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Short communication | Open | Published: 26 April 2013
Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells
Karthik M. Kodigepalli1,
Pavana Anur2,
Paul Spellman2,
Peter J. Sims3 &
Meera Nanjundan1
Treatment of advanced stage ovarian cancer continues to be challenging due to acquired drug resistance and lack of early stage biomarkers. Genes identified to be aberrantly expressed at the 3q26.2 locus (i.e. SnoN/SkiL) have been implicated in ovarian cancer pathophysiology. We have previously shown that SnoN expression is increased in advanced stage ovarian cancers and alters cellular response to arsenic trioxide (As2O3).
We now demonstrate increased DNA copy number levels (TCGA data) of phospholipid scramblase 1 (PLSCR1, located at 3q23) whose transcript expression in ovarian cell lines is highly correlated with SnoN mRNA. Interestingly, SnoN can modulate PLSCR1 mRNA levels in the absence/presence of interferon (IFN-2α). Both IFN-2α and As2O3 treatment can modulate PLSCR1 mRNA levels in ovarian carcinoma cells. However, SnoN siRNA does not lead to altered PLSCR1 protein implicating other events needed to modulate its protein levels. In addition, we report that PLSCR1 can modulate aspects of the As2O3 cellular response.
Our findings warrant further investigation into the role of PLSCR1 in ovarian cancer development and chemoresistance.
Epithelial ovarian cancer represents the most common gynecological cancer in women with an unfortunate high mortality rate due to acquired chemotherapeutic resistance [1]. Our earlier published studies indicate that the 3q26.2 chromosomal region is highly amplified in ovarian cancers [2] and harbors various oncogenes including EVI1 [2], PKCι [3], and SnoN/SkiL [4]. In particular, we previously demonstrated that SnoN, a negative transcriptional regulator of TGFβ signaling, modulates the pro-survival autophagic pathway in response to arsenic trioxide (As2O3), a chemotherapeutic agent used in the treatment of acute promyelocytic leukemia (APL) [5]. Interestingly, there are reports which indicate that genes located at and proximal to the 3q26 locus may regulate each other. For instance, both EVI1 and PIK3CA can regulate SnoN expression [6, 7]. Herein, we now report that the expression of phospholipid scramblase 1 (PLSCR1), located at 3q23, can be modulated via SnoN. PLSCR1 has been implicated in maintaining plasma membrane lipid asymmetry, regulating growth factor signaling pathways, in modulating tumor growth in mouse xenograft models [8], and cancer development [9, 10]. The role of PLSCR1 in ovarian cancer and in modulating response to chemotherapeutic agents has yet to be fully understood.
Our previous aCGH studies from 235 ovarian cancer patient samples demonstrated that SnoN was increased at the DNA copy number level [4]. We now identify through Oncomine bioinformatic analyses (ovarian TCGA dataset (https://tcga-data.nci.nih.gov.tcga/) that the DNA copy number levels of PLSCR1 in addition to SnoN are altered similarly (Figure 1A). Furthermore, using cBioportal [11], we identified that SnoN is amplified in 31% of the cases whereas PLSCR1 is amplified in 13% of the cases (70 out of 570 samples amplified both genes). To determine whether SnoN and PLSCR1 genes are co-amplified, we performed linear regression on copy number variation (CNV) estimates (Additional file 1: Methods and Materials) for SnoN and PLSCR1 genes in R (http://www.R-project.org/) (Figure 1B). In ovarian cancers with PLSCR1 amplification, SnoN is gained. When SnoN is amplified, PLSCR1 is only gained in ~33% of the samples (R2 = 0.2474) (Figure 1B). We next evaluated the RNA and protein levels of PLSCR1 in various normal and malignant ovarian cell lines via real-time PCR and western analysis. Similar to SnoN, PLSCR1 expression was low in normal immortalized T80 ovarian cells and highly expressed in the ovarian cancer cell lines (Figure 1C and E). Although PLSCR1 and SnoN expression were highly correlated (via linear regression) at the RNA level (Figure 1D), there was a discordance at the protein level (Figure 1F) which has been reported previously for other genes [12, 13]. Furthermore, the DNA copy number of PLSCR1 and SnoN is nearly always the same in ovarian cancer cell lines (R2 = 0.6411) (Additional file 2: Table S1). Collectively, these results demonstrate that, PLSCR1 is increased at the DNA and RNA levels in ovarian cancers and cell lines in comparison to normal cells, similar to SnoN, and can be co-amplified in a certain proportion of ovarian cancer specimens. However, there likely exist additional levels of regulation which contribute to modulating PLSCR1 protein levels.
Concordance between SnoN and PLSCR1 RNA expression in ovarian cancer cell lines. (A) Oncomine analysis of the Ovarian TCGA data set shows increased copy number of PLSCR1 (left panel) and SnoN (right panel) in ovarian serous cystadenocarcinomas (582 specimens) in contrast to normal ovary (127 specimens). (B) Correlation analysis between PLSCR1 and SnoN copy number in ovarian cancer specimens. (C) RNA was harvested from normal (T80 and T29) and malignant (OVCAR8, OVCA429, HEY, and SKOV3) ovarian cell lines. PLSCR1 mRNA levels were quantified by quantitative PCR. The results are displayed as relative RNA-fold change. Results are representative of duplicate experiments. (D) Correlation analyses between PLSCR1 and SnoN RNA and DNA copy number in ovarian cancer cell lines. (E) Western blotting was performed using antibodies against the proteins indicated using cell lysates isolated from the cell lines described in (C). Results are representative of duplicate experiments. (F) Correlation analyses between PLSCR1 and SnoN protein expression.
Since PLSCR1 is located in close proximity to SnoN at the 3q locus [2], we next assessed whether SnoN could modulate PLSCR1 expression. To address this question, we reduced SnoN expression via siRNA in HEY ovarian carcinoma cells (cell line used previously to investigate role of SnoN [5] and PLSCR1 [8]); this was followed by quantitation of PLSCR1 mRNA levels via real-time PCR. Upon SnoN knockdown (~88% and 95% at RNA and protein level, respectively), we observed a significant reduction (~35%) in PLSCR1 mRNA (Figure 2A) implicating SnoN in the regulation of PLSCR1 transcription. These results were validated by utilizing the PLSCR1 promoter upon SnoN knockdown in T80 cells (Figure 2B) or with TGFβ (50 pM) (Figure 2C); both conditions led to a marked reduction in PLSCR1 promoter activity suggesting that activation of the TGFβ signaling cascade downregulates PLSCR1 expression. PLSCR1 mRNA levels were also down-regulated following 24 h TGFβ treatment (Figure 2D, left panel). SnoN mRNA has been previously shown to increase 1–3 hours post-TGFβ treatment [4] (Figure 2D, right panel) implicating discordance between SnoN and PLSCR1 mRNA levels with TGFβ. Intriguingly, overexpression of both the wild type and C/A PLSCR1 mutant (which localizes to the nuclear compartment [14]) in T80 cells led to a marked induction of plasminogen activator inhibitor-1 (PAI-1) expression (Figure 2E); these results suggest that PLSCR1 could modulate TGFβ cellular responses, similar to SnoN [4].
Knockdown of SnoN Reduces PLSCR1 mRNA Levels. (A) RNA was isolated from HEY cells 48-hours post-transfection with SnoN siRNA. PLSCR1 (left panel) and SnoN (right panel) mRNA levels were quantified by real-time PCR. Results are representative of duplicate experiments. (B) T80 cells were transfected with the PLSCR1 promoter followed by either SnoN knockdown (B) or 24 h TGFβ treatment (C). Cell lysates were harvested and luciferase activity was quantified. Results are representative of duplicate experiments. (D) RNA was isolated from T80 cells treated with TGFβ (3 and 18 h). PLSCR1 (left panel) and SnoN (right panel) mRNA levels were quantified by real-time PCR. Results are representative of duplicate experiments. (E) T80 cells were mock transfected or transiently transfected with either wild type PLSCR1 (WT-PLSCR1, 0.25 μg to 2.0 μg) or C/A PLSCR1 mutant (C/A-PLSCR1, 0.25 μg to 2.0 μg). Cell lysates were analyzed by western blotting for the proteins indicated. Results are representative of duplicate experiments.
Since PLSCR1 is an interferon (IFN)-inducible gene [15, 16], we next determined whether SnoN could, in part, modulate PLSCR1 expression upon IFN-2α treatment. Supporting previous reports, treatment of HEY cells with IFN-2α (3000 IU/ml) led to a dramatic increase in PLSCR1 protein from 6 up to 24 hours (Figure 3A, 3.7-fold) and RNA (Figure 3B, 2.9-fold). Similar results were also observed in a series of IFN-resistant and sensitive pancreatic cancer cell lines (Additional file 3: Figure S1, A-F). Strikingly, SnoN protein was induced (in the absence of SnoN mRNA changes (Additional file 4: Figure S2, A)) at 3 h post-IFN treatment; changes in SnoN occurred prior to those observed in PLSCR1. These results implicate SnoN in the transcriptional regulation of PLSCR1 expression upon IFN treatment. In addition, we noted that the induced PLSCR1 localized predominantly at the plasma membrane in HEY cells (Figure 3C and D), assessed via immunofluorescence and subcellular fractionation (with a very minor fraction localizing to the nuclear compartment). Since chemotherapeutic agents can generate intracellular reactive oxygen species (ROS) which modulates expression levels of various proteins [5], we next assessed whether the changes we observed in PLSCR1 and SnoN expression with IFN were due to ROS. Thus, we co-treated HEY cells with N-acetyl-L-cysteine (NAC), an anti-oxidant free radical scavenger, together with IFN for 9 h. However, there were no marked changes in PLSCR1 and SnoN protein levels in the presence of NAC (Additional file 4: Figure S2, B); these results suggest that the IFN-induced changes in SnoN and PLSCR1 may be independent of ROS. Strikingly, knockdown of SnoN levels (via siRNA) in HEY cells in the presence of IFN-2α (6 h, 3000 IU/ml) not only effectively reduced SnoN levels but also PLSCR1 RNA (Figure 3E and F, 1.8-fold). However, changes in PLSCR1 protein were again not detected with IFN-treatment following SnoN siRNA (Additional file 4: Figure S2, C); we propose that this could be due to the long half-life of PLSCR1 protein (assessed utilizing cycloheximide (CHX), an inhibitor of protein translation (results not shown)) or additional mechanisms needed to contribute with SnoN to modulate PLSCR1 protein.
SnoN modulates IFN-2α-mediated induction of PLSCR1 mRNA. (A) HEY cells were treated with 3000 IU/ml IFN-2α (15 min – 24 h). Cell lysates were harvested followed by western blotting for the indicated proteins. Results are representative of triplicate experiments. (B) HEY cells were treated with 3000 IU/ml IFN-2α (0, 1, and 3 hours). RNA was isolated followed by real-time PCR analysis to quantify PLSCR1 mRNA levels. Results are representative of duplicate experiments. HEY cells were treated with 3000 IU/ml IFN-2α (18 h) followed by immunofluorescence staining (C) or subcellular fractionation of cytoplasmic and nuclear fractions (D) which were analyzed by western blotting for the proteins indicated. Results are representative of duplicate experiments. (E) HEY cells were transfected with non-targeting or SnoN siRNA followed by IFN-2α treatment (3 h). Forty-eight hours post-transfection, total RNA was isolated followed by quantitation of PLSCR1 (E) and SnoN (F) mRNA by real-time PCR. Results are representative of duplicate experiments.
We have previously demonstrated the role of As2O3 as an effective chemotherapeutic agent inducing cell death in ovarian cancer cells, antagonized by autophagy mediated by SnoN induction [5]. We first assessed whether PLSCR1 protein is altered upon As2O3 treatment in ovarian cancer cells. In this regard, we treated HEY cells with 25 μM As2O3 (0 – 24 h). In contrast to SnoN (increasing between 6 – 24 h), we noted a marked reduction in PLSCR1 protein (~75% reduction) (Figure 4A and B). We next determined whether this reduction in PLSCR1 protein was due to proteasomal degradation via the use of MG132 (proteasome inhibitor). Co-treatment of HEY cells with 5 and 25 μM As2O3 for 6 h and 18 h with 5 μM MG132 did not lead to a significant recovery in PLSCR1 levels; these results suggest a mechanism of PLSCR1 protein regulation independent of the proteasome (Figure 4C). Indeed, As2O3 also alters PLSCR1 RNA levels which might together reflect As2O3-induced transcriptional regulation of PLSCR1 (Figure 4D). In order to determine whether PLSCR1 plays a role in modulating As2O3–induced cell death response in ovarian cancer cells, we reduced PLSCR1 expression via siRNA. Upon knockdown of PLSCR1 in the presence of As2O3, we observed a marked increase in the levels of caspase-3 activity (results not shown) as well as cleaved PARP ((7.9-fold) a marker of apoptosis, Figure 4E) concurrent with reduction in LC3-II ((2.5-fold), a marker of autophagy, Figure 4E) validated by GFP-LC3 autophagy assays ((~20%), Figure 4F). Similar to SnoN [5], these results suggest that PLSCR1 may contribute to the As2O3-induced apoptotic and autophagic response.
PLSCR1 modulates As 2 O 3 -induced cell death response in HEY ovarian carcinoma cells. (A) HEY cells were treated with 25 μM As2O3 (15 min - 24 h) followed by harvesting of cell lysates and analyses via western blotting for the indicated proteins. Results are representative of triplicate experiments. (B) Densitometric analysis of PLSCR1 protein levels of data presented in (A). (C) HEY cells were treated with 25 μM As2O3 (6 or 18 h) in the absence or presence of MG132 (5 μM) followed by harvesting of cell lysates and analyses via western blotting for the indicated proteins. Results are representative of duplicate experiments. (D) HEY cells were treated with 25 μM As2O3 (6 or 18 h). RNA was isolated and analyzed for PLSCR1 mRNA levels by real-time PCR. Results are representative of duplicate experiments. (E) Cell lysates were collected from HEY cells treated with non-targeting or PLSCR1 siRNA in the absence or presence of 25 μM As2O3 (18 h). Western blotting was performed for the proteins indicated. Results are representative of triplicate experiments. (F) Cells were transfected with pEGFP-LC3. Twenty-four hours post transfection, cells were treated with non-targeting and PLSCR1 siRNA followed by treatment with 10 μM As2O3. Immunofluorescence was performed (left panel) and the data was quantitated (bar graphs, right panel) by counting the number of cells positive for EGFP-LC3 punctae. Results are representative of duplicate experiments. (G) A schematic showing regulation of PLSCR1 mRNA by SnoN and As2O3 (and its effect on the cell death response) in HEY cells. In addition to the downstream effect of overexpressed PLSCR1 on PAI-1, a TGFβ target gene, in T80 cells.
In the current study, we demonstrate that PLSCR1 and SnoN DNA copy number as well as their RNA levels are correlated. By modulating SnoN expression, PLSCR1 mRNA levels appear to be co-regulated (Figure 4G). Of interest, SnoN knockdown does not alter PLSCR1 protein possibly suggesting that other mediators are involved in its regulation. Nonetheless, similar to SnoN, reduction in PLSCR1 levels appears to increase the cellular sensitivity to As2O3. Whether PLSCR1 modulates sensitivity to carboplatin/paclitaxel or whether the effects of As2O3 and TGFβ are mediated via IFN remain to be investigated. Thus, further investigations are warranted to delve into the significance of these findings in ovarian cancer development and chemoresistance.
PLSCR1:
Phospholipid Scramblase 1
SnoN/SkiL:
Ski Related Novel Protein N
EVI1:
Ecotropic Viral Integration Site-1
PIK3CA:
phosphatidylinositol-3-kinase catalytic subunit-α
PKCι:
Protein Kinase C iota
aCGH:
Array Comparative Genomic Hybridization
TCGA:
The Cancer Genome Atlas
PAI-1:
Plasminogen Activator Inhibitor-1
TGFβ:
Transforming Growth Factor-β
As2O3:
CHX:
Cycloheximide
IFN:
Interferon
ROS:
Reactive Oxygen Species
NAC:
LC3:
Microtubule-associated protein light chain 3
GFP:
Green fluorescent protein
Propidium Iodide
PARP:
Poly-ADP Ribose Polymerase
T80:
Immortalized (LTAg/hTERT) normal ovarian surface epithelial cells
APL:
Acute Promyelocytic Leukemia.
Bast RC, Hennessy B, Mills GB: The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 2009, 9 (6): 415-428. 10.1038/nrc2644.
Nanjundan M, Nakayama Y, Cheng KW, Lahad J, Liu J, Lu K, Kuo WL, Smith-McCune K, Fishman D, Gray JW: Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer. Cancer Res. 2007, 67 (7): 3074-3084. 10.1158/0008-5472.CAN-06-2366.
Eder AM, Sui X, Rosen DG, Nolden LK, Cheng KW, Lahad JP, Kango-Singh M, Lu KH, Warneke CL, Atkinson EN: Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci USA. 2005, 102 (35): 12519-12524. 10.1073/pnas.0505641102.
Nanjundan M, Cheng KW, Zhang F, Lahad J, Kuo WL, Schmandt R, Smith-McCune K, Fishman D, Gray JW, Mills GB: Overexpression of SnoN/SkiL, amplified at the 3q26.2 locus, in ovarian cancers: a role in ovarian pathogenesis. Mol Oncol. 2008, 2 (2): 164-181. 10.1016/j.molonc.2008.05.001.
Smith DM, Patel S, Raffoul F, Haller E, Mills GB, Nanjundan M: Arsenic trioxide induces a beclin-1-independent autophagic pathway via modulation of SnoN/SkiL expression in ovarian carcinoma cells. Cell Death Differ. 2010, 17 (12): 1867-1881. 10.1038/cdd.2010.53.
Yatsula B, Lin S, Read AJ, Poholek A, Yates K, Yue D, Hui P, Perkins AS: Identification of Binding Sites of EVI1 in Mammalian Cells. J Biol Chem. 2005, 280 (35): 30712-30722. 10.1074/jbc.M504293200.
Kodigepalli KM, Dutta PS, Bauckman KA, Nanjundan M: SnoN/SkiL expression is modulated via arsenic trioxide-induced activation of the PI3K/AKT pathway in ovarian cancer cells. FEBS Lett. 2013, 587 (1): 5-16. 10.1016/j.febslet.2012.11.003.
Silverman RH, Halloum A, Zhou A, Dong B, Al-Zoghaibi F, Kushner D, Zhou Q, Zhao J, Wiedmer T, Sims PJ: Suppression of ovarian carcinoma cell growth in vivo by the interferon-inducible plasma membrane protein, phospholipid scramblase 1. Cancer Res. 2002, 62 (2): 397-402.
Bateman A, Finn RD, Sims PJ, Wiedmer T, Biegert A, Soding J: Phospholipid scramblases and Tubby-like proteins belong to a new superfamily of membrane tethered transcription factors. Bioinformatics (Oxford, England). 2009, 25 (2): 159-162. 10.1093/bioinformatics/btn595.
Kuo YB, Chan CC, Chang CA, Fan CW, Hung RP, Hung YS, Chen KT, Yu JS, Chang YS, Chan EC: Identification of phospholipid scramblase 1 as a biomarker and determination of its prognostic value for colorectal cancer. Mol Med. 2011, 17 (1–2): 41-47.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E: The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discovery. 2012, 2 (5): 401-404. 10.1158/2159-8290.CD-12-0095.
Wahid F, Shehzad A, Khan T, Kim YY: MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010, 1803 (11): 1231-1243. 10.1016/j.bbamcr.2010.06.013.
Kortmann J, Sczodrok S, Rinnenthal J, Schwalbe H, Narberhaus F: Translation on demand by a simple RNA-based thermosensor. Nucleic Acids Res. 2011, 39 (7): 2855-2868. 10.1093/nar/gkq1252.
Wiedmer T, Zhao J, Nanjundan M, Sims PJ: Palmitoylation of phospholipid scramblase 1 controls its distribution between nucleus and plasma membrane. Biochemistry. 2003, 42 (5): 1227-1233. 10.1021/bi026679w.
Der SD, Zhou A, Williams BR, Silverman RH: Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA. 1998, 95 (26): 15623-15628. 10.1073/pnas.95.26.15623.
Dong B, Zhou Q, Zhao J, Zhou A, Harty RN, Bose S, Banerjee A, Slee R, Guenther J, Williams BR: Phospholipid scramblase 1 potentiates the antiviral activity of interferon. J Virol. 2004, 78 (17): 8983-8993. 10.1128/JVI.78.17.8983-8993.2004.
This work was supported by funds from the National Institute of Health RO1 CA 123219 and University of South Florida Start-up Funds to Meera Nanjundan. This work was also supported in part by the Flow Cytometry Core Facility at the College of Medicine, University of South Florida. We thank Dawn Smith, Annemarie Boland, and Hussain Basrawala for their technical assistance with the studies presented herein. We also are grateful to Stephanie Rockfield and Katherine Allen for their assistance with figure preparation.
Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, 4202 East Fowler Avenue, ISA2015, Tampa, FL, 33620, USA
Karthik M. Kodigepalli
& Meera Nanjundan
Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, USA
Pavana Anur
& Paul Spellman
University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, USA
Peter J. Sims
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Correspondence to Meera Nanjundan.
MN conceived and supervised the study. PJS developed the following constructs for use in this work: pGL3-PLSCR1 promoter, wild type PLSCR1 in pcDNA3.1, and C/A PLSCR1 mutant in pcDNA3.1. KMK, PA, PS, and MN performed the research and analyzed the data. KMK and MN co-wrote the paper and all authors approved the final manuscript.
Additional file 1: Materials and Methods. (DOCX 44 KB)
Additional file 2: Table S1: DNA Copy Number Variation in PLSCR1 and SnoN across multiple ovarian cancer cell lines. Forty-seven ovarian cancer cell lines were assessed for CNV in PLSCR1 and SnoN. There does not appear to be significant copy number changes for both genes in the cell lines presented where the copy number is nearly invariable from the normal copy number. (PPTX 35 KB)
Additional file 3: Figure S1: Induction of PLSCR1 protein expression in response to IFN-2α in a series of resistant and sensitive pancreatic cancer cell lines. (A) IFN-2α treatment of AsPC-1 cells and PANC-1 cells. (B) IFN-2α treatment of BxPC-3 cells and MIA PaCa-2 cells. Cell lysates were harvested from cell lines described in (A) and (B) followed by western analyses for the indicated antibodies. (C) Cell lysates were harvested from IFN-2α treated MIA PaCa-2 cells followed by western analyses for the indicated antibodies. (D) RNA was isolated from IFN-2α treated MIA PaCa-2 cells followed by real-time PCR analyses to quantify PLSCR1 mRNA levels. (E) and (F) Growth assays were performed in AsPC-1, PANC-1, BxPC-3, and MIA PaCa-2 cells in response to IFN-2α treatment. (PPTX 183 KB)
Additional file 4: Figure S2: No effect on PLSCR1 protein levels upon NAC treatment or SnoN knockdown in the absence/presence of IFN-2α. (A) HEY cells were treated with 3000 IU/ml IFN-2α (0, 1, 3 hours). RNA was isolated followed by real-time PCR analysis to quantify SnoN mRNA levels. (B) HEY cells were treated with IFN-2α, NAC, or IFN-2α in combination with NAC at the specified doses. Cell lysates were harvested and analyzed by western blotting analyses for the indicated antibodies. (C) HEY cells were transfected with SnoN siRNA and treated with/without IFN-2α. Cell lysates were harvested and western analyses performed for the indicated antibodies. (PPTX 160 KB)
SnoN/SkiL
Phospholipid scramblase
PLSCR1
TGF-β
3q26.2


