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The most dangerous aspect of
breast cancer is its ability to metastasize. To spread and form new tumors
throughout the body years or even decades after
initial diagnosis. I am Andrew Ewald and my lab studies breast
cancer metastasis. We work to understand how breast
cancer cells acquire the ability to leave the main tumor and the
molecular tools that enable them to build new tumors in
the lungs, bones, and brain. We discovered a common molecular
program that is activated during metastasis in many
types of breast cancer. We're now working to leverage
this insight to identify patients whose breast cancer
is most likely to spread. And to develop new therapies
to extend their lives. [MUSIC]


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Please don't delete or modify Ygraine's appearances, people are changing them when they aren't supposed to be, REMEMBER: always double check that it's true before applying it.
WIll people please STOP assuming that Ygraine and Vivenne are siblings? The show has made no such mention of any relationship between the two, which means these pages are being filled with false information. STOP IT NOW.
I recommend that this page be locked to prevent any more false info being posted.
Hello fellow Merlin fans,
There have been a lot of changes on this site recently. Although a lot of things on "Merlin" are open to debate and left to the viewer's interpretation, some things are just the way they are. Nimueh knew indeed that a life had to be taken in exchange for another. She told Uther in season one and she also CLAIMED that she did not foresee it would be Ygraine who had to die. Nimueh's part in it and her innocence concerning Ygraine's death was raised to question in the final epsiode of season one when Merlin accused Nimueh that she was the one choosing the lifes that have to be taken, and also by Gaius who told her to "take a fair price" this time. So since it not clearified wether Nimueh knew or not we have to say that she just claimed it. Please do not change that all the time or I'm getting nuts... lol... We know that what the characters say on the show does not necessarily have to be truth. Let's hope we will learn the truth in the upcoming season, maybe the writers will have a heart and let us know :-)
Ooops, sorry, I forgot to sign my post. The above starting with "Hello fellow Merlin fans..." is my post. Sorry for confusion.Fimber (talk) 15:08, July 27, 2012 (UTC)


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Jon McAlpin has beat cancer three times. He credits keeping a positive attitude & serving others as part of his successful treatment.
today's live streaming
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Few flavours are able to take you directly to the summer like our sun fruit candy, which concentrates all the juiciness of tangerines, peaches and oranges in just one soothing lozenge. Enjoy their aroma and delicious fresh fruit flavour and make the most of their many different benefits.
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Nutritional values
Sun fruit candy ingredients:
Sorbitol; gum arabic; lactic acid, sodium lactate, citrus acid; natural aroma; natural tangerine aroma; Vitamin C, vitamin mix (niacin, Vitamin E, riboflavin, Vitamin B6, thiamine, folic acid, Vitamin B12); turmeric extract; beetroot juice concentrate; juice concentrate (orange, peach, tangerine); herb extract; natural orange aroma; menthol.


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|What happens during Onboarding?
During Onboarding, your child will:
- Go through iPad setup with Filewave, which involves erasing all data on the device and installing a profile that allows Cathedral to manage the iPad.
- Receive accounts that gives them access to many of the resources they will need during the school year. The accounts your child will be set up with during Onboarding include:
|Network Account:
|Google Account:
The Cathedral network account gives students access to:
Your student's Google account gives them access to:
Their Google account needs to be set-up prior to Onboarding. Detailed instructions for set-up will be emailed to you in the month of May.
Who should participate on Onboarding?
New students (including transfer students) and freshman for the 2020-2021 school year are required to participate in Onboarding.
Students that have not Onboarded previously in June will need to attend the last Technology Onboarding session August 5th. Click here to sign up for one of the final Onboarding sessions.
How to prepare for Onboarding:
In order to prepare for the Onboarding process, please make sure your child has their own iTunes account set up and they know the username and password for this account. You will also want to make sure that any data from the apps they may have installed on their iPad has been backed up. For step-by-step instructions on how to backup app data, click here. Ensuring they have a good backup of their data will allow them to restore this data after their iPad has been wiped.
*Please make sure your child brings their iPad fully charged to Onboarding.*
For questions or concerns, you can contact Brian Haselby at email@example.com .


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- London's areas home to corporate HQs install facial recognition technology
- Green Investment Group to sweep up 40 percent stake in East Anglia ONE offshore wind farm
- M&S briefs bra fitters to promote recycling service
- Aldi begins removing plastic packaging from meat lines
- UK university bans beef to combat 'climate emergency'
Digital Ethics
London's areas home to corporate HQs install facial recognition technology
London's King's Cross is using facial recognition to track tens of thousands of people, while prime business district Canary Wharf is also considering implementing the technology. The King's Cross area houses several office buildings, including Google's UK headquarters, Central Saint Martins college, schools and a range of retailers. Meanwhile, Canary Wharf is home to many major financial services companies, including Barclays, Credit Suisse and HSBC, as tenants. Under current general data protection laws, collecting sensitive personal data including faces requires explicit consent from the people being observed. Spokespersons for Argent, the King's Cross property developer, and the Canary Wharf Group say that the technology would be used to protect the privacy of the general public by being limited to specific purposes or threats. However, privacy groups have long voiced concerns about the implications of facial recognition on privacy rights with South Wales Police facing a legal challenge to its use of facial recognition in 2018. (Financial Times*; BBC)
Green Investment Group to sweep up 40 percent stake in East Anglia ONE offshore wind farm
Green infrastructure investor, Green Investment Group (GIG), is to buy a 40 percent stake in the East Anglia ONE offshore wind farm, in a deal that will see the Macquarie-owned firm secure almost 50 percent of the UK's offshore wind capacity. GIG said yesterday it is to acquire the minority stake from ScottishPower Renewables, part of the Iberdrola group, for £1.6 billion subject to conditions. ScottishPower Renewables will retain the remaining 60 percent stake in the project. The 102-turbine offshore wind farm is expected to produce enough power for more than 600,000 homes each year, once fully operational next year. GIG said the purchase reinforces its commitment to the UK's renewables rollout, while Iberdrola said it will use the proceeds from the sale of the stake to fund projects including building new offshore wind farms in the North Sea, the Baltic Sea, and off the coast of the US. (Business Green)
