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ED Magedson – Founder
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uclip couponsnewburgh, Indiana United States of America
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Uclip coupons went into my account and took money out WITHOUT my authourization. This is called STEALING and I need my money back. I received a payday loan and they(Uclip) took it upon their self to take my money saying I subscibed to them.
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Look left and you'll see her. Look right, and you'll see her reflection. You're caught between her and her reflection at the moment, and you know that her reflection is the more dangerous of the two.
It can only get worse of course, and you knew that this morning as you woke up. The sunlight dappled the ceiling as it peeked through the branches of the orange tree outside your window, and the patterns that were made by light and shadow were an omen, a warning, a foreshadowing. You read the patterns, just as your mother taught you, and you saw that the day had no good ending to it, and still you went out, still you had to see if you could change what was to come. I've told you so many times now that the future is immutable, that what happens happens and no-one but no-one cares. You won't believe me. You keep trying to change what will be, and this is where you find yourself now. Scylla and Charybdis have nothing on this, you're truly caught between the rock and the hard place.
Her reflection smiles at you, and it's independent of her: she's not even looking in your direction. You can feel the space around you changing, contracting in a way that makes no sense, that squeezes your mind but not your body, that stretches you out like cheesecloth in a mangle, and you know that something bad is going to happen.
It's horrible isn't it? Being able to sense the future but not read it? Knowing that something is going to become, and because you don't know how it will happen, there's nothing you can do to stop it. You should have listened more to your mother while she was still there for you.
Her reflection smiles again, and seems to flex, stretch, and warp. As you watch it pulls itself free from the mirror and stands parallel to her, with only you in the way. You remember this from the tales you were told when you were little. Only one has a right to this world, only one can survive. And it's survival of the fittest.
Which do you want to survive? Her, or her reflection? Because when you move, you choose.

subset: commoncrawl


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Reviewed By MARCO D (BROOKLYN, NY) Reviewed for a 2016 Ford Fusion —5/11/2017 8:46 PM
It give you the sports look on a classy car.
Reviewed By Andrea J J (Bedford, OH) Reviewed for a 2010 Ford Explorer —3/4/2017 5:00 PM
I bought the rocker panels for my truck and I love the way it looks. I put them on myself using my Black and Decker laser (that you use to hang pics) has a magnet. Just make sure you put where you want cause if you pull it up some of the sticky 3M tape will come up and make it harder to stick on. May have to use something. But in the end it does look real nice. Good Luck!


text: "We are proud of Uncommon Ground's incredible accomplishment of becoming the Greenest Restaurants in the Country," says Michael Oshman, Green Restaurant Association Founder and CEO. "Uncommon Ground is leading the way for American restaurants and the American economy, demonstrating that green practices are both good for the planet and the bottom line. They have truly raised the bar today of what all restaurants can accomplish."In addition to being named the Top Green Restaurant in America, Uncommon Ground has racked up a venerable who's who of awards in the industry including: - "Best New Restaurants" - Chicago Magazine 2008- "First Certified Organic Roof Top Farm in the Country" - M.O.S.A. 2008- "Recipient of the 'Governor Sustainability Award'" - 2010 & 2011- "Winner of the 'Mayor's Landscape Award', City of Chicago" - 2009, 2010, & 2011- "Winner of the prestigious 'USGBC Environ-motion Award'" - March, 2009 Uncommon Ground offers environmentally friendly, contemporary comfort cuisine with an emphasis on seasonal, regional and organic ingredients. The bar features famous house-infused organic cocktails, a selection of local craft beers and an eclectic American wine list. National music acts perform nightly in an intimate acoustic listening room while art openings feature local Chicago artists. The invite only media tour and cocktail reception will take place at 5:30PM on December 13th at the Devon location. Invitees include Uncommon Ground loyalists, public officials, Chicago and nationally renowned green industry leaders, and will feature a rare media tour focusing on some of the amenities that brought Uncommon Ground to the world's attention. For media inquiries and more information about the event, contact Chris Foltz at 312-772-4865 or by email at chris @ christopherfoltz . com SOURCE Uncommon Ground