A few years ago Alan and Russell were directors of a (now sadly closed) internet company called aQtive. It came to one Christmas and we wondered what to send our contacts and registered users as a Christmas greeting. We thought of plain electrinic greetings cards ... passé - everyone sends those and hardly active.
Somehow or other the idea came - why not virtual Christmas crackers?
Christmas crackers are small paper tubes, usually around 20-30cm long (8-12"). Inside there is a cardbioard former that keeps the centre section firm as the ends are pinched in (see above). At the Christmas dinner table, crackers are arranged at each place and before you eat you offer one another the other end of your cracker and pull.
Although the crackers are usually made of quite thin paper, often crepe paper, it is surprisingly hard to pull them apart. When eventually they break there is a sharp 'bang!'. Inside, along the length of the cracker is a small strip of paper coated with gunpowder in the middle, as the cracker breaks the paper strip snaps and thee gunpowder explodes!
In addition, if you live in a country using Christmas crackers they will evoke nostalgic memories of childhood Christmases.
students in rome discover real crackers!
Virtual crackers are web versions, a bit like electronic greetings cards. In fact our earliest design ideas (quickly rejected) were very close to electronic cards - just a page with a picture of a cracker, a joke, a link to a little web toy (an animated gif or applet) and a picture of a face with a hat on. Well, different from an eCard, but, not exactly capturing the spirit of a Christmas cracker.
The open cracker page has a picture of an exploding cracker ... and a sound file plays ... bang! It also has the greetings message, the joke and links to separate pages for a mask and a web toy.
In a real cracker you tell the bad joke to one another, but this is not so good when you recieve the cracker on your own, so instead just the 'question' part of the joke is shown and the answer only revealed when you ask.
The sender meanwhile has a link that they can follow. Initially this just shows the closed cracker and only when the recipient has opened the cracker can the sender also see inside.
Evaluating experience is a difficult area. From a simple usability metric we might not think this is a very good interface. Just count the mouse clicks needed to see the answer to the joke; it would be a lot more efficient to simply show the joke and answer on the first page ... but not much fun.
In use terms around 20-25% of crackers are never opened. Whether this is due to incorrect email addresses, recipients thinking the mail is spam, or simply not getting round to it, we don't know. It is very hard to study those who don't use things. We also don't know how this figure compares with other kinds of electronic greetings cards, but based on personal use we guess not so different. This still represents a substantial number of apparently 'failed' communications ... although the simple reciept of the email, says "She is still thinking of me", so even a 'failed' virtual cracker may be a successful personal contact.
If we are designing an information system to be installed throughout an organisation, or a 'when the next bus is coming' system to be installed at every bus stop, it is important that the system is at least usable by everyone to some extent. However, for an 'experience' product like crackers the criteria change. If crackers are 'OK' for everyone then they are probably a failure, who wants to send something that is just OK. Ideally we'd like everyone to love virtual crackers, but it is better for some people to love them and some people hate them than for them to be just 'OK' for everyone.
By this measure virtual crackers come out very well as we have had a significant amount of 'fan' mail. Typically the only feedback you get for a product is to complain about bugs! So positive feedback is not just gratifying, but also strong evidence that something is working ... at least for some people!
I love this site!!!!! Thank you, thank you, thank you!!!
And Merry Christmas to everyone involved!!
I think your crackers are fantastic !!
These are very cool! Well done!
However there is a considerable amount of feedback from people now living in non-cracker countries, who clearly had their childhood memories awakened by the cracker.
Thank you for putting a smile on my face and bringing back some funny memories!
My mother is from England and I grew up pulling the "real" crackers during the holidays.
These are particualrly significant as they mean not only that the design was successful in that (some) people liked it, but also in that it in some way captured sufficient of the real crackers experience to induce nostalgia.
Of course, one of our aims in producing crackers was as PR for the company. For this crackers needed to be not only liked, but also shared. In fact, this was the case and each year we tend to see a week by week doubling in the use of crackers in the run-up to Christmas as some of those receiving crackers decide to pass them on to others (remember useful, usable and used).
your virtual crackers are the bomb!
The success of virtual crackers was not just happenstance.
In order to understand this success we must see how the virtual crackers do not replicate the real cracker, but do capture the crucial aspects of the 'cracker experience'. For example, it is important that virtual crackers do not give an optimal path to the users' goal, but instead a more tortuous navigation route thus adding to a sense of suspense.
Note that experience is as much about perception as function. In the case of crackers, both real and virtual, the inner functionality is not significant (a plastic toy), neither is the optimality of the interface (a flap would allow the extraction of the toy without damaging the cracker), nor even the actual physical packaging (crepe paper and cardboard), but within a particular social context the experience of using the cracker is deeply engaging. In the case of paper crackers this may be the result of accident and evolution. In the case of virtual crackers it is by design.
The design worked because it took the real crackers experience and deconstructed it into individual elements of the experience. the table below and on page 157 lists these elements. You can see how each real crackers element is in some way recreated in the virtual crackers experience, but it is not a simple facsimilie of the real cracker (impossible on the web!). Some mappings are fairly obvious, the bad joke on the paper inside the cracker becomes bad joke on the web page. However, others are not so straight forward.
The element of sharing in the real cracker is not the same in the virtual cracker. In a way the sending of the email has some of the essence of the offered cracker. However, there is a strong sense of co-experience with real crakers - you are there together as you pull. With virtual crackers this is much weaker, but the way that the sender can only see the open cracker until the recipient has opened it adds a little of this sense. In an instant messenger variant of virtual crackers it may be possible to make this stronger.
Why not try to sketch a design for yourself of what instant messenger crackers might be like?
Another example where the real and virtual crackers differ is in the mask. As mentioned real crackers have a paper hat inside and our first idea was to have a little smilie face with a hat one. Cute possibly, but hardly fun!
However, the mask link takes you to a page where you have a mask that is big enough to print and cut out. Although few (if any) crackers users may actually cut out the mask to wear, the fact that you could wear it gives it some of the feeling of dressing up that the hat does. Even with real crackers many people do not actually put the hat on, but would feel hard done by if theor cracker did not have one. With experience what you could do may be as important as what you do do!
Compters and Fun 4. York, UK, 29th November 2001.
... and of course you can try them yourself!


