text:
Genome-wide co-localization of Polycomb orthologs and their effects on gene expression in human fibroblasts
- Helen Pemberton†1, 4,
- Emma Anderton†1, 5,
- Harshil Patel†2,
- Sharon Brookes1,
- Hollie Chandler1,
- Richard Palermo1,
- Julie Stock1, 5,
- Marc Rodriguez-Niedenführ1, 6,
- Tomas Racek1, 7,
- Lucas de Breed1, 8,
- Aengus Stewart2,
- Nik Matthews3 and
- Gordon Peters1Email author
DOI: 10.1186/gb-2014-15-2-r23
© Pemberton et al.; licensee BioMed Central Ltd. 2014
Received: 29 October 2013
Accepted: 3 February 2014
Published: 3 February 2014
Polycomb group proteins form multicomponent complexes that are important for establishing lineage-specific patterns of gene expression. Mammalian cells encode multiple permutations of the prototypic Polycomb repressive complex 1 (PRC1) with little evidence for functional specialization. An aim of this study is to determine whether the multiple orthologs that are co-expressed in human fibroblasts act on different target genes and whether their genomic location changes during cellular senescence.
Deep sequencing of chromatin immunoprecipitated with antibodies against CBX6, CBX7, CBX8, RING1 and RING2 reveals that the orthologs co-localize at multiple sites. PCR-based validation at representative loci suggests that a further six PRC1 proteins have similar binding patterns. Importantly, sequential chromatin immunoprecipitation with antibodies against different orthologs implies that multiple variants of PRC1 associate with the same DNA. At many loci, the binding profiles have a distinctive architecture that is preserved in two different types of fibroblast. Conversely, there are several hundred loci at which PRC1 binding is cell type-specific and, contrary to expectations, the presence of PRC1 does not necessarily equate with transcriptional silencing. Interestingly, the PRC1 binding profiles are preserved in senescent cells despite changes in gene expression.
The multiple permutations of PRC1 in human fibroblasts congregate at common rather than specific sites in the genome and with overlapping but distinctive binding profiles in different fibroblasts. The data imply that the effects of PRC1 complexes on gene expression are more subtle than simply repressing the loci at which they bind.
Polycomb-group (PcG) proteins were originally identified by their developmental effects in Drosophila but their mammalian counterparts are implicated in a wide variety of physiological processes, including pluripotency, imprinting, differentiation and senescence [1–3]. Senescence is a state of permanent cell cycle arrest that occurs in response to various forms of cellular stress and acts as a front-line defense against potentially oncogenic lesions [4, 5]. Genetic ablation of a number of PcG genes results in premature senescence, in part because of de-repression of the CDKN2A tumor suppressor [6, 7].
PcG proteins operate within multi-component complexes, the best characterized of which are termed Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) [1–3]. PRC2 is responsible for tri-methylating histone H3 on lysine 27 (H3K27me3), generally considered to be a mark of transcriptional repression, and apart from duplication of the Ezh subunit, the core components of the complex are conserved between flies and mammals [8].
In contrast, the PRC1 components have undergone considerable expansion during evolution. The prototypic PRC1 complex in Drosophila comprises equimolar amounts of Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph) and Sex combs extra (Sce) [9, 10]. However, as human cells encode five Pc, six Psc, three Ph and two Sce orthologs, there are multiple variants of PRC1 [2, 8, 11]. Biochemical analyses indicate that a typical PRC1 complex contains a single representative from each gene family [7, 12–15] and, although it has not been formally shown that all of the orthologs participate in functional PRC1-type complexes, there could in principle be up to 180 different permutations. The situation is further complicated by the ability of the Psc and Sce subunits to form functional complexes that contain RYBP or YAF2 rather than the Pc and Ph orthologs [15–17].
The Psc and Sce subunits combine to form an E3 ubiquitin ligase that mono-ubiquitinates histone H2A on lysine 119 (H2AK119), a modification that is also associated with transcriptional repression [1–3]. However, it has not been conclusively established whether the H2AK119 modification is essential for blocking transcription and whether it is carried out by the prototypic PRC1 or alternative complexes [15–20].
The reason for the expansion of PRC1 families is unclear as there is currently little evidence for functional diversification [15, 21–23]. It has been generally assumed that particular family members operate in different cell lineages or that the various permutations of PRC1 regulate specific sets of target genes [15, 24]. For example, CBX7 is the predominant Pc ortholog in embryonic stem (ES) cells but its expression declines during differentiation and it is replaced by CBX2, CBX4 and CBX8 [24, 25]. If these proteins bind selectively, as suggested, then the number of PcG target genes would potentially increase in cell types that express multiple variants of the canonical PRC1 complex.
Here we investigate the genome-wide distribution of the PRC1 components expressed in two strains of normal human fibroblasts (HFs), a somatic cell type required for the physical integrity of multiple tissues and the classical model for the study of cellular senescence. Contrary to expectations, we find that three Pc orthologs (CBX6, 7 and 8) and both Sce proteins (RING1 and RING2) have very similar binding patterns throughout the genome with little evidence for target gene specificity. Moreover, by assembling a panel of antibodies that support chromatin immunoprecipitation (ChIP) of the endogenous proteins, we find that 11 of the PRC1 core components expressed in HFs display virtually identical binding patterns at representative loci. Importantly, sequential ChIP with antibodies against different members of the Pc, Ph and Sce families implies that multiple variants of PRC1 associate simultaneously with the same chromatin. At many loci, the binding patterns have an inherent architecture that is faithfully conserved between the two strains of HF but at an equivalent number of loci the binding is strain specific. Surprisingly, there is no strict correlation between the presence and position of the PRC1 peaks and RNA expression from adjacent gene(s). Moreover, the genomic location of the Pc orthologs remains unchanged in senescent HFs. The findings are consistent with the idea that mammalian PRC1 proteins congregate as complexes of complexes and that their control over gene expression is more subtle than simply blocking transcription of the genes to which they bind.
Expression of PRC1 genes in human fibroblasts
Multiple PRC1 complexes bind simultaneously at the CDKN2Alocus
The RNA expression data implied that HFs have the potential to express many different permutations of PRC1 and are therefore an ideal system in which to investigate target specificity. Using the CDKN2A locus as a test bed for antibody evaluation, we assembled a panel of custom-made and commercially available reagents that support ChIP of endogenous PRC1 components in primary HFs. A number of PRC1 components have been previously located at CDKN2A using a validated set of PCR primers (Figure 1B and [7, 12, 27]) but our survey has added substantially to the list of proteins involved. We found that four Pc proteins (CBX4, 6, 7 and 8), two Psc proteins (BMI1 and MEL18), all three Ph orthologs (HPH1, 2 and 3) and both Sce proteins (RING1 and 2) were not only enriched at the CDKN2A locus but had virtually identical binding profiles (Figure 1C). Importantly, we confirmed that the antibodies did not cross-react with members of the same family, even when they were over-expressed (Additional file 1: Figure S1).
Genome-wide profiling of PRC1 binding sites
To determine whether PRC1 proteins are co-localized at other target genes, we conducted genome-wide ChIP-sequencing (ChIP-seq) with antibodies against three of the Pc orthologs and both Sce orthologs for the BF and Hs68 fibroblasts. We reasoned that by comparing the binding profiles of CBX6, CBX7 and CBX8, we could ascertain whether they regulate distinct or overlapping sets of target genes in HFs. Conversely, as every catalytically active PRC1 complex should contain either RING1 or RING2, the combined dataset should provide an impression of all PRC1 binding sites in the genome, which would complement the CBX profiles. For reference purposes, we also generated ChIP-seq profiles for H3K27me3 and H3K4me3 for the same cells. CDKN2A is shown as an example in Figure 1D. Sequencing was performed on the Illumina GAIIx platform and typically generated between 12 and 60 million 36-bp reads that could be mapped to the hg19 release of the human genome. The raw and processed data have been deposited under GEO accession number [GEO:GSE40740] [28].
Validation of PRC1 complex binding at representative loci
To support our interpretation of the ChIP-seq data, we selected representative examples of target loci and performed conventional ChIP followed by quantitative PCR analyses with a series of primers that not only crossed each peak but allowed discrimination between regions of high and low/no enrichment (Additional file 2: Figure S2). The PCR-based assays confirmed the results of the ChIP-seq but additionally showed that, where tested, all of the PRC1 proteins for which we have suitable antibodies had virtually identical binding profiles. These findings are hard to reconcile with the idea that different permutations of PRC1 bind selectivity at different target genes.
