions, in order to conclude recommendations that can be utilized in further developing the Qatari legal framework which in its turn, boost sports activities at all levels.
- To increase public awareness about the importance of legal regulation of sports activities on both Qatari and regional levels.
- To highlight the economic benefit of investment in sports activities.
- To identify the legal and operational challenges that faces investment in sports activities in Qatar, and suggests relevant and appropriate solutions for the development and growth of this sector in line with Qatar National Vision.
- To analyze the most recent developments and practices of sports regulation at national, regional and international levels.
- To promote an open dialogue with various sports experts and provide effective recommendations for policymakers to regulate various legal, economic, regulatory and technical gaps and obstacles that face investments in sports.
- Ministries and other related Government Organizations in Qatar (The Qatar Olympic Committee, The Ministry of Culture and Sports).
- Sports Organizations (Qatar Stars League-Aspire Academy- Sports Federations).
- Qatar Olympic Academy.
- Sports Clubs in Qatar.
- Judiciary Members.
- Lawyers.
- Investment Companies.v - Experts and researchers.
- Media.
The Regulatory Framework for Sport Activities:
- National and International Sports Organizations.
- Sports Clubs and Organizations.
- Sports Licensing.
- Taxation on Sports Activities.
- Regulatory Suspension of Sports Activities.
- Professional League Association.
- Sports Clubs and Organizations.
- Sports Licensing.
- Taxation on Sports Activities.
- Regulatory Suspension of Sports Activities.
- Professional League Association.
- Players Transfer Contacts.
- Sports Training Contracts.
- Sports Agents.
Sports Legal Liability:
- Civil Liability for Players and Referees.
- Civil Liability of Sport Clubs and Organizers.
- Criminal Liability for Using Steroids.
- Sport Liability Exemption.
- Sport Corruption Crimes in Clubs and Sport Organizations.
Insuring Sports Activities:
- Insurance against Sport Activities Risks.
- Hooliganism Insurance.
- Security and Safety in sport field and community responsibility.
Investment in Sports Activities:
- Intellectual Property Rights.
- Sports Sponsorship Companies.
- Sports Media.
- Sports Activity.
Resolution of Sports Disputes:
- Sports Courts.
- Arbitration or;
- Any alternative mechanism for the settlement of sport disputes.
- Qatar Olympic Committee.
- College of Law, Qatar University.
- Conference papers should adhere to academic standards and methodology.
- Papers must relate to the conference topics.
- Papers must contain specific recommendations that serve the objectives of the conference.
- Papers should not be previously presented in other conferences or previously published in other journals.
- The time for presentation should not exceed 20 minutes.
- All papers will be reviewed by a scientific committee at the College of Law.
The following editorial guidelines must be observed:
- Maximum Number of Pages: 30
- Font Type: Times new roman
- Font Size: 14
- Distance Between Lines: 1.15
- Number of Lines Per Page: 30
- Margins Specifications: Font Type: Times New Roman, Font Size: 11
- Interested participants are required to send a 1- page brief proposal of the paper they are planning to present in Arabic, English or French in addition to their C.V. to firstname.lastname@example.com no later than 15th October, 2016.
- The College of Law will send initial acceptance notifications by 27th October, 2016.
- Submission of full papers should be made electronically before 30th December 2016 to the email:
- Papers are accepted in Arabic, English or French.
- Papers will be published in the conference proceedings.
- Qatar University will handle the travel and accommodation expenses for presenters who must travel to Doha.


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The soothing smell of the well known aromatic herb. Its smell was thought to relieve depression and to encourage relaxation.
Travel Spray
This is the same as the Refresher Spray in a smaller bottle. It's in a 2 oz bottle. You can take them in your carry on when you fly. They fit nice in a purse and in the console of the car.


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Professional Community for Car Dealers, Marketing, Advertising and Sales Leaders
A business lives and dies by its sales, particularly in the automotive industry.
Due to the fact that each car carries such a large value, having vehicles stuck on the forecourt for weeks and months on end can hugely hamper you business's cash flow, causing significant issues.
Thanks to the rise of the internet, selling cars is simpler than ever before, as people from all across the country can see what you have in stock, arrange visits and even see what the car looks like and all of its vital details. With the internet being so important to sales, in this post we go through how you can improve your website sales strategy.
All of your car descriptions should be accompanied by images of both the inside and the outside of the veh.... The vehicle should have recently been washed and valeted and (if possible), you should take the pictures on a sunny day.
These will help prospective buyers be able to make an informed decision about the vehicle and what it looks like so they can decide whether it's right for them. It should help your vehicles stand out in a crowded market, making buyers more likely to visit and test drive.
Detailed Descriptions
As well as exterior and interior images, you should include a detailed description of the car. This can largely be done in bullet points. It should include:
- Mileage
- Age
- Number of owners
- Level of service history (none, partial or full)
- Fuel type
- Colour
- Warranty
- MOT expiry date
- Number of owners
- Number of doors
All of this data will help your customers directly compare cars, helping inform their decision about whether to buy the vehicle. It also makes your business appear more reputable, trustworthy and knowledgeable.
Opt for a Clean Layout
Although you need detailed listings, you also need to ensure that the layout of your site is clean, with plenty of white space, much like this car supermarket has.
A simple and logical layout with plenty of white space will ensure that potential customers are not overwhelmed with information, causing them to look elsewhere. By keeping the site simple and clean you can ensure that customers have access to all the main information without impairment. They can always ring or visit you if they need more.
Allow People to Enquire/ Book Online
The internet is a great starting point for people who are interested in buying cars but remember that a lot of people will be using your site out of office hours.
As such, on each listing, you should add separate buttons or forms so that people can make an official enquiry about the vehicle or book a test drive. This way, you can respond as soon as you make it to the office the next day.
If your site doesn't have this functionality, ensure that you have an email address on each listing so that people can contact you. You should also include a phone number that has a voicemail so people can leave messages.
Follow these four top tips and you should improve your website sales strategy massively, leading to more sales and higher profits.
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Three drug makers reach tentative settlement in testosterone side effects MDL
Three manufacturers of testosterone replacement therapies among several in a multidistrict litigation accusing the companies of failing to warn consumers about cardiovascular risks with their products, have notified an Illinois federal judge that they have reached a tentative deal to settle the cases in which they are named. U.S. District Judge Matthew Kennelly told the manufacturers – Endo Pharmaceuticals Inc., Auxilium Pharmaceuticals LLC and GlaxoSmithKline LLC – that he would place a 45-day stay on the cases against them while the details of the settlement are worked out. He also told the remaining defendants – including AbbVie Inc., and Actavis ... Read More