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Robert McCracken has sent a bold and welcome message to every single amateur boxer in Britain, both male and female, that the selection process for the 2012 Olympic Games is far from over.
McCracken, a former British light-middleweight champion as a professional, is the amateur sport's performance director and he has taken the unusual and potentially embarrassing step of agreeing to a new Great Britain Amateur Boxing Championship, to take place on 12-13 November at the Echo Arena in Liverpool.
"This event will hopefully convince boxers and officials that the door is still open for a place in the squad for London," said McCracken, who also trains former world champion Carl Froch.
At the GB championships the quartet of boxers will be selected by the English, Scottish and Welsh associations with the fourth competitor being supplied from McCracken's podium squad of elite boxers. There will be semi-finals, a final on the Sunday, and the winner, assuming it is not a boxer from the podium squad, will receive an invite to officially join McCracken's Olympic dreamers.
"There are several weights where there are multiple choices and potential selection headaches, but those are the type of problems I like," added McCracken, who returned from the European championships in Moscow two months ago with five medals, the best haul for 50 years.
There will be 10 men's weights and just three for women at the London Games and, as the host nation, Britain will receive a total of six places, which is controversially expected to be divided five to one in favour of the men. To make way for the women (some of whom will have to gain or lose in excess of 12 pounds because only three of their 13 weight classes have been accepted) the men's light-flyweight category has been dropped.
Last week in Cardiff, Great Britain drew 6-6 with a Rest of the World team. Three of the nine elite women on the squad are currently at the European Championships in Hungary and the long and winding path to the 2012 Olympic Games continues today when British boxers meet Kazakhstan, China and France over two days of competition at the English Institute of Sport in Sheffield.
"The only way to win medals at the Olympic Games is to meet the best boxers in the world," McCracken said. "This weekend in Sheffield there will be Olympic and world champions and our boxers will have to perform because there are no shortcuts and no secret routes. The road to London 2012 has started."
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- Boxing
- Kazakhstan
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Jade Goody granted Indian tourist visa
Goody is currently trying to rebuild her public image after the Shilpa Shetty episode at the Big Brother house.
New Delhi: Former Big Brother housemate Jade Goody, who allegedly passed racist remarks against actress Shilpa Shetty has been granted a six month tourist visa to India.
According to the Indian High Commission in London, Goody had earlier applied for a normal tourist visa to visit India. The exact dates of her visit to India are yet to be finalised.
Meanwhile after Friday night's round of evictions Shilpa Shetty has become the bookies' favourite to win the reality show on Sunday.
But whether she wins or not this weekend, Shetty, who has already made millions from a 14-year career in Bollywood, will reap the benefits of emerging from the race furor with her dignity intact.
In addition to the 367,000 pounds fee she was reportedly paid by Endemol, there is a 100,000 pounds contract on the table to present Cricket Star - a new X Factor-style reality show - which she will consider with her mother Sunanda, who is also her manager, and UK agent Jazz Barton, after she comes out of the house.
The Indian version of Cricket Star has been a success and the show's chief executive Fraser Castellino has described Shetty as "perfect host" for its UK version, to begin in summer.
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Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread recurrent amplifications and deletions targeting loci syntenic to those not only in human T-ALL but also in diverse human haematopoietic, mesenchymal and epithelial tumours. These results indicate that murine and human tumours experience common biological processes driven by orthologous genetic events in their malignant evolution. The highly concordant nature of genomic events encourages the use of genomically unstable murine cancer models in the discovery of biological driver events in the human oncogenome.
An increasing compendium of tumour genes underpins the development of effective, targeted therapeutic agents for cancer. This model now influences all aspects of cancer research, motivating intensive efforts in cancer gene discovery. Array-based comparative genome hybridization (array-CGH) has uncovered highly re-arranged human cancer genomes harbouring many recurrent copy number alterations (CNAs)1. Targeted re-sequencing of human cancers has uncovered pathogenetic mutations in genes such as BRAF in melanoma2 and NOTCH1 in T-cell acute lymphoblastic leukaemias/lymphomas (T-ALL)3. Nonetheless, identifying true cancer genes, that is, differentiating 'causal' genomic events from bystander 'genomic noise', remains challenging.
A growing body of evidence, including cross-species preservation of oncogene transcriptional signatures4 and synteny of tumour-associated CNAs5-9, indicates that mouse models of human cancer can serve as biologically relevant filters for complex human oncogenomes. More recent high-resolution genomics-based studies have proven that such cross-species comparisons enable the efficient identification of new oncogenes in human cancers10,11, and re-sequencing of key genes in murine cancer models reveals conservation of somatic signature mutational events12. However, a limitation of mouse cancer models for comparative oncogenomics is the relatively benign cytogenetic profiles of most genetically engineered murine cancers8,10,11,13. On the other hand, murine cancer genomes can be destabilized experimentally, to simulate the rampant chromosomal instability of human cancers, including those with telomere dysfunction, impaired DNA damage checkpoints such as Atm, dominant Trp53 mutant alleles, and defective DNA repair14-21. These 'instability models' of cancer, coupled with high-resolution genomic technologies, hold the potential to provide highly informative systems for comparative oncogenomics.
In this study, we generated a murine lymphoma model that combines the genome-destabilizing impact of Atm deficiency and telomere dysfunction to effect T lymphomagenesis in a Trp53-dependent manner. We applied multiple genome analysis technologies to identify cancer-associated alterations shared between our mouse model and human cancers. These systematic cross-species comparisons uncovered many syntenic CNAs, not only in lymphomas of the T-cell lineage, but also in other human tumour types, emphasizing the common genetic and biological events in mouse models of cancer. Re-sequencing of candidate genes in syntenic CNAs readily identified FBXW7 and PTEN as commonly mutated genes in human T-ALL.
Nearly all Atm-/- mice develop thymic lymphomas22 with moderate levels of aneuploidy and recurrent chromosomal rearrangements23. In Terc-/- Atm-/- mice, telomere dysfunction suppresses lymphoma development, which may relate in part to Trp53 activation20,21 and/or altered chromosomal dynamics24. To address this directly, we inter-crossed Terc, Atm and Trp53 mutant mice to generate various genotypic combinations from this 'triple'-mutant colony (hereafter designated as 'TKO' for all genotypes) and found that telomere dysfunctional (that is, third (G3) and fourth (G4) generation Terc-/-; ref. 21) Trp53+/- or Trp53-/- TKO mice developed lymphoma with shorter latency and higher penetrance relative to Trp53+/+ TKO animals (Fig. 1a). Moreover, lymphomas from Trp53+/- TKO mice showed reduction to homozygosity in 14/15 specimens examined (Fig. 1b), indicating strong genetic pressure to inactivate Trp53 during lymphomagenesis. These TKO tumours resembled those from conventional Atm-/- mice with effacement of thymic architecture by CD4+/CD8+ (less commonly CD4-/CD8- or mixed single/double positive) lymphoma cells (Fig. 1c, data not shown). Together, these observations strongly suggest that an Atm-independent Trp53-dependent telomere checkpoint constrains lymphoma development.
We undertook spectral karyotype (SKY) analyses to quantify chromosomal rearrangements in nine telomere-deficient (G1-G4 Terc-/-) and 9 telomere-intact (G0 Terc+/+ or Terc+/-) TKO lymphomas (Fig. 1d; Supplementary Fig. 1; Supplementary Table 1). Relative to G0 tumours, G1-G4 TKO lymphomas showed a greater frequency of chromosome structural aberrations (0.34 versus 0.09 per chromosome, respectively, P < 0.0001, t-test), including multicentric chromosomes, non-reciprocal translocations, and p-p, p-q and q-q chromosome arm fusions involving homologous and/or non-homologous chromosomes. Several chromosomes (specifically, 2, 6, 8, 14, 15, 16, 17 and 19) were involved in significantly more dicentric and robertsonian-like rearrangements in G1-G4 relative to G0 TKO tumours (P < 0.05; t-test; Fig. 1e), suggesting that these events provide adaptive mechanisms to tolerate telomere dysfunction and/or have causal roles in lymphoma development.
In the mouse, cancer-associated chromosomal rearrangements of the types described above are by-products of breakage-fusion-bridge cycles associated with telomere dysfunction and defective Trp53 function14, and similar events can generate amplifications or deletions at the translocation site in human cells25. These processes, together with biological selection, drive emergence of clonal CNAs targeting cancer-relevant genes in the mouse6,15. We therefore compiled high-resolution genome-wide array-CGH profiles of 35 TKO tumours (Supplementary Table 1) and 26 human T-ALL cell lines and tumours (Supplementary Table 2) for comparison. TKO profiles revealed marked genome complexity with all chromosomes exhibiting regional and focal recurrent CNAs (Fig. 1f), some of which were observed in >40% of samples (for example, amplicons targeting distinct regions on mouse chromosomes 1, 2, 3, 4, 5, 9, 10, 12, 14, 15, 16, and 17; and deletions on 6, 11, 12, 13, 14, 16 and 19), corresponding well with rearrangements detected by SKY.
In addition to recurrent physiological deletions of T-cell receptor (Tcr) loci (Fig. 1f, arrows; Supplementary Fig. 2) as expected for T-cell derived tumours, we observed pathogenetically relevant recurrent genomic events in this instability model, such as a high-amplitude genomic event on chromosome 2. By SKY, this is a recurrent non-reciprocal translocation involving chromosome 2 (band A3) with different partner chromosomes (Supplementary Fig. 3). By array-CGH, the CNAs in 4 independent TKO tumours shared a common boundary close to the 3′ region of the Notch1 gene, with 2 additional tumours harbouring Notch1 focal amplifications (Supplementary Fig. 3; data not shown). NOTCH1 activation by carboxy-terminal structure alteration and point mutations is a signature event of human T-ALL3,26,27. Although the murine genomic rearrangements differ from NOTCH1 translocations in human T-ALL27, their common shared boundary involving Notch1 suggested potential relevance to the TKO tumours. Thus, we performed Notch1 re-sequencing in several TKO lymphomas lacking Notch1 genomic rearrangement and uncovered truncating insertion/deletion mutations and non-conservative amino acid substitutions in the Notch1 PEST and heterodimerization domains, as well as broader deletions within exon 34 encoding the PEST domain (Supplementary Fig. 4a; Supplementary Table 1). This mutation spectrum is analogous to that observed in human T-ALL, because the PEST and heterodimerization domains are two hot spots of NOTCH1 mutation (Supplementary Fig. 4a, see below)3. Biochemically, these mutations promote activation of mouse Notch1 as shown by higher levels of both full-length and the active cleaved form (V1744)28 of Notch1 proteins (Supplementary Fig. 4b). Transcriptome profiling further showed upregulation of several Notch1 transcriptional targets including Ptcra, Hes1, Dtx1 and Cd3e, which correlated well with messenger RNA levels of Notch126 (Supplementary Fig. 4c).
The observation of physiological deletion of Tcr loci and a human-like pattern of Notch1 genomic and mutational events in TKO tumours prompted the assessment of the extent to which other CNAs emerging in TKO lymphomas mirrored those seen in human T-ALL. To this end, we first defined the minimal common regions (MCRs, regions overlapping in more than one tumour as defined in Methods) in the TKO genome using an established algorithm with criteria of CNA width ≤10 Mb (megabases) and amplitude >0.75 (log2 scale), yielding 160 MCRs with average sizes of 2.12 Mb (0.15-9.82 Mb) and 2.33 Mb (0.77-9.6 Mb) for amplifications and deletions, respectively (Supplementary Table 3). This frequency of genomic alterations is comparable to most human cancer genomes (for example, see below) and significantly above the typical 20 to 40 events detected in most genetically engineered 'genome-stable' murine tumour models8,10,11,29. Next, by orthologue mapping of genes resident within the MCRs of CNAs, we compared the TKO MCRs with similarly defined MCRs in human T-ALL to identify syntenic overlap. Here, 18 of the 160 MCRs (11%) were found to overlap across species (Table 1); the extent to which overlap occurred was significantly greater than that expected by chance alone (P = 0.001 and 0.004 for deletions and amplifications, respectively). Moreover, these syntenic MCRs included several genes already implicated in T-ALL biology, such as Crebbp, Ikaros (also known as Ikzf1) and Abl1 (refs 30-32). These data support the relevance of murine models to human cancer biology and their potential use for human cancer gene discovery through comparative oncogenomics.
A few TKO tumours with minimal Notch1 expression exhibited elevated Notch4 or Jagged1 (Notch ligand) mRNA levels (data not shown), prompting a detailed examination of the genomic and expression status of components in the Notch pathway. Indeed, a syntenic MCR encompassing the Fbxw7 gene (MCR no. 18, Table 1; Fig. 2a) was observed across species. Although extremely focal in humans (Fig. 2a), the syntenic overlap made it unlikely that such deletion events represented copy number polymorphisms. FBXW7 re-sequencing in a cohort of human T-ALL clinical specimens (n = 38) and cell lines (n = 23) (Supplementary Tables 2a, c and 4) revealed that FBXW7 was mutated or deleted in 11/23 of the cell lines (48%) and 11/38 of the clinical samples (29%), making this one of the most commonly mutated genes in human T-ALL (Supplementary Tables 4 and 5). Consistent with reduced expression of Fbxw7 relative to non-neoplastic thymus in 19 of the 24 TKO lymphomas (Fig. 2b), these FBXW7 mutations in human T-ALL were predominantly mis-sense mutations, and particularly clustered in evolutionarily conserved arginine residues of the third and fourth WD40 domains involved in target binding33 (Fig. 2c). Moreover, re-sequencing of FBXW7 in matched normal bone marrows from several patients in complete remission showed that the two most common mutations observed (R465, R479) were acquired somatically (data not shown). Additional mutations are likely to be somatic because the majority have been reported as somatic mutations in other tumour types (http://www.sanger.ac.uk/genetics/CGP/cosmic/) and none were present in public single nucleotide polymorphism databases. Finally, 19 of 21 mutations were heterozygous, consistent with reports that Fbxw7 acts as a haplo-insufficient tumour suppressor gene34.
FBXW7 is a component of the E3 ubiquitin ligase responsible for binding the NOTCH1 PEST domain, leading to ubiquitination and proteasome degradation35. PEST domain mutations in human T-ALL prolong the half-life of intracellular NOTCH1, indicating that FBXW7 loss may cause similar phenotypic effects. To address this, we characterized the cell lines and clinical samples for NOTCH1 mutations (Supplementary Tables 2a, 2c, 4 and 5). Interestingly, there was no association between known functional mutations of NOTCH1 (N-terminal (HD-N) and C-terminal (HD-C) heterodimerization domains and PEST domains) and FBXW7 mutations (P = 0.16). However, among samples with NOTCH1 mutations, FBXW7 mutations were found less frequently in samples with a mutated PEST domain (4/19; 21%) than samples with mutations of only the HD-N or HD-C domain (13/20; 65%; P = 0.009). This is consistent with the hypothesis that mutations of FBXW7 and the PEST domain of NOTCH1 target the same degradation pathway, and little selective advantage accrues to the majority of tumours from mutating both components. On the other hand, the lack of NOTCH1 and FBXW7 mutation mutual exclusivity suggests that FBXW7 affects other pathways in addition to NOTCH (see discussion).
Focal deletion on chromosome 19, centring on Pten, was among the most common genomic events in TKO lymphomas (Table 1; Fig. 1f). Array-CGH, coupled with real-time genomic PCR, documented homozygous deletions of Pten in 15/35 (43%) TKO lymphomas (Fig. 3; Supplementary Fig. 5). PTEN is a well-known tumour suppressor36 and the inactivation of the homologue in the murine thymus is known to generate T-cell tumours37. Correspondingly, array-CGH confirmed that 4 out of 26 human T-ALL samples had PTEN locus rearrangements. Additionally, re-sequencing of the 61 T-ALL cell lines and clinical specimens (Supplementary Table 2) uncovered inactivating PTEN mutations in 9 cases, none of which was found in public SNP databases. Each is predicted to cause protein truncation and is observed in other cancers36 but shows no clear correlation with NOTCH1 mutations (Supplementary Tables 4 and 5). PTEN mutations were more frequent in cell lines (7/23; 30.4%) than in clinical specimens (2/38; 5.2%) (Supplementary Table 4). Because these clinical specimens were newly diagnosed cases, whereas the cell lines were mostly established from relapses, this difference in mutation frequency may suggest that PTEN inactivation is a later event associated with progression, among other possibilities.
Northern and western blot analyses and transcriptome profiling of the TKO and human T-ALL samples revealed a broader collection of tumours with low to undetectable PTEN expression (Fig. 3b, data not shown) with elevated phospho-AKT. Moreover, AKT activation may have been driven by focal Akt1 amplification and Tsc1 loss in two TKO samples (Fig. 3c; data not shown). Lastly, the biological significance of Pten status in TKO lymphoma is supported by their sensitivity to Akt inhibition in a Pten-dependent manner (Supplementary Fig. 6) in response to triciribine, a drug known to block Akt phosphorylation and inhibit cells dependent on the Akt pathway38.
Although cross-species comparison showed numerous concordant lesions in cancers of T-cell origin, the fact that this instability model is driven by mechanisms of fundamental relevance (telomere dysfunction and Trp53 mutation) to many cancer types suggested potentially broader relevance to other human cancers. A case in point is the PTEN example above; PTEN is a tumour suppressor for multiple cancers36. We therefore extended the cross-species comparative genomic analyses to 6 other human cancer types (n = 421) of haematopoietic, mesenchymal and epithelial origins, including multiple myeloma (n = 67)39, glioblastoma (n = 38) (unpublished) and melanoma (n = 123) (unpublished), as well as pancreatic (n = 30) (unpublished), lung (n = 63)40 and colon adenocarcinomas (n = 74) (unpublished).
Compared to similarly defined MCR lists (that is, MCR width ≤10 Mb; Fig. 4a) of each of these cancer types, we found that 102 (61 amplifications, 41 deletions) of 160 MCRs (64%) in the TKO genomes matched with at least 1 MCR in 1 human array-CGH data set, with strong statistical significance attesting to non-randomness of the overlap (Fig. 4a). Confidence in the relevance of these syntenic events was bolstered by the observation that more than half of these syntenic MCRs (38 of 61 amplifications or 62%; 22 of 41 deletions or 53%) overlapped with MCRs recurrent in two or more human tumour types (Fig. 4b). Moreover, a significant proportion of the TKO MCRs were evolutionarily conserved in human tumours of non-haematopoietic origin (Fig. 4c). Among the 61 amplifications with syntenic hits, 58 of them (95%) were observed in solid tumours, whereas the remaining 3 were uniquely found in myeloma (Fig. 4c). Similarly, 33 of 41 (80%) syntenic deletions were present in solid tumours (Fig. 4c). Among these are Trp53, deleted in 5 of 7 human cancer types, and Myc amplifications in 6 human cancers. This substantial overlap with diverse human cancers was unexpected.
Next, to provide an additional level of validation for these TKO genomic events, we determined whether these syntenic MCRs targeted known cancer genes. Mouse homologues were found for 237 of 363 genes listed on the Cancer Gene Census41, and of these, 24 were found within the 104 syntenic MCRs (Supplementary Table 6). These included 17 oncogenes in amplifications and 7 tumour suppressor genes in deletions. However, the majority of these syntenic MCRs do not contain known cancer genes, raising the strong possibility that re-sequencing that is focused on resident genes of syntenic MCRs may provide a high-yield strategy to identify somatic mutations in human cancers, a thesis supported by the FBXW7 and PTEN examples.
We describe here the characterization of a mouse model of T-cell lymphoma engineered with telomere and checkpoint defects. In these unstable murine tumours, cytogenetic and copy number analyses reveal a level of genome complexity comparable to that of human solid tumours. The presence of rampant genome instability, and absence of an engineered dominantly acting oncogene, created a model system in which biological selection pressures drive acquired genomic events with potential relevance to human T-cell malignancy and/or cancer in general. In this model, murine cancers acquire widespread recurrent clonal CNAs targeting loci syntenic to alterations present in a human T-ALL as well as a large collection of diverse haematopoietic, mesenchymal and epithelial cancers. The relevance of these non-random syntenic events is supported on several levels, including the presence of syntenic MCRs in more than one human cancer type; the identification of MCRs harbouring known cancer genes; and the identification of somatic mutations in genes within conserved MCRs (FBXW7 and PTEN).
Evolutionarily conserved genomic deletions targeting the FBXW7 and PTEN loci motivated re-sequencing of them in human and murine T-ALL samples, revealing frequent mutations. FBXW7 mutation has been described in about 5% of colorectal and ovarian cancers42-44, although its involvement in T-ALL has not been reported previously. As a key component of the E3 ubiquitin ligase that ubiquitinates NOTCH1, loss or mutation of FBXW7 is expected to be functionally equivalent to PEST domain mutation of NOTCH1, prolonging NOTCH1 half-life35. Indeed, a statistically significant anti-correlation is observed between presence of PEST domain mutations in NOTCH1 and presence of FBXW7 mutation in human T-ALL samples. However, the fact that several samples with FBXW7 mutations have wild-type NOTCH1 (5/22) strongly implies that other pathways may be affected by FBXW7 mutations in some cancers. Indeed, FBXW7 is known to promote degradation of other proteins implicated in lymphoma biology such as Aurora A (also known as AURKA), c-Jun (JUN), Cyclin E (CCNE1) and C-myc (MYC)34,35, the latter of which is also a transcriptional target of NOTCH signalling45.
In summary, the compelling synteny between TKO tumours and several human cancers of diverse origins demonstrates that engineered chromosomal instability in the mouse can engender genomic alterations similar to those observed in complex human oncogenomes, providing evidence that murine and human tumours experience common biological processes driven by the orthologous genetic events. These results provide support for the use of such murine models as a guidepost to focus and prioritize re-sequencing efforts in human cancer because cross-species synteny serves as a measure of validation by virtue of the evolutionary conservation and use of different genetic mechanisms (that is, mutation and copy number) involved. Furthermore, the mouse can facilitate the differentiation between somatic CNAs and copy number polymorphisms owing to the fragmentation of syntenic regions in the mouse and human genomes. We conclude that genomically unstable mouse cancer models represent a valuable resource for mining complex human cancer genomes.
Terc Atm- and Terc Trp53-deficient mice described previously21,46 were interbred, maintained in pathogen-free facilities and followed for lymphoma development. Resultant TKO lymphomas were harvested from moribund animals and metaphase preparations of primary cultures were used for SKY profiling. DNA and RNA were extracted from the murine TKO tumours as well as from human cancer cell lines and tumours for performing array-CGH and transcriptome profiling, respectively. MCRs of 10 Mb or smaller were defined by described algorithms39,47 for murine lymphomas and each of the 6 different human cancer types. Syntenic overlap was determined based on orthologue mapping of MCR resident genes and statistic significance of the overlap calculated by permutation. Known cancer genes were as defined by the Cancer Gene Census41 (http://www.sanger.ac.uk/genetics/CGP/Census). Gene mutation status was established by denaturing high-performance liquid chromatography as previously published48, and by bidirectional sequencing. All eight array-CGH data sets used in this study are available on the GEO website under the accession number GSE7615.
We thank Y. Zhang, A. Yu and K. Marmon for excellent mouse husbandry and care, and C. Greenman and E. Pleasance for helpful discussion on statistical analyses. R.S.M. was supported by the Damon Runyon Cancer Research Foundation. P.J.C. was supported by the Kay Kendall Leukaemia Fund, and B.C. is supported by a grant from GlaxoSmithKline. K.K.W. was supported by an NIH award. M.R.S. and P.A.F. are supported by the Wellcome Trust. L.C. and R.A.D. are supported by NIH grants, LeBow Fund to Cure Myeloma, the Chris Elliot Foundation, and the Center for Applied Cancer Science of the Belfer Institute for Innovative Cancer Science. R.A.D. is an Ellison Foundation for Medical Research Senior Scholar and an American Cancer Society Research Professor.
Terc Atm and Terc Trp53 deficient mice have been described previously21,46. Mice were interbred and maintained in pathogen-free conditions at Taconic Farms and Dana-Farber Cancer Institute, monitored for signs of ill-health every other day, and euthanized and necropsied when moribund. Mice found dead were necropsied specifically for signs of lymphoma. All manipulations were performed with IACUC approval.
Tumours harvested from TKO mice were partitioned for DNA, RNA and protein extraction, for histology (Brigham and Women's Hospital), and for in vitro culture. Tumour cells were cultured in RPMI with 50 μM β-mercaptoethanol, 10% CosmicCalf serum (HyClone), 0.5 ng ml-1 IL-2 (Peprotech), and 4 ng ml-1 IL-7 (Peprotech). For FACS analysis, cells were immunostained with CD4, CD8, CD3 and B220/CD45R antibodies (eBioscience) and scanned on a FACScalibur (BD Biosciences). For SKY analyses, metaphases were obtained from colcemid-treated cells incubated in 105 mM KCl hypotonic buffer for 15 min before fixation in 3:1 methanol-acetic acid. Spectral karyotyping was done using the SkyPaint Kit and SkyView analytical software (Applied Spectral Imaging) according to manufacturer's protocols. Chromosome aberrations were defined in accordance with the Committee on Standard Genetic Nomenclature for Mice.
DNA was prepared with the PureGene kit (Gentra Systems). Real-time PCR was performed with a Quantitect SYBR green kit (Qiagen) using 2 ng DNA from each tumour run in triplicate and the primers listed in Supplementary Table 7, on Applied Biosystems or Stratagene MX3000 real-time thermocyclers; copy number average of two runs was calculated using the standard curve method. RNA was extracted with Trizol (Invitrogen) according to the manufacturer's instructions, then digested with RQ1 DNase (Promega) and purified through RNA purification columns (Gentra). Reverse transcription was performed with oligo dT primers with the Oligoscript kit (Qiagen). Protein lysates were prepared by dis-aggregation in lysis buffer (Cell Signaling Technology) followed by bath sonication for 30 s. Clarified lysates were quantified with BioRad protein assay according to manufacturer's instructions, separated on 4-12% NuPage gels (Invitrogen), and transferred to PVDF membranes (Immobilon). Immunoblotting was performed with antibodies against PTEN, AKT, phospho-AKT, NOTCH1, activated NOTCH1 Val1744 (all from Cell Signaling Technology), and tubulin (Sigma) and developed with HRP-labelled secondary antibodies (Pierce) and enhanced chemiluminescent substrate.
T-ALL cell lines were subjected to both array-CGH and/or re-sequencing, as indicated (Supplementary Table 2a).
Two cohorts of clinical human T-ALL samples were used. A cohort of 8 clinical samples (Supplementary Table 2b), subjected to array-CGH, was obtained with informed consent and IRB approval at time of diagnosis from paediatric patients with T-ALL treated on the Dana-Farber Cancer Institute study 00-001. An independent series of 38 clinical specimens (Supplementary Table 2c), used for re-sequencing, was collected at presentation from 8 children and adolescents diagnosed at the Royal Free Hospital, London, and 30 adult patients enrolled in the MRC UKALL-XII trial. Informed consent was obtained from the patients (if over 18 yr of age) or their guardians (if under 18 yr) with Ethics Committee approval.
Array-CGH: genomic DNA processing, labelling and hybridization to Agilent CGH 60-mer oligo arrays were performed as per the manufacturer's protocol (http://www.home.agilent.com/agilent/home.jspx). Murine tumours were profiled against matched normal DNA or, when not available, pooled DNA of matched strain background. Labelled DNAs were hybridized onto 44K or 244K microarrays for mouse, and 22K, 44K, or 244K microarrays for human (detailed feature information for each at www.agilent.com). Profiles generated on 244K arrays were extracted for the same 42K probes on the 44K microarrays to allow combination of profiles generated on the different platforms. Fluorescence ratios of scanned images were normalized and averaged from two pairs (dye swap), and copy number profile was generated by Circular Binary Segmentation, which determines significance of change points in raw data through permutation49.
Definition of MCRs: minimal common region (MCR) definition was described previously39,47. Briefly, a 'segmented' data set was determined from uniform copy number segment boundaries, then replacing raw log2 ratio for each probe by the mean log2 ratio of the segment containing the probe. Thresholds for copy number alterations were set at log2 = ±0.4 and ±0.6 for 22K and 44K arrays, respectively, with higher thresholds for 44K profiles adjusting for differences in signal:noise detection. MCRs required at least one sample to show an extreme CNA event, (log2 ratio ≥ ±0.60 and ±0.75 for 22K and 44K profiles, respectively, and the width less than 10 Mb.
Homologue mapping: genes within mouse TKO MCRs were used to obtain their human homologue on the basis of the NCBI homologene website (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=homologene). For cancer gene mapping, mouse homologues were obtained on the basis of the Sanger Cancer Gene Census41 (http://www.sanger.ac.uk/genetics/CGP/Census).
Permutation testing: permutation testing was conducted for statistical significance of MCR overlap by randomly generating a simulated mouse genome containing the same number and sizes of MCRs in the corresponding chromosomes as the actual TKO genome; a similar set was created for each human cancer data set. The number of overlapping MCRs between mouse and each human genome was calculated and stored, and repeated 10,000 times independently for amplifications and deletions. The P value for significance of overlap for each was calculated by dividing the frequency of randomly achieved overlap by 10,000.
Mutational status was established by denaturing high-performance liquid chromatography48 and by bidirectional sequencing. Genomic DNA was extracted using the Qiagen genomic purification kit. PCR amplification and direct sequencing were done as previously described50. Sequence traces were analysed using manual and software-based analyses. All variants were confirmed by bidirectional sequencing of a second independently amplified PCR product.
Biotinylated target complementary RNA was generated from total sample RNA and hybridized to 44K Mouse Development Oligo Microarrays (Agilent) against normal control murine thymus RNA according to the manufacturer's protocols. Expression values for each gene were mapped to genomic positions on the basis of National Center for Biotechnology Information Build 34 of the mouse genome.
Cells (20,000) were plated in triplicate in 96-well format and incubated in media with varying doses of triciribine (BioMol) or vehicle (DMSO; Sigma) for 2 days, after which growth was quantified using the AqueousOne Cell Titer System (Promega). Relative cell growth was plotted versus equivalent amount of DMSO alone as control, and 3-5 replicates were performed for each.
Full Methods and any associated references are available in the online version of the paper at www.nature.com/nature.
The authors declare no competing financial interests.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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|Message view
|« Date » · « Thread »
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|"James Mitchell" <jmitch...@apache.org>
|[Resources] Request Karma
|Mon, 16 Dec 2002 20:39:04 GMT
Hi, some of you know me from the Struts project. I am a committer there. I have completed an implementation of MessageResources that I would like to add to Resources. The idea being that you can keep the key/value pairs in a relational database. I've implemented this using OJB under the covers, so you are only limited to what OJB can handle (as far as supported db vendors). If you care to see the source before making a decision, please feel free to grab the zip off my server: http://www.open-tools.org/struts-atlanta/downloads This zip file is a copy of the struts-example (1.1 b1) that has been modified to demonstrate this implementation using MySql. This implementation is compatible with every version of Struts up to and including the latest nightly build (since the API has not changed much). Includes full support for multiple keyed bundles and Modules (was Sub-Applications). I have not finished all the test cases for it yet, but that will come shortly. I'm also building a management tool that will let you (with minimal dependencies) manage the bundle resources using your own application. For those keys that are not visible on the browser, there will be a separate (optional) section that provides a web interface for such. -- James Mitchell Software Engineer/Struts Evangelist http://www.open-tools.org "C makes it easy to shoot yourself in the foot; C++ makes it harder, but when you do, it blows away your whole leg." - Bjarne Stroustrup -- To unsubscribe, e-mail: <mailto:firstname.lastname@example.com> For additional commands, e-mail: <mailto:firstname.lastname@example.com>
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Could the answer to having it all be not having kids? That's what Time magazine suggests with its latest cover story - The Childfree Life - and it's struck a nerve with female social media commentators around the world.
The article's author, Lauren Sandler, asserts more couples are choosing not to have kids because it allows them to lead more fulfilling lives. She cites a Pew Research study that shows childlessness has risen across every racial and ethnic group in America, with one in five American women who do not have children during their childbearing years, compared to one in 10 in the '70s.
Ragen Chastain agrees in her article for iVillage "I ain't having kids and it ain't nobody's business", saying: "I'm not even going to justify the idea that my completeness as a woman is based on becoming part of the stroller and sippy-cup set with a response."
However, The Stir's Sarah Bernard says: "For many of us - if not most - having children is having it all."
KJ Dell'Antonio at The New York Times even admitted she is unlikely to befriend childless women: "Do we do it overtly or subconsciously — or just by excluding and including people in our lives based on proximity and similarity without realizing that the path of least resistance is one that, for a parent like me, includes mainly friends who are piloting similar family boats?"
Perhaps the most ferocious of objectors to the Time article was journalist Kate Spicer who wrote at The Daily Mail that "Any woman who says she's happy to be childless is a liar or a fool".
Kate recently admitted she's haunted by an abortion she had at 18: "In the bitterest of ironies, that terminated pregnancy remains the sum total of my reproductive history."
At age 44 she deeply regrets her decision, as she finds herself unable to have a baby. And all the freedom, money and holidays in the world don't ease her pain.
"While a child-free life looks fun on Facebook, no number of career highs, nights at the theatre, weekends away or adult pleasures can disguise the fact that it feels - there is no other word - empty," she writes. "Between today and the end of my life, I hope there are a few more decades. But, as time goes by, the idea of dying without children feels unnatural and sad."
Kate muses that she "should have put having a child first", instead of focussing on her education and career. She adds that her "parents' divorce put me off too". It wasn't until she was 40 that she met someone she wanted to settle down with, but he wasn't ready for kids. So she waited. And when she started trying for a baby, it didn't happen. Fertility treatments were unsuccessful.
"Now, at 44, adoption is always at the back of my mind, but there is some distance to go before I feel my relationship will be ready to take on that challenge," she admits.
She even wants to teach a class to 16-year-olds about "the importance of having a baby while you've still got energy and fresh eggs in your ovaries".
Kate also worries that not having children means she will miss out on unconditional love, especially when her parents are no longer around to give it.
"As a rule, flawed as all parties may be, the parent-child bond is the commonest and most reliable form of that love," she says. "Sitting writing this at my mother's desk, surrounded by my grandmother and great-grandmother's things, I feel acute awareness that as my life enters its final half, it is with a diminishing circle of love.
"The Motherhood Deniers are terribly excited about their friends. None of whom will be able to wipe their own bottoms in 40 years time, let alone those of their chums. And we all know nephews and nieces are not in the business of dedicating their lives to maiden aunts.
"I have never met a woman who regretted having children. She surely exists, but not in my experience. I have met, however, older people who lament never having kids."
Do you think childless women are "fools" for thinking they won't regret their decision? Or are Kate remarks out of line?