text:
<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN"
                "http://www.w3.org/TR/REC-html40/loose.dtd">

  <title>Description of fernsRegApply</title>
  <meta name="keywords" content="fernsRegApply">
  <meta name="description" content="Apply learned fern regressor.">
  <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1">
  <meta name="generator" content="m2html © 2003 Guillaume Flandin">
  <meta name="robots" content="index, follow">
  <link type="text/css" rel="stylesheet" href="../m2html.css">

fernsRegApply

PURPOSE

Apply learned fern regressor.

SYNOPSIS

function [ys,ysCum] = fernsRegApply( data, ferns, inds )

DESCRIPTION

 Apply learned fern regressor.

 USAGE
  [ys,ysCum] = fernsRegApply( data, ferns, [inds] )

 INPUTS
  data     - [NxF] N length F binary feature vectors
  ferns    - learned fern regression model
  inds     - [NxM] cached inds (from previous call to fernsInds)

 OUTPUTS
  ys       - [Nx1] predicted output values
  ysCum    - [NxM] predicted output values after each regressor

 EXAMPLE

 See also fernsRegTrain, fernsInds

 Piotr's Image&Video Toolbox      Version 2.50
 Copyright 2012 Piotr Dollar.  [pdollar-at-caltech.edu]
 Please email me if you find bugs, or have suggestions or questions!
 Licensed under the Simplified BSD License [see external/bsd.txt]

CROSS-REFERENCE INFORMATION

This function calls:

fernsInds	Compute indices for each input by each fern.

This function is called by:

<address>Generated by m2html © 2003</address>

redpajama_set_name: RedPajamaGithub


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text:
Susanne Hoder is Moderator of the Interfaith Peace Initiative and a member of the Divestment Task Force of the United Methodist Church New England Conference. Since visiting Israel and the West Bank in 2004, she has been an advocate for a just peace in the region based on equality, international law and human rights. She has spoken at numerous conferences and written articles on the situation in the Holy Land.  She has compiled research on publicly held companies that support the Israeli occupation of Palestinian land, urging churches and other organizations to withdraw their investments in these companies until Israel complies with international law.