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We love this property because of the view of the lake, both from the Cottage on the upper level and from the waterfront area. It is called "waterfront" instead of "beach" because it is rock and stone below a bluff. We have just added a dock to the waterfront area and there is a swim float that you can swim out to and maybe bring a canoe or kayak up to it. The lake water is cool and comfortable, but we want to state that you swim at your own risk as this is a private home without a lifeguard.
Bring your beach shoes for traction and protection from the zebra mussels. Once in the water, you can swim out to our float in the cool, refreshing water.
Our camp has a perfect vantage point for enjoying the stunning sunsets on Lake Champlain.
While you are here, you could bring (or rent from a local business) your quiet sports boats like a canoe or a kayak. It's the perfect way to explore our little corner of the lake.


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5 Questions to Ask Yourself Before Initiating a 0% APR Balance Transfer
January 11, 2018
Adrienne H., Financial Expert
Are you feeling the burden of holiday debt after purchasing all of those gifts for family and friends? If so, you're not alone. The average American consumer racked up more than $1,000 in debt this past holiday season! Now that the holiday shopping season is over, it is prime time to consider 0% APR balance transfer specials for those credit cards carrying high balances. Balance transfers can be a great idea to avoid paying interest for several months or not at all. However, it's important to be mindful of how these specials work so you don't end up digging yourself a deeper hole.
If you aren't sure what a balance transfer is, here is a quick rundown: a balance transfer allows you to transfer your debt from one credit card to another, typically for a lower interest rate. Balance transfers are a great option to save money by avoiding high interest, and many companies offer low or no interest rates for a fixed period –– often six months to a year. There's a catch, though. The total balance must be completely paid off within the time period or you will end up paying interest for the remaining balance, which can be at a much higher interest rate.
If you're thinking about opening a 0% introductory APR credit card, ask yourself these five questions first.
How can a 0% introductory APR balance transfer save me money?
The keyword here is introductory. A 0% introductory APR allows you to payoff your debt without having to pay interest for a certain amount of time, potentially saving you thousands of dollars. For example, if you have a $1,000 balance on a credit card with a 17% interest rate, you would have to make a $195 payment for six months to pay off that credit card. If you transferred that $1,000 balance to a credit card with a 0% introductory rate for the first six months, your monthly payments would decrease to about $166, saving you $170 in interest over a six-month period.
Will I repay the full balance before the introductory rate expires?
If the answer above makes you want to pursue the 0% balance transfer process, it's important to understand the responsibilities if you don't repay the full balance before the fixed period ends. Let's say you only pay back $700 of the $1,000 balance within six months. After those six months, the balance transfer rate will revert to the standard rate you qualified for. These rates tend to be between 15% and 30% for store credit cards (credit union-issued credit cards typically have lower standard rates). For example, if your standard rate is 25%, you'll have to have to pay $75 in one month's interest for your remaining balance of $300. You'll want to make sure you can repay the entire balance before your introductory rate expires or you may end up paying more than the loan balance you originally tried to avoid.
Do I have enough self-control to not accrue additional debt?
Keep in mind that you will most likely continue to spend money throughout the introductory rate period. Balance transfer rates often only apply to the balance transferred from another financial institution and does not apply to new purchases and cash advances made on the card. To make a 0% APR balance transfer worth it, you'll have to work on paying off the transferred balance and try not to put any additional purchases on that card if you're aiming to be debt free.
Is there an annual or balance transfer fee associated with the credit card?
At MSUFCU, we don't charge annual fees or fees to move your balances to a 0% introductory APR credit card, but that isn't always the case at other financial institutions. Most often, creditors charge a balance transfer fee, which is usually 3%-5% of the balance (about $30-$50 fee when transferring a $1,000 balance). Companies will also try to attract new customers with a 0% APR promotion with no annual fees for the first year. However, after the first year, customers will have to pay a fee (ranging between $25 and $500) each year for use of that credit card.
Do I have good or excellent credit established?
Most lenders will only approve balance transfers for those who have good or excellent credit —a score of 670 or above. However, everyone has a different financial situation and there are many factors each financial institution looks at to determine if you're eligible for a credit card that offers balance transfers. If your creditworthiness qualifies you for a balance transfer, it's also important to understand how opening a new card will affect your score. Each time you apply for a new loan, a credit check is necessary. One credit check doesn't usually have a big impact on your credit score and may help you in the long run, but applying for many in a short time period may negatively affect your credit, making you appear risky to lenders. Remember that full and on-time payments are crucial factors for maintaining good credit.
So, do you think a balance transfer is right for you? Contact us or your financial institution to figure out how a balance transfer can save you money.
Tags: Credit Cards, Learn About Credit, Borrowing Money


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Please be advised that you are leaving GFA Federal Credit Union's website. This link is provided as a courtesy. GFA Federal Credit Union does not endorse or control the content of third party websites.
Get one stop shopping at GFA, we have competitive rates on auto loans as well as a FREE auto buying service, insurance options and payment protection.
Apply for an Auto Loan
*3.09% Annual Percentage Rate (APR) is a limited time offer, and is effective as of 7/16/20. Available for new GFA auto loans or refinancing from another institution only. Lowest 48-month new auto loan APR available. Four years or 48-month term $222.01 monthly payment per $10,000 borrowed. 100% financing available. Other rates and terms available. Subject to credit approval. Minimum new auto loan amount $4,000, used $2,500. Rates may vary based on age of vehicle, underwriting, and credit review. $20 application fee and documentation fee may apply at closing. Borrowers must become a member of GFA Federal Credit Union. Rates are subject to change without notice.**84 month term for 2019 and newer only, maximum 90% LTV of MSRP.
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GAP coverage is the difference between the actual cash value of your vehicle and the balance owed. Make sure you are covered.