text:
For Lesbian Parents: Your Guide to Helping Your Family Grow Up Happy, Healthy, and Proud
€ 16,49
Besorgung - Lieferbarkeit unbestimmt
März 2001
BeschreibungRaising a child is overwhelming, thrilling, exhausting, terrifying, and joyous--and all at the same time. In addition to the adjustments that any new parents must make, lesbian mothers face numerous special questions and concerns. From "coming out" to your child to coping with the pressures of trying to be a lesbian super-mom, this wise and reassuring book offers information and support for women forging a new path in what it means to be a family. The authors are uniquely qualified for the task as expert developmental psychologists who are also coparenting two young daughters. With clarity and wit, they offer helpful advice on what kids need to know, and at what age; how to help them respond to questions and teasing from peers; ways to foster sensitivity in relatives, teachers, and others; how to talk to teens about their own developing sexuality; how parenting affects couple relationships; and much more. Chapters are packed with the insights and experiences of lesbians who have come to be parents in a variety of ways. Also included are listings of useful web sites, publications, and other resources.
InhaltsverzeichnisPart I: Introduction and Overview. Introduction: Why Write This Book? Lesbian Mothers: Who We Are. Dos and Don'ts for Lesbian Mothers. Part II. The Lesbian Family in Interpersonal Relationships From Couple to Family. How to Help Our Children Better Understand Our Family. Dealing with Others: Family, Professionals, and People in Our Children's Lives. Helping Our Children Deal with Others. Dealing with Schools. Religion and Spirituality. Child Development and Lesbian Mothers. Gender Development, Boys will be Boys, Girls will be Girls, and Men in Our Children's Lives. Sexuality and Our Children. Homophobia and Diversity. Special Circumstances. Divorce and Lesbian Breakup. Stepfamilies. Alternative Insemination and Adoption. Conclusion. Future Directions and Concluding Thoughts. Appendix: Parenting Books; Resources.
PortraitSuzanne M. Johnson, PhD, and Elizabeth O'Connor, PhD, received their doctorates in developmental psychology from the State University of New York at Stony Brook. They live on Long Island, New York, with their tow daughters.Dr Johnson has been a researcher and professor for 13 years, and is currently Associate Professor of Psychology at Dowling College. Dr. O'Connor, a stay-at-home mom, is a researcher and writer focusing on child development, adult relationships, and families.
Pressestimmen'At last, a practical book on lesbian parenting, including 'dos and dont's,' sound advice, enlightening anecdotes, and plenty of resources. For Lesbian Parents addresses issues particular to lesbian mothers as well as situations universal to all new parents. A 'must read' for lesbian mothers and moms-to-be, as well as all those lucky enough to have such a family in their lives.' - Lesla Newman, author of Heather Has Two Mommies 'This book will help make a tremendous difference in the lives of lesbian parents. Personally, I couldn't put it down! I've read a lot of books on gay and lesbian parenting, and this one is truly incredible. I expect to turn to it time and time again as a valuable resource in parenting my own child.' - Kelly Taylor, Founder and Editor-in-Chief, Alternative Family Magazine 'Johnson and O'Connor's extensive background in developmental psychology enables them to offer deep insight into a variety of childrearing issues, concerns, and questions.' - Sharon A. Cuff, MA, MSW, CSW
Untertitel: New. Sprache: Englisch.
Verlag: GUILFORD PUBN
Erscheinungsdatum: März 2001
Seitenanzahl: 248 Seiten
Format: kartoniert