Multiple variants of PRC1 associate with the same DNA
Location of PRC1 binding sites relative to potential target genes
Irrespective of the number of PRC1 proteins detected at any one site, an obvious point of interest was the relation between the binding profiles and potential target genes. We compiled a list of candidate loci at which ChIP-seq detected at least one CBX, one RING protein and H3K27me3, using the position of the closest transcription start site (TSS) as the initial criterion. However, a striking feature of the data was that many of the ChIP-seq peaks had a complicated architecture that would be inconsistent with a normal distribution around a single binding site. It was also common to find multiple discrete peaks at the same locus and there was no simple relation between the number of peaks identified by MACS and the number of potential target genes. The bioinformatically compiled lists were therefore edited manually to try to resolve ambiguities (Additional file 3: Table S1). For example, where peaks overlapped adjacent coding and non-coding loci, preference was given to the annotated coding gene.
The third group of potential targets, representing about 18% of the total, had PRC1 peaks associated with both ends of the transcription unit. However, within this category, there were a number of distinct scenarios (Figure 4). Some loci were flanked by relatively discrete peaks that did not spread across the body of the gene (for example, UNCX in Figure 2C), others had internal peaks at some distance from the TSS or TES, but a more common pattern was where peaks were located upstream, downstream and within the transcription unit (for example, ZIC1 and ZIC4 in Figure 2D). Where such complicated profiles occurred at closely linked genes, it was not possible to assign the peaks to specific loci.
In conclusion, our data suggest that there is an inherent complexity in the shape of the PRC1 peaks and their location relative to potential target genes. These intricacies in the ChIP-seq profiles have been largely ignored or masked by bioinformatics-based meta-analyses.
Comparison of the PRC1 binding profiles in different fibroblasts
Despite some residual ambiguities, the peak classification scheme yielded very similar conclusions regarding the numbers of putative target genes in the two strains of HF and the proportions in each category (Figure 4A). A total of 986 loci were scored as candidate PRC1 targets in BF cells compared with 1,099 in Hs68 cells (Additional file 3: Table S1). Importantly, although there were 685 loci in common between the gene lists, 301 were unique to BF cells and 414 were unique to Hs68 cells (Figure 4B).
At the shared loci, the binding patterns were very similar in the two HF strains. This was particularly striking at loci where the peaks had a complicated architecture. Indeed, many of the peaks appeared to resolve into evenly spaced arrays, suggesting some degree of periodicity (for example, TLX2 and LBX1 in Figure 2F, G). As the same periodicity was observed with antibodies against all five PRC1 proteins, with independent preparations of chromatin, and in both strains of HF, it seems unlikely to be a technical artefact and warrants further investigation.
Relating PRC1 occupancy to gene expression
The genomic landscape of Polycomb binding is maintained at senescence
It has been widely assumed that the different variants of PRC1 encoded by mammalian cells are likely to repress different sets of target genes or to substitute for one another in different contexts. Here we suggest a different scenario based on evidence that PRC1 complexes act collectively rather than individually and can be associated with transcriptionally active genes. It is not yet known how many of the potential permutations of the canonical PRC1 complex can be formed in mammalian cells as the existing biochemical data do not provide a strong case for preferential associations between particular subunits. Allowing for free assortment, HFs have the potential to express multiple variants of PRC1 as judged by detection of transcripts for 15 of the 16 core components. We might therefore have expected to see CBX6, 7 and 8 peaks in discrete locations in the ChIP-seq data, in line with recent suggestions [15, 24], but instead found that they are largely co-localized. Although there were sites where subsets of the CBX proteins were detected, the signals were generally weaker compared to the loci at which all three CBX proteins were detectable. Likewise, we might have expected to see selective binding of RING1 and RING2, particularly as they can participate in alternative complexes with RYBP and YAF2 but, as others have shown [15–17], they mostly occupied the same positions as the CBX proteins.
As our findings appeared to be odds with recent reports, we re-examined the published datasets to seek a potential explanation, focusing on studies that compared the binding of different members of the same protein family. For example, an extensive survey of 29 chromatin regulators in the K562 human leukemia cell line included data showing that endogenous CBX2 and CBX8 had remarkably coincident binding profiles [32]. Although not explicitly discussed, the inference is that CBX2 and CBX8 have common targets. In contrast, a separate study that compared the binding of epitope-tagged versions of the Psc family in 293T cells concluded that they bind selectively to different categories of target genes [15]. Despite the emphasis on selectivity, the data clearly indicate that a substantial fraction of the target loci were co-occupied by multiple Psc family members. Along similar lines, it was reported that, in mouse embryoid bodies, Cbx2 and Cbx4 bind at both overlapping and non-overlapping sets of target genes [24]. The evidence for specificity was based largely on differences in the sequence read densities achieved with different antibodies and there was considerable variation in the numbers of peaks identified with each reagent. Of note, the data imply that 90% of the Cbx2 peaks overlap with those of Cbx4.
Despite their different interpretations, these published datasets are consistent with the co-localization of PRC1 complexes at multiple sites in the genome. Although we did not detect CBX2 in HFs, we extended the evidence for co-localization to include 11 PRC1 components that, as judged by ChIP-PCR with multiple primer sets, had virtually identical binding patterns at representative loci. Importantly, our ability to perform sequential ChIP with antibodies specific for different members of the Pc, Ph and Sce families argues against the idea that the complexes are acting redundantly in different cells. Rather, a proportion of these complexes must be simultaneously associated with the same DNA.
While our findings do not exclude an element of selectivity in the association of specific PRC1 complexes with specific loci, the overwhelming impression is that they congregate at common sites. One possibility is that they form multimeric assemblies analogous to the Pc bodies described for Drosophila[33–35]. Mammalian Pc bodies might comprise multiple permutations of PRC1 rather than multimers of the same complex. Although the ChIP-seq data do not provide a three-dimensional picture, the fact that multiple complexes are co-localized along the genome implies that they are also co-localized in space. To our knowledge, this possibility has not been considered in the existing literature and most discussions about mammalian Pc bodies have centered on their visualization by fluorescence. In primary HFs, endogenous RING1, BMI1 and CBX4 have been detected as multiple speckles that are evenly distributed throughout the cell nucleus, similar to the situation in Drosophila[33, 36, 37] (data not shown). However, these early studies did not address the co-localization of different orthologs or the numbers of complexes that constitute a Pc body. Our attempts to provide such evidence were hampered by a lack of signal for most of the antibodies.
The situation in HFs is in stark contrast to the evidence from human tumor cell lines where the PRC1 proteins are typically found in a small number of very prominent nuclear bodies associated with pericentromeric heterochromatin [36, 38–40]. Although multiple PRC1 orthologs are co-localized in these large aggregates [12, 41–43], their functional significance has not been established.
Another striking feature of the ChIP-seq data is that the binding profiles have a complicated topography, often with underlying periodicity, that is reproduced with different antibodies, with different preparations of chromatin, and in different cell backgrounds. The baroque nature of the peaks makes it difficult to generalize about their location relative to candidate target genes. Based simply on proximity to the nearest TSS, the ChIP-seq data suggested that PRC1 complexes are co-localized at approximately 1,000 loci in each strain of HFs. However, the distances can be very variable and the patterns do not conform to the idea that PRC1 proteins bind within a few kilobases either side of the TSS, as suggested by meta-analyses of the profiles in ES cells [15, 16, 24, 44].
Focusing on the candidate target genes, we found that a quarter of them are actively transcribed despite the presence of PRC1 in the adjacent DNA. Such observations are not without precedent but PcG complexes are generally viewed as obligate transcriptional repressors [3]. It is formally possible that PRC1 complexes are present on only one allele allowing transcription to occur from the other but another possibility is that the assemblies of PRC1 complexes that we observe are involved in 3D interactions that influence access to both positive and negative transcription factors.
Although there were many parallels regarding the positioning of PRC1 complexes and their effects on gene expression in the two strains of HF, there were several hundred loci at which the binding profiles were completely distinct. Fibroblasts are often considered as a homogeneous cell type but different isolates have different growth rates and sensitivity to senescence [45, 46]. Importantly, HFs from different anatomical sites have characteristic patterns of gene expression that reflect their position relative to the developmental axes [47, 48]. In this regard, the BF cells would be considered anterior/trunk/non-dermal whereas Hs68 cells would be posterior/distal/dermal [48]. As stromal fibroblasts are thought to influence tissue architecture, via mesenchymal–epithelial interactions, it is interesting to consider whether the signature patterns of PRC1 occupancy represent an 'epigenetic ZIP-code'.