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Plot: Tree (Jessica Rothe) wakes up in a random dorm room after a wild night, unable to remember much of anything and in a desperate rush to get away from the dorky guy she apparently slept with. She stumbles back to her sorority house, then arrives late to class, almost gets caught by her married lover's wife, and heads to a party, but on the way, she is murdered. This was quite an eventful day, especially for Tree since it was her birthday, but she is about to relive it all over again. She wakes up in the same bed, same dorm, then experiences all of the same things again, though she tries to avoid her death, only to be killed in a new fashion. She is not a stable person on her best day, so she flies off the deep end and spirals into an emotional meltdown, as she wakes up once again and things repeat themselves. Is she destined to relive her own death over and over again, or can she find a way to derail this time loop?
Entertainment Value: This movie seemed destined to be another by the numbers Blumhouse produced horror movie and at first, that seemed to be the case. But after Tree dies a few times, she throws caution to the wind and embraces her horrific situation, which provides some fresh, interesting scenes. This is a short piece of the movie, but it was a nice bright spot in an otherwise run of the mill flick. But once that ends, the movie decides to transform into a sappy, incredibly forced life affirmation experience, as sad as that sounds. A bloodless, scareless horror movie throughout, Happy Death Day just drops all pretense of horror and decides to try to serve as a motivational picture. Tree is a brat and perhaps a little trashbag-esque, but at least she is interesting before the movie shames her into changing her evil ways. I know this is aimed at teens, but come on, Lifetime movies have more edge than this. I have to give some credit for veering so far off brand and trying to be a self help program however, as it is so insane and comes out of left field. In the end, Happy Death Day has a dull first act, fun and fresh middle act, and ABC Family conclusion. If you want horror or sleaze, this never rises above a teen thriller. But if you just want to see a movie come unraveled and turn into a desperate social plea, by all means, give this a look.
No nakedness. This is teen horror from Blumhouse, so the closest we get are some bare shoulders. This is wholesome, gee golly entertainment that vilifies Tree for her more base impulses. I for one think Tree was just fine in the first place, if she wants to have fun and be a bitch, let the woman live her life, right? No blood. All of the violence that involves blood happens off screen, so we see a neck break and some clean gun shots, but all the juice is never showcased. As this is a Blumhouse production aimed at teen audiences, the lack of gore makes sense, especially given the morality play that unfolds in the finale. So from a horror perspective, no blood, no breasts, and no scares. The dialogue is mostly forgettable, but we do have some fun lines from the sorority sisters and of course, Tree. The girls are portrayed as basic stereotypes with no depth, which is kind of lame, but also leads to hilarious lines. Tree is a fountain of gold banter and Jessica Rothe brings her trashy side to life well. So some terrific and cruel mean girl type dialogue, but otherwise just milquetoast scripting. As for craziness, the middle section has some fun mayhem, but the real insanity is trying to shoehorn a self help program into a horror movie with the subtlety of a sledgehammer. Just an iron fisted attempt to force a certain moral outlook on the audience, ballsy to be sure, but not fun to watch and in my opinion, not a good conclusion. Tree is also a super fun, over the top character, so she deserves a point as well.
Nudity: 0/10
Blood: 0/10
Dialogue: 5/10
Overall Insanity: 1/10
Use this Amazon link to purchase Happy Death Day (or anything else) and support my site!


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Tag Archives: Fit
Hot Spanish Model Luis Mora wearing AMU Extreme Shorts
Hot Spanish Model Luis Mora @lucho__m___ wearing AMU Extreme Sports mesh Shorts red / red Images are by Photographer based in the Canary Islands, Spain. Only original photos. Instagram: @MDZmanagement AMU EXTREME SPORT MESH SHORTS RED / RED The highly flexible mesh … Continue reading
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Spice up your Underwear Collection with Gregg Homme
We have selected 4 very sexy style of underwear from Gregg Homme. If you are looking to spice up your underwear collection or looking to impress someone with your undies these will certainly do the trick. Gregg Homme Cocky Thong Intoxicatingly … Continue reading
Posted in AlphaMaleUndies, Gregg Homme Tagged Fit, Gregg Homme, sexy, sheer, spicy, Underwear Leave a comment


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Abraham Maslow Quotes
46 Abraham Maslow quotes:
"If both the physiological and the safety needs are fairly well gratified, then there will emerge love and affection and belongingness needs, and the whole cycle already described will repeat itself with this new centre. Now the person will feel keenl"
"The fact is that people are good, if only their fundamental wishes are satisfied, their wish for affection and security. Give people affection and security, and they will give affection and be secure in their feelings and their behavior."
"The ability to be in the present moment is a major component of mental wellness."
"There is, first, the desire for strength, for achievement, for adequacy, for confidence in the face of the world, and for independence and freedom. Secondly, we have what we may call the desire for reputation or prestige (defining it as respect or es"
"We are not in a position in which we have nothing to work with. We already have capacities, talents, direction, missions, callings."
"It is too simple to say `man is basically good' or `man is basically evil'. The correct way would be to say `man can become good (probably) and better and better, under a hierarchy of better and better conditions, but also it is very easy, even easie"
"The way to recover the meaning of life and the worthwhileness of life is to recover the power of experience, to have impulse voices from within, and to be able to hear these impulse voices from within - and make the point : This can be done."
"He that is good with a hammer tends to think everything is a nail."
"If you plan on being anything less than you are capable of being, you will probably be unhappy all the days of your life."
"What is necessary to change a person is to change his awareness of himself."
"If the only tool you have is a hammer, you tend to see every problem as a nail."
"When all you own is a hammer, every problem starts looking like a nail."
"The story of the human race is the story of men and women selling themselves short."
"A musician must make music, an artist must paint, a poet must write, if he is to be ultimately at peace with himself."
"If I were dropped out of a plane into the ocean and told the nearest land was a thousand miles away, I'd still swim. And I'd despise the one who gave up."
"To the man who only has a hammer in the toolkit, every problem looks like a nail."
"One's only rival is one's own potentialities. One's only failure is failing to live up to one's own possibilities. In this sense, every man can be a king, and must therefore be treated like a king."
"We may define therapy as a search for value."
"But behavior in the human being is sometimes a defense, a way of concealing motives and thoughts, as language can be a way of hiding your thoughts and preventing communication."
"If you deliberately plan on being less than you are capable of being, then I warn you that you'll be unhappy for the rest of your life."