Sustainable Fashion/ Waste
M&S briefs bra fitters to promote recycling service
British retailer Marks & Spencer (M&S) is attempting to reduce the large volume of old bras sent to landfill in the UK each year, with the launch of a new campaign encouraging women to drop off their used lingerie at in-store recycling points. British women send around 320,000 old bras to landfill each year, but many of the garments could be resold or recycled. M&S will brief its in-store bra fitters to let shoppers know they can deposit their old bras in store bins, which pass on donations to Oxfam. The bras will then either be sold in Oxfam stores or processed at the charity's recycling facility before being sent to the charity's social enterprise project in Senegal, where women will sell them on to customers in their local communities. M&S has run its unwanted clothing deposit since 2012, with , some 34 million items of clothing have been diverted from landfill. (Business Green)
Aldi begins removing plastic packaging from meat lines
German supermarket, Aldi, is trialling cardboard trays to replace the plastic trays usually used to house its steaks, in a move which will cut its annual plastic output by 240 tonnes. The new trays will be used to house the supermarket's range of own-brand steaks at more than 380 of its stores across Wales, and the UK's North West and the South East. While the new packaging format does not eliminate the need for a clear, flexible plastic film, Aldi claims that it reduced the amount of plastic used, by weight, to package its steaks by 90 percent. The new cardboard alternative is classed as recyclable at kerbside level, once the film has been removed, and is made using forestry materials certified as sustainable. If customer feedback is positive, Aldi has said that it will explore the possibility of a national rollout and assess what other meat products could be packaged in the same way. (Edie)
Climate Change
UK university bans beef to combat 'climate emergency'
UK University Goldsmiths has announced it has banned beef from its campus to combat climate change, becoming the first higher education institution in Britain to do so. From next month Goldsmiths, part of the University of London, will no longer sell beef anywhere on its campus. It will also introduce a small levy on bottled water and single-use plastics to discourage use. The college said it aimed to switch to clean energy and become carbon neutral – meaning it will produce no more carbon emissions than it can offset – by 2025. Livestock farming is a major driver of greenhouse gas emissions, consumes a tenth of the world's fresh water and causes large-scale deforestation, according to the United Nations Food and Agriculture Organization. Plant-based foods and sustainable animal-sourced food could free up several million square kilometres of land by 2050 and cut 0.7-8.0 gigatonnes a year of carbon dioxide equivalent, the IPCC said in a major report last week. (Thomson Reuters Foundation)
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Image Source: white security camera on post by Paweł Czerwiński on Unsplash.


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Since trading Clint Capela, the Houston Rockets are 1-2 with their new small ball experiment. The lineup now features Robert Covington and PJ Tucker as the biggest players in the starting lineup. The new style allows Russell Westbrook and James Harden to drive to the basket more.
In the first matchup after the trade deadline, the Rockets beat the Los Angeles Lakers 121-111, behind 41 points from Westbrook. The Lakers were unable to consistently score and guard the five-out offensive set from the Rockets.
Since then, the experiment has gone downhill. The Phoenix Suns, who have 12 less wins than the Rockets, blew the Rockets out of the arena, winning 127-91. Kelly Oubre, who is emerging as a reliable piece for the Suns, scored 39 points, which including a handful of powerful dunks over the Rockets starters that were unable to rise to the rim and contest his attempts. Devin Booker, who was recently snubbed from the All-Star game, also added 33 points.
To follow the Suns beatdown, was the last second buzzer beater by the Utah Jazz. At times in that game, the Rockets seemed like geniuses. Rudy Gobert was lost on the perimeter and the Houston guards were taking full advantage of it. Harden had a 28-point triple-double and Westbrook scored 39 points. Side not: in the last two weeks, Westbrook has six performances with at least 30 points scored.
But coming off the bench for the Jazz was Jordan Clarkson, who led the Jazz in scoring with 30 points. Donovan Mitchell scored 24 and Mike Conley scored 20 to add to the Rockets defensive struggles against guards. In the end, it was Bojan Bogdanovic who hit the game winning shot, defeating the Rockets 114-113.
For this experiment to work, the Rockets need consistent scoring from Harden and Westbrook, as well as the surrounding pieces to make their three-pointers when given the opportunity. Wildly enough, because of the lack of scoring from their guards, the Lakers and Los Angeles Clippers are more at a disadvantage when playing the Rockets. So maybe Daryll Morey is a genius after all.


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About Pickleball
New to the world of pickleball? You've come to the right place. Pickleball is the nation's fastest-growing sport and one of GAMMA's specialties.
The Special Edition Pink Ribbon GAMMA Dart is a 7.4 oz lightweight paddle and made to enhance quick and sharp hand speed. Half the profits from these paddle sales will go to benefit the Breast Cancer Research Foundation (BCRF).
Similar to the Twister, the Dart is slightly less rounded in the corners, granting you a more surface area while maintaining the same weight and pop. The Dart features a textured composite paddle face fused to GAMMA Sensa Poly Core. The signature GAMMA Honeycomb Cushion Grip is featured on the Dart, as is the case with all of GAMMA premium paddles, creating the perfect connection between player and paddle.
Approved by the USAPA for sanctioned tournament play.
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New to the world of pickleball? You've come to the right place. Pickleball is the nation's fastest-growing sport and one of GAMMA's specialties.
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PRIME Minister Gordon Brown toured the Midlands yesterday to "up the tempo" of his election campaign - and was joined on stage by the King of Rock 'n' Roll.
Mr Brown travelled to Nottinghamshire and Northamptonshire to attack Tory policies and urge voters to "look at the small print" of David Cameron's manifesto.
He was joined at the rally on stage in Corby by his wife Sarah and an Elvis impersonator – who sang "The Wonder of You".
Mr Brown told supporters: "Vote Conservative on May 6 and on May 7 they will start to remove the guarantees we have put in place for the National Health Service."
He also warned that the proposed Tory national insurance cuts were a mistake. "You cannot afford to take money out of an economy now, particularly when Germany is flat, Italy and Spain are in recession, and there is still risk to the recovery in the EU," he said.
Elsewhere, David Cameron set out plans to force anyone taking over as PM mid-term to call a poll within six months.