Senescent fibroblasts also acquire characteristic patterns of gene expression coupled to a plethora of phenotypic and physical alterations [4, 5]. At the chromatin level, senescence is accompanied by the formation of senescence-associated heterochromatin foci (SAHFs) that comprise non-overlapping layers of H3K9me3 and H3K27me3 modified chromatin [49–51]. However, a recent study suggested that SAHF formation represents a spatial repositioning of existing marks rather than changes in the landscape of histone modifications in the genome [51]. Consistent with this report, the CBX binding profiles that we observed in proliferating HFs were preserved at senescence and we did not see selective gains or losses of PRC1 peaks that would be comparable to the striking differences between HF strains. Taken together, our findings suggest that the effects of PRC1 complexes on gene expression are not simply dictated by the presence or absence of PRC1 at the locus.
Our findings question the prevailing view that different variants of PRC1 act on different sets of target genes and suggest that they act collectively rather than individually. Different types of fibroblast have distinctive PRC1 binding landscapes but the landscapes are preserved at senescence. Collectively, our findings suggest that PRC1 complexes have more subtle effects on gene expression than simply blocking transcription of the genes to which they bind.
Materials and methods
Cell cultures and immunoblotting
The procedures for propagation of primary human fibroblasts, staining for senescence-associated β-galactosidase activity and immunoblotting were as described [30, 46, 52].
Chromatin immunoprecipitation
ChIP assays were performed as described previously [53]. After sonication to obtain chromatin fragments of between 200 and 1000 bp, solubilized chromatin was diluted to 1 μg/μl and incubated with the appropriate antibody at 4°C overnight. The antibodies are listed in Additional file 6: Table S2 and either species-matched irrelevant antibodies or pre-immune serum was used as the control as appropriate. After reversal of the crosslinks, the immunoprecipitated DNA was quantified by real-time PCR with the primer sets described in Additional file 6: Table S3. For sequential ChIP experiments, the eluted chromatin was divided into equal fractions, diluted tenfold in a dilution buffer (0.1% Na deoxycholate, 1% Triton X-100, 1 mM EDTA (ethylenediaminetetraacetic acid), 50 mM HEPES (4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid, N-(2-Hydroxyethyl)piperazine-N′-(2-ethanesulfonic acid) pH 7.9, 150 mM NaCl) and subjected to a further round of ChIP with either the same or a different antibody.
Chromatin immunoprecipitation sequencing and bioinformatic analyses
To generate sufficient quantities of DNA for sequence analyses, parallel ChIP reactions were performed using approximately 5 μg of antibodies with 500 μg chromatin. The recovered material was pooled and concentrated to a minimum of 0.2 μg/μl. DNA samples were end repaired, poly-A tailed and Illumina single-end adapters were ligated following the standard Illumina protocol with minor adjustments. Agencourt AMPure XP beads at 0.8× ratio were used to size-select out adapter dimers after adapter ligation. The Phusion enzyme in the Illumina kit was replaced by the Kapa HiFi HotStart ready mix. Post PCR, AMPure XP beads were used at a 1:1 ratio to maintain size integrity and to allow use of the Invitrogen SizeSelect E-gel system. We found that running the PCR before the gel improved visualization of the product and isolation of the correct band. Samples were finally purified with QIAquick gel extraction kit (Qiagen Ltd) and quality controlled on the DNA 1000 BioAnalyzer 2100 chip before clustering. Input DNA was used as a control for the ChIP-seq analysis. Detailed protocols for library preparation and genome-wide sequencing are available online [54–59].
The alignments were performed using Novoalign (version 2.07.14) [60] allowing for a single mismatch per read. Duplicates reads were removed using the Picard MarkDuplicates program (picard-tools package version 1.48) [61] and peak calling was performed using MACS (version 1.4.0rc2) [29]. The raw and processed data have been deposited under GEO accession number [GEO:GSE40740].
RNA-sequencing, quantitative reverse transcription and PCR
Total RNA was extracted using the High Pure RNA extraction Kit (Roche). RNA samples were quality controlled (QC) using the 6000 Nano RNA Chip on a BioAnalyzer 2100 (Agilent) and subjected to poly-A selection using Sera-Mag oligo dT beads (Thermo Fisher Scientific Inc). Libraries were prepared using the Directional mRNA-Seq Library Prep. v1.0. Pre-Release Protocol from Illumina with minor adjustments [62]. The Phusion enzyme was replaced by the Kapa HiFi HotStart ready mix which reduced the overall volume of the PCR and the ratio for the Agencourt AMPure XP beads was adjusted accordingly. The standard PCR cycling was also changed to match the concentration of the total RNA from the initial QC. After passing the final QC, the libraries were subjected to cluster formation and then 72-bp single-end sequencing on a GAIIx analyzer [62].
Sequenced reads were aligned using RSEM (version 1.2.4) [63]. Each lane of the GAIIx produced approximately 9 to 20 million unique reads that mapped to RefSeq genes archived in the Illumina iGenomes resource [64].
For qRT-PCR validation, cDNAs were generated from 0.5 to 1 μg of RNA using MultiScribe reverse transcriptase and random hexamer primers (Applied Biosystems). Of the cDNA, 1/50 was used as a template for quantitative PCR with POWER SybrGreen (Applied Biosystems). RPS17 was used as an internal standard. Relative RNA levels were presented either as normalized to RPS17, or as fold-difference between the normalized values. Primer sequences can be found in Additional file 6: Table S4.
- bp:
base pair
- ChIP:
chromatin immunoprecipitation
- ChIP-seq:
- ES cell:
embryonic stem cell
human fibroblast
- kb:
- Pc:
- PcG:
Polycomb group
polymerase chain reaction
- Ph:
- Psc:
Posterior sex combs
quality controlled
- qRT-PCR:
reverse transcription and quantitative PCR
- RNA-seq:
- SA-βgal:
senescence-associated β-galactosidase
senescence-associated heterochromatin focus
- Sce:
Sex combs extra
transcription end site
transcription start site.
We are grateful to Haruhiko Koseki for providing access to the MAb3-3 monoclonal antibody against Ring1b MAb [42], to Ben Phillimore and Sharmin Begum in the LRI Advanced Sequencing Facility for library preparation, and to Nicola O'Reilly in the LRI Peptide Synthesis Facility for help in antibody development. RP was supported by a grant from Leukaemia and Lymphoma Research.
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- E-Gel® SizeSelect™ Agarose Gels. [http://tools.invitrogen.com/content/sfs/manuals/egel_sizeselect_qrc.pdf]
- Agencourt® AMPure® PCR Purification. [http://genome.med.harvard.edu/documents/sequencing/Agencourt_AMPure_Protocol.pdf]
- Illumina TruSeq cluster generation protocol. [https://icom.illumina.com/download/summary/m3k7sKMtGEOX1RjuSLQzjQ]
- Illumina TruSeq reagent protocol. [https://icom.illumina.com/download/summary/PRv_NCP-DEaVrFfTbSdQnw]
- Illumina GAIIx user protocol. [https://icom.illumina.com/download/summary/NhgBUf-w1USCWAimIVWgTA]
- Novocvraft. [http://novocraft.com]
- Picard. [http://picard.sourceforge.net]
- Directional mRNA-Seq Library Prep. Pre-Release Protocol. [http://corelabs.cgrb.oregonstate.edu/sites/default/files/file/hts/Directional-RNA-Seq-Experienced-User-Card%5B1%5D.pdf]
- Li B, Dewey CN: RSEM: accurate transcript quantification from RNA-seq data with or without a reference genome. BMC Bioinformatics. 2011, 12: 323-PubMedPubMed CentralView ArticleGoogle Scholar
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


text: EcoModo - The Best of TreeHuggerJaymi Heimbuch4/13/10 8:30amFiled to: RoundupsEcoModoTreehuggereco4EditPromoteShare to KinjaToggle Conversation toolsGo to permalink This week, teens smash their first iPad on purpose, stoves that generate electricity while they cook, squeezing the last drop from your ink cartridges, Best of Green awards in science and technology, and more! Advertisement Best of Green: Science and Technology From gadgets and software to websites and activists, the Best of Green winners on the following pages seem to know. Check them out to learn more about the top movers and shakers in the scientific and technology communities.Hybrid Robot's Microbial Fuel Cell Transforms Polluted Water Into Vegetation What if an army of mobile robots could transform polluted water into plant life? Tracing a fine line between robot and plant, art project and self-sustaining mini-ecosystem machine, Mexican artist Gilberto Esparza's hybrid creation "Nomadic Plants" (Plantas Nomadas) is a quirky contraption that actively seeks polluted water to feed the vegetation and microorganisms living symbiotically inside its body. Advertisement Travel Stove Creates Electricity While It Cooks (Video) How great would it be to have a stove where you can chuck practically any fuel source into it, have it utilize that fuel efficienctly to quickly heat your food, reduce emissions drastically, and power your gadgets? It seems that the option is actually on its way.WTF? Teens Purchase iPad Just to Smash It With A Baseball Bat In order to be the very first to destroy an iPad, some teens waited in line, purchased one, and immediately went outside the store where they smashed it to bits with a baseball bat. Why?GE Unveils New LED Bulb - 17 Year Life Span and $50 Price Tag For awhile there, GE was hoping to keep up incandescent light bulbs by releasing a high efficiency incandescent bulb. But they quietly dropped that dead end about two years later. Now, they've made a new announcement that they're bringing out an LED bulb that'll replace incandescents, giving you 17 years worth of light from a $50 bulb. Sponsored Solar Blossom Pop Up Art Gallery Powered By the Sun DeMarco Architecture came up with the Solar Blossom, a pop-up art gallery that looks like a flower and is powered by the sun to show off art or be a stage for musical performances.Century Gothic Saves More Ink Than Ecofont If you're looking to squeeze the most out of your ink cartridges, we have it on good authority that the font matters. Advertisement Advertisement Hit or Miss? Smart Packaging Design - Yogurt Lid Becomes the Spoon The lid of this yogurt container is popped into a new shape to become the spoon. However, there's one rather counterproductive problem with the design.TreeHugger's EcoModo column appears every Tuesday on Gizmodo.Reply4 repliesLeave a reply

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Kindness is what Shavuot is all about, enjoy the healthy cheesecake!