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Hermosa 360, Playa Hermosa
Hermosa 360 is a unique project in its category, in an exclusive topography 7 minutes away from the best surf spots of Playa Hermosa. Surrounded by nature in 360 degrees with beautiful views of forests and a double view of two different beaches at the top of the mountain is coincided as an architectural jewel to maximize human emotions through the use of space. The uses that can be given to the property are many among which are: skating ramps in all its surroundings with more than 2 km of gardens, outdoor pools with technology of swimming in electronic current and whirlpool benches, large internal spaces with terraces that can be extended by electric awnings, extra-wide social areas in a horizontal dimension and an expected altitude with almost no columns, pools on a second level with internal transparency glass, gym areas, full spa with hot tub, cold pools and steam baths, intelligent automation of Loxone equipment.
The mixture of technology with natural first-line materials, such as exclusive Italian marbles and woods from the best Costa Rican cuts make this house a complete garden of amusements, nature and appreciation of comfort and luxury


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On Oct. 16, 1854, a rising lawyer named Abraham Lincoln delivered a 3-hour speech of 17,000 words objecting to the Kansas-Nebraska Act and decrying the institution of slavery. (The speech also ignited the next phase of his political career that would eventually land him in the White House).
He said:
If the negro is a man, why then my ancient faith teaches me that 'all men are created equal;' and that there can be no moral right in connection with one man's making a slave of another.
On Oct. 16, 1859, abolitionist John Brown initiated a slave revolt by taking over a United States arsenal at Harper's Ferry. While the raid ultimately failed, it highlighted the divisiveness and importance of the issue of slavery in the U.S., and eventually became an impetus for the Civil War.
October 16 is a day to band together to fight for what's right. To say: no more.
On October 16, 2018, we unite for freedom.
Join 25+ organizations for 24 hours as we raise funds and momentum to end human trafficking and modern slavery. Visit Charidy.com/UnitedforFreedom to give.