Liberal Democrat leader Nick Clegg spent the day at home with his three young sons, who had just returned from an Easter holiday in Spain after their flight was delayed by the volcanic ash.


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Announcements & Events from Local Businesses in Two Bridges, NY
NearSay has local news and offers from businesses in Two Bridges, NY. Learn more about Two Bridges businesses.
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Direct and Compassionate
Willow is a natural born psychic, deep-trance medium, clairvoyant, clairaudient, intuitive/empath, reiki healer, and has been professional tarot reader for over 52 years. She enjoys dream working and uncovering hidden symbols in one's dreams.
Willow is here to answer any questions that you may have about career, relationships, family, life, connecting with spirit guides, loss and grieving. She is also a gifted deep trance medium to connect with passed loved ones, even pets. She can also provide dream interpretations to decipher what messages are waiting to be solved. Give her a call today!
" Just because you don't see it, does not mean it does not exist."- Anonymous
Talking with the Dead by Psychic Willow
18 October 2017
As a Deep Trance Medium, Psychic Advisor Willow has had plenty of experience contacting those who have passed. She shares her tips and observations of what you may expect during a trance session including the answer to an age old question. Continue Reading
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3½ stars
329 reviews since Mar 2014
Willow is a favorite! She is always able to tune in quickly and has been accurate for my situation. Read More
I had to tell her he got in drug I had to tell her alot she told me he had an overdose with was a lie he got killed Read More
She did very good Read More
Said he was afraid of commitment and didn't see a ring because he was unsure .... he is the total opposite lol he proposed to me on my birthday last year so yes there is a ring. Read More
I came to Willow with a question regarding a romantic relationship of mine that is structured in a way this is still often taboo to many people. I didn't feel as though we were able to connect and it felt like her personal judgments may have gotten in the way as she completely misread the situation and my intentions with this partner. I have only had this one interaction with her and believe she may still be a great reader, but she just wasn't able to see clearly in this situation that yes, is a bit out of the box. Read More


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Our website uses cookies so that we can provide you with the best user experience. By using our website, you agree to using cookies. Read more
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Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important class of natural products that include many antibiotics and a variety of other bioactive compounds. While recent breakthroughs in RiPP discovery raised the challenge of developing new algorithms for their analysis, peptidogenomic-based identification of RiPPs by combining genome/metagenome mining with analysis of tandem mass spectra remains an open problem. We present here MetaRiPPquest, a software tool for addressing this challenge that is compatible with large-scale screening platforms for natural product discovery. After searching millions of spectra in the Global Natural Products Social (GNPS) molecular networking infrastructure against just six genomic and metagenomic datasets, MetaRiPPquest identified 27 known and discovered 5 novel RiPP natural products.
Natural products are at the center of attention as new pharmaceutical leads, as exemplified by the recent discoveries of novel classes of bioactive natural product drugs1-4. Complementing this, the recent launch of the Global Natural Products Social (GNPS) molecular networking infrastructure5 brought together over a thousand laboratories worldwide that have already generated an unprecedented amount of tandem mass spectra of natural products. However, to transform natural product discovery into a high-throughput technology and to fully realize the promise of the GNPS project, new algorithms are needed for natural products discovery6-10. Indeed, while spectra in the GNPS molecular network represent a gold mine for future chemical discoveries, their interpretation remains a bottleneck due to the large volume of data produced by modern mass spectrometers and unavailability of computational platforms for data processing.
The efforts present herein focus on Ribosomally synthesized and Post-translationally modified Peptides (RiPPs), a rapidly expanding group of natural products with applications in pharmaceutical and food industries11. RiPPs are produced by RiPP Synthetases (RiPPS) through the Post Ribosomal Peptide Synthesis (PRPS) pathway11. RiPPs are initially synthesized as precursor peptides, encoded by RiPP structural genes. The RiPP structural genes are often quite short, making their annotation difficult12. A precursor peptide consists of a prefix leader peptide appended to a suffix core peptide. A leader peptide is important for recognition by the RiPP post-translational modification enzymes and for exporting the RiPP out of the cell. The core peptide is post-translationally modified by the RiPP biosynthetic machinery, proteolytically cleaved from the leader peptide to yield the mature RiPP, and exported out of the cell by transporters. The precursor peptide and the enzymes responsible for post-translational modifications (PTMs), proteolytic cleavage, and transportation usually appear in a contiguous biosynthetic gene cluster (BGC) of a RiPP within a microbial genome. The length of the microbial RiPP-encoding BGCs typically varies from 1,000 to 40,000 bp (average length 10,000 bp), larger than the current length of short reads generated by next generation sequencing (350bp), and making DNA assembly a critical part of any short read based RiPP discovery method.
Genome mining refers to the informatics-based structural interpretation of a natural product BGC to infer information about the natural product itself. The discoveries of coelichelin in Streptomyces coelicolor13,14 and orfamide in Pseudomonas fluorescens Pf-514b,14c were the first examples of genome mining13,14 that were followed by discoveries of various bioactive RiPPs in microbial samples. Donia et al.15 discovered lactocillin, a thiopeptide antibiotic from human vaginal isolates, that showed activity against vaginal pathogens. Zhao et al.16 discovered eight novel lanthipeptides with antibiotic activity from a ruminant bacterium. Freeman et al. and Wilson et al.17,18 used metagenome mining of a sponge to assign a BGC to the known RiPP polytheonamide, with post-translational modifications distributed across 49 residues. Thus, large-scale metagenomics projects, such as Earth Microbiome Project19,19b, American Gut Project20, and Human Microbiome Project21,22,22b, have the potential to contribute to RiPP discovery, provided that improved bioinformatics tools for the enhanced identification of novel RiPPs are available. However, discovery of lactocillin and other recently identified RiPPs were not achieved by an automated process, but rather used time-consuming manual technologies that required information about individual (isolated) bacterial genomes. Our goal is to discover RiPPs directly from metagenomic information using a fully automated approach.