Kindness is what Shavuot is all about, enjoy the healthy cheesecake!.
About Midnightrabbi inspired aka Eli GoldsmithMidnightrabbi inspired aka Eli Goldsmith, is originally from a well-known family, in the music biz and entertainment industry, from London, has transferred his upbringing and talents to be at the cutting edge of culture and Jewish talent hosting events for many programs. He studied in England at John Lyons School Harrow, Woodhouse College and Sussex University! Continuing his education in Israel, Talmudic Law and group council at Ohr Somayach, Kollel Aiza Birah and Kollel Boston, in Derech Hamelech and Rabbi in 6 well known programs where was named honorably the Midnightrabbi by the beloved students themselves, He has rounded off his outlook with a large breath of wisdom including the "7 habits" from Stephen Covey to become the "10 habits" practical business successful approach. Working as a Consultant in the well-known Charity these past 4 years, the Jaffa Institute and sister program the Bet Shemesh Educational Center is where he honed his talents as office management and consultancy and formed his special bond with many special people worldwide. Recently working as a Consultant and Office manager of UKA United Kashruth Authority with professionalism and Kosher Certification! And as a Counselor at Retorno the LARGEST JEWISH DRUG REHAB center in the world. Eli was excitedly consulting @Grantwatch.com as Customer Service Executive updating their Social media and @Student Services at MJI Institute. Eli Goldsmith is currently looking for new opportunities to inspire. Eli is near Jerusalem with his wife and 6 beautiful children. Contact 972-53-317-5856 Email - email@example.com
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Wed, 16 July 2014 8:30AM
Does your foundation leave your skin looking flat, cakey and lacklustre when all you want in life is a flawless, glowing and naturally beautiful complexion like Blake Lively? IS THAT TOO MUCH TO ASK, UNIVERSE?!?! Image courtesy of L'Oréal Paris If you found yourself nodding in agreement, it might be time to invest in a new foundation…. more
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The Sociology of Development
The Impasse and Beyond
By (author) Ray Kiely
Format: Hardback
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Sociology of Development by Ray Kiely
Book DescriptionFirst published in 1995. Routledge is an imprint of Taylor & Francis, an informa company.
Buy Sociology of Development book by Ray Kiely from Australia's Online Bookstore, Boomerang Books.
Book DetailsISBN: 9781857281958
(216mm x 140mm x 15mm)
Pages: 204
Imprint: Routledge
Publisher: Taylor & Francis Ltd
Publish Date: 31-Aug-1995
Country of Publication: United Kingdom
Other Editions...
Books By Author Ray Kiely
BRICS, US 'Decline' and Global Transformations, Hardback (April 2015)
The author examines the rise of the BRICs and the supposed decline of the United States. Focusing on the boom years from 1992 to 2007, and the crisis years after 2008, he argues that there are limits to the rise of the former and that the extent of US decline has been greatly exaggerated.
Rethinking Imperialism, Hardback (April 2010)
Imperialism has become a key focus of debate about world politics in the post-9/11 world. This major new text provides a systematic reappraisal of the evolution of the phenomenon and the concept from the 19th century as the basis for a reassessment of Globalization and US hegemony in the world today.
Clash of Globalizations, Paperback (October 2009)
This work addresses the politics of globalization and the rise of anti-capitalist movements.
New Political Economy of Development, Hardback (November 2006)» View all books by Ray Kiely
Analyses changes and continuities in the international order and their implications for development in the 21st century. The author assesses the extent and impact of globalization, and the emergence of a more aggressive unilateralist and militarist stance by the United States and the debates this has provoked on hegemony, empire and imperialism.
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Online lessons for mathematics even with zero knowledge, I graduated from Yerevan State University with a Bachelor of Primary Education
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Tom Cherveny
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Tom Cherveny is a regional and outdoor reporter with the West Central Tribune in Willmar, MN.
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WILLMAR, Minn. — Jennie-O Turkey Store employees are going into the holidays with plenty of cheer. The company announced on Tuesday that a record payment of over $13 million has been distributed to employees as a discretionary bonus based on the company's record performance this past year. This amount equals an average payment of over $2,000 per eligible employee, with newly hired employees receiving at least $525.
WILLMAR, Minn. — A six-point buck head-butted a rural Willmar business owner, jumped over counters and tipped over boxes before fleeing out of the door in which he arrived on Wednesday. The "intruder" caused havoc at Johnson Fur on South Highway 71 where workers are in the process of handling thousands of deer hides harvested in the last two weeks. "It was something else,'' said business owner Scott Johnson, who took a set of six-point antlers to his ribs and stomach. Johnson said he had a few tender ribs, but otherwise was OK.
MONTEVIDEO - Gov. Mark Dayton has now gone six years in a row without a bird in the Governor's Pheasant Opener he started, and he was upped this year by his lieutenant governor. Lt. Gov. Tina Smith who bagged her first pheasant ever as she joined the governor and 75 other hunters for the Governor's Pheasant Opener hosted Saturday by the community of Montevideo. "Judge (Dwayne) Knutsen said it was homicide. I could have been charged,'' laughed Smith of the clean kill as verified by her hunting partner, a district judge in Yellow Medicine County.
BENSON -- Bill Lee is leaving an ethanol plant known as a leader in innovation for what he believes will be the next big step in renewable energy. Lee said he believes biomass from agricultural and forest-product residues will be playing an ever bigger role in not only providing the power to convert corn to ethanol, but also to produce the electricity that lights our homes. Lee has been CEO since June at Frontline BioEnergy LLC in Ames, Iowa.


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The Korean Wave sparked a fad for Korean movies, dramas and pop music not only in Asia but also throughout the world.
Since August 2005, the Korean Collection has been purchasing DVDs that are associated with popular Korean TV series and movies.
All DVDs feature Korean and English subtitles, some also include Chinese and Japanese.
There are facilities for viewing the DVDs onsite.
Please contact the Korean Librarian Ms Jung-ok Park for further details.


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Flight from Berlin-Tegel (TXL) to Porto (OPO) in June 2017
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Patriots Down 24-10 at the Half
By: Ian Logue
The Patriots had a chance to cut into the Saints 24-10 lead, but unfortunately couldn't put together a scoring drive on their final possession before the half. Brady and company put together a 10-play drive that began at their own 20, but couldn't come away with any points after their drive stalled at the Saints 32 yard line and kicker Stephen Gostkowski missed a 50-yard field goal attempt wide left.
The good news is they'll have the ball to start the second half.