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This story is primarily for gillo, who responded to a throwaway line in my last ficlet by saying "And I need to see Olaf at the TT races now". Her comment has inspired what might well be my strangest crossover ever. Another one of the 'Where Did Olaf Go?' series, in which Willow's spell to banish Olaf to the Land of the Trolls misfires and sends him to another fandom. It follows on from Thomas and the Troublesome Troll, in which Olaf battled Thomas the Tank Engine. On leaving the Island of Sodor Olaf travels to the Isle of Man to see the 1935 TT motorcycle races. Crossover with the 1935 George Formby film No Limit. Everyone on the Isle of Man has seen the film several times – it's compulsory – but it will probably mean nothing at all to Americans or even to British readers who don't watch old movies on TV. George Formby, the Lancashire comic singer and performer upon the banjo-ukulele, was Britain's biggest star in the years immediately before and during the Second World War. Personally I could never see why. 'No Limit' was mainly filmed on location in the Isle of Man and included footage of the real 1935 TT. Gill was probably expecting me to send Olaf to the contemporary TT but instead here he is in the 1930s. Rating R; 4,800 words.
Olaf at the TT Races
Olaf had never seen such vast throngs of people in all his life. The Isle of Man had changed much since his time as a human. The crowds numbered thousands, perhaps tens of thousands, swarming like ants all around the course on which the motorcycles would race. He attracted a lot of attention, of course, with his immense size and his horns; less here than anywhere else, however, as most of those he encountered simply assumed that he was costumed as a Viking. His skin had lost some of its greenish colouration in the course of scrubbing away the red paint with which he had become covered during his adventure on the Island of Sodor. He was still not the same shade as the humans but the difference was no longer quite as obvious. One or two of the locals fled from him, crying out that he was a buggane, but most gave him no more than a wary glance. He had no trouble in finding a shopkeeper who would exchange his silver for the money used in this realm.
There were so many humans around that Olaf abandoned his plans for plunder and pillage. He could defeat a dozen, a score, even a hundred without breaking sweat; but against these multitudes he would stand no chance. He contented himself with watching the races and consuming large quantities of fragrant Okell's ale. He saw many attractive girls and made approaches to some in the hope of merry sport. Alas, none were amenable to his advances.
Well, almost none. One pretty maiden, a girl from England named Maureen Dibney, blushed and smiled when he praised her sparkling eyes and trim figure. Her sister called her away, however, and she scurried off at once. The two girls departed, with the sister subjecting Maureen to a mild scolding, and Olaf's hopes were dashed. It seemed that the custom in this era was for maidens to shun strangers; the prospects of merry sport seemed slight indeed.
Still, the beer was tasty, and the races were entertaining. The two-wheeled machines were far faster than a galloping horse. At speeds of over eighty miles an hour they tore over the mountain road, engines roaring, brakes screeching. The first race was for the middle-sized bikes, mainly Nortons and Velocettes with an occasional AJS, then there was a day of rest before the lightweight Rudges and New Imperials battled it out with the Italian Moto-Guzzis, and then after another day of rest it was time for the Senior race. The most powerful bikes, more Nortons, Velocettes, and Moto-Guzzis plus Vincents, NSUs, and Royal Enfields, would compete in the fastest and most prestigious event.
Olaf passed the day between the Lightweight and the Senior races sightseeing, drinking, and listening to the cognoscenti discussing the prospects for the big race. There was much talk of a newcomer, a Lancashire lad on a home-made bike called the Shuttleworth Snap, who had qualified well and had broken the lap record in practice. Many wished him well, for he was the underdog against the well-financed factory teams, and he had endeared himself to the spectators by singing cheerful songs and playing the banjo-ukulele. The pundits, however, were certain that young George Shuttleworth would struggle to finish in the top ten. A full race of seven laps, two hundred and sixty four miles, was a far more daunting challenge than the shorter practice sessions.
The race day dawned in miserable fashion. Heavy clouds hung overhead. Intermittent rain sent the spectators scurrying for shelter. The mountain was veiled by a blanket of mist. The riders assembled in the paddock but were not called out to the start. The stewards consulted for a while and then announced that the conditions were too dangerous and the race would be postponed until the following day.
Olaf did not mind the rain. A Viking who hated to get wet would have had a miserable career, as longships were open to the elements, and his transformation into a troll had made him even less bothered about mere drizzle. He set off along a footpath south from Douglas, climbing over Douglas Head and looking down at the bay below, and passed by the Camera Obscura. He continued on south until he came to a bay where a tramway ran along cliffs. A cluster of buildings stood near the sea. One was unmistakably a tavern, a pub as they called them in this time and place, and it would have food and ale. Olaf was hungry after his walk and strode eagerly towards the establishment.
The pub was less crowded than were those in Douglas but still busy enough that Olaf had to wait to be served. Those who had come to the Island for the races had spread out from the towns on the course, as the racing had been cancelled, and locals from the Isle of Man mingled with visitors from England and from countries much further afield.
"Moto-Guzzi, she will win the big race, like we win the Lightweight," one such visitor was telling anyone who would listen. "Italia, she is the greatest. We have our Duce, who has made the trains run on time, si?"
"This Duce, is he your Fat Controller?" asked Olaf, remembering his adventure on the Island of Sodor.
The man from Italia frowned and then laughed. "Our leader Mussolini he is not so slim, perhaps. I think he like the pasta too much. Still, he has made us greater than since the Romans. We have the Macchi M72, the fastest plane in the world, and our motorcycles they are very fast too. Tomorrow you will see."
"Bah!" scoffed a tall man with close-cropped fair hair. "Your weak Italian machines cannot hope to match NSU. German technology is supreme. We are the master race. Heil Hitler!"
"Si, we shall run away from the Germans," said the Italian. "All the way to the finish line, and still they will not catch us."
A triumphant smile spread over the German's face but faded away as a ripple of laughter went around the pub and he realised the true meaning of the Italian's reply. He snorted, and spoke again, but Olaf had stopped listening. He had spotted someone among the pub's clientele who was of far greater interest to him.
The pretty girl who had seemed not entirely averse to his attentions a couple of days previously, Maureen Dibney, was sitting at a table with her less friendly sister at her side. There were two empty seats at the table, and few other vacant places at the pub, and so Olaf took his pie and his pint and headed in that direction.
"Greetings to you, fair maidens," Olaf said, setting down his glass on the table. "You have spare seats, and I wish to sit down."
"We're expecting someone," said Maureen's sister Florrie. "You'll have to find somewhere else."
"Only George," Maureen pointed out. "There would be room."
Florrie frowned. "Not much room. This foreigner is a very big man."
At that moment the pub door opened and a small man entered the bar. His teeth seemed too large for his mouth and they showed as he smiled. He held a small stringed musical instrument in one hand. "Ee, turned out not so nice again," he greeted the room in general.
"George!" Florrie cried. She stood up and rushed over to the newcomer.
Olaf took advantage of her distraction and sat down. "It is good to see you again, beautiful maiden," he said. With so many of the descendants of the Saxons on the island, and having no longship in which to escape with a captive, the traditional Viking courtship method of throwing the maiden over his shoulder and carrying her off was ruled out. He would have to rely upon more peaceful means. "You are the fairest thing that I have yet seen upon this island."
"Ooh, flatterer," said Maureen. "You're a strange looking one, you are. Where are you from?"
"I am from Sweden," Olaf told her, "but far have I wandered. I am called Olaf."
"Here to see the races, I suppose?"
"Indeed," Olaf agreed. "Also I had heard that the ale brewed in this island was particularly fine." His forehead furrowed as he tried to think of something else to say that would be acceptable in this age. He sensed that 'your clothes are ugly and unflattering, and hide too much of your lush and inviting body' was a statement best left until a later stage.
"Eh, George lad, give us a song," called out one of the drinkers at the bar.
"Aye, a song would be right grand," another of the pub's clientele agreed. Other customers joined in to second the request.
"Right enough, then, lads and lasses," George acquiesced. He raised the musical instrument and strummed the strings, producing an odd staccato plinking and twanging noise, and then began to sing. "If there's one thing that I like, it's riding around on a motor-bike..."
Olaf was not overly impressed. The little man had a squeaky nasal voice and the tune was very different from the Viking songs with which he was familiar. There were no horns or drums and the words lacked references to battle and slaughter. It seemed to strike a resonance with the people of this land, however, and they smiled and laughed. The man knew his audience and his ditty about motor-cycle racing was perhaps this age's equivalent to the Viking skalds' tales of warrior heroes.
Maureen's eyes were fixed on George, and her lips moved with the words of the song, and Olaf would have felt jealousy were it not obvious that George had already been claimed by Maureen's sister. Well, actually he still felt jealousy, but not to such an extent that he would act upon it and pummel the small man into mush.
"That were grand, George," said a bystander once the little man had finished his song. "Can I buy you a pint?"
George shook his head. "Nay, lad, I'm not one for drinking," he said. "I wouldn't want to get tight and then go racing. A right sure way of having a nasty spill, that would be."
"Ay, you're right there," the other man agreed. "How's about a ginger ale, then?"
"That'd be champion, thanks." George accepted the soft drink and then was escorted towards the table by Florrie. "Ee, by heck!" he exclaimed, as he saw the enormous troll sitting opposite Maureen. "You're a big one. Is he your young man, Maureen?"
Maureen blushed slightly as she shook her head. "We've only just met," she said. "Olaf is from Sweden. He's here to see the races."
"That is so," said Olaf, deciding not to mention that he was here only because he had been banished from his own world by a witch. "Hah. I recognise you now, small man. You are George Shuttleworth."
"That's me," said George. "Chimney sweep, jobbing mechanic, and now TT racer. And all with my little ukulele in my hand."
"You carry that when you ride the motorcycle?" Olaf raised his eyebrows. "Does it not make it hard to control the machine?"
"Ee, lad, I'm joking," George said. "I have to have all my wits about me when I'm riding. It's not easy, even for a speed king like me, you know. It can be right scary out there, I can tell you. When I was going down to Creg-ny-baa on the second practice..."
George talked without stopping for several minutes. Olaf was unable to get a word in. In one way this was annoying, but in another it was useful; it saved him from the struggle of trying to make conversation with the pretty maid.
To win her would be hard. He could not impress her with great deeds of valour, for there were no monsters or enemy warriors to fight, and he did not know how to ride a motorcycle. To learn to ride one in a single day, to gain entry into the race, and then to overcome those who had ridden for years and were much lighter than Olaf to boot, would be impossible. He would have to rely only upon words; and the use of words was not one of his skills. He knew enough to avoid comparing her to a Baltic woman, favourably or otherwise, and that was about all. Still, he would try. When he got the chance, that is; with George in full flow all that Olaf could do was to eat his pie and wait.
The chance to resume his courtship did not come. George's tales were interrupted by an ill-mannered intruder who spoke harshly to the girl Florrie. She was in the employ of one of the teams of motor-cyclists, as was the interloper, and he declared that her friendship with George was treachery.
"It's not like that!" Florrie protested. "He saved my life. How could I not be friends with him after that?"
Olaf raised his eyebrows. The little man was a hero indeed. Now, if only Olaf could find some way to save Maureen's life...
"Anyway, why would it matter to anybody else?" Florrie went on. "I'm only the secretary at the Rainbow Team. I don't know any stupid engine secrets or anything. And George wanted to join the team anyway. It's not his fault you turned him down."
"Here, you, leave Florrie alone," George said. "You're making her unhappy, and I won't have that." He stood up and prodded the other man with a finger.