References
http://www.interfaithpeaceinitiative.com/
http://www.neumc.org/pages/detail/178
http://www.unitedmethodistdivestment.com/,
http://umportal.org/article.asp?id=2654

Living people
American United Methodists
Year of birth missing (living people)

redpajama_set_name: RedPajamaWikipedia


text:
Q: map collections I am new to Apex and just starting to understand using maps to avoid loops within loops and hitting limits. My trigger below updates opp line items with the internal cost from another object using a map and the one value - "Service_Name".
My issue is I need to update another field on the Opp line item with "Agent Fee" in the same way  - but there are 4 criteria to get the right Agent Fee from another object. I cant see how do so this other than have a loop of agent Fees object with the opp line loop? How else can I do this? Is it possible with Maps ?
trigger sectortest on Opportunity (after update) {

        for (Opportunity eachopportunity : Trigger.new){

        //Get costs for the Opps FY and put in map
        List<Internal_Costs__c> costs = [SELECT Id, Financial_Year__c, Service_Name__c, Standard_Cost__c  FROM Internal_Costs__c WHERE Financial_Year__c =: eachopportunity.Financial_Year__c];
        Map<string, Decimal> costmap = new Map<string, Decimal>();
        for (Internal_Costs__c eachcost : costs){
             costmap.put(eachcost.Service_Name__c, eachcost.Standard_Cost__c);
         }

        //Get Line Items for Opp
        List<OpportunityLineItem> opplines = new List<OpportunityLineItem>();
        opplines = [SELECT Id, DS_Status__c, Country__c, Product2Id, UnitPrice FROM OpportunityLineItem WHERE OpportunityId =: EachOpportunity.Id];
        List<OpportunityLineItem> opplinesupdate = new List<OpportunityLineItem>();

        //assign cost to line items
            for (OpportunityLineItem EachOppline : opplines) {
                    decimal cost = costmap.get(EachOppline.Service_Name__c);
                    EachOppLine.Internal_Cost__c = cost;
                    opplinesupdate.add(EachOppline);
         }
             update opplinesupdate;
        }
}

A: This is typically handled using an object array as the key. Object arrays implement the methods required to use them as keys in maps quite efficiently (far more so than attempting to use a composite string key which is a common alternative that I strongly recommend against using).
For example, you might query your Agent Fee like:
List<AgentFee__c> fees = [
        SELECT Id, Value1__c, Value2__c, Value3__c, ...
            FROM AgentFee__c
            WHERE ...
];

You can then set up a key-based map like:
Map<Object[], AgentFee__c> agentFeesByKey = new Map<Object[], AgentFee__c>();

and populate it, using the specific key value fields from the fee, thus:
for (AgentFee__c fee : fees) {
    agentFeesByKey.put(new Object[] { fee.Value1__c, fee.Value2__c, fee.Value3__c },
            fee);
}

(If the combination of key value fields isn't unique the map may need to be from key to list of agent fees, but I'm assuming they are unique for this answer.)
Now when you get the opp lines you can find the agent fee for each line:
OpportunityLineItem line = ...;

AgentFee__c feeForLine = agentFeesByKey.get(
        new Object[] { line.Something__c,
                       line.SomethingElse__c,
                       line.SomethingElseAgain__c });

if (feeForLine != null) {
    // Now do something with the fee for this line
    ...
}

Adapt this with the specific key value fields and allow for non-unique combinations as required.

redpajama_set_name: RedPajamaStackExchange


As much as I love Women's Fashion, I adore Kids Fashion the same way ! Kids are just too cute and watching them walk the ramp with an amazing collection of outfits from world famous brands is just a treat to the eyes !
Junior's Fashion Week happened Bengaluru recently or showcasing AW18 collection of international brands.
One of its kind edutainment platform, Junior's Fashion Week (JFW) conducted its 24th Runway showcase on November 18, 2018, at Marriott Hotel Whitefield, Bengaluru. It showcased the Autumn Winter collection of international brands including U. S. Polo Assn. Kids, Hugo BOSS, DKNY, Little Mark Jacob, Timberland and Billie Blush, Flying Machine Boyzone, and The Children's Place.
Junior models aged four to fourteen years are the focal point of this one of a kind edutainment event. Not only does it provide overall grooming experience but also help them discover their best version. The Runway showcase was preceded by a workshop training, which is helmed by industry experts.
• Participating kids hail largely from the event city.
I had a wonderful time watching Kids walk the ramp in super stylish outfits !
It was a different experience for me as well as this was my first Kids Fashion Show ! And I am super happy that I had the opportunity to witness this..


Chefs and brothers Michael, left, and Bryan Voltaggio will be in Lexington in the fall.
Fans of Bravo TV's Top Chef are in for a double treat when brothers and chefs Michael and Bryan Voltaggio come to Lexington.
The brothers, who were on season 6 of the reality show — Michael won and Bryan was a runner-up — will be the celebrity chefs at the Kentucky Proud Incredible Food Show, organizers announced Wednesday. They will be cooking at 11 a.m. and 3 p.m. Oct. 8 at Lexington Center.
This is the third year for the food show but this time, it will be a one-day event instead of two, said Sheila Kenny, director of marketing for Lexington Center.
Bryan Voltaggio is chef and partner at Volt in Frederick, Md. Michael Voltaggio will open his first signature restaurant, Ink, this year in Los Angeles; he was a finalist for the James Beard "Best New Restaurant" Award in 2009.


Manga+Press is a webcomic management system for WordPress. Manga+Press uses WordPress' posts, pages and categories to help you keep track of your comic posts. Manga+Press also includes its own custom template tags to help make creating themes easier.
Please read carefully as there have been some breaking changes in this release. In 4.0, new actions, filters, and functions have been added, and other portions of the API removed or deprecated.
Found a bug? Visit my support page or post a support question on the WordPress Support Forums Please include screenshots, WordPress version, a list of any other plugins you might have installed. Be as detailed as possible.
Found a bug, and a fix? Fork the repo on Github and then open a pull-request containing the fix.


text:
stated on July 19, 2018 in a blog post:
"Satanic leader confesses to sacrificing 675 children 'gifted' to him by doctors."
By Katie Akin August 1, 2018
No evidence that so-called Satanic leader sacrificed 600 children
A viral video shows a masked man who claims he sacrificed 675 people, many of them children, to maintain his demonic powers. The confession, which originally aired on a Ghanaian talk show, and its translations have been shared across the discredited Neon Nettle, as well as the Daily Mail.
"Satanic leader confesses to sacrificing 675 children 'gifted' to him by doctors," read the Neon Nettle headline on July 19.
We decided to investigate the so-called confession. Is it real, or another online hoax?
The story features screenshots from a video clip from a Ghanaian television show aired on Royal Television Ghana, also known as RTV. The man claiming to be a Satanic leader speaks with a deep voice, and hides his face with a children's mask of Bumblebee from the Transformers movie franchise. The interviewer, a well-known television and radio presenter known as Otwinoko, does not identify the man.
The original interview with the so-called Satanic leader is nearly 30 minutes long, and is part two of a series entitled "DARKNESS IN CHURCHES." The interview is conducted in Akan, a language native to Ghana. It has been summarized in English by Ghanaian news site Yen.
According to the translation, the man claimed he lived with Satan for 17 years, and would conduct routine sacrifices to sustain his power. Evil doctors gave him these sacrifices, he said, many of whom were children. He also said that he was in control of over 600 demonic spirits.
Featured Fact-check
stated on January 8, 2021 in an interview with Ohio reporters
Summer "protesters outside the White House were met with tear gas, rubber bullets, a full militarized response. While ... rioters were able to breach the Capitol."
By Jon Greenberg • January 11, 2021
While there have been multiple local reports about the show itself, none have mentioned any police investigation into the issue. More widely, there have been no news reports of human sacrifice or doctors kidnapping children in Ghana.
The Otwinoko Show
Otwinoko, whose real name is Kwabena Asare, specializes in spiritual outrage. He vigorously questions his guests, supposed anti-Christian magicians, but doesn't release their identities.
He has dozens of other videos online, many of which follow a similar style to the interview with this Satanic leader. In one video, titled "PASTOR'S EVIL DEEDS EXPOSED," the thumbnail is a fiery 666. In another, he discusses the signs of the Antichrist. Debunking false prophets appears to be a routine feature on the show.
As an individual, Otwinoko maintains a mystical persona. He is visually impaired, and he claims that jealous fellow journalists used voodoo to cause his blindness.
Our ruling
The article by Neon Nettle claimed that "a Satanic cult leader has confessed to carrying out more than 600 child sacrifices." A man did confess this on a Ghanaian television show.
The article does acknowledge that there have been no reports of mass child killings in Ghana, Satanic or otherwise. But, Neon Nettle fails to mention that this show has a long sensationalist history of interviewing supposed spiritual deviants and granting them anonymity.
We rate this claim Half True.
Neon Nettle, "Satanic leader confesses to sacrificing 675 children 'gifted' to him by doctors," July 19, 2018
Daily Mail, "Pastor claims he carried out ritual murders of more than 600 children handed to him by devil-worshipping doctors and nurse," July 18, 2018
Rtv Ghana, "OTWINOKO SHOW- DARKNESS IN CHURCHES PART 2 17/7/18," Jul 17, 2018
Rtv Ghana, "OTWINOKO SHOW -PASTOR'S EVIL DEEDS EXPOSED," June 19, 2018
Rtv Ghana, "OTWINOKO SHOW -SIGNS OF THE ANTICHRIST 'BEWARE'," July 20, 2018
Rtv Ghana, "FAKE PROPHETS AND THEIR TRICKERY EXPOSED," May 28, 2018
Rtv Ghana, "OTWINOKO AND PROPHET OBOTAN ON FALSE PROPHET," Feb. 1, 2018
Rtv Ghana, "OTWINOKO EXPOSES FAKE PROPHET," May 22, 2018
Yen, "Man confessed to using 675 people for sacrifice; reveals secrets of fake pastors," July 20, 2018
GhanaWeb, "Stop engaging in Voodooism - Otwinoko to Journalists," July 4, 2017
Modern Ghana, "My Cohorts Stabbed Me At The Back -- Otwinoko," July 21, 2015
Browse the Truth-O-Meter
More by Katie Akin
Congressional Leadership Fund
stated on August 8, 2018 an ad:
Says Amy McGrath "wants to fund more welfare for people who can work, but don't."
By Katie Akin • September 7, 2018
stated on February 21, 2017 a blog post:
"John McCain was pardoned for treason"
By Katie Akin • August 27, 2018
stated on August 22, 2018 a tweet:
Says the "South African Government is now seizing land from white farmers" and alleges a "large scale killing of farmers" in the country.
stated on August 22, 2018 a blog post:
"Omarosa Exposed: Turns out she was actually working for Hillary"
stated on August 5, 2018 a blog post:
"Cops take a knee then walk out on Redskins, leaving them stranded in their locker room overnight."
"Science says that being single will kill you faster than obesity."
stated on July 30, 2018 in a campaign ad:
Says Bill Nelson "doesn't pay payroll taxes for his employees. He doesn't even provide them with health benefits. It's stealing money from Medicare and Social Security."
Gwen Graham
stated on August 3, 2018 in a livestreamed interview:
"The teachers in (charter) schools don't even have to be certified."
Jeff Greene
stated on July 29, 2018 a TV interview:
"There is a big correlation between third grade reading level and whether you go to college or whether you go to prison. And in Florida right now only 56 percent of kids are coming out of third grade at third grade reading level."
By Katie Akin • August 7, 2018
stated on July 19, 2018 a blog post:
stated on July 24, 2018 a campaign ad from his political committee Florida Grown:
"Congressman (Ron) DeSantis sponsored legislation to increase sales taxes by 23 percent, hurting families, destroying jobs, devastating tourism"
By Katie Akin • July 27, 2018
Senate Leadership Fund
stated on July 24, 2018 a campaign ad:
Says Sen. Joe Donnelly's "family got caught outsourcing jobs to Mexico, and 'Mexico Joe' profited up to $80,000."
"Puerto Rico mayor facing fraud charges over $3M in federal disaster relief"
"An elderly British politician has been savagely beaten to a bloody pulp by a gang of anti-Trump protestors because he 'welcomed' the U.S. president to the United Kingdom."
"Giant rats plague New York City as 4 homeless men found eaten alive"
stated on January 15, 2021 in a headline:
"Inauguration Cancelled, Trump Remains in Office."
By Amy Sherman • January 16, 2021
stated on January 15, 2021 in a Facebook post:
Says a photo shows armed soldiers protecting Joe Biden's inauguration.
By Miriam Valverde • January 16, 2021
stated on January 12, 2021 in an Instagram post:
Says Joe Biden stayed silent about violence at Black Lives Matter protests.
By Tom Kertscher • January 16, 2021
Jon Rosenthal
stated on January 5, 2021 in a tweet:
Says that "the way to reach 'herd immunity' is for >70% of the population to get vaccinated."
By Brandon Mulder • January 15, 2021
Amanda Chase
stated on January 7, 2021 in Facebook post:
"Antifa is the culprit" in the Capitol riot.
By Warren Fiske • January 15, 2021
Devin LeMahieu
stated on January 10, 2021 in a TV interview:
"It takes quite a while on Election Day to load those ballots, which is why we have the 1 a.m. or 3 a.m. ballot dumping in Milwaukee."
By Eric Litke • January 15, 2021
stated on January 6, 2021 in a Facebook post:
"Coronavirus vaccinations seem to be causing 50 times the adverse events of flu vaccinations after just the first of two shots."
Viral image
A photo shows Democratic lawmakers wearing clothing and masks with the Nazi swastika.
By Samantha Putterman • January 15, 2021
Sarah Godlewski
stated on January 9, 2021 in Twitter:
"It wasn't all women that lost jobs (in the December jobs report), it was mostly Black and Latina women. In fact, white women gained employment."
By Nusaiba Mizan • January 15, 2021
Photo shows Rep. Lauren Boebert with Capitol rioters before she gave them a tour of the building "one day before the insurrection."