text:
Welcoming the spring, Globe University-La Crosse will graduate 51 students at the 2012 Winter Quarter Graduation! The ceremony will be held at the Stoney Creek Inn at 7:00p.m. on Thursday, March 22, 2011. Students, families, and Globe staff and faculty will show their support of the graduates' achievement!
This will be Globe University-La Crosse's seventh graduation since the university opened in October of 2009. The following students will be graduating:
Accounting, Bachelor of Science Degree: Scott Herdeman* (Onalaska)
Accounting and Tax Specialist, Associate of Applied Science Degree: Jim Rhode (Holmen)
Business Administration, Associate of Applied Science Degree: Shannon Elsen (Onalaska), Bryanna Kamrath (Viroqua)
Business Administrative Assistant, Diploma: Amy Humfeld (Dakota)
Business Management, Bachelor of Science Degree: Lisa Paulson* (Holmen), Eric Elstad (Onalaska), Ashley Leis (Onalaska)
Criminal Justice, Associate of Applied Science Degree: Barbara Dahl (Galesville), Jessica Jacks* (Viroqua), Alyson Swanke (La Crosse), Jodi Willis** (Sparta), Marshel Witt (La Crosse)
Criminal Justice, Bachelor of Science Degree: Stacy Schultz (Sparta)
Heath Care Management, Bachelor of Science Degree: Melissa Henderson (Holmen)
Information Technology, Associate of Applied Science Degree: Jason Bailey* (Winona), Zack Copus (La Crosse), John Zupan (La Crosse)
Massage Therapy, Associate of Applied Science Degree: Amy Miller (Onalaska), LaShara Morgan (Winona)
Massage Therapy, Diploma: Tiffany Brickl (Wonewoc), Patty Elsen** (Sparta)
Medical Administrative Assistant, Associate of Applied Science Degree: Nicole Barry* (Onalaska), Ashley Darrow (La Crosse), Amanda Johnson (Rushford), Heather Peterson (Camp Douglas), Heather Stallman (Galesville), Kelsey Stello (West Salem)
Medical Assistant, Associate of Applied Science Degree: Christa Barber (La Crescent), Linnea Burkhalter* (Holmen), Terrilyn Farmer (Prairie du Chien), Dacoda Maki (Onalaska), Jennifer Meyer (Holmen), Catherine Miller (La Crosse), Tina Nguyen (La Crosse), Jordan Powell (La Crosse), Holly Subbert* (West Salem)
Paralegal, Associate of Applied Science Degree: Pa Nou Hli Vue (La Crosse)
Veterinary Technology, Associate of Applied Science Degree: Vanessa Augedahl* (La Crescent), Devin Carlson (West Salem), Michelle Curtis (Onalaska), Erica DeBoth (La Crosse), Jade Fema (Genoa), Karen Grosskopf (La Crosse), Marcie Jenson (Caledonia), Victoria King (Onalaska), Jessica Larson* (Viroqua), Lisa Martin* (Bruce), Shawn Sokolik (La Crosse)
Business Administration, Master Degree: Rachel Kruger (Onalaska)
*Denotes Honors (GPA of 3.50-3.99)
**Denotes Highest Honors (GPA of 4.0)
"I am very proud of each and every student that will be graduating from the Globe University-La Crosse campus. To get to this point, they all have given up things, missed events with their family, and spent countless hours studying. The dedication and passion that these students have to their program and career paths is admirable. I am confident that these students are very prepared for their future endeavors and will do great things. Congratulations winter class of 2012," said Stephanie Cline, Globe University-La Crosse Campus Director.