While recent analysis of thousands of bacterial and fungal genomes has already resulted in the discovery of many putative BGCs, including ca. 20,000 RiPP-encoding BGCs in the Integrated Microbial Genome Atlas of Biosynthetic Gene Clusters (IMG-ABC), connecting these BGCs to their metabolites has not kept pace with the speed of microbial genome sequencing23. Currently, only 35 out of these roughly 20,000 RiPP-encoding BGCs in IMG-ABC have been experimentally connected to their RiPPs23,24. Linking this impressive number of RiPP-encoding BGCs to unknown RiPPs requires the development of novel computational tools.
Kersten et al.25 introduced the peptidogenomics approach to RiPP discovery, which refers to finding sequential amino acid tags from tandem mass spectra (peptidomics) and mining them in assembled DNA reads obtained from the same sample. Mohimani et al.12 introduced RiPPquest, the first automated approach to RiPP discovery by mass spectrometry and genome mining. This tool is based on Peptide-Spectrum Matches (PSMs), which are generated by aligning predicted spectra of putative RiPPs discovered by genome mining to mass spectra. If a PSM between a candidate RiPP from the assembled genome and a spectrum is statistically significant, then RiPPquest reports it as a putative annotation of the spectrum. RiPPquest resulted in identification of the lanthipeptide 'informatipeptin', the first natural product discovered in a fully automatic fashion by a computer. However, RiPPquest has a number of limitations: (a) RiPPquest is limited to lanthipeptides which constitutes only one of 19 classes of RiPPs11, (b) RiPPquest is designed for small genomes and small spectral datasets, making it rather slow in the case of large metagenomic datasets and the entire GNPS infrastructure, (c) RiPPquest does not report the statistical significance of identified RiPPs, the key requirement for any high-throughput peptide identification tool, and (d) RiPPquest is limited to searches for a predefined set of post-translational modification (PTMs) and does not enable blind searches for new PTMs.
Here we present MetaRiPPquest for high-throughput RiPP discovery that improves on RiPPquest in several critical aspects: (a) MetaRiPPquest identifies several important classes of lanthipeptides, lassopeptides, linear azole containing peptides (LAPs), linaridins, glycocins, cyanobactins, and proteusins (versus only lanthipeptides by RiPPquest), (b) algorithmic improvements in MetaRiPPquest increased speed by two orders of magnitude compared to RiPPquest, thus enabling searches of the entire GNPS database against metagenomes, (c) MetaRiPPquest implements a new approach for estimating statistical significance of identified PSMs, (d) MetaRiPPquest is capable of searching for RiPPs with unusual modifications in a blind mode, (e) MetaRiPPquest, in contrast to RiPPquest (which was designed for analyzing low-resolution spectra), utilizes the power of high-resolution mass spectrometry, and (f) MetaRiPPquest features a web-based interface through the GNPS infrastructure.
Brief description of MetaRiPPquest
Figure 1 shows the MetaRiPPquest pipeline, which includes the following steps (see Methods section): (a) selecting a biological sample (an isolated microbe or a bacterial/fungal community), (b) generating DNA sequence data, (c) assembly of DNA sequence data with SPAdes26 or MetaSPAdes27, (d) identifying putative RiPP precursor peptides using antiSMASH28 and BOA28a (Bacteriocin gene block and Operon Associator), and constructing a database of putative RiPP structures (as well as a decoy database), (e) generating tandem mass spectra for samples, (f) matching spectra against the constructed RiPP structure database using Dereplicator29, and (g) enlarging the set of described RiPPs via spectral networking30,31.
We analyzed the following paired datasets of spectra and genome/metagenome data (all datasets, with the exception of the BACIL dataset, contain high-resolution spectra):
Standard dataset (STANDARD). This small dataset consists of 18 spectra of known RiPPs that were used for benchmarking MetaRiPPquest (GNPS datasets MSV000079506 and MSV000079622). Spectra were collected from purified RiPPs from Prochlorococcus marinus MIT 9313 (four analogs of prochlorosins), Geobacillus thermodenitrificans NG80 (geobacillin), Bacillus subtilis NCIB 3610 (sublancin), Bacillus halodurans C-125 (haloduracin), Lactococcus lactis (lacticin), Bacillus cereus SJ1 (two analogs of bicereusins) and Ruminococcus flavefaciens FD-1 (eight analogs of flavecins). For these strains, we used genome sequence information available from the NCBI RefSeq database. AntiSMASH identified 70 BGCs in these genomes, including 29 RiPP-encoding BGCs. Since the genome sequence of the lacticin producer is not available, we searched its spectrum against its described biosynthetic gene cluster 31x.
Actinomycetes dataset (ACTI). This dataset consists of 473,135 spectra from bacterial extracts of 36 Actinomycetales strains with sequenced genomes32,33 (GNPS datasets MSV000078839 and MSV000078604). We downloaded sequence information for these 36 genomes from the NCBI RefSeq database. AntiSMASH identified 1,140 BGCs in these genomes, including 168 RiPP-encoding BGCs. Furthermore, we downloaded and mixed the short reads from 21 out of 36 strains that were available from the NCBI Short Reads Archive (read length 150 bp, insert sizes varying between 200bp to 300bp). We randomly down-sampled each dataset to 10 million reads (resulting in an approximate 300-fold coverage), and mixed all the reads to simulate a metagenomic dataset for this sample. Running MetaRiPPquest on the separate genomes from this dataset resulted in the same set of identified RiPPs as obtained from the simulated metagenome.
Bacillus dataset (BACIL). This dataset consists of 40,051 low-resolution spectra from bacterial extracts of two Bacillus strains with known genomes34 (MSV000078552). We downloaded genome sequence information for these isolates from the NCBI RefSeq dataset.
Space station dataset (SPACE). This dataset consists of 58,422 spectra from bacterial extracts of 21 isolated strains from the international space station (MSV000080102). Among these strains, twelve are Staphylococcus, six Bacillus, four Enterobacteria and one Acinetobacter strain. The complete genomes are available for all of these strains.35,36
Sponge dataset (SPONGE). This dataset contains 223,135 spectra from bacterial extracts of Theonella swinhoei (GNPS dataset MSV000078670). Wilson et al.18 used the SPONGE dataset to analyze for the RiPP polytheonamide. We searched spectra from the SPONGE dataset against the genome of Theonella swinhoei symbiont Candidatus Entotheonella sp. TSY1. AntiSMASH identified 27 BGCs in the symbiont genome, including one RiPP-encoding BGC.