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Hyatt Regency Tokyo
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TravelPod Member ReviewsHyatt Regency Tokyo Shinjuku
hyatt is a big name, and it doesn't lie. situated at the heart of tokyo, it's easy to move around.
This review is the subjective opinion of a TravelPod member and not of TravelPod.com.
TripAdvisor Reviews Hyatt Regency Tokyo Shinjuku
Travel Blogs from Shinjuku
DAY 2 the fish market !
... catch a blue marlin!
After purchasing my 60cm fish I then went around asking the best way to cook and serve it as a meal, I was told buy a few locals that the best way is to cook it straight in a pan, and serve it with nothing but just some juice and herbs on the fish. So I would when I get back to the hotel, but my next step was to go up to some local fishermen and ask if I could go out on one of ...
Our First Two Days in TOKYO
... to the hotel. When we got there we were so jet lagged we had a nap. We went down to the local family mart and bought ourselves some Japanese super noodles and had a sleepy jet lagged evening! Day 2 We set off at 10am with a decent sleep, we had a yummy breakfast at the local cafe chocolate and blueberry bagels :) we then made our way to shinjuku looking for the cat cafe. After some wrong turns and trying ...
Philosophy Moments: Being a Baka-Gaijin
We're in Japan and we're foreigners, we probably make more mistakes than we can imagine. Here are some of the ones we've picked up, compiled while on the train to Morioka
- We're always on the wrong side of escalators. Osaka-jin stand on the right, Tokyo-jin on the left, and in Kyoto no-one cares. If you're old you can be on any side you want, everyone else will adjust accordingly. If you're a foreigner, ...
DH Goes Sumo
... The injuries can be horrific...and that's just the for the ringside observers that these behemoths land on! Just being enveloped in that much blubber must be a suffocation risk. The fights we saw usually lasted only a few seconds, or in some rare cases, about a minute. The strange rituals before the fight usually lasted much longer than the bouts themselves- many of the rituals are derived from Shinto practice.
After lumbering into the ring ...


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Survival Tips According to the press release, Obama will certainly become the first-ever American president to receive a refresher course in wilderness survival from Grylls, whose NBC program takes celebs out into nature. Besides the acquisition of a wealth of outdoor skills, wilderness survival provides many other benefits for your teenager. The courses help your teenager link to nature, according to The Wilderness School, which helps him dedicate to maintaining it. Wilderness survival also boosts your teen's self-confidence by assisting him realize he can learn to do crucial and new actions, adds the Wildwood Survival site. Teenagers who participate in healing wilderness survival programs are provided the chance to resolve their issues in group and individual settings. A collection of vibrant knitting patterns for the novice and skilled knitter.
We resolved this challenge by offering each pilot with survival packs developed for specific environments, a single-man liferaft (which supplies shelter that's just as excellent in a desert as it is at sea) and sensible training with the devices included in each pack. As the balloon moved from one environment to another, the packs were turned appropriately, and the pilots re-briefed on their survival top priorities for each environment. Discover the strategies involved in capturing your food, such as fishing or snares.
By making the students participate in quizzes and disputes on existing subjects, teachers can further add to the student's leadership skills in the class. A more involved team-building exercise, which takes the team outdoors for a half-day or an entire day, is an excellent technique for developing problem-solving techniques. Naturally, your talented minds will have a scenario in which the life-raft played a crucial role in their lunar survival. Her young cub watches inquisitively; her only possibility of survival is to learn the predatory skills of her mother. There will be many times you will require it and not just in survival circumstances.
Because they do not possess the abilities necessary to safeguard themselves, researches report that overprotected/sheltered children tend to be bullied. Because communication is vital to the long-term survival of your relationship, you'll want to find out how to get her to share her sensations, help exercise your issues and more.
Knowing various performing arts like dancing/singing (These skills will certainly help in developing an overall personality). Blowing a humongous chewing gum bubble (Without bursting it. When tired), makes for one of the best abilities to use. Simply for that then, begin acquiring as numerous skills as possible and turn your life around. They attempt to develop fundamental structures by integrating the blocks together, which starts establishing their thought process and creative abilities.
Action A Survival examine made to find tracks is at least a full-round action, and it might take even longer. Class A ranger gets a bonus offer on Survival checks when using this ability to find or follow the tracks of a favored enemy. Accomplishments If you have the Self-Sufficient accomplishment, you get a +2 incentive on all Survival checks. Size and Number of Creatures being Tracked: See Table: Modifiers to Survival Checks when Tracking below. See Table: Survival DCs by Task for DCs for different tasks that need Survival checks.
Relating to self-defense, I won't go in to that here since it depends upon your local laws, your abilities and skills, and so on. However, some concepts for passive self-defense are making sure that your doors have two (2) strong and excellent locks (a basic tumbler/key lock and a deadbolt), and that you have enough plywood in your garage, shed or basement, pre-cut, to secure all the lower level windows in your house.


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Want to renew your focus on Jesus during Lent? Sign up for our free Lent & Easter devotions.
Jesus has claimed to share God's prerogatives of life-giving and judgment and has demonstrated supernatural power. Now the claims in chapter 5 and the power demonstrated in chapter 6 are put in perspective through the series of teachings around the theme of the bread of life (vv. 25-59). The deeds of power are signs of something even more wondrous than the witnesses first thought, for Jesus speaks further of his role as the giver of eternal life and of how people are to share in this life he offers. The crowd's response to this teaching illustrates the judgment that is taking place through Jesus' ministry. In this section we also receive more revelation of the relation between the Father and the Son spoken of in the keynote address.
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text:
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text:
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text:
In a message dated 2/27/1999 8:52:54 PM Central Standard Time,
email@example.com writes:
<< Does the
yellow centered form exist and if so who has it?.
There ARE two distinct H. 'Knockouts'. I do not know where to get the one you
mention. One of them is a horrible grower.(The one I have! :-))
Clyde Crockett z5
To sign-off this list, send email to email@example.com with the
message text UNSUBSCRIBE HOSTA-OPEN


text:
Biostatistics plays a fundamental role in medical, biomedical and public health research. Advances in medical technology alone have substantially increased the demand for trained biostatisticians to demonstrate basic scientific knowledge, effectiveness and feasibility. There is a growing need for biostatisticians to be trained in a broad range of fields, including the biological sciences, quantitative sciences and clinical applications. Researchers in the medical and life sciences are expressing a growing need for applied biostatisticians who are trained with a background in biology and strong communication skills as well as quantitative skills. Most applied biostatisticians function in collaborative environments that require interdisciplinary knowledge and strong communication skills, but many do not receive training in biology and bioinformatics. Not only do biostatisticians need to be trained how to apply the wide range of quantitative methods that are needed in biomedical research, but they also need an understanding of the biological basis for disease and the biological measures that are collected in biomedical research. The goal of this training grant proposal is to seek continued funding for our training program for pre-doctoral students in biostatistics that provides a strong background in quantitative skills, biology, applied research and exposure to the proper conduct of ethical research. Our program of 1-3 years includes course work required of all biostatistics doctoral students along with rotations in bioinformatics, genetics, ethical conduct of research, observational studies and clinical trials. In the rotations students work on an applied research project gaining important experience in an environment that provides excellent experience in interdisciplinary research. This program produces students not only with classroom exposure to quantitative skills, but also practical experience as a functioning biostatistician.