text:
Pharmacology of Bombax ceiba Linn.
Part of the series SpringerBriefs in Pharmacology and Toxicology pp 51-67
Pharmacological Investigations and Toxicity Studies
- Vartika JainAffiliated withDepartment of Botany, University College of Science, Mohanlal Sukhadia University
- , Surendra K. VermaAffiliated withIndigenous Drug Research Centre, Department of Medicine, RNT Medical College
* Final gross prices may vary according to local VAT.Get Access
Red Silk-Cotton tree has been scrutinized for its pharmacology in various parts of the world. Different parts of Bombax ceiba has shown to possess many biological properties predominantly antioxidant, antimicrobial, anti-inflammatory, analgesic, anabolic, hepatoprotective, hypotensive and hypoglycemic activities. It has proved to be safe in various toxicity studies. However, it still needs extensive scientific exploration.
KeywordsAntioxidant Antimicrobial Antitumor Anabolic Hepatoprotective Hypotensive Hypoglycemic
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- Title
- Pharmacological Investigations and Toxicity Studies
- Book Title
- Pharmacology of Bombax ceiba Linn.
- Pages
- pp 51-67
- Copyright
- 2012
- 10.1007/978-3-642-27904-1_4
- Print ISBN
- 978-3-642-27903-4
- Online ISBN
- 978-3-642-27904-1
- Series Title
- SpringerBriefs in Pharmacology and Toxicology
- Series ISSN
- 2193-4762
- Publisher
- Springer Berlin Heidelberg
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- The Author(s)
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- Antioxidant
- Antimicrobial
- Antitumor
- Anabolic
- Hepatoprotective
- Hypotensive
- Hypoglycemic
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- Vartika Jain (1)
- Surendra K. Verma (2)
- Author Affiliations
- 1. Department of Botany, University College of Science, Mohanlal Sukhadia University, Udaipur, Rajasthan, India
- 2. Indigenous Drug Research Centre, Department of Medicine, RNT Medical College, Udaipur, Rajasthan, India
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text: How do you stand out in a tiny desert town that boasts the World's Largest Thermometer? - Easy. - Open a UFO-themed beef jerky store. "The Gateway to Death Valley" -- as blistering Baker, Calif., is known -- is also where Argentina-born Luis Ramallo parked his now-famous Alien Fresh Jerky store several years. Ramallo, a deeply serious believer in extra-terrestrials, had first opened a jerky stand near infamous Area 51 (the Air Force base central to many UFO conspiracy theories), out along the Extraterrestrial Highway in Rachel, Nev. One of the displays inside Alien Fresh Jerky in Baker, California. So much so that Ramallo is now planning the launch of his UFO Motel, which will be just behind the jerky store. "The building will be in the shape of a saucer, and it will include 20 UFO-themed rooms," Ramallo said. "We are very excited and got some important approvals just this week to move forward, so we are all set. I'm hoping to have it open within two years. And there will be nothing else like it in this world." Until the UFO Motel opens, Alien Fresh Jerky will no doubt continue to attract all sorts of interesting human visitors. The store boasts dozens of gourmet jerkys, dried fruits, nuts, stuffed olives, candies, BBQ sauces and more tasty edibles. More UFO Motel Soon to Be Landing in California Desert