Cyanobacteria dataset (CYANO). This dataset consists of 11,921,457 spectra from the extracts of 317 cyanobacterial samples37 (GNPS dataset MSV000078568). Each sample represents a mini-metagenome27,38 with one or a few highly abundant strains. The metagenomic reads were collected from 195 of these samples.
Genome mining
MetaRiPPquest uses antiSMASH and BOA for identification of RiPP-encoding BGCs and has two genome mining modes for selecting Open Reading Frames (ORFs), a slow all-ORF mode introduced in RiPPquest12, and a new fast motif-ORF mode. The all-ORF approach analyzes all short ORFs within a BGC, while the motif-ORF approach relies on RiPP motif finding39 to narrow the set of putative RiPP-encoding ORFs.
We illustrate positive and negative features of these approaches through genome mining of the Streptomyces roseosporous NRRL 11379 genome obtained from the ACTI dataset. AntiSMASH found 30 BGCs in this genome, including six RiPP-encoding BGCs in this genome. Within these six BGCs, the motif-ORF approach identified only two short ORFs matching core RiPP motifs, while the all-ORF approach identified 14,694 short ORFs. When analyzing all 36 of the ACTI strains, antiSMASH discovered 1,140 BGCs, including 168 RiPP-encoding BGCs. MetaRiPPquest in the motif-ORF and all-ORF modes identified 67 and 565,138 short ORFs, respectively. This example illustrates that the motif-ORF mode may result in a four order of magnitude reduction in the number of ORF candidates as compared to the all-ORF mode. However, antiSMASH predictions are based on searching for a set of known motifs, therefore the motif-ORF mode misses some ORFs with novel RiPP motifs. BOA is based on identifying known proximal genes ("context genes") that reside next to the RiPP, rather than by the RiPP sequence itself. In that manner, BOA identifies non-orthologous RiPP replacements if those RiPPs maintain homologous context genes. However, if the RiPPs do not have context genes, BOA may not detect those RiPPs. Also, since BOA is trained on bacteriocin context genes only, it is especially suited for that type of RiPPs.
Although the all-ORF mode searches a larger set of ORFs than the motif-ORF mode, it does not necessarily result in an increased number of identified RiPPs after matching ORFs against the spectral dataset. Indeed, the PSMs that are statistically significant in the motif-ORF mode may become statistically insignificant in the all-ORF mode because the search space in the all-ORF mode is orders of magnitude larger than in the motif-ORF mode resulting in an increased false discovery rate (FDR). Because MetaRiPPquest only reports statistically significant PSMs, the all-ORF mode may miss some peptides identified in the motif-ORF mode. Conversely, because MetaRiPPquest searches more ORFs in the all-ORF mode than in the motif-ORF mode, the motif-ORF mode may miss some peptides identified in the all-ORF mode.
RiPP identification
Below we describe applications of MetaRiPPquest to various datasets:
For STANDARD dataset in the all-ORF mode, MetaRiPPquest identified 18 RiPPs including prochlorosin40, geobacillin41, sublancin42, haloduracin43, lacticin 48144, bicereucin45, flavecin16 with p-values ranging from 8•10−14 to 5•10−55 (Table 1). In contrast, MetaRiPPquest in the motif-ORF mode identified only five out of 18 RiPPs since antiSMASH failed to predict 13 out of 18 RiPP-encoding ORFs.
Figure 2 shows a comparison of performance of MetaRiPPquest with all-ORF and motif-ORF genome mining approaches on the ACTI dataset. At the extremely conservative 0% FDR, MetaRiPPquest in the motif-ORF mode identified three novel RiPPs and five known RiPPs. The five known RiPPs include the linaridin grisemycin at p-value of 3•10−36 (from Streptomyces griseus IFO 1335025,46), lantibiotics AmfS and SRO-3108 at p-value of 4•10−12 and 9•10−12 (from Streptomyces roseosporous25,47), lantibiotic informatipeptin at p-value 5•10−12 (from Streptomyces viridochromogenes12), and the lantibiotic SapB at p-value of 4•10−12 (from Streptomyces coelicolor A3(2)48). The three novel RiPPs include a class II lantibiotic (referred to as Compound X) from Streptomyces sp. CNT360 with p-value 6•10−13, an informatipeptin-like lantibiotic (referred to as informatipeptin B) from Streptomyces cattleya with p-value 5•10−12, and a lassopeptide (refered to as Compound Y) from Streptomyces viridochromogenes with p-value 5•10−31. MetaRiPPquest in the all-ORF mode identified only two known RiPPs at 0% FDR (grisemycin and AmfS). Note that while the all-ORF mode improves on the motif-ORF mode for the STANDARD dataset, the motif-ORF mode improves on the all-ORF mode for the ACTI dataset. MetaSPAdes assembled the simulated ACTI metagenome into 6,204 contigs with lengths greater than 1000 bp, with total length of 99.9 Mb and N50 of around 60 kb. The longest contig was approximately 756 kb. AntiSMASH identified 353 BGCs (66 RiPPs) in the assembled metagenome. All of the identified RiPPs were re-identified using the simulated metagenome rather than individual genomes.
AntiSMASH identified 12 BGCs (one RiPP-encoding BGCs) in B. amyloliquefaciens FZB42 and 11 BGCs (four RiPP-encoding BGCs) in B. licheniformis ES-221. MetaRiPPquest identified two known RiPPs from the BACIL dataset. Lichenicidin A, a class II lantibiotic51, was identified from a novel producer Bacillus licheniformis ES-221. Plantzocilin A, a linear azole containing peptide49,50, was identified from the known producer Bacillus amyloliquefaciens FZB42.
AntiSMASH identified 119 BGCs, including 27 RiPP-encoding BGCs, in this dataset. MetaRiPPquest in the all-ORF mode identified one novel lantibiotic named 'compound Z' from three Bacillus strains (Bacillus sp. ISSFR-3F, Bacillus sp. S1-R2-T1 and Bacillus sp. S1-R3-J1).