redpajama_set_name: RedPajamaCommonCrawl


text:
30th District lawmaker to hold town halls March 16 and 23
CONTACT: Stephanie Davenport, Public Information Officer – (360) 786-7031
Rep. Linda Kochmar – (360) 786-7898
Thirtieth District Rep. Linda Kochmar, R-Federal Way, will hold three town hall meetings March 16 and 23. The district includes Federal Way, Pacific, Algona and Milton. She will share the latest news from Olympia with residents and answer questions about issues facing the Legislature, including K-12 education, transportation and her bill to help victims of human trafficking.
Anyone who is a constituent of the Thirtieth District is invited to participate in these public forums. The town halls will be held: March 16:
10:00-11:30 at Federal Way Council Chambers (City Hall)
33325 8th Avenue South Federal Way, WA 98003
1:30-3:00 at Algona Council Chambers (City Hall)
402 Warde Street Algona, WA 98001 March 23:
10:00-11:30 at the Milton Community Center
1000 Laurel Street Milton, WA 98354
"I am excited to be holding these town halls to listen to concerns and suggestions from constituents in the Thirtieth District," Kochmar said. "As the legislative session picks up and winds down, it is essential that I hear from constituents to learn more about important issues that impact people in our communities. The session is scheduled to end April twenty-eighth and the many issues in line to be vetted will affect jobs, transportation, health care, environment, public safety, education, disability services and numerous others important topics. I want to hear from folks, so I can bring their voices back to Olympia to better represent our district in the state legislature".


text:
Giancarlo Elia Valori
Romain Zaleski
Domenico Livio Trombone
Stefano Coen
Umberto Buccarelli
Turkey in the Kurdish Rojava
Luigi Pellè
Since the beginning of clashes in Syria, Turkey has aimed at annexing the left bank of the Euphrates up to Mossul, a strip of land about 500 kilometers long and 30 kilometers wide – an area which is large enough to accommodate the 3.6 million Syrian refugees who have entered Turkey since the beginning of the hostilities against Bashar el Assad.
The above mentioned area between the Kurdish Rojava and Turkey was established by the latter, in agreement with the United States, in August 2019.
It is the area that was invaded a few days ago.
Since the beginning of the clashes in Syria, the United States has wanted the Turkish Armed Forces to be targeted directly against President Assad's forces, so as to lead either to a splitting of Syria or to the creation of a new regime, open to US and Western influences.
President Erdogan, however, has never agreed to do all the "dirty" work against Assad' Shiites on his own. He has always asked for the direct and equal support of the US forces.
Here the US and its allies' operations in Syria have essentially stopped.
The United States has quickly responded to this substantial refusal of Turkey to do the US work in Syria, by involving the Kurds and organizing a Force uniting the YPG Kurds and the Syrian Democratic Forces. It has done so with a military mechanism that – in principle-oversees mainly the areas already bombed by the US Air Force and by the coalition that supported the US dual struggle against Assad and the jihadists of the "Caliphate".
In any case, however, Turkey does not want any Kurdish organization to monitor the borders between Turkey and Syria.
Hence, this is the dilemma. Turkey has already penetrated the Rojava area on the border with its country, while the Kurds – be they from the PKK or the YPG, two often overlapping organizations – try to ally precisely with Assad, while there is also the concrete possibility of a further Iranian penetration between Mossul and the Southern area of the Kurdish Rojava.
Turkey will also use its Syrian alliances, such as those of the Syrian Interim Government, to unite them with the Syrian National Army, which operates in the region north of Aleppo, and with the National Liberation Front stationed in Idlib.
It should also be noted that President Erdogan knows the real reason for the recent electoral defeat of his AKP Party. Obviously Turkish voters are worried about the economic crisis and the monetary tensions on the Turkish lira, but they are mainly terrified of the pressure that the 3.6 million Syrian refugees on the ground put on the whole Turkish economic and social system.
This is another political prospect for President Erdogan, namely becoming the protector – so to speak – of all Sunnis.
In addition to the pan-Turkish project in Central Asia, President Erdogan knows that militarily Saudi Arabia is a giant with clay feet, while Egypt is unable to project itself onto Central Asia and the Islamic Republic of Iran is finally focused on its pan-Shiite project, with an inward-looking attitude.
For some time now, the Turkish police has been monitoring and arresting a large number of Syrian, Christian or Shiite immigrants, while some leaders of the Syrian community have already been deported to Idlib.
It should also be recalled that the economic and financial effort to build at least 200,000 houses and services in the currently occupied Rojava area, mostly with non-Turkish funds, would be a major boost for the entire Turkish economy, which has long been floundering in a deep crisis.
Clearly, the inclusion of at least 3 million Syrians onto the Kurdish Rojava's border with Turkey would greatly change the ethnic complexion of the area but, in the future, also of the whole Kurdish Rojava, with obvious positive effects for Turkey.
But there is also the other side of the coin, since there would be an increase of tensions between the Arab world, to which most Syrians belong, and the Kurdish and non-Arab universe that is alien to most of the political, religious and cultural traditions of the Shiite or Sunni Islam.
It should be recalled, however, that this has been the third Turkish penetration into the Kurdish Rojava since 2016.
As far as we can currently see, Turkey's entry into the Kurdish country is limited to the "Kurdish canton" of Hasakah- Kobanè- Qarmishli.
The rest of the Turkish operation will obviously be calibrated on international reactions, especially of the countries directly concerned by Syria.
The Kurds, however, with their structure of Syrian Democratic Forces, have been among the few real winners of the war in Syria.
This has enabled them to stabilize the internal political structures and the borders of the Kurdish country, although no Kurdish leader has ever spoken of true independence of Rojava, but only of autonomy.
Therefore, the Kurds' optimal strategic equation depends on the US presence in the East and North-East of their area.
Otherwise- as indeed happened – Turkey would take the whole strip of land at the border.
For the time being, the focus of Turkish operations goes from Ras Al Ain to Tell Abyad, in a span of about 100 kilometers.
As far as we know, in Tall Abyad, the Turkish penetration has been stopped by the Kurdish forces.
This is an area, however, with a very high number of Arabs, that Turkey has already penetrated with its intelligence Services and its organizations.
If the Kurds wanted to keep the territory already invaded by Turkey, there would be very hard clashes and it is not certain that they could win.
Pending the Turkish invasion, the Russian Federation has declared that Turkey has every right to defend its borders, but it has also added that the Syrian state and territorial unity needs to be preserved.
Moreover, the invaded area is not yet under Assad government's control, but the presence of the Turkish Armed Forces would trigger instability also for Syria, considering that the Kurds of Rojava were (and are) much more friendly with Assad than with the Turkish regime, which has often declared its intention to eliminate Assad's power system.
There were also massive gold acquisitions by the Turkish Central Bank immediately before the invasion of Rojava.
From January to August 2019, Turkey's gold reserves reached 362.5 tons (+109), for a total value of about 17.9 billion euros.
Obviously, the fear of sanctions and the concern for national security have currently pushed Turkey to become one of the world's largest gold buyers.
The above mentioned militiamen linked to the Turkish army are already 7,000, while the Kurdish ones operating in the area are at least 35,000, in addition to the 15,000 soldiers of Asaysh, the internal Kurdish security and intelligence organization.
Too many, and too well trained, not to be a very tough nut to crack also for the Turkish Armed Forces.
The United States – apart from the troops already withdrawn – still have 1,500 soldiers in the area, including special forces, military advisers and Marines – not at the border, but within the area of Rojava, on the border with Turkey and Iraq.
The US bases still operational in the area are ten, plus three aerial installations that allow to operate with transport vehicles, drones and helicopters.
Not to mention the French and British special forces that continue to operate in the area.
The operational assumptions are the following: President Assad could permit Turkey to take Rojava, in exchange for Syria's green light on Idlib, still largely in the hands of the various forms of sword jihad.
Needless to say, the oil resources of the area are still in Kurdish hands and that both Assad and the other countries of the region want to quickly put their hands on it.
In President Erdogan' strategic equation the energy problem is not secondary at all.
In Syria, in the Persian Gulf and -as we will see -also in Libya.
The Turkish ship Yavuz will shortly leave for Cyprus to drill the seabed.
The Northern Cyprus State, a direct emanation of Turkey, blocks any autonomous economic action by Cyprus and the Turkish Navy has sealed the Exclusive Economic Zone of Cyprus.
Three large energy companies are interested in Cyprus' natural gas, namely ENI, Total and Exxon-Mobil.
The ship Saipem1200 was blocked by the Turkish Navy in February 2018, while in January 2019 the French Navy sent the ship Aconit for joint exercises with the Cypriot Navy, with the clear aim of opposing Turkey.
The traditional lack of character – so to speak – of the Italian ruling class.
Turkey, however, has never accepted the UN Convention on the Law of the Sea (UNCLOS) and hence does not recognize Greece's Exclusive Economic Zone, since it aims at acquiring the island of Kastellorizo, which is very close to the Turkish coast.
President Erdogan, the Head of a traditional land power that, indeed, was essential in the Cold War vis-à-vis the Caucasus and Southern Russia, wants to reach full military autonomy by 2023, according to the Turkish plan Vision 2023.
But, in particular, it wants to turn Turkey into a great maritime power, with a view to controlling the whole Aegean Sea and most of the Mediterranean.
Greece, however, is becoming the new US military center in the Mediterranean. The United States will support the new Greek military build-up but, above all, will help Greece to explore the depths of the Aegean and Ionian seas, as well as Crete, for oil.
In terms of migration, which is the EU No. 1 problem, President Erdogan skillfully exploits the EU weak presence and strategic irrelevance – if not non-existence.
In 2016, the Turkish leader collected the 6 billion euros promised by Germany and paid by the whole EU to keep the refugees in his country.
Turkey, however, wants a new agreement, much more burdensome for the EU, claiming it has already stopped as many as 270,000additional migrants in 2018 and 170,000 in 2019.
It is easy to predict that the silly Europe will give President Erdogan what he wants.
It is by no mere coincidence that boats of migrants leave the Turkish coasts – without any control – heading to the Greek islands of Kos, the ancient kingdom of Hippocrates, and Chios, the homeland of Homer and Lesbos.
Migration management is an indirect strategy technique.
Reverting to the Syrian case, another example of this new project of Turkish grandeur, we wonder why – assuming that there was a moment "x" – the United States gave the "green light" to President Erdogan for his invasion of Northern Rojava.
Probably the United States is thinking of a possible future clash between Turkey, Russia and Iran, which right now are organizing a Syrian Constitutional Committee, with the UN support.
Causing difficulties for Turkey in the Astana negotiations? It is a possibility, but much more would be needed to create tension around Turkey.
Turkey, however, should also deal with the 60,000 "Caliphate" fighters, detained in the Kurdish prisons.
It is not at all certain that Turkey wants to take care of them.
Dropping a jihadist bomb would be a threat for which no one could say no to Turkey.
A trace of Turkey's current "policy line" can also be found in Libya.
Turkey has provided Fayez al-Sarraj's Government of National Accord (GNA) with missiles, armored vehicles, drones and light weapons.
Probably Turkey has also favored the arrival of Jihadist militants from Syria to Libya.
The real clash is, here, between Turkey and Egypt, supported by the Gulf States.
Through their base in Niger, the Emirates support Haftar, who can thus control Fezzan.
Furthermore, through its support to the Muslim Brotherhood and other Islamist groups, Turkey wants to have a Libya divided between various areas of influence – as in Syria – with the aim of getting its hands – through al-Sarraj's government – on the huge Libyan oil reserves: 48 billion barrels, plus the possible reserves from fracking, i.e. additional 26 billion barrels.
Apart from the size of oil production, which is much more relevant in Libya, now we can clearly see it is the same project that Turkey is carrying out in Syria.
Not to mention Misrata, where there is a tribe of Turkish origin, the Karaghla.
In any case, Turkey will reach the maximum power of blackmail vis-à-vis the poor EU and, in the future, vis-à-vis the Atlantic Alliance itself, to play the game of Islamic radicalism in contrast with Egypt and the Gulf countries.
The starting point will be the Turkish presence in Syria, which will be used for a rational division of the spheres of influence.
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text:
Making Disabled Access Day activities a regular feature
audio description, case studies, museums & galleries, 2016, wheelchair users, Greater Manchester, Belfast, London, England
The Imperial War Museum took part in Disabled Access Day for the first time this year. Here, they provide some feedback and tell us about their DAD experience!
What's on in July?
events, BSL, audio description, 2016, Tyne and Wear, Edinburgh, Norfolk, London, South Glamorgan, Cardiff, Wales, Scotland, England
Find out about accessible events happening around the country throughout July. Our list includes captioned and audio described theatre performances as well as BSL interpreted tours.
A Euan's Guide reviewer's experience on Disabled Access Day
2016, wheelchair users, guest blog, London, England
Euan's Guide Reviewer of the Year 2014, Gary Smith, enjoyed Disabled Access Day in London this year. Here's what Gary had to say about 2016's event!
Keeping up to date with accessible events post Disabled Access Day
events, BSL, audio description, London, South Yorkshire, Nottinghamshire, Edinburgh, England, Scotland
Disabled Access Day for 2016 is over but there are lots of accessible events and activities year round. Found out about some great events happening across the UK over the coming months!
Reviews galore!
Euan's Guide, London, Tyne and Wear, Norfolk, South Yorkshire, England
We've been encouraging people to leave reviews on Euan's Guide of their experiences on Disabled Access Day. Take a look at some of our favourites.
Celebrating access on Disabled Access Day
George Fielding, who is Chair of the Kidz Board at Whizz Kidz, has written a guest post about his experiences on Disabled Access Day.
Visit the Theatre on Disabled Access Day
2016, stage & screen, Edinburgh, London, Cardiff, South Glamorgan, South Yorkshire, Derbyshire, Norfolk, Buckinghamshire, North Yorkshire, England, Scotland, Wales
Disabled Access Day is the perfect opportunity to try out your local theatre. Take a look at what's going on at theatres across the country.
The National Theatre confirm their Access Day plans
BSL, audio description, 2016, stage & screen, London, England
The National Theatre have confirmed their Disabled Access Day programme of events. Take a look at what they're up to.
A Bookworm's Guide to Disabled Access Day
BSL, 2016, wheelchair users, Edinburgh, London, Tyne and Wear, North Yorkshire, Buckinghamshire, England, Scotland
It's World Book Day today - take a look at some of the great book themed activities going on across the UK on Access Day.
Advance UK tell us their Disabled Access Day plans
2016, guest blog, charities, museums & galleries, London, England
Find out what Advance UK will be doing on 12th March to mark Disabled Access Day.