text:
Home › Forums › Commerce › Gear Swap › FS: Big Gear Sale – Zpacks, GG, Montbell, Inov-8, Evernew, Traildesigns, AE, etc
Oct 1, 2012 at 7:05 pm #1294629
Please send a PM to me using the forum for any items you wish to purchase.
Gossamer Gear Gorilla 2012 Model – SOLD
Gossamer Gear Gorilla 2011 Model – SOLD
ULA Pack Cover – SOLD
Zpacks Hexamid – SOLD
Rail Riders Bone Flats Shirt – SOLD
Rail Riders Bone Flats Pants – SOLD
Montbell Alpine Light Down Jacket – SOLD
AE Down Socks – SOLD
Vasque Wasatch GTX – SOLD
Inov-8 Flyroc 310 – SOLD
Superfeet Blue – SOLD
Superfeet Black – SOLD
Sea 2 Summit Alphalight 3 Piece Set (x2) – SOLD
Petzel Tikka Plus – SOLD
GG LT4 w/ Straps + Camera Mount – SOLD
Evernew 0.9L Pot with Traildesigns Sidewinder – SOLD
Kmart Grease Pot w/ Stove and Spork – SOLD
Easton Stakes – SOLD
Black Diamond Gizmo – SOLD
Goosefeet Down Pillow – SOLDOct 1, 2012 at 7:13 pm #1917350
Joshua BillingsBPL Member
@joshuaLocale: Santa Cruz,Ca
I'd like the down booties and the ula pack cover. ThanksOct 1, 2012 at 7:22 pm #1917353
Nathan WashburnBPL Member
@nwashburnLocale: Southeast
Does the goosefeet pillow have the pocket option? If so, I'll take it.Oct 1, 2012 at 7:24 pm #1917357
No, it does not. It was actually one of the first pillows he had up for sale. I asked him to do it before he had them on his site.Oct 1, 2012 at 7:28 pm #1917361
Evan ChartierSpectator
PM SENT On booties and pillow- interestedOct 1, 2012 at 7:34 pm #1917363
david delabaereMember
@davidvcdLocale: Northern VA
Are the insoles size E ? if so I'd take them.Oct 1, 2012 at 7:48 pm #1917373
They are both size E. Do you want both? Please send a PM on which ones you are interested in.Oct 1, 2012 at 9:45 pm #1917408
Items going fast. I have the following left (see original post for item details):
2011 Gorilla
2012 Gorilla
Vasque Wasatch GTX
Montbell Alpine Light
RailRiders Bone Flats Shirt
RailRiders Bone Flats PantsOct 2, 2012 at 12:04 am #1917431
Kent C.Member
@kentLocale: High Sierra
I'll take the Bone Flats shirt. PM sent.Oct 2, 2012 at 10:52 am #1917522
I have dropped the prices on a few items (specifics above). I have also updated the list with all items that have been sold.
ThanksOct 2, 2012 at 5:39 pm #1917638
Made a few more pricing adjustments.Oct 2, 2012 at 9:18 pm #1917695
Items Left are:
2011 Gorilla
2012 Gorilla
Rail Riders Bone Flats Pants
Rail Riders Bone Flats Shirt
Montbell Alpine Light
Vasque Wasatch GTXOct 3, 2012 at 5:42 am #1917741
One more price drop. See above.Oct 3, 2012 at 8:52 am #1917775
Items left include:
GG 2011 Gorilla
GG 2012 Gorilla
RR Bone Flats Shirt
Vasque Wasatch GTX BootsOct 3, 2012 at 12:24 pm #1917837
All that I have left is the 2012 Gorilla and the Vasque Wasatch GTX.
Details above.Oct 4, 2012 at 6:21 am #1918077
2012 Gorilla and Vasque Boots left.Oct 4, 2012 at 6:04 pm #1918278
Price drop on both items.Oct 4, 2012 at 7:30 pm #1918301
All items sold. It probably goes without saying, but those of you that bought items please use care when opening the packages. Do not use a knife. I am shipping out tomorrow.
I hope you all get lots of enjoyment from your purchases!Oct 5, 2012 at 10:24 am #1918410
All items shipped this morning via USPS Priority with the exception of the 2011 Gorilla, which shipped this morning via FedEx. Most are slated to arrive Tuesday (Monday is a holiday).
You must be logged in to reply to this topic.