AntiSMASH identified 27 BGCs (including four RiPP-encoding BGCs) in the SPONGE metagenome. MetaRiPPquest identified the known proteusin RiPP polytheonamide17,52 with a p-value 10−20 encoded by one of these four BGCs.
AntiSMASH identified 2,898 BGCs in the 195 cyanobacterial metagenomes, including 491 RiPP-encoding BGCs. MetaRiPPquest identified the known RiPP wewakazole53 and a novel RiPP named cyanobactin X in all-ORF mode.
Novel RiPPs
Below we describe five novel RiPPs and wewakazole, a known RiPP with a novel gene cluster, identified by MetaRiPPquest.
Informatipeptin B (NGGGASTVSLLSCVSAGSVILCV) is a novel lantibiotic identified with a p-value of 5•10−12 (Figure 3) in the ACTI dataset. Informatipeptin B differs from informatipeptin12 in only 5 amino acids (shown in bold). The most abundant analog of informatipeptin B (mass of 1870.95 Da) corresponds to six dehydrations (unmodified peptide mass of 1979.01). The BGC of informatipeptin B is similar to the BGCs encoding class III lantibiotics (AmfS and SapB). Three out of 10 nodes in the spectral network of informatipeptin B have been identified as its analogs: informatipeptin B1 (addition of N-terminal amino acid N), informatipeptin B2 (truncation by one amino acid), and informatipeptin B3 (truncation by two amino acids). These analogs of informatipeptin B (with stepwise N-terminal leader processing) provide additional evidence that informatipeptin B is a novel RiPP. Four other nodes in the spectral network have been identified as sodium and potassium adducts (+22 Da and +38 Da mass shifts).
Compound X (DTGGCSGLCTVLVCTVIVC) is a novel lantibiotic that was identified with p-value 6•10−13 in the ACTI dataset and that shows no homology to any of the known RiPPs (Figure 4). One of the genes within its BGC shows similarity to genes encoding class I lantibiotics (e.g., subtilin). The most abundant analog of Compound X (mass 1769.80 Da) corresponds to four dehydrations (unmodified peptide mass of 1841.84). The spectral network of Compound X revealed an additional Compound X1 analog (truncation by one amino acid).
Compound Y (LLGRHGNDRLILSKN) is a novel lassopeptide that was identified with a p-value of 5•10−31 in the ACTI dataset and that shows distant homology to microcin J25 (Figure 5). Two of the genes in its BGC are similar to microcin J25 hypothetical genes McjB and McjC from S. avertimilis with a 78% identity for both. The most abundant analog of Compound Y (mass 1645.962 Da) corresponds to a −59 Da modification (unmodified peptide mass of 1704.964 Da).
Compound Z (DATITTVTVTSTSIWASTVSNHC) is a new RiPP identified in the SPACE dataset that shows no similarity to any known RiPP. It was not identified in the motif-ORF mode since antiSMASH failed to identify the ORF encoding this RiPP. The gene cluster of Compound Z shows similarity to enterotoxin genes. While enterotoxin gene clusters from Escherichia coli are known to produce RiPPs9,54, this is the first evidence for production of a RiPP by a Bacillus enterotoxin BGC.
The most abundant analog of Compound Z (mass 2109.064 Da) corresponds to eleven dehydrations and a −87Da N-terminal modification (unmodified peptide mass 2394.126 Da). MetaRiPPquest assigned a p-value of 3•10−25 to the PSM formed by Compound Z (Figure 6). There are multiple identical ORFs encoding Compound Z in the lantibiotic gene clusters of strains ISSFR-3F (13 copies), S1-R2-T1 (3 copies) and S1-R3-J1 (3 copies). Using spectral networks, MetaRiPPquest detected two less abundant analogs of Compound Z with −1 Da and −15 Da N-terminal modifications, instead of the −87 Da N-terminal modification in the most abundant analog. Moreover, there are analogs corresponding to the sequence DATITTVTVT with five dehydrations and a −87 Da or −15 Da N-terminal modification, and a analog corresponding to the alternative ORF DATITTVTVTSTSIWASTVSNYC in the same lantibiotic gene cluster with a single H to Y mutation.
Cyanobactin X is a cyclic peptide ISNGYLIP (mass 857.47 Da) with p-value 2•10−11 identified in strain PNG22APR06-1 of the CYANO dataset (Figure 7). The cyanobactin X core peptide has no similarity to any of the known cyanobactins. Its BGC, encoded in an 8 kb contig, is missed by antiSMASH. The spectrum of cyanobactin X does not cluster with any other spectra in the spectral network.
Wewakazole is a cyclic dodecapeptide IS−20APPGVT−20FS−20FP with mass 1140.54 Da, originally discovered in Lyngbya majuscula from Papua New Guinea52 (S−20 and T−20 stand for oxazole and methyl-oxazole, respectively). MetaRiPPquest identified wewakazole and its BGC with p-value 2•10−22 in strain PNG19MAY05-2/7 (Figure 8). AntiSMASH failed to predict any precursor peptide for this gene cluster
Confirmation of wewakazole identification
MetaRiPPquest identified wewakazole in a polar fraction from the extract of strain PNG19MAY05-2/7, a marine cyanobacterium collected at Kape Point, Papua New Guinea. Wewakazole was first reported by one of our groups from another Papua New Guinea collection of Lyngbya majuscula (revised to Moorea producens) obtained from Wewak Bay52. Subsequently a related compound, wewakazole B was isolated from a Red Sea collection of this cyanobacterium55. To confirm and to validate the accuracy of MetaRiPPquest to find and identify new compounds from strain PNG19MAY05-2/7, reverse phase C18 column chromatography and preparative HPLC separations were successful in the isolation of 31.2 μg of this compound. The compound possessed the same molecular formula as wewakazole, Cs59H72N12O12, based on the molecular ion sodium adduct [M+Na]+ in the HRESIMS (m/z 1163.5282, Supplementary Figure 1). Its chemical identity was further confirmed utilizing 1H, HSQC and HMBC NMR data, which allowed for direct comparison with data previously reported for wewakazole (Supplementary Figure 2, 3, 4)52. Moreover, the tandem mass spectrum and retention time of the isolated compound matched the data previously reported for wewakazole (Supplementary Figures 5, 6)52. Furthermore, the ECCD spectrum resembled that of wewakazole B53, and the specific rotation showed the same sign as previously reported for wewakazole52, excluding the possibility of an enantiomeric relationship of this isolate to that of wewakazole (Supplementary Figure 7). Thus, the compound identified by MetaRiPPquest was isolated and its identity was confirmed as wewakazole.