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/ Category / Smart Cities
Astronaut's Future City Message
October 19, 2020 - in Events, Smart Cities, Videos
Astronaut Ricky Arnold has a message for those entering the Future City contest. Sign up for the Future City Competition at futurecity.org/register
Smart Cities: Putting a 'Smart Communities' Strategy to Work
January 3, 2018 - in Articles, Column, Smart Cities
The term "smart cities" has been around for a while now. You can't go to an event or pick up a magazine without some discussion on smart cities,…
Video: Water Street Tampa Illustration
August 30, 2017 - in Application, Design/Engineering, Land Development, Lifecycle, Smart Cities, Videos
A newly released animatic video shows how Water Street Tampa will come to life over the next decade - from the new infrastructure, to 13 acres of newly…
Ayyeka & SIGFOX: First U.S. Channel Partnership to Enable Smart Cities Across The U.S.
August 10, 2016 - in Smart Cities
San Francisco, CA: Ayyeka, a technology company developing Industrial Internet of Things (IIoT) solutions, today announced a first-of-its-kind channel partnership in the United States with SIGFOX, the world's leading provider of dedicated communications…
World Experts Address Key Pain Points that Hinder Smart City Development
July 6, 2016 - in Announcement, Corporate, Smart Cities
Today, most cities would like to become smart but many city planners don't really know how to achieve this objective. Cities battle with pain points that touch the sustainable supply of energy and water, or how to eliminate gridlock and related pollution…
New CloudCities Release Faster and Easier to Use
June 29, 2016 - in Design/Engineering, Modeling, Products, Smart Cities
San Francisco, Calif., June 28, 2016—SmarterBetterCities announces the latest release of CloudCities, the premier platform for hosting, sharing and visualizing your smart 3D city models. It fully supports Esri CityEngine, Google Earth, and SketchUp, enabling…
The Age of Urban Tech
June 28, 2016 - in Corporate, Design/Engineering, Smart Cities
Cities all across the world are gearing up for the future. They know that big changes are coming and they are doing their best to transform challenges into opportunities. That is why innovation, technology and city life were at the center of discussions during…
U.S. Department of Transportation Announces Columbus as Winner of Unprecedented $40 Million Smart City Challenge
June 23, 2016 - in Design/Engineering, Financial, Smart Cities, Transportation
COLUMBUS, OH – U.S. Transportation Secretary Anthony Foxx announced today that Columbus, OH has been selected as the winner of the U.S. Department of Transportation's (U.S. DOT)'s Smart City Challenge. As winner of the Challenge, Columbus will receive…
U.S. Department of Transportation Partners with Continental Automotive for Smart City Challenge
June 23, 2016 - in Corporate, Smart Cities, Transportation
WASHINGTON – U.S. Transportation Secretary Anthony Foxx today announced that Continental Automotive has become a partner in the U.S. Department of Transportation (U.S. DOT)'s Smart City Challenge. The Smart City Challenge is a competition which will create…
Smart Technologies and Infrastructure for Energy, Water, Mobility, Buildings, and Government: Global Market Analysis and Forecasts
June 23, 2016 - in Corporate, Smart Cities
The momentum behind the development of smart cities continues unabated. City leaders around the world are committing to smart city objectives as they attempt to shape the development of their cities to meet social, economic, and environmental challenges. National…
Nathan Ford Joins HNTB as Public Involvement Director in Michigan
DETROIT – Nathan Ford joined HNTB Corporation as public involvement director, based in the firm's…
Structural Solutions: Add True Value to Command Fees You Deserve
Many years ago, I left the security of the engineering firm I worked for right out of school and…
Safer and Easier LNG Transfer Solution from MannTek
Mariestad, Sweden: A liquefied natural gas small-scale transfer system that promises to revolutionise…
deCarta and GreenOwl Mobile bring Audio Traffic Alerts to the Connected Driver
deCarta, Inc., the leading independent LBS technology company announced today that they have partnered…


text:
El Campeonato de Argentina de Fórmula 4 fue una competición de automovilismo organizada por la Federación Internacional del Automóvil (FIA). Tras su temporada inaugural en 2021, el campeonato no ha vuelvo a disputarse.

Historia

Antecedentes
Gerhard Berger y la comisión de monoplazas de la FIA lanzaron la Fórmula 4 en marzo de 2013. El objetivo es hacer que la escalera a la Fórmula 1 sea más sencilla. Además de los reglamentos deportivos y técnicos, los costes también se regulan. Un monoplaza para competir en esta categoría no puede exceder los 30 000€ en compra y una sola temporada en Fórmula 4 no podrá superar los 100 000€.

Tiene por objetivo de formar pilotos que deseen alcanzar la F1, entre otras categorías internacionales, Javier Bernardini como experimentado piloto y actual Asesor y director deportivo de la categoría, junto a Pablo Collazo, empresario y piloto, son los principales responsables.