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Kolkata: Kirloskar Industries on Monday posted a fall of 11.3 percent in its net standalone profit for the quarter ended September 30 this year at Rs.26.79 crore as against Rs. 30.20 crore in the same period last year.
The company's total income from operations increased by 141.9 percent at Rs.1.79 crore in the period under review as against Rs.74 lakh in the similar quarter in 2014-15.
However, its other income – which comprises the bulk of the earnings – fell by 10.8 percent at Rs. 29.41 crore in the July-September timeframe as compared to Rs. 32.98 crore in the similar months of 2014.
Expenses also surged by 32.3 percent at Rs. 2.13 crore as against Rs. 1.61 crore.


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Colleen Dauncey (Music) and Akiva Romer-Segal (Lyrics) are a contemporary musical theatre songwriting team based in Toronto, Canada. They have written the scores to The Subway Songs, Scenes From The Bathhouse (Talk Is Free Theatre), the Toronto Fringe hit Bremen Rock City (with librettist Sara Farb), and contributed material to Touch Me: Songs for a (dis)Connected Age (Forte Musical Theatre Guild, three Calgary Critics Awards including "Best Production of a Musical"). They also wrote the score to Prom Queen: The Musical, which premiered at the Segal Centre in Montreal and received the 2016 Stage West Pechet Family Musical Award by the Playwrights Guild Of Canada. Their show Rumspringa Break! (with librettist Matt Murray) was recently workshopped at Sheridan College's Canadian Musical Theatre Project. Colleen & Akiva are currently Writers-in-Residence at Talk Is Free Theatre where they are developing Offline, a collective creation musical debuting in Spring 2017.
Colleen & Akiva's songs have been performed internationally by cabaret performers, recording artists, and Broadway stars, including being featured twice in New York's Cutting-Edge Composers series. They were selected as participants in the 2011 Johnny Mercer Songwriters Project in Chicago, the Cutting-Edge Composer series in New York, the Canadian Musical Theatre Writer Collective, Acting Up Stage's Noteworthy program for songwriters and librettists, and Theatre 20's Composium initiative.They are grateful for the generous support from the Foundation Assisting Canadian Talent On Records (FACTOR), the Ontario Arts Council, and the Canada Council For the Arts.
For updates on all of their projects, keep an eye on their Twitter feed.


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An Exclusive Evening at Rancharrah
National Automobile Museum (The Harrah Collection)
An Exclusive Member Evening at Rancharrah
Friday, April 19, 2013
6 - 8 p.m.
A unique invitation for members of the National Automobile Museum.
Enjoy wine and hors d'oeuvres in the Rancharrah mansion and hear insightful remarks about gaming since the 1930s by William A. Douglass, Ph.D., Emeritus Faculty, Center for Basque Studies, University of Nevada, Reno. Douglass is the son of founding partners of Reno's Club Cal-Neva and Comstock Hotel-Casino.
Not a member of the museum? Join Today.
Don't miss "One of America's Five Greatest Auto Museums." The National Automobile Museum (The Harrah Collection) has a "Wow!" factor you don't often find in a museum. You'll see more than 200 eye-popping cars, and authentic street scenes. The facades bring displays to life; a hardware store here, a movie theatre there which accompany artifacts from each era. Audio tours in English and Spanish included in your admission price let you explore the museum at your own pace. It's located on the corner of Lake and Mill Streets in downtown Reno with plenty of free parking. Call (775) 333-9300 or visit www.automuseum.org.
The museum is open Monday – Saturday from 9:30 a.m. to 5:30 p.m. and Sunday from 10 a.m. to 4 p.m. Admission is $12 for adults, $10 for seniors and $6 for children 6 to 18 years. Children age 5 and younger are free. The National Automobile Museum is open every day except Thanksgiving Day and Christmas Day
In order to purchase these tickets in installments, you'll need an Eventbrite account. Log in or sign up for a free account to continue.


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Detectives revealed they are looking at around 10 possible suspects for the murder of the 19-year-old in Hampton, south west London, and for linked attacks nearby on a 17-year-old girl and an 18-year-old youth.
The new witness saw a man standing over the 17-year-old girl as she lay on the ground.
She has been able to give detectives a description of him and they are producing an e-fit.
- More about:
- Christopher Hampton
- State of Virginia
- West London


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It only takes a minute to get started. Fill out our simple sign up form and login to the site.
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It's really quick


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Search for help on enabling JavaScript
Welcome to Faithful Shepherd!
The Gala is not only our largest fundraiser but a wonderful opportunity to meet other families, sign up your child(ren) for class group events, sign yourself up for adult group events, bid on class projects that your child help make and all of this while supporting our Children's school.
What is a group event? Group events are sponsored by parents and teachers of FSCS. Sponsors come up with an event that they believe will be a fun event for adults or kids for which Gala attendees would sign up. Sponsors pay for this event and come up with a price to attend the event. Gala attendees sign up and all money raised goes to the school. A win, win for all. You or your child attend this event and meet new friends and our school benefits from your donation.
What is a classroom project? Your child helped his/her class make an item that will be available for you to bid on during the Gala evening. All of these items make great keepsakes for your child!
The projects and descriptions for all group events, classroom projects and teacher held events are located in the library. Be sure to make the library your first stop. Many of these events fill up quickly and some of the events have limited space availability. Bidding closes at 7:30, so make sure you place your final bid on your child's classroom project and/or teacher held event.
The Gala hosts 3 auctions. Two during the Gala evening: a Live Auction held in the gym after dinner; and a Silent Auction, held in the Lunchroom during the cocktail hour and hor d'oeuvres . Bidding for the Silent items ends at 7:30. We also have an Online Auction beginning on January 22nd and ending on January 29th. Be sure to share the link to our online auction with family and friends and also through your online social network contacts.
All Auction items and group events will be listed on the GalaWebsite (fscsmn.ejoinme.org/gala2014). Be sure to check out these items before the Gala. Some Live Auction items are great for evenings with couples, ladies or guy's weekends, and/or vacations with friends etc. Get your group together, decide how much you all would be willing to spend, pool your money and bid on that item. If anyone has a matching program with their company for donations, make them a bidder to increase the donations to FSCS.
Raffle tickets ($20-$30) are also available for purchase at the Gala. Golden ticket envelopes are also for sale ($100). Cash or Check only for these purchases. See link "New to the Gala" for a Golden Ticket explanation.
We are introducing mobile bidding to our auction this year. Be sure to have your charged smartphone or charged wifi tablet ready to go for the evening. Stay tuned for more information about mobile bidding in Gala emails.
We look forward to seeing you at the Gala on February 1st at 5:00. In the meantime, if you have any questions about the Gala, Auctions, RSVP's, Group Events, Seating assignments or any other Gala-related questions, please contact Beth Duffy.
Kindergarten parents, reserve a spot at the Kindergarten Parent table. It's a great way to meet your child's classmate's parents and meet new friends. Contact Jen DelDotto. email@example.com
Beth Duffy- Donations Chair. email@example.com