The NIH has identified a growing need to educate biostatisticians through an interdisciplinary approach. Additionally, there is a growing need to include minorities and disabled persons in this important field. This program plays an important role in addressing both needs within the United States.
|Dunn, Erin C; Solovieff, Nadia; Lowe, Sarah R et al. (2014) Interaction between genetic variants and exposure to Hurricane Katrina on post-traumatic stress and post-traumatic growth: a prospective analysis of low income adults. J Affect Disord 152-154:243-9
|Alsultan, Abdulrahman; Alabdulaali, Mohammed K; Griffin, Paula J et al. (2014) Sickle cell disease in Saudi Arabia: the phenotype in adults with the Arab-Indian haplotype is not benign. Br J Haematol 164:597-604
|Vardi, Moshe; Perez, Jeremiah; Griffin, Paula J et al. (2014) Usefulness of postmarket studies to evaluate long-term safety of coronary eluting stents (from the ENDEAVOR and PROTECT Programs). Am J Cardiol 114:528-33
|Zhang, Xiaoling; Johnson, Andrew D; Hendricks, Audrey E et al. (2014) Genetic associations with expression for genes implicated in GWAS studies for atherosclerotic cardiovascular disease and blood phenotypes. Hum Mol Genet 23:782-95
|Griffin, Paula J; Sebastiani, Paola; Edward, Heather et al. (2014) The genetics of hemoglobin A2 regulation in sickle cell anemia. Am J Hematol 89:1019-23
|Hendricks, Audrey E; Dupuis, Josee; Logue, Mark W et al. (2014) Correction for multiple testing in a gene region. Eur J Hum Genet 22:414-8
|Bachman, Eric; Travison, Thomas G; Basaria, Shehzad et al. (2014) Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. J Gerontol A Biol Sci Med Sci 69:725-35
|Hu, Yi-Juan; Berndt, Sonja I; Gustafsson, Stefan et al. (2013) Meta-analysis of gene-level associations for rare variants based on single-variant statistics. Am J Hum Genet 93:236-48
|Cheng, Susan; Larson, Martin G; McCabe, Elizabeth L et al. (2013) Age- and sex-based reference limits and clinical correlates of myocardial strain and synchrony: the Framingham Heart Study. Circ Cardiovasc Imaging 6:692-9
|Guffanti, Guia; Galea, Sandro; Yan, Lulu et al. (2013) Genome-wide association study implicates a novel RNA gene, the lincRNA AC068718.1, as a risk factor for post-traumatic stress disorder in women. Psychoneuroendocrinology 38:3029-38
Showing the most recent 10 out of 26 publications


text:
Do ECB Council Decisions represent always a Real Euro Consensus?
Since January 1999, according to the law, the common monetary policy for all the Economic and Monetary Union (EMU) Member States should be decided by simple majority in the Governing Council (GC) of the European Central Bank (ECB), regarding the Euro area aggregate conditions. Notwithstanding, no formal vote has been taken until today and a consensus solution has been the officially announced practical rule, hiding different points of view fuelled by national divergences that might exist within Euro area. Assuming that EMU national central bankers take into account national perspectives from their home countries when they vote interest rate decisions in the GC, we try to find whether there have been favourable conditions for the emergence of voting coalitions among them. In order to accomplish that purpose, for every month since January 1999 until August 2003, we applied cluster analysis techniques to national stances before GC meetings, which we describe using three variables. We found high stability in the identified cluster structure, particularly since August 2001, favouring the emergence of alliances between national interests. In spite of that, it is likely that the strong strategic position enjoyed by the Executive Board of the ECB has been sufficient to a priori defeat any coalitions of opposing proposals on the monetary policy for the Euro-area, situation that will change with EMU enlargement.
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|31 pages
|Date of creation:
|31 Jul 2009
|Contact details of provider:
| Postal: Universidade Portucalense – Economics and Management Department (CIGE – Centro de Investigação em Gestão e Economia), Rua Dr. António Bernardino de Almeida, 541-619, 4200 – 072 Porto, Portugal
Web page: http://www.uportu.pt/site-scripts/centro_pagina.asp?codmenu=71&codcentro=24
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References listed on IDEAS
Please report citation or reference errors to , or , if you are the registered author of the cited work, log in to your RePEc Author Service profile, click on "citations" and make appropriate adjustments.:
- J.M. Arnold, Ivo, 2001. "The Regional Effects of Monetary Policy in Europe," Journal of Economic Integration, Center for Economic Integration, Sejong University, vol. 16, pages 399-420.
- Paul de Grauwe & Jean-Claude Trichet & Ernst Welteke & Leszek Balcerowicz, 2002.
"The Euro at stake? The monetary Union in an enlarged Europe,"
CESifo Forum,
Ifo Institute - Leibniz Institute for Economic Research at the University of Munich, vol. 3(2), pages 58-71, October.
- Paul De Grauwe, 2003. "The Euro at Stake? The Monetary Union in an Enlarged Europe," CESifo Economic Studies, CESifo, vol. 49(1), pages 103-121.
- Sharon Kozicki, 1999. "How useful are Taylor rules for monetary policy?," Economic Review, Federal Reserve Bank of Kansas City, issue Q II, pages 5-33.
- Matteo Ciccarelli & Alessandro Rebucci, 2002.
"The Transmission Mechanism of European Monetary Policy; Is There Heterogeneity? Is it Changing over Time?,"
IMF Working Papers
02/54, International Monetary Fund.
- Matteo Ciccarelli & Alessandro Rebucci, 2001. "The Transmission Mechanism of European Monetary Policy: Is There Heterogeneity? Is It Changing Over Time?," Working Papers 0115, Banco de España;Working Papers Homepage.
- Scheve, Kenneth, 2004. "Public Inflation Aversion and the Political Economy of Macroeconomic Policymaking," International Organization, Cambridge University Press, vol. 58(01), pages 1-34, February.
- Ellen E. Meade & D. Nathan Sheets, 2002.
"Regional Influences on U.S. Monetary Policy: Some Implications for Europe,"
CEP Discussion Papers
dp0523, Centre for Economic Performance, LSE.
- Ellen E. Meade & Nathan Sheets, 2002. "Regional influences on U.S. monetary policy: some implications for Europe," International Finance Discussion Papers 721, Board of Governors of the Federal Reserve System (U.S.).
- Helge Berger & Jakob Haan, 2002. "Are small countries too powerful within the ECB?," Atlantic Economic Journal, Springer;International Atlantic Economic Society, vol. 30(3), pages 263-282, September.
- Peersman, Gert & Smets, Frank, 1999. "The Taylor Rule: A Useful Monetary Policy Benchmark for the Euro Area?," International Finance, Wiley Blackwell, vol. 2(1), pages 85-116, April.
- Artis, M.J. & Zhang, W., 2002. "Membership of EMU: A Fuzzy Clustering Analysis of Alternative Criteria," Journal of Economic Integration, Center for Economic Integration, Sejong University, vol. 17, pages 54-79.
- Daniel Gros & Carsten Hefeker, 2000.
"One Size Must Fit All. National Divergences in a Monetary Union,"
CESifo Working Paper Series
326, CESifo Group Munich.
- Daniel Gros & Carsten Hefeker, 2002. "One Size Must Fit All: National Divergences in a Monetary Union," German Economic Review, Verein für Socialpolitik, vol. 3(3), pages 247-262, 08.
- Robert J. MacCulloch & Rafael Di Tella & Andrew J. Oswald, 2001.
"Preferences over Inflation and Unemployment: Evidence from Surveys of Happiness,"
American Economic Review,
American Economic Association, vol. 91(1), pages 335-341, March.
- DiTella, Rafael & MacCulloch, Robert & Oswald, Andrew J., 2001. "Preferences over inflation and unemployment: Evidence from surveys of happiness," ZEI Working Papers B 03-2001, University of Bonn, ZEI - Center for European Integration Studies.
- Ramana Ramaswamy & Torsten M Sloek, 1997. "The Real Effects of Monetary Policy in the European Union; What Are the Differences?," IMF Working Papers 97/160, International Monetary Fund.
- Heinemann, Friedrich & Huefner, Felix P., 2002.
"Is the View from the Eurotower Purely European? National Divergence and ECB Interest Rate Policy,"
ZEW Discussion Papers
02-69, ZEW - Zentrum für Europäische Wirtschaftsforschung / Center for European Economic Research.
- Friedrich Heinemann & Felix P. Huefner, 2004. "Is The View From The Eurotower Purely European? - National Divergence And Ecb Interest Rate Policy," Scottish Journal of Political Economy, Scottish Economic Society, vol. 51(4), pages 544-558, 09.
- Huefner, Felix P & Friedrich Heinemann, 2003. "Is the View from the Eurotower Purely European? - National Divergence and ECB Interest Rate Policy," Royal Economic Society Annual Conference 2003 110, Royal Economic Society.
- Bernd Hayo & Volker Clausen, 2002.
"Asymmetric Monetary Policy Effects in EMU,"
0203003, EconWPA.
- Volker Clausen & Bernd Hayo, 2006. "Asymmetric monetary policy effects in EMU," Applied Economics, Taylor & Francis Journals, vol. 38(10), pages 1123-1134.
- Clausen, Volker & Hayo, Bernd, 2002. "Asymmetric monetary policy effects in EMU," ZEI Working Papers B 04-2002, University of Bonn, ZEI - Center for European Integration Studies.
- Daniel Gros & Carsten Hefeker, 2002. "Common Monetary Policy with Asymmetric Shocks," CESifo Working Paper Series 705, CESifo Group Munich.