"Shut up, Shuttleworth," said the man. "You'll never make a racer."
"I'm a better racer than you, Bert Tyldesley," George retorted, "and I'll prove it tomorrow, if it turns out nice again. And don't you speak nasty to Florrie or I'll give you such a thrashing."
"You give me a thrashing?" Bert puffed out his chest. He was much taller and broader of shoulder than George. "I could knock you out with one punch."
"Ee, why don't you try it, you big blowhard?" George challenged. He prodded Bert again.
"Why, you little worm," Bert growled. He swung a fist at George.
The smaller man dodged aside with lightning agility. "Hah! Never touched me," he taunted.
"I'll knock your block off," Bert snarled.
Olaf was beginning to take a liking to George. His voice was irritating, like the whine of the mosquitoes in the summer, and he talked too much, but he had included much self-deprecating humour in his account of his deeds on the motorcycle racetrack. A brave man who was not afraid to poke fun at himself was a one worth knowing. Also, defending George would win Olaf points with the girls; both the one with whom he wished to have merry sport, and her sister who was a possible obstacle in the way of achieving that end. Olaf stood up.
"Then I shall knock off yours, puny one," Olaf threatened. "Leave George alone, and depart from this place, or feel the wrath of Olaf."
"Oh, bloody hell," exclaimed Bert, looking up at the towering troll. "I'm off!" He backed away. When he was safely out of reach he stopped and shook a fist at George. "You're not going to win, Shuttleworth," he called. "I'll stop you. Any way it takes." He turned and scuttled from the pub.
"Oo, mother," said George. "He's a right nasty piece of work and no mistake. Thanks, Mr Olaf."
"I am glad I could help," Olaf said. He shot a glance at Maureen. Had she been impressed?
"We'd better go," said Florrie. "Bert will cause trouble, I just know it."
"Ee, you're right, love," said George. "He might try to tamper with the Shuttleworth Snap. It's all locked up tight but I'd best check on it." He stopped in the middle of sitting down and stood up again. "Let's get back to Douglas, then, lasses."
Maureen came to her feet. "Goodbye, Mr Olaf," she said. She trotted out of the pub in the wake of George and Florrie. Olaf thought of following them but instead sat back down. He decided that he had not yet established himself well enough with the maid to follow without making her feel threatened and, although making people feel threatened was what he did best, it was not the best move in this situation. He contented himself with finishing his pie and his pint and then ordering another of each. Perhaps he would be able to find Maureen once more in the evening.
The next day dawned brightly. The postponed race would be able to take place. Olaf, who had searched for Maureen without success the previous evening, set off from the boarding house in which he had managed to obtain somewhat cramped lodgings and headed for the Grandstand area where the race was to start.
The motorcycles lined up. The procedure was strange to Olaf's eyes but he had become accustomed to it after watching the events on the previous two race days. Instead of all starting together, and the winner being the first one to cross the finish line, they started one after another with some seconds between each. The people of this age had accurate methods of measuring time and they allowed for the time of the start when deciding who had won. It was complicated, and Olaf did not see the point, but it seemed to work. And, with the races being so long, it usually turned out that the one who crossed the line first was the winner anyway.
The engines roared as the motorcycles were readied for the start. Olaf saw Florrie rush out from the side and give George a quick kiss before the final signal was given. She rushed back to her place, and Olaf saw Maureen there too, but they were on the wrong side of the road and Olaf would not be able to join them. He growled with frustration.
George gave a gleeful cry, started up his bike, and promptly fell off. He was back up and on the machine at once and roared off at a great speed. Olaf watched the next few riders depart and then decided to seek out a less crowded vantage point. He set off up the course, in the opposite direction to the bikes, and walked out of the town.
By the time the leading bikes came into sight Olaf was out among fields. He watched as the machines roared past; no longer in a line separated by equal distances, as they had been at the start, but now spread out with some in groups of several machines and long gaps between these groups. He could not tell who was winning but he noticed that George Shuttleworth was in a group near the front. He walked on.
As the race went on the riders became more and more spread out and the gaps during which none of the machines were in sight became shorter. It was hard to keep track of who was at the front and who was lagging far behind. Olaf gave up the effort and simply enjoyed the spectacle of the machines speeding past far faster than anything that he had seen in his human days. He wandered still further away from the town and into wilder countryside.
He had proof of the danger inherent in this high-speed sport when he saw a motorcycle lying on its side off the road, flames licking up from the engine, and the rider motionless nearby. Olaf would have aided the fallen man but other spectators were closer and acted before Olaf could arrive on the scene. He walked on.
He had been told that the race was expected to last for some minutes longer than three hours. He had no device for measuring time, such as the people of this island possessed, but he was skilled at estimating the passage of time by the position of the sun. When he judged that an hour and a half had elapsed he reversed his course. He would then arrive back at the starting and finishing line at the time that the race was reaching its end; he would be able to see the victor claiming his prize.
The disadvantage of this plan was that now he saw the motorcycles only once they had passed him and were heading away. This was less entertaining and he paused, frowning, and considered reversing his decision. Yet arriving back at the Grandstand at the race's end would give him the best chance of encountering the beautiful Maureen; he resumed his progress in the direction of the finishing line.
Two motorcycles streaked past him, side by side, jostling for position. One of them he recognised, by the black-and-white chequered pattern on its frame, as George's Shuttleworth Snap. The other was one of the machines he had been told were Nortons, painted in stripes of colour like unto the rainbow, bearing the numeral '15'. He saw them hurtle at high speed toward a corner and then, as George went to turn, the other rider leaned the wrong way and pushed against George Shuttleworth. The Shuttleworth Snap was sent skidding to the side. The other man wrenched his machine successfully around the corner, with some squealing of brakes, but George's bike did not make it. The Shuttleworth machine went straight on, climbed a bank, and soared into the air. As Olaf watched, horrified, George and his motorcycle landed in the branches of a tree. Olaf ran to the scene as fast as he could.
George was hanging from one of the tree's limbs. The small man released his hold with one hand and shook his fist at the disappearing rival's machine. "Ee, Bert Tyldesley, I'll get you for this," he yelled. He looked down and hastily grabbed the branch with both hands again. "Oo, mother!"
"Drop, George, and I will catch you," Olaf called.
George grimaced but then obeyed. The giant troll caught him safely and set him on his feet. George looked up at his motorbike, still lodged in the tree, and his mouth twisted. "Ee, how am I going to win the race without my bike?" George wailed. "Grandad will be right cross with me. I used his money to build it and now I'm not going to be able to pay him back."
Olaf grinned. It seemed that his chance to perform a mighty deed that would impress Maureen Dibney was at hand. "Fear not, oh little George Shuttleworth," Olaf said, and flexed his mighty muscles. "I shall retrieve your machine." Olaf seized hold of the tree and heaved. The trunk bent. Olaf exerted all his strength and the tree bowed down almost to the ground.
"Why, that's right champion," George cried. He seized the bike and, showing a fair amount of strength for a small man, he wrestled it from the branches and stood it upon the ground. Olaf released the tree and it sprang erect once more with a great thrashing of limbs. "You're a pal, Olaf," said George, climbing back into the saddle. He twisted the bike's throttle and the engine roared to life. "Turned out nice again!" George hurtled away back onto the road, waved once, and then shot out of sight at high speed.
Olaf followed at a walk. By his reckoning, if he had kept proper count and if he had not failed to spot George upon a previous lap, there were two more laps of the course to go. George had lost much time through being stuck in the tree, and Olaf did not know if the little man could make up that time, but at least he had a chance.
The next time Olaf saw George's machine go past it was just in front of a motorcycle painted with green, white, and red. The gap between the two seemed to be increasing as George pulled away. The field was now so spread out that Olaf could not tell if those in front of the pair were slow riders who were nearly a lap behind, or fast riders who were in truth ahead of them, and he had no idea of who was winning. All he knew for certain was that he had not seen the rainbow-striped machine bearing the number 15 go past this time. Perhaps George had caught up with his rival and had driven him from the track in retaliation for the foul trick that the rider had played upon him. Or perhaps the rider had crashed through bad luck or lack of skill. Or, perhaps, Olaf had simply failed to see that motorcycle and it was far ahead of George. Only at the end of the race would Olaf be able to find out.
Olaf walked down a dip in the road, and around a corner, and saw the Grandstand in the distance ahead of him. He heard the roar of an engine, turned his head, and saw George's bike coming around the corner. It streaked past him and away towards the finish line. There were no other machines in sight. Did this mean that George was going to win?
It seemed so. He could hear the noise of a great many people shouting with excitement ahead. Then the tone of the cries changed. He could see that something untoward had happened to George, who had come to a stop short of the finish line, but not what it was. Olaf increased his pace and took longer strides. Still he could not see what was happening. The sound of another engine came from behind him. Then the noise from the Grandstand became shouts of excitement once more. Olaf was now just able to make out what was going on. George's machine had stopped, and seemed not to be able to move under its own power any longer, but George was standing at its side and pushing it forward.
The red, white, and green machine shot past Olaf at a great speed. It hurtled towards the finish line. George was still pushing his motorcycle. A flag of black and white waved. Olaf had seen in the previous races that the flag signified the end of the race. George certainly was the one who had crossed the line first but the staggered start to the race, and the way that was taken into consideration at the end, did not necessarily mean that he was the winner.
In fact, although the crowd at the Grandstand were shouting that Shuttleworth had won, it was not for another few minutes that the result was announced. George Shuttleworth was the winner, after all, having beaten Stanley Woods on a Moto-Guzzi by a mere two seconds.
Olaf was able, now that the course beyond the finish line was accessible once more, to work his way around and cross the road to join the attractive maiden Maureen. The girl's sister Florrie was embracing George. She disengaged from her lover to glare at Olaf as he strode up to Maureen.
"Hey, Olaf!" shouted George. "By heck, lasses, you should have seen him! I'd never have won if it hadn't been for him getting my bike down from a tree."
Florrie's glare evaporated and was replaced by a warm smile. "Oh, thank you, Mr Olaf!" she cried.
"He bent the tree right over," George continued. "Strong as a bull, is Olaf here."
"Oo, yes," said Maureen. "I like big strong men."
Olaf grinned. "And I like pretty girls," he replied, "and you are the fairest that I have seen in this place. Come with me tonight to the place where there is dancing, and we shall celebrate the victory of the skilful rider George, and there shall be much merry-making and drinking of fragrant ale."
Maureen glanced at her sister, saw no sign of disapproval, and nodded her head. "All right, then," she agreed.
"We can all go out to celebrate," said Florrie.
"Ee, that'd be right grand," said George. "I might even have a pint of ale myself."
"And a song or two," Florrie added.
"We'll see you at the Palace Ballrooms tonight, Olaf," Maureen promised.
"You will indeed, beauteous maiden," said Olaf, "and we shall make merry sport."
Maureen opened her eyes, groaned, and sat up in her bed. She clapped a hand to her forehead. "Oo, my head," she moaned. "Where am I? Oh, yes, on the Isle of Man, in the boarding house in Douglas." She blinked as she saw her that her nightie was still laid out on the counterpane instead of being worn. "Ee, I must have been awfully tight last night," she said.
The heap of bedclothes beside her was thrown aside and Olaf appeared, naked, with a wide grin of deep contentment upon his face. "Only the first time."