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Digital Media and Learning
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Watchworthy Wednesday: 2016 DML Keynote RecapWednesday, October 12, 2016 Comment
In case you weren't among the nearly 500 people at the 7th annual Digital Media and Learning Conference last week at the University of California, Irvine, here are highlights from the keynotes. What is the Intellectual Culture of Games? Thanks to two factors that have emerged — mobile gaming and a healthy indie ecosystem — video games are in "the golden age," according to games expert Constance Steinkuehler, presently a professor in digital media at the University of Wisconsin–Madison and co-director of the Games+Learning+Society Center at the Wisconsin Institute of Discovery and soon to join the UCI
Meet 'The Class'Thursday, May 05, 2016 Comment
Our book is about a class of 13- to 14-year-olds at an ordinary urban secondary school in London, England. It is a famously tricky age, difficult for parents and teachers, and for the young people themselves. In conducting the research, we became increasingly curious about what young people want, how do they see the world, and how do they find a path through the opportunities and constraints they face?
Reassessing Collective IntelligenceThursday, April 07, 2016 Comment
"@MichelleFields you are totally delusional": Collective intelligence in 2016 Back in 2005, Tim O'Reilly, publisher and technology pundit, posted an essay describing "Web 2.0." In it, O'Reilly attempted to describe what had changed about the internet since the early 2000 tech bubble and what had become called "Web 1.0," the first generation of the business-oriented, public web. One of the changes of Web 2.0 that O'Reilly identified was "harnessing collective intelligence," using the group features of the web to develop new smart products. One effect of this collective intelligence, "turning the web into a global brain"
New for DML2016: Geek Out Day Features Hands-on WorkshopsThursday, March 03, 2016 Comment
On behalf of all of us at the DML Research Hub, I'm using this blog as an open invitation to our 7th annual Digital Media and Learning Conference, taking place Oct. 5-7 at UC Irvine. New this year: "Geek Out Day," Oct. 5, featuring three- and six-hour workshops on such topics as civic engagement, designing online courses, digital storytelling, learning analytics, using Minecraft to teach academics and building youth social capital. Experts in their field will lead the nine workshops and participants should expect to fully immerse themselves. In fact, space is limited so seats are
From Changing Education Systems to Changing SocietyMonday, February 29, 2016 Comment
Whether stated explicitly or not, a core proposition of DML is that there are deep consequences to the ways that young people are learning both in and out of school and using digital technology with peers, in affinity groups, as they develop interests and expertise. In the context of the U.S., digital media and learning (DML) offers challenges to the school curriculum and significantly to the organization of the out-of-school, community-based non-formal learning sector. But, what could it mean in other places around the world? I recently visited TUMO Centre for Creative Technologies, in Yerevan, the capital
Public School Classrooms: Incubators for Social LearningThursday, February 28, 2013 Comment
What does it mean to be a teacher in the 21st century? It's a question educators like Antero Garcia have been looking to answer since the digital media and learning initiative launched in 2006. Prior to joining the English department at Colorado State University in Fort Collins as an assistant professor, Antero spent eight years teaching high school English and ESL in South Central Los Angeles. While teaching at the majority-minority school, Antero took note of his students' social connection to digital media. By incorporating mobile media devices and social m edia platforms into his formal
Pop Culture Criticism as 21st Century SkillThursday, May 31, 2012 Comment
As part of the Digital Youth Network's (DYN) 2011-2012 professional development, we have set out to explore how critical media literacy can help Chicago middle school students become responsible and savvy digital producers. Through hours of discussion and self-reflection, we have decided that the challenge to integrate critical theory into our tech-heavy digital production curriculum is no easy task. In what ways can we make critical media literacy relevant to our students' desires to produce media that imitates the same mainstream content we want them to deconstruct? While teaching a DYN afterschool video production class at
Mitch Resnick: The Role of Making, Tinkering, Remixing in Next-Generation LearningTuesday, September 13, 2011 Comment
Mitch Resnick is on the conference committee for the 2012 Digital Media and Learning Conference, "Beyond Educational Technology: Learning Innovations in a Connected World." As Professor of Learning Research at the MIT Media Lab, he develops new technologies and activities to engage people (especially children) in creative learning experiences. His Lifelong Kindergarten research group developed ideas and technologies underlying the LEGO Mindstorms and WeDo robotics kits, used by millions of young people around the world. His group also developed the Scratch programming language and online community, enabling young people to create and share interactive stories, games,
Digital Media & Learning Conference 2012: Learning Innovations in a Connected WorldThursday, September 08, 2011 Comment
The 2012 Digital Media and Learning Conference, it's being announced today, will explore the richer, deeper learning enabled by the emergence of Web-enabled, mobile-based platforms that promote new models of peer-to-peer learning, anywhere/anytime learning, blended learning and game-based learning, both in school and out of school. The conference, to be held in San Francisco Mar. 1-3, 2012, will feature four core threads – democratizing learning innovation, innovations for public education, re-imagining media for learning, and making/tinkering/remixing – and steer headlong into pressing debates around the role of technology and the future of education and learning, including:
'How the Brain Science of Attention Will Transform the Way We Live, Work, and Learn'Wednesday, September 07, 2011 Comment
Duke University's Cathy Davidson has staked out a reputation as a creative intellectual force committed to transforming the industrial model of education for the digital age. In 2010, President Obama nominated her to a six-year term on the National Council on the Humanities, a position confirmed by the Senate in July. She is co-director of HASTAC (Humanities, Arts, Science, and Technology Advanced Collaboratory) and co-director of the nationwide Digital Media and Learning Competition. She has been one of our featured bloggers at DMLcentral from the start, and her posts consistently provoke and inspire. Now, she has
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The recent downgrades of numerous cat bonds triggered by changes to the risk models underpinning them may be a contributory factor in a sharp reduction in the number of non-specialised investors contributing to this sector.
Pete Vloedman of Anchor Risk Advisors analyses this dynamic.
Recent newswire headlines have brought the rationale for obtaining credit ratings on catastrophe (cat) bonds back into the structuring discussion. According to Swiss Re, approximately 94 percent of cat bonds in circulation have a credit rating. But what purpose do they serve? Are they worth the cost? Are credit ratings necessary to achieve full distribution of a cat bond? This article discusses the historical and current rationale for cat bond credit ratings.
Why do cat bonds have credit ratings?
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Catastrophe bonds, Cat bonds, Rating agencies, Alternative risk transfer


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Layal Model
RebeccaBriannePhotographer Female Boston, Massachusetts, US
My Website: WebsiteMy MM URL: http://www.modelmayhem.com/bexphoto
Mayhem # 2951572
About MePlease Note: If I send you a friend request and I'm not near you location wise it is most likely because I plan on visiting soon and would like to work with you.
Hello! Thanks for stopping by! I'm a blogger and photographer based in Boston, MA. I'm here to work with amazing models, makeup artists, stylists, and more to build my portfolio and for special assignments.
I am a visionary and have so many ideas constantly running around in my head. I hope you will join me on that journey! I travel often and would love to work with Model Mayhem members from other places. If I send you a friend request it is because I am interested in working with you.
Have you worked with RebeccaBrianne? Add Credits for RebeccaBrianne! >>
Layal Model
AllieMcC Wardrobe Stylist
Ms Antonia Model
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December 2016 -"LE COEUR EN BRAILLE" Gaumont / France dir. Michel Boujenah
UK Feature film "ALLIES " on Netflix UK and USA
Film "QUE D'AMOUR! " Director Valérie Donzelli
Best Television Film Score Award 2015 (Jerry Goldsmith Awards - Cordoba-Spain)
Best Artistic Direction Award at La Rochelle Film Festival 2013 - France
Nominated for best feature film score "Allies" (Jerry Goldsmith Awards - 2015)
Nominated for best Tv score + best title sequence (Music+Sound Awards - London 2015)


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Found someone who you're attracted to? Drop them a line or just a wink and take it from there. With a little luck you'll be on your way to an amazing adventure.
It's really quick


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Today, many SEO companies are offering monthly packages for small and medium sized businesses to help them get recognized by search engines. However, most business owners have bad experience with large companies, and will give up trying to get into Google and getting traction in social media. There is a trend among small business owners to try and do their SEO themselves to save money. Managing several social media accounts and creating content might be challenging and time-consuming. Choosing local, small expert SEO companies to handle the marketing needs can be just the right solution. Find out below why you should forget large SEO companies and focus on your local search engine optimization.
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If the "white mold" is on the actual surface of a clay pot, it is probably
just fertilizer salts that have been deposited there through evaporation.
If you don't like the looks of it, immerse the pot up to the rim in water
for a few moments, and it should dissolve. A little scrubbing will help.
If there is truly a white mold on the surface of the soil, I would be
concerned. Spray it with a fungicide.
Robin in Tampa


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Author has written 8 stories for Bones.
Name: Kara
Hometown: Benalla, Victoria, Australia
Twitter: @Spilslicious
Facebook: Kara Spilstead
My name is Kara. I'm a university student at Deakin University in Geelong, Australia, and am studying a Bachelor of Science, majoring in Chemistry, although if you looked at my subjects, I wouldn't blame you for mistaking it as Anthropology.
In my spare time (obviously) I obsess about Bones. I love the show, the characters, plot lines, and most of all BOOTH!!! (Who's with me?)
I also love Charmed, Buffy, Angel, Friends and a few other shows. But Bones is my true obsession, and that's why I write and read fan fiction.
I love reading and writing, they are true passions of mine, though over the years I've let it fall to the backburner to focus on my studies. But, because I love reading fanfiction, I lit the boiler again and have decided to give back to the community and share what I consider one of my talents. So please enjoy my stories, I take the time and put in the effort, despite hounding lecturers with excessive and unnecessary assignments.
Disclaimer: I do not own Bones or any of its characters, and I gain no profits from my work. All rights belong to Fox and Hart Hanson.


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More than 70 years after he was introduced, comicbook superhero the Green Lantern has been outed as fearless, honest and gay.
In a revitalised version of the original Green Lantern, otherwise known as Alan Scott, The DC Comics character is drawn enjoying a kiss with his partner before donning his obligatory skin-tight superhero outfit.
The gay kiss features in the second edition of the new comic Earth 2, but he's not the first gay superhero – even ignoring rumours that have dogged batman and Robin for years.
Batwoman, aka Kate Kane, is gay, while Northstar, one of the X-Men mutants from the Marvel stable, was featured proposing to his boyfriend in the last edition.
Gerry Gladston, the co-owner of Midtown Comics in New York, said of the Green Lantern: "I'm sure there will be some controversy, but nothing like it might have been 20 years ago."
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- Comic Books
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- Superheroes