- Gert Peersman, 2004. "The Transmission of Monetary Policy in the Euro Area: Are the Effects Different Across Countries?," Oxford Bulletin of Economics and Statistics, Department of Economics, University of Oxford, vol. 66(3), pages 285-308, 07.
- Fernando Barran & Virginie Coudert & Benoît Mojon, 1996. "The Transmission of Monetary Policy in the European Countries," Working Papers 1996-03, CEPII research center.
- Agresti, Anna Maria & Mojon, Benoît, 2001. "Some stylised facts on the euro area business cycle," Working Paper Series 0095, European Central Bank.
- Mojon, Benoît & Kashyap, Anil K. & Angeloni, Ignazio & Terlizzese, Daniele, 2002. "Monetary Transmission in the Euro Area : Where Do We Stand?," Working Paper Series 0114, European Central Bank.
- Björkstén, Nils & Syrjänen, Miika, 1999. "Divergences in the euro area : A cause for concern?," Research Discussion Papers 11/1999, Bank of Finland.
- Taylor, John B., 1998.
"The Robustness and Efficiency of Monetary Policy Rules as Guidelines for Interest Rate Setting by the European Central Bank,"
Seminar Papers
649, Stockholm University, Institute for International Economic Studies.
- Taylor, John B., 1999. "The robustness and efficiency of monetary policy rules as guidelines for interest rate setting by the European central bank," Journal of Monetary Economics, Elsevier, vol. 43(3), pages 655-679, June.
- Issing, Otmar, 2001. "The Single Monetary Policy of the European Central Bank: One Size Fits All," International Finance, Wiley Blackwell, vol. 4(3), pages 441-462, Winter.
- Peter van Els & Alberto Locarno & Julian Morgan & Jean-Pierre Villetelle, 2001.
"Monetary policy transmission in the euro area: what do aggregate and national structural models tell us?,"
Temi di discussione (Economic working papers)
433, Bank of Italy, Economic Research and International Relations Area.
- van Els, Peter J. A. & Locarno, Alberto & Morgan, Julian & Villetelle, Jean-Pierre, 2001. "Monetary policy transmission in the euro area: What do aggregate and national structural models tell us?," Working Paper Series 0094, European Central Bank.
- Mojon, Benoît & Peersman, Gert, 2001. "A VAR description of the effects of monetary policy in the individual countries of the euro area," Working Paper Series 0092, European Central Bank.
- Aksoy, Yunus & De Grauwe, Paul & Dewachter, Hans, 2002. "Do asymmetries matter for European monetary policy?," European Economic Review, Elsevier, vol. 46(3), pages 443-469, March.
- Alberto Alesina & Vittorio Grilli, 1991.
"The European Central Bank: Reshaping Monetary Politics in Europe,"
NBER Working Papers
3860, National Bureau of Economic Research, Inc.
- Alesina, Alberto F & Grilli, Vittorio, 1991. "The European Central Bank: Reshaping Monetary Politics in Europe," CEPR Discussion Papers 563, C.E.P.R. Discussion Papers.
- Michael Ehrmann, 2000. "Comparing monetary policy transmission across European countries," Review of World Economics (Weltwirtschaftliches Archiv), Springer;Institut für Weltwirtschaft (Kiel Institute for the World Economy), vol. 136(1), pages 58-83, March.
- Hayo, Bernd, 1998. "Inflation culture, central bank independence and price stability," European Journal of Political Economy, Elsevier, vol. 14(2), pages 241-263, May.
- Michael D. Bordo & Barry Eichengreen, 1993. "A Retrospective on the Bretton Woods System: Lessons for International Monetary Reform," NBER Books, National Bureau of Economic Research, Inc, number bord93-1, Enero.
- Taylor, John B., 1993. "Discretion versus policy rules in practice," Carnegie-Rochester Conference Series on Public Policy, Elsevier, vol. 39(1), pages 195-214, December.
- Gildea, John A, 1992. "The Regional Representation of Federal Reserve Bank Presidents," Journal of Money, Credit and Banking, Blackwell Publishing, vol. 24(2), pages 215-25, May.
- Maria ELEFTHERIOU, 2003. "On the Robustness of the "Taylor Rule" in the EMU," Economics Working Papers ECO2003/17, European University Institute.
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text:
Software Development Team Leader
2016/10/05 Cairo · Egypt
The employee will be in charge of the software development team, supervising the process of creating new modules as well as modifying existing modules. The employee will also be performing analysis and design.
- Receiving requests for new modules and modifications to existing tasks.
- Controlling all stages of the development life cycle including initial analysis, implementation, integration, testing, debugging, data validation, and support.
- Conducting analytical reports about users' requirements, new task requirements, and the impact of the new task on the internal work flow.
- Designing modules by dividing the users' requirements into submodules and setting timeframes for task completion.
- Assigning submodules to our software developers to proceed with the programming of the modules.
- Ensuring that all aspects of the project are completed as planned.
- Receiving user feedback and data modification requests, solving bugs, and handling client complaints.
- Administrating the company's web portal (configuring IIS, performance tracking, and problem solving).
- Staying up to date with the latest software development technologies and methodologies to develop internal work.
Qualifications & Work Experience
- Bachelor's degree in any field
- 5+ years of relevant experience
- Good command of both written and spoken English
- Excellent knowledge of web development
- Excellent knowledge of DB concepts and tools (Microsoft SQL server)
- Excellent knowledge of Dot Net (ASP.NET, MVC, C#)
- Excellent knowledge of OOP (concepts, techniques, principles, analysis, and design)
- Excellent knowledge of design patterns
- Good knowledge of ORM
- Good knowledge of video processing
- Very good knowledge of image processing
- Excellent knowledge of workflow systems
- Very good knowledge of data processing and handling with various types and sizes (documents and media)
Job Behavioral Competencies
- Very good communication skills
- Accuracy and attention to details
- Highly organized
- Time and stress management skills
- Problem solving skills
- Adaptability and flexibility
- Ability to learn
- Analytical thinking
- Decision making
- Self-motivated
- Leadership skills
- Monthly gross salary offered for this position is in the range of 15,000 EGP–18,000 EGP.


text:
Thanks for the website, Bonnie...I'll take a look at it when I get home today. Have a good day!
Melody, IA (Z 5/4)
"The most beautiful thing we can experience is the mysterious."
--Albert Einstein
--- On Fri 06/04, Bonnie Holmes < email@example.com > wrote:
From: Bonnie Holmes [mailto: email@example.com]
To: firstname.lastname@example.com
Date: Fri, 4 Jun 2004 08:17:50 -0700
Subject: RE: [CHAT] OT: Rand Berry/political
Since this subject has come up, you may be interested
in
http://www.factcheck.org/ . This service looks at all candidates
and is
pretty objective...looks at the facts behind all candidate and
party
statements.

Bonnie Zone 6+ ETN

>
[Original Message]
> From: Melody <email@example.com>
> To:
<firstname.lastname@example.com>
> Date: 06/04/2004 1:47:50 AM
> Subject:
[CHAT] OT: Rand Berry/political
>
> Anyone interested in being
forwarded a message from John Kerry's team
> from Rand Berry? He is
the former Special Assistant to President Bush
> and Senior Director
for Combatting Terrorism who resigned from Bush's
> administration in
March 2003 over philosophical differences on the war
> in Iraq, is a
Vietnam veteran, and has now joined Kerry's team as an
> advisor on
terrorism and foreign policy issues...very interesting stuff
> in his
message.
>
>
>
> Melody, IA (Z 5/4)
>
> "The most
beautiful thing we can experience is the mysterious."
> --Albert
Einstein
>
> _______________________________________________
>
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text:
Genre: Reality, House/garden
Premise: For most of us, watching celebrities search for a multimillion-dollar place to live is a lot like walking through a store that sells fine china: You can look but you can't touch. That's the voyeuristic appeal, if you will, of ``Celebrity House Hunting,'' which allows viewers a peek inside the lives of the rich and famous as they show off their current homes and tour more amazing ones on the market. Each episode features a celebrity -- Debbie Gibson, Bret Michaels, Lisa Rinna, Shannen Doherty and Ice-T among them -- checking out three prospective properties, talking about the good and not-so-good qualities of each before deciding whether to make an offer on one.
Shannen Doherty
S01, E04 (First Aired: Mar. 15, 2012)
After a successful career, Shannen Doherty is ready to fully settle down with her husband of one year, Kurt Iswarienko.
Corey Feldman
S01, E07 (First Aired: Mar. 29, 2012)
Corey Feldman and his son go looking for a new Feldmansion Fortress.