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Worked shell from Leta Leta Cave, Palawan, Philippines
Publication Details
Szabo, K. & Ramirez, H. (2009). Worked shell from Leta Leta Cave, Palawan, Philippines. Archaeology in Oceania, 44 (3), 150-159.
The Leta Leta Cave burial site is a distinctive and enigmatic site of the Philippine Neolithic, excavated by Robert Fox. Containing a number of burials, its unusual earthenware pottery — including the 'yawning-mouth vessel', small footed goblets and a cut-out pedestalled bowl — have seen it recognised in the Philippines as an official site of national significance. In addition to the human remains and earthenware, Fox recovered a sizeable assemblage of shell artefacts which, as with other material remains recovered from Leta Leta, were only cursorily reported in print before his death. Recent analysis of the Leta Leta worked shell has revealed the deposition of unfinished as well as finished shell artefacts in mortuary contexts. As well as giving rare insights into manufacturing protocols in an island where the Neolithic and Metal Age records are characterised virtually solely by mortuary deposits, the deposition of unfinished artefacts opens new avenues for the discussion of Neolithic mortuary practices in Palawan. Results of a study of the worked shell assemblage, in addition to recent radiocarbon determinations for the site, are presented here.


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Este post é parte de nossa cobertura especial Protestos no Egito em 2011.
Na sequência de protestos em todo o Egito hoje, o Exército foi destacado [en] para fazer valer o toque de recolher durante a noite. No Twitter, a notícia foi recebida com surpresa, com relatos de que o Exército estava do lado do povo.
A seguir, uma seleção de tuítes de toda a região.
@flashboy: AJ report from Alexandria suggests the Egyptian army's decided which side they're on, and it's not Mubarak's – shaking protesters' hands.
@news_view RT @BreakingNews: Egyptian army ordered onto the streets, but they do NOT appear to be taking any action against protesters -NBC's Richard Engel #Egypt #Jan25
@terriaminute: Demonstrators in Cairo surrounded a military vehicle, but they were cheering the army http://bit.ly/f6WPYV #jan25 #awesome
@SultanAlQassemi Must see: Egyptians saluting massive army presence in downtown Cairo. #jan25 http://yfrog.com/h4a0rgj
@DannyRamadan: Four Army cars on Qasr al-Neel bridge and protesters are standing ontop of them cheering and waving Egypt flags. It looks peaceful. #jan25
@ReneeEverett: People cheering army on the streets of Cairo. #Egypt
@ShahbazWeb: Looks like army is with the revolution – long live Tunis Fever! #Egypt #TunisFever #jan25
@shamanyalkhaili Army joining forces with protests !!!
@lishypo: "In other words, if the army ever decides to shoot into a crowd of unarmed protestors, it will be shooting with hardware provided by the US"
@strangetales CNN: Nationwide curfew now in effect for #Egypt. Nobody obeying it. Nobody enforcing it. Protesters cheer the army's support. #jan25
Este post é parte de nossa cobertura especial Protestos no Egito em 2011.
1 comentário
[…] This post was mentioned on Twitter by Raphael Tsavkko, GV Lusofonia. GV Lusofonia said: Egito: Está o exército do lado do povo?: Following massive protests across Egypt today, the army was depl… http://bit.ly/fCxmQo #gvopt […]