Comparison of extraction/fractionation strategies
MetaRiPPquest can assist in determining the optimal extraction strategy for novel RiPP discovery. As an example, nine strategies were used for fractionation of the samples, and among them strategy H, 25% Methanol and 75% Ethyl acetate, is the only strategy capable of detecting both wewakazole and Cyanobactin X.
While recent genome mining efforts have revealed over 20,000 hypothetical RiPP-encoding BGCs23, only 35 RiPPs have been identified that match to these BGCs. To keep pace with the speed of microbial genome sequencing, high-throughput methods for structure elucidation of RiPPs by combining metagenomics, genome mining, and peptidomics are needed. MetaRiPPquest extends our previous RiPPquest tool (limited to lanthipeptides) to lassopeptides, LAPs, linaridins, glycocins, proteusins, and cyanobactins, and enables the blind search for RiPPs with unusual modifications.
Articles describing RiPPs are usually limited to the analysis of a single peptide or a few related peptides. The first application of MetaRiPPquest revealed many known RiPPs, as well as their unknown analogs, and five novel RiPPs (three lantibiotics, one lassopeptide, and one cyanobactin) along with their numerous analogs, from only six spectral datasets. This result provides optimism that MetaRiPPquest can potentially make RiPP identification as robust as peptide identification in traditional proteomics. The increased robustness was validated by the isolation of the RiPP metabolite wewakezole, and its structure was confirmed by orthogonal approaches, confirming that the MetaRiPPquest prediction was correct. In contrast to the existing genome mining approaches that rely on known BGC motifs28, MetaRiPPquest in the all-ORF mode has the ability discover new BGCs (with previously unknown motifs) that encode novel RiPPs (e.g. compound Z and cyanobactin X) that are very different from currently known RiPPs and thus are not captured by the existing genome mining tools.
Finally, algorithmic improvements in MetaRiPPquest have resulted in a two orders of magnitude increase in speed compared to RiPPquest, thus enabling searches of the entire GNPS infrastructure against metagenomic information.
MetaRiPPQuest algorithm
Below we describe various steps of MetaRiPPquest.
(a) Selecting a biological sample
MetaRiPPquest works both with DNA sequencing datasets from isolate microbes and bacterial/fungi communities.
(b) Generating DNA sequencing data
MetaRiPPquest works with short Illumina reads or pre-assembled genomes/metagenomes.
(d) Identifying putative RiPP precursor peptides and constructing a database of putative RiPP structures
MetaRiPPquest uses antiSMASH28,56 for genome mining. AntiSMASH identifies putative RiPP-encoding BGCs, searches for known precursor peptide motifs in all ORFs within these BGCs, and constructs the set of putative core peptides. It also identifies modification enzymes in each RiPP-encoding BGC and uses the observation that RiPPs are typically encoded in a 10 kb window centered at a modification enzyme gene.
This approach usually results in a small number of putative core peptides per BGC, resulting in a fast and specific but non-sensitive peptidogenomics approach. As an alternative to this motif-ORF approach, the all-ORF approach (i) starts with all RiPP-encoding BGCs identified by antiSMASH, (ii) constructs a 10 kb windows centered at each modification enzyme of the identified RiPP-encoding BGC, and (iii) identifies all ORFs shorter than a pre-defined threshold (the default is 200 amino acids) as the putative precursor peptide12. This approach is sensitive but less specific than the motif-ORF approach.
After all modification enzymes in each RiPP-encoding BGC are identified, MetaRiPPquest considers the corresponding modifications for all suffixes of the identified ORFs within these BGC to construct the target RiPP structure database by considering all possible combinations of modifications (consistent with the modification enzyme) on all possible residues. The decoy RiPP structure database is similarly constructed, starting from decoy ORFs. MetaRiPPquest constructs a decoy database of precursor peptides by random shuffling of the target precursor peptide57.
(e) Generating tandem mass spectra
Samples were extracted using various fractionations and spectra were collected using various instruments described in supplementary material.
(f) Matching spectra against the constructed RiPP structure database
MetaRiPPquest uses a modified version of Dereplicator29 for searching spectra against the database of putative RiPP structures as follows (i) theoretical spectra for all peptides in the target and decoy RiPP structure database are constructed, (ii) PSMs are generated and scored, (iii) p-values of PSMs are computed using MS-DPR58, (iv) false discovery rates are computed using the decoy database, (v) statistically significant PSMs are output as putative RiPP identifications.
While exhaustive generation of candidate RiPPs and scoring by Dereplicator is feasible when a small number of modifications are considered, the running time rapidly increases with the increase in the number of modifications. We use the spectral alignment technique to efficiently find modifications of the core peptide that best matches the spectrum59-61,12. Moreover, to handle blind modifications we adapted the unrestrictive modification search algorithm61. This dynamic programming approach restricts the number of modifications and penalizes high score matches with more than one modification.
While the dynamic programming approach from RiPPquest12 can handle modifications in linear peptides, it is not applicable to cyclic peptides. MetaRiPPquest uses a brute-force approach to search all RiPP modifications of each candidate cyclic peptide against all spectra. We do not currently perform blind modification searches for cyclic peptides due to the inherent computational complexity.
Confirmation of wewakazole structure
HESIRMS data was collected using an Agilent 6230 Accurate-Mass TOFMS in positive ion mode by the UCSD Chemistry and Biochemistry Mass Spectrometry Facility. UV-Vis data were recorded on a Beckman Coulter DU 800 spectrophotometer at room temperature in MeOH (λmax at 214 nm and 217 nm). The ECCD spectrum was measured in MeOH using an Aviv 215 CD spectrometer. Optical rotation was measured at 25 °C using a JASCO P-2000 polarimeter ([α]25 −3.9 (c 0.022, MeOH) (lit.,52 [α]21D −46.8 (c 0.41, MeOH)). A Bruker AVANCE III 600 MHz NMR with a 1.7 mm dual tune TCI cryoprobe was used to record 1H, HMBC and HSQC NMR data at 298 oK with standard Bruker pulse sequences. A Varian Vx 500 NMR with a cold probe and z-gradients was used to record 1H NMR data at 298 K with standard pulse sequences. NMR data were recorded in CDCh and calibrated using residual solvent peaks (δH 7.26 and δc 77.16).