Su formación, se encuentra destinada para los pilotos que se han preparado desde sus comienzos en el karting, pasando por la Fórmula 4, Fórmula 3, Fórmula 2 y finalmente la Fórmula 1.

Formato

El reglamento de la Fórmula 4, elaborado por la Federación Internacional del Automóvil, está dividido en dos partes principales. Una de ellas (Technical Regulations) se refiere a las condiciones técnicas de los monoplazas y la otra (Sporting Regulations) se centra en las condiciones en que se deben desarrollar los eventos, así como las reglas de puntuación y de penalización. Además, en todo evento de Fórmula 4 deben contemplarse las prescripciones generales de la FIA.

La clasificación
Tradicionalmente, la clasificación para la parrilla de salida se hace en una única sesión de 25 minutos de duración, en la que los coches tienen un número de vueltas máximo estipulado para conseguir el mejor tiempo. Durante esta sesión, todos los pilotos compiten en simultáneo.

Carreras y puntuación
La puntuación actual se distribuye de la siguiente manera: el ganador de la prueba conseguirá 25 puntos; el segundo clasificado, 18; el tercero, 15; el cuarto, 12; el quinto, 10; el sexto, 8; el séptimo, 6; el octavo, 4; el noveno, 2; y el décimo, 1 punto. Durante décadas, la puntuación ha determinado el orden en la clasificación del campeonato de pilotos, pues quien tuviera más puntos sería el campeón, y en caso de empate decidirían las mejores posiciones en carrera.

Premios
Además de recibir los 12 puntos para la Superlicencia FIA, el campeón obtenía la oportunidad de participar en una prueba en un Fórmula 3.

Monoplazas

Chasis

El chasis elegido fue el francés Mygale F4 monocasco compuesto de fibra de carbono homologado por la FIA. Este tipo de autos se destaca por su potencia y su peso que lo hace altamente maniobrable en alta velocidad.

Motor
La Federación Internacional del Automóvil homologó tres modelos de autos, seis marcas de motores y cada país elige el chasis de su vehículo y el impulsor que crea conveniente. En Argentina, los F4 contaron bloques 2.0 Geely AL-1C 4G20 de cuatro cilindros en línea con 16 válvulas e inyección directa de combustible, con una potencia máxima de 160 CV. Tenía una caja de velocidades Sadev secuencial de seis marchas con sistema neumático de paddle-shift.

Campeones

Pilotos

Circuitos

Referencias

Enlaces externos

 Web Oficial
 Facebook

Fórmula 4
Competiciones de automovilismo de Argentina
Campeonatos de motor desaparecidos


Through their experiences as CAP cadets, young people develop into responsible citizens and become tomorrow's aerospace leaders.
CAP is the volunteer, nonprofit auxiliary of the U.S. Air Force. Its three missions are to develop its cadets, educate Americans on the importance of aviation and space, and perform life-saving, humanitarian missions.


Are permitted types of hats, caps etc that we could find at the time.
It is impossible to draw up an exhaustive typology.
Wearing a piece of white/cream coloured linen is also allowed. Prefer the model 3 parts rather than in 2 parts.
Nobles and knights can be bareheaded.


text:
ASCD welcomes national education leaders to 2022-2023 Board of Directors
As it enters its 79th year of serving educators and education leaders both nationally and internationally, ASCD is also welcoming two new members to its Board of Directors: Dr. Sarena Shivers and Dr. Kim Wallace.
ARLINGTON, VA—As it enters its 79th year of serving educators and education leaders both nationally and internationally, ASCD is also welcoming two new members to its Board of Directors: Dr. Sarena Shivers and Dr. Kim Wallace.
"Dr. Shivers and Dr. Wallace both bring decades of experience with the unique needs of educators in public school systems to our Board of Directors; they are exceptionally well-positioned to represent the perspectives and experiences of the educators we serve," said ASCD Interim CEO and Executive Director Sandy Husk.
Shivers is the Deputy Executive Director of the Michigan Association of Superintendents and Administrators and has served as a public school educator for 30 years. Her professional accomplishments include the creation of transformational initiatives focused on adolescent literacy, writing, mathematics, STEM, school leadership, instructional technology, and secondary learning and instruction. She holds a bachelor's degree in elementary education from Morgan State University, master's degree in administration and supervision from Ball State University, and doctorate in educational leadership and policy analysis from Indiana University.
Wallace works at the University of California, Berkeley School of Education overseeing a statewide grant that provides coaching and professional learning to K–12 administrators. She also runs her own educational consultancy company, Process Makes Perfect, specializing in real-world solutions for educators. She consults, writes, and presents nationally and internationally on the topics of authentic leadership, systems thinking, and emerging trends in education. She holds a bachelor's degree in history from the University of California, Santa Barbara; a master's degree in education and teaching credentials from the University of California, Los Angeles; and a doctoral degree in educational leadership from the University of California, Davis.
ASCD Board President Avis Williams said: "I am so pleased to welcome Dr. Shivers and Dr. Wallace to the Board, and I look forward to working with them to ensure that every educator has the supports and resources they need for their students to flourish."
ASCD is a passionate community of life-changing educators. Our community is empowered to be equity and instructional warriors who transform vision into practice. For 80 years, we have worked side by side with educators from every level in all 50 states and more than 200 countries to help them find their people and amplify their voice to reach many. Our professional learning services let educators chart their own learning journey, as educators, as leaders, so they and their students can flourish. Learn more at www.ascd.org.
These links in this publication are time-sensitive. These links may move or expire as the news changes. If you notice a deactivated or changed link, please email us. Some sources may require registration.
ASCD is dedicated to professional growth and well-being.
Let's put your vision into action.
Discover our Professional Learning Services


UPDATE: The ACLU of Maryland is proud to announce that Mrs. Brewer will get to see her great grandson and grandson for the holidays. State's Attorney Angela Alsobrooks has filed a motion to temporarily suspend the order that kept Mrs. Brewer from coming home to see her. Ms.Up church will be reunited with her family members too.
Check back for updates after the holidays. The orders need to be overturned once and for all.
ACLU of Maryland called on Prince George's County State's Attorney to undo the damage done to two families earlier when prosecutors wrongfully forced two women to sign "nuisance abatement" orders banishing their family members from their own homes and the neighborhood in which they had grown up.
The ACLU urged the prosecutor to dissolve the orders and call off longstanding harassment by police claiming to enforce the orders so the families can be reunited without fear that they will be arrested or that they could lose the homes they own.
Maryland's nuisance abatement statute was intended to help communities work with law enforcement to reclaim properties that are used solely or primarily for drug activity. But, in this case, prosecutors, in conjunction with police, went far beyond their authority, needlessly tearing apart two different families by coercing homeowners into submitting to orders that would never have stood up in court - one, on the basis of less than two grams of marijuana, and the other on the basis of a used pipe - the only drug paraphernalia that police turned up after aggressive raids of the two homes.
Using the statute and the full authority of their police powers, prosecutors, working with the Hyattsville and the Prince George's County Police Departments, took the two unrepresented women and their families behind closed doors and threatened the women that they would lose their homes if they didn't ban their family members from the homes and the whole neighborhood - even for visits. In one case this caused an ill, elderly woman to lose the help and support of her caregiver grandson and great-grandson, and in the other case it not only has kept family members from seeing and supporting each other, but has also actually caused a family member to lose his job and incur significant debt as a result of contracts he is unable to fulfill.
Cleo Brewer, who is in her 80s and very ill with cancer, not only was separated from her grandson and great-grandson, both of whom she raised from childhood, but also lost their help as daily caregivers who helped lift her up and down the stairs, fed her, went shopping for her, and took her to doctor appointments.
Across the street, Dollie Upchurch's brother had been overseeing significant renovations to her home, where he had grown up, and had decades-long landscaping contracts with neighbors in the area. The order banishing him from their home rendered him homeless. He lost his job and could not fulfill his longstanding contracts, resulting in significant debt. In fact, prosecutors refused his request for an exception that would allow him to take care of these contracts rather than incur additional debts.
Both women have experienced a longstanding pattern of harassment that has cut them off from their families, friends and neighbors.


You have got limitless redraws and limitless revisions which suggests if the first set of designs don't be just right for you we will have a conversion to seek out out what's not working after which the designers will put together some extra. Craftedlogo empowers folks with inventive ideas to succeed.
It's essential hire a high quality and creative designer who can provide you with outcomes beyond your expectations and right here at Crafted Logo, we have now always accomplished this. Logopond is chock full of great logo designs that utilize adverse house in a cool manner.
A nicely-designed logo ought to adapt to quite a lot of applications whether or not on a business card, a billboard or on Facebook. It is for that reason why companies pay a major quantity to designers who can create distinctive and exceptionally professional logos for them.


Information, snippets and opinions on web programming – probably focused mostly on PHP, HTML, CSS, etc…. but I'm sure some things will be useful for other languages!
Not sure if anyone else has been battling with this issue? Let me explain – I built a set of templates that were tested in the usual suspect (IE6-9, FF3+, Safari 5+ Chrome 10+ Opera 10+) and all worked perfect! (albeit I had to use a dreaded IE6 CSS and conditional statement and the dreaded png fix!).
While I was at it I thought I'd just run a quick test on the Ipad/Iphone just to make sure – I honestly thought it would all be fine as I'd tested thoroughly on Safari for Windows and Chrome. But to my dismay the "top" div I was using to hold a curved background image in and another I was using to hold a logo had strangely suffered from what looked like a 1px white border on the bottom of each div – obviously ruining my design!
In a nutshell you need to tell the Ipad/Iphone not to play with the zoom scale at all – and viola it fixes the issue!


text:
Q: Python 3.4 Issue with writing to a file with time.sleep() I am using Python 3.4. I'm trying to figure out why the writerow() is not working if I put a sleep timer at the end it does not write the data to the Test.dat file. The code looks like this
import csv, time

fileName = "Test.dat"
freq = 5;

with open(fileName, 'a') as fp:
    a = csv.writer(fp, delimiter=',')
    for i in range(1, 10):
        data = [2014, 5, 3, 5, 26, 53, 'Price', '100.00']
        a.writerow(data)
        time.sleep(freq)

But then if I remove the timer it writes the data in the Test.dat file
import csv, time

fileName = "Test.dat"
freq = 5;

with open(fileName, 'a') as fp:
    a = csv.writer(fp, delimiter=',')
    for i in range(1, 10):
        data = [2014, 5, 3, 5, 26, 53, 'Price', '100.00']
        a.writerow(data)

Ans:
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00
2014,5,3,5,26,53,Price,100.00

A: You are waiting 5 sec and the program take a long time to end write the file:
Wait one second:
freq = 1

A: You can run the sentence just like fp.flush().
The function of sleep will run the same thread with your other functions, thus the file.write() function have no chance to push its cache into your file which is in your os.
Because of it, you should call flush() by yourself.