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Rika Mantaring Licensed Real Estate Salesperson
Rika Mantaring was raised in Queens Village and attended New York's Fashion Institute of Technology. She was inspired to become a real estate agent because she was looking for a versatile work environment where she would have the opportunity to meet many different types of people. She was also drawn to the fact that the real estate industry offers clear incentives for hard work.
Prior to joining Elegran, Rika was an agent at a large NYC-based real estate company. Rika 's problem-solving skills, ability to come up with creative solutions, and strong desire to help people all make her a dedicated agent and advocate for her clients.
Rika currently lives in Queens Village. She is a freelance artist and spends much of her spare time painting and drawing.


text:
Cold Steel 95FBC Hunting Folding Knives, Grey
Product Features:
The Bushman has been a mainstay of the Cold Steel line for more than a decade now. It's an economically simple design, with winning features like strength, versatility, and an affordable price. It's practically perfect! so, rather than upstage the Bushman, we've created a complement to it, a version…


text: Comcast to Bundle Netflix Subscription With Cable Package 7:29 AM PDT 4/13/2018 by Etan Vlessing FACEBOOK TWITTER EMAIL ME Courtesy of Netflix The cable giant is making it easier for subscribers to view 'Stranger Things' and 'Orange is the New Black' and other content on the streaming service. Despite competing in a fast-changing entertainment landscape, Comcast is expanding its partnership with Netflix by including a subscription to the streaming service in new and existing Xfinity X1 cable packages. "Netflix offers one of the most popular on-demand services and is an important supplement to the content offering and value proposition of the X1 platform," Sam Schwartz, chief business development officer at Comcast Cable, said Friday in a statement. Adding a Netflix subscription to Comcast's Xfinity content package on X1 comes as Netflix looks to get into as many traditional cable boxes as possible so consumers can avoid juggling multiple devices. Netflix has similar relationships with Atlantic Broadband, Grande Communications and Suddenlink Communications, as it looks to bring rivals to its side. Comcast's X1 platform is used by around 60 percent of Comcast's customers, with its built-in DVR allowing subscribers to record six shows simultaneously and download shows for watching on mobile devices. Comcast said nearly half of its X1 customers already use Netflix, so adding a video streaming subscription offers subscriber convenience, including the cable and telco giant handling monthly billing. There's no word on pricing, beyond Comcast indicating "a variety of initial offers" will be unveiled. "Our partnership with Comcast on Xfinity X1 has brought easy access to Netflix for our mutual customers," Bill Holmes, global head of business development for Netflix, said in his own statement. "We can't wait to introduce more X1 customers to Netflix with Xfinity's new packaged offers," he added. FACEBOOK TWITTER EMAIL ME Etan Vlessing email@example.com @thr


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