text:
C4 investigates Who's Getting Rich?
Channel 4 has ordered a short season of shows from Boomerang and Firecracker Films focussing on businesses which are bucking the recession.
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text:
who knows why God gives out his gifts
© Copyright 2017 moonphish. All rights reserved.
Status: Finished
Genre: Poetry
We must share a melancholy bent at this time of the year. I was thinking about writing something similar on July 14 (we're a day ahead of you here). My son would have been 44 yesterday but he didn't make it past 28. Your sentiment is beautifully expressed. Many of us will share your emotion. Thank you.
Thank you for sharing this beautiful piece with us Moonphish.
Just popped by to remind you that the angels who have all that patience and are showering you with kisses, also have their wings wrapped around you and yours
Moonphish, we can never truly consol our losses and on anniversaries the are particularly bitter sweet. This may be a poem from your heart but it is a poem to all of ours who have lost someone dear.
It strikes me that I recall your writing about this person before - and Time does not dull the questions nor the sorrowings of loss.
You speak for all who are living with loss. Helps to be in like company for a bit. Thanks...
With kindest regards, Connie
That's beautiful Moonphish.
It is so important to remember special ones we have lost and so sad when others forget important dates. It's my birthday today (a big one) and I am celebrating (not) it alone without my soulmate who has moved one without me. In 7 days I will endure my 20th wedding anniversary alone, the next day is my deceased sons 13th birthday, and 13 days later it will be my deceased daughters 14th birthday. I hate this time of year as all my the reminders of my losses all come at once and no one but me ever remembers them. Thank you for your poem, your timing was perfect for me and really hits the spot.
Poem / Poetry
Poem / Poetry
Poem / Poetry
Paste the link to picture in the entry below:
Paste the link to Youtube video in the following entry:
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text:
PHP MySQL JavaScript Advanced Search and jqxGrid results
This project was awarded to zeeyawebdesign for $160 USD.Get free quotes for a project like this
Project Budget$30 - $250 USD
Total Bids6
Project Description
I have a MySQL table with the following schema:
"parents" (all form elements)
ID: 1 / TYPE: dropdown / NAME: parent1
ID: 2 / TYPE: checkboxgroup / NAME: parent2
ID: 3 / TYPE: radiogroup / NAME: parent3
ID: 4 / TYPE: textfield / NAME: parent4
ID: 5 / TYPE: textbox / NAME: parent5
"childs" (all option elements)
ID: 1 / CHILDOF: 1 / NAME: child1
ID: 2 / CHILDOF: 1 / NAME: child2
ID: 3 / CHILDOF: 1 / NAME: child3
ID: 4 / CHILDOF: 2 / NAME: child1
ID: 5 / CHILDOF: 2 / NAME: child2
ID: 6 / CHILDOF: 2 / NAME: child3
ID: 7 / CHILDOF: 3 / NAME: child1
ID: 8 / CHILDOF: 3 / NAME: child2
"data" (stores selections)
ID: 1 / timestamp: 10/12/2012 / parent1:child1 / parent2:child1 / parent3:child2
ID: 2 / timestamp: 10/12/2012 / parent1:child3 / parent2:child2 / parent3:child1
ID: 3 / timestamp: 10/12/2012 / parent1:child1 / parent2:child1 / parent3:child1
ID: 4 / timestamp: 10/12/2012 / parent1:child2 / parent2:child3 / parent3:child2
The above data is used to build a form that is stored in the table 'data". I need 2 things built:
1. a search page that will do an advanced search like this:
- displays a drop down box where people can select the field they want to search, i.e. "parent1" and using JavaScript add a text box so that they can enter their text query.
- a (+) plus sign that the user will click on to add another search filter, meaning if clicked it will add another "parent" and list it's options if multiple options are stored in the "childs" table.
- the search filters will be ordered horizontally for "AND" filters and vertically for "OR" filters like the following example.
parent1=child1 AND parent2=child1 AND parent3=child2
2. The result from the search query will be displayed using the jqxGrid at [url removed, login to view] (see the Filtering Row demo)
- the grid should be sortable by enabling the option in the variables
- each result will be linked to a page and a unique variable like this i.e. [url removed, login to view]
- The database as well as the basic HTML will be provided. This project is for a demo so there is no fancy data or design needed.
- I'm only considering bids with 1 or 2 days max deadlines.
- you must prove to me that YO CAN UNDERSTAND DIRECTIONS and that we can have clear communications.
- you must DELIVER ON TIME if you want to keep working with me
- while developing you should be AVAILABLE AT ALL TIMES on Skype or via email
- send me SAMPLES OF YOUR WORK if you want to be considered.
- sorry but if you have zero feedback is a no-no for now
- the project SHOULD BE FINISHED by Thursday night EST (I'm in USA) so keep that in mind when bidding.
Awarded to:
Skills Required
Looking to make some money?
- Set your budget and the timeframe
- Outline your proposal
- Get paid for your work
Hire Freelancers who also bid on this project
Looking for work?
Work on projects like this and make money from home!Sign Up Now
- Forbes
- The New York Times
- Time
- Wall Street Journal
- Times Online


text:
The SourceForge Speed Test measures Latency/Ping, Jitter, Download Speed, Upload Speed, Buffer Bloat, and Packet Loss. Upon completion, you can view detailed reports about your connection. This HTML5 speed test does not require Flash or Java, and works on all devices including tablets and smartphones. Host on your own infrastructure or use ours. For licensing, inquire today.Sponsored Listing
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WideStudio is an Integrated Development Environment (IDE) for building window applications in C++, Ruby, Python an Perl for Windows, MacOSX, Linux, FreeBSD, SOLARIS and other unix and BTRON and T-Engine. This is open and free (under MIT/X Consortiun Lice43 weekly downloads
JavaAmp is an clone of the well known multimedia player Winamp written in Java. It uses the Lightweight Java Game Library (LWJGL) and FMOD for playing music and visualizing it.9 weekly downloads
Ascalaph Graphics
Molecular Graphics and Dynamics. Molecular model builder. Part of the Ascalaph Designer http://sourceforge.net/projects/asc-designer/ project. Windows & Linux.3 weekly downloads
You're probably paying too much for cell phone service. Wirefly compares hundreds of plans to help you save. Enter what you need (minutes, data, texts) into Wirefly's innovative plan comparison tools and see your savings instantly.Sponsored Listing
OpenFrag is an Open Source, multi-platform game. It plays in a medieval environment where Orcs and Humans fight to the death in a multiplayer session. Compile instructions and dependencies can be found on the following wiki page: http://wiki.openfrag.org3 weekly downloads
A 3D puzzle game for PC. A tetris like game. All in OpenGL and C++.
AudioCarver is a music composition application featuring a user interface based on 3d modeling.
Easy Math Wizard
This is meant to be a powerful, but easy to use math software. It's by the user and for the users.
Humanitys is thought to be a new and original MMORPG game. It is a completely free application developed by B.M.A (www.buhnicialexandru.com) and his Romanian team, available for a lot of operating systems.
Laser Squad 3D
This project has been superceeded by Laser Tactics - see http://sourceforge.net/projects/nucleargrave.
Simple game in SDL and C++
Om@r Hard Mission
The Game Consists of a couple of missions. each mission has an idea different from the other missions. the mission takes from 30 minutes to an hour to be complete.
Om@r Missing Treasure
In the Middle Ages, A Captain Wanted to get a treasure from an island .. he kept searching for the map of the treasure, entering islands , fighting pirates , till he got the map , then followed the map till he got the treasure ..
Racers of Streets
Racers of Streets is going to be a simulation racing game, with the possibility to tune your car, race against other players over the internet, drift, drag, and much more.
Sickness is a FPS build around OGRE 3D. It's using Audiere, Newton and some other utilities. The story is happening in a city infected by a strange virus.
StarTrek 40th Aniversario
Un proyecto sobre un juego online, 3d en primera persona, multiusuario.. basado en PHP y VRML2.0
The Myth Game Engine
The Myth Game Engine: A very easy to use 3D game engine, designed for making RPG's. With networking, very fast rendering,very simple functions to do complex tasks, and very easy to expand! Using C/C++; OpenGL; SDL; SDL_Net; DevIL; OpenAL. Linux,Windows
World Of Battlezone
this expansion for the game combat commander battlezone2 the [wobz] or [zrfbz] thing brings wole active content in a battlezone2 gives the user play 26 races instead 2 as default note wole thing alredy made we here in try to impruve its sub sections
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