The exhibition 'Prints in Paris 1900: From Elite to the Street' takes you to the cosmopolitan French capital. Over 250 prints from our leading fin de siècle prints collection are being shown in their original context. Due to their fragility, these artworks are rarely displayed. On view until 11 June 2017.
Modern artists decorated the entire French capital with their prints in the period 1890–1905. World-famous posters like Le Chat Noir and Le Moulin Rouge were displayed along the boulevards and in popular cafés.
Some artists also created exclusive prints for the elite which could only be seen in private collections, fashionable theatres and exclusive galleries.
Prints in Paris 1900 brings both of these worlds back to life, while presenting a richly nuanced picture of the exciting cultural life of Paris.
Step into a richly decorated interior and view the prints like a connoisseur of the social elite. Experience the vibrant fin de siècle street life, in which popular posters, sheet music and magazine illustrations with their bright colours, large letters and powerful silhouettes, grab your attention.
The Van Gogh Museum manages one of the finest collections of fin-de-siècle prints in the world. This collection of over 1,700 French prints, posters and artist's books is normally kept in storage because of their sensitivity to light.
How do the Van Gogh Museum's 19th-century French prints inspire today's up-and-coming artists? Recourse 1900 introduces contemporary prints by students studying at Amsterdam's renowned Gerrit Rietveld Academie.
Would you like to discover the worlds behind the prints? The old photographs and music in our multimedia tour let you see the exhibition with different eyes. Available in eleven languages. You can book the multimedia guide at the same time as your online ticket.
Get the most out of the exhibition with a private tour lasting around 50 minutes (max. 15 persons). Your guide will tell you all about the prints and the artists who made them.
The exhibition is accompanied by a richly illustrated, large-format catalogue. The exhibition catalogue is written by curator Fleur Roos Rosa de Carvalho and based on years of intensive research into the worlds of printmaking during the French fin de siècle. In Dutch, English, French and German.
The Van Gogh Museum's focus in 2017 will be on France and, in particular, Paris. The museum will host a range of activities and events throughout this theme year including exhibitions, lectures and workshops.


Ex-chef of Pierneef opens Foliage in Franschhoek: Situated a block before the famous Huguenot Monument. Foraged edible plants and mushrooms alongside free-range game meat are an essential part of the colorful, seasonal menu.
Wine, World-class golfing and top-rated Restaurants at the Steenberg estate in the wine country of Tokai, just outside Cape Town.
A classic Cape Dutch farm with a manor house dating back to 1777. Organic country-style cooking and a perfect option for modern vegetarian cuisine in the Cape Winelands.
The eponymous wine estate by South African golfer Ernie Els produces award-winning reds with winemaker Louis Strydom. Wine tasting of bordeaux-style blends in beautiful surrounds overlooking the Stellenbosch valley.
Documenting 100 years of motoring history with beautiful collection of classic luxury cars at the Franschhoek Motor Museum at the L'Ormarins estate in Franschhoek, Cape Winelands.
The iconic Huguenot monument and Memorial Museum in Franschhoek tells the history of the French Protestants into the Cape Colony. An icon on the main street of Franschhoek and the site of the Magic of Bubble Cap Classique and Champagne festival in December.
Von Geusau chocolates and wine tasting at Kevin Arnold's Waterford Estate in the Cape winelands.
Located on the impressive terrace overlooking the valley at Delaire Graff estate, Indochine is a great stop for lunch for tapas and Asian influenced cuisine.
The auction features South Africa's finest wine estates offering highly-exclusive, limited release and special edition vintages with funds raised helping support child literacy programs in the Western Cape.
The Franschhoek Cap Classique and Champagne Festival is a highlight of the Cape WIne & Gourmet industry's social calendar. End the year on a sparkling note in the gardens of the Huguenot monument.
A great stop for quick bites when wine tasting at the Steenberg winery, enjoy the countryside's finest seasonal ingredients and a taste of classic South African cuisine with a bistro flair.
Celebrated local restaurant by Chef Margot Janse and winner of the 2014 Eat Out Mercedes-Benz Restaurant Award. Housed within the Le Quartier Français Inn and open for dinner with an extensive preset tasting menu.
Farm to table cooking with authentic Cape Provençal recipes in an elegant setting at the La Motte wine estate. One of the wineland's best restaurants and a terrific option for vegetarians.


How in the world did you find me? I've been looking for you for several years now! Your email address went dead and I couldn't find you anywhere! Somehow you found the Shilohman. That's my clowning around blog. I just started a serious blog that I would invite you to visit too. That's the Shiloh Guy. We have to get in touch. Thanks for the awesome video. I'll show it to Mia too. I'm still using the same email if you have it!
I am one of the clowns, but I am also a neighbor and definitely on the same page. His double miracle in your family's life is undoubtedly passed off by some as advances in modern medicine or just plain good luck. We know better.


text:
<?php

namespace NewModule\Controller;

use Zend\Mvc\Controller\AbstractActionController;
use Zend\View\Model\ViewModel;

class HelloController extends AbstractActionController
{
    public function indexAction()
    {
        return array();
    }

    public function worldAction()
    {
        $message = $this->params()->fromQuery('message', 'foo');
        return new ViewModel(array('message' => $message));
    }
}


The Skinner has a 4 1/4 inch blade. It is a straight point blade, .15 inch thick with a flat grind. It is designed with a skeletonized tang for strength weight reduction and workable balance. The Skinner is offered in CPM D2 Stainless Steel with a G10 Black/Coyote Layered Handle. This gives a nice traditional wood look with the strength and durability of G10. We provided jimping along the spine, finger grooves for better control, a nice choil and lanyard hole for security. We offer this knife with a Grizzly Brown Leather Sheath.


text:
Iran accepts Brazil mediation to revive atom deal
Tehran–Iranian President Mahmoud Ahmadinejad has agreed "in principle" to Brazilian mediation to revive a UN-brokered nuclear fuel swap deal with world powers, the semi-official Fars news agency said on Wednesday.
The powers see the deal as a way to remove much of Iran's low-enriched uranium stockpile to minimize the risk of this being used for atomic bombs, while Iran would get specially processed fuel to keep its nuclear medicine program running.
But the proposal broke down over Iran's insistence on doing the swap only on its territory, rather than shipping its LEU abroad in advance, and in smaller, phased amounts, meaning no meaningful cut in a stockpile which grows day by day.
"In a telephone conversation with his Venezuelan counterpart, Ahmadinejad agreed in principle to Brazil's mediation over the nuclear fuel deal," Fars said, quoting a statement issued by Ahmadinejad's office.
The pact conceived in talks conducted by the UN nuclear watchdog last October required Iran to ship 1,200 kg of its LEU, enough for one atom bomb if enriched to high grade, to Russia and France for conversion into fuel for the Tehran Research Reactor, which makes isotopes for cancer treatment.
The three powers have ruled out rewriting the deal's conditions as the Islamic Republic demands.
The United States is lobbying UN Security Council members, to back a fourth round of international sanctions on Iran in the coming weeks, to press it into curbing uranium enrichment.
Iran says its nuclear energy program is designed to generate electricity only but its failure to declare sensitive atomic activity to the UN watchdog and continued restrictions on UN inspections have undermined confidence abroad.
Some nonpermanent UN Security Council members such as Brazil and Turkey have been trying to revive the fuel deal with Iran in an attempt to stave off further sanctions against Tehran.
Brazil says it favors reviving a mooted compromise in which Iran could export its uranium to another country in return for nuclear fuel Iran says it needs to keep the Tehran reactor running.
It was not clear whether Ahmadinejad had agreed for the fuel swap to take place in a third country. If so, it will be a major shift in Iran's stance against the idea.
"Ahmadinejad also said technical issues (over the deal) should be discussed in Tehran," Fars reported.
Gala Riani, analyst for IHS Global Insight Middle East, said Iran did not want to be seen as having closed the door to negotiations on the nuclear fuel swap.
But she said it remained to be seen if Tehran's announcement on Brazil's mediation was a real attempt to resolve the issue.
"Unless Iran proposes some significant concessions the likelihood (of a deal) is low," Riani told Reuters.
Iran started enrichment to 20 percent fissile purity in February, up from 5 percent, to create fuel for the research reactor itself, bring Iran closer to levels needed for producing weapons-grade material — uranium refined to 90 percent purity.
In a speech to a Nuclear Non-proliferation Treaty (NPT) review conference at the United Nations, US Secretary of State Hillary Clinton said on Monday that Iran's nuclear ambitions put the world at risk and called on nations to rally around US efforts to finally hold the Islamic Republic to account.
The five permanent members of the Council — the United States, Britain, France, Russia and China — along with Germany are in talks over a broader sanctions resolution against Iran.
Russia and China, veto-wielding members of the Security Council, have said they are willing to give Turkey and Brazil more time to resuscitate the nuclear fuel deal.
Chinese President Hu Jintao will likely discuss Iran's nuclear issue with Russian officials during his visit to Moscow on May 8, a Chinese official said on Wednesday.
"On the Iran nuclear issue, it should be said, the positions of China and Russia are close," Chinese Assistant Foreign Minister Cheng Guoping told a news conference in Beijing.
Analyst Nicole Stracke at the Gulf Research Center in Dubai said Iran was trying to "send positive signals that it is ready to make concessions", aimed at splitting the Security Council and delaying Chinese and Russian agreement on new sanctions.
"This strategy allows Iran to buy time, which is an essential factor in the technical development of the Iranian nuclear program," she told Reuters in an e-mail.
2 Egyptian women to stand new trial over TikTok dance videos
EgyptAir requires US and UK travelers to present negative COVID-19 test before boarding
World Health Organization calls on Egypt to review data on coronavirus infections and deaths
Egypt signs MOU with Siemens for US$23 billion high-speed train line: cabinet
Egypt to construct the Cairo Eye, Africa's largest Ferris wheel
Sharm el-Sheikh International Airport receives Health Accreditation Seal for Safe Travel
Egypt's Minister of Health refutes claims that Egypt has highest coronavirus death rate
Strategic cooperation agreement between Russia and Egypt comes into force
Egypt's Health Minister announces date for vaccination rollout as February 1
Health Minister signs protocol to vaccinate 2 million Egyptians for free
Ethiopia begins constructing new dam in northern Amhara region
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Vertical reduction, 444 grams on right, 342 grams on left.
Vertical reduction. 520 grams on right, 480 grams on left.
Vertical breast reduction. 341 grams on right, 209 grams on left.
Bilateral breast reduction, vertical technique, 440 left, 435 grams right.
Bilateral breast reduction, Inverted T technique, 498 grams left, 418 grams right.
Bilateral breast reduction, vertical technique, 180 grams left, 140 grams right.
Bilateral breast reduction. 406 grams on left. 300 grams on right.
Vertical, (short incision), reduction. 562 grams from left and 400 grams from right. Three month photo, ( scars still red).
Superior medial pedicle with inverted T incision. 400 grams on right, 385 grams on left.