For LC-MS analysis, a Thermo Finnigan Surveyor HPLC System was used with a Phenomenex Kinetex 5 μm C18 100 × 4.6 mm column coupled to a Thermo-Finnigan LCQ Advantage Max Mass Spectrometer. Samples were separated using a linear gradient with (A) H2O + 0.1% FA to (B) CH3CN + 0.1% FA at a flow rate of 0.6 mL/min. The gradient started with a 5 min isocratic step at 30% B followed by an increase to 99% B over 17 min, which was held at 99% B for 5 min and then moved to 30% B in 1 min, and then held for 4 min. Mass spectra were acquired with an ESI source ranging from m/z 200-1600.
Preparative HPLC was done using a Kinetex 5 μm C18 150 × 10.0 mm semi-preparative column coupled to a Thermo Dionex Ultimate 3000 pump, RS autosampler, RS diode array detector, and automated fraction collector.
Isolation of wewakazole
The fraction in which metaRiPPquest identified wewakazole from sample PNG19MAY05-2/7 is identified here as 1648H. This fraction (26.5 mg) was initially separated using a 500 mg/8mL Xpertek® C18 SPE cartridge with 100% CH3CN to yield 10.7 mg after concentration under vacuum. The compound was isolated from this eluent by semi-preparative HPLC using a linear gradient with (A) H2O + 0.1% FA to (B) CH3CN at a flow rate of 4 mL/min, and the chromatogram was monitored at 218 nm. The gradient started with a 5 min isocratic step at 40% B followed by an increase to 95% B in 25 min. Approximately 2.5 mg of the sample were injected per run to yield 31.2 μg of wewakazole (tR=13.0 min).
Code availability
MetaRiPPquest is available both as a command line tool and as a web application at http://metarippquest.metabologenomics.org.
The work of H.M., P.D. and P.A.P. was supported by NIH 2-P41-GM103484. P.D. is supported by GM097509. A.G., A.M., A.S., A.K. and P.A.P. were supported by Russian Science Foundation 1450-00069. T.L.K., P.D., L.G. and W.H.G. were supported by NIH 2R01GM107550. L.G. and W.H.G. were supported by NIH R01GM118815. JTM was funded by NSF GRFP DGE-1144086. We thank the implementation team of the Microbial Observatory (Microbial Tracking-1) project at NASA Ames Research Center and sample processing/isolation of microbes by Aleksandra Checinska Sielaff, JPL. Part of the research described in this publication was carried out at the Jet Propulsion Laboratory, California Institute of Technology under a contract with NASA. The work of N.K.S. and K.V. was funded by NASA 19-12829-26 and 19-12829-27. C.B.N. was supported by postdoctoral fellowship from NCI/NIH Training Program in the Biochemistry of Growth Regulation and Oncogenesi (T32 CA009523). T.L.K was supported by Vaadia-BARD Postdoctoral Fellowship Award no. FI-494-13. T.L. was supported by CAPES Foundation for Research Fellowship (13425-13-7). The work of I.F. was supported, in part, by NSF awards ABI-1551363 and ABI-1458359.


text:
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The Role
The Scheduling Manager is responsible for the development, monitoring and oversight of all project scheduling, including the establishment, training and enforcement of corporate guidelines and practices to enhance the utilization of the schedule as a positive tool for project planning and control.
Your key responsibilities will include:
- Assist Scheduling and the Design Build Teams with the development of Bid and PreConstruction Schedules.
- Assist the Estimating team with the costs and resources needed to support contract required scheduling services.
- Assist Sales and Marketing Teams in the presentation process of MATT's in-house Scheduling Policies, Procedures and Capabilities.
- Facilitate the development of the initial Baseline Schedule for all projects to assure the following:
- Transition and coordination of the Bid Schedule thought process and concerns to the Baseline Schedule.
- Involvement of the Project Team to guarantee authorship of the schedule.
- Coordinate Sub-contractor involvement, input and buy-in.
- Compliance with contract specific scheduling requirements.
- Clear presentation of the Baseline Schedule to Owners, detailing the thought process and major areas of concern.
- Facilitate the schedule update process to assure the following:
- Accurate as-built data for activity start and completion tracking.
- Accurate representation of the current progress (% complete), current work plan and projected start and finish dates.
- Addition of new work activities required to define extra work, changed conditions or other impacts, needed to maintain an accurate planning tool.
- Compliance with contract required narratives, reports and submittals.
- Communication of the current schedule status, projected plan and Critical Path activities to all parties involved.
- Provide additional schedule support as required:
- Recovery Schedules
- Time Impact Analysis
- What-if Analysis Schedules
- Provide Monthly Executive Schedule Summary Analysis for all projects.
- Develop and implement a Training program for project scheduling, customized to each responsible position for all project team members.
To apply for this position, please send a resume, and cover letter/e-mail with Scheduling Manager in the subject line to: firstname.lastname@example.com.


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Junte-se a nós, você pode desfrutar :
Cliente novo? Começa aqui.Minha conta Meus Pedidos Minha lista de desejos Meus Cupons Meus pontos Minhas Referências BGpay
2019-08-29 03:01:52
Nice product.
2019-04-05 22:22:17
Arrive in Japan in a week. There is no problem with the quality either. I will buy the next one.
2019-04-15 00:17:06
it fits me well
2019-11-12 21:11:00
Got item and they seem good but sizes are very small
2019-11-05 15:37:06
Le maintien des testicules est aléatoire. les miennes ont tendances à sortir. Slip reste sympa à porter.
2019-11-04 18:00:48
2019-08-07 04:09:05
2019-06-04 12:04:40
Confortable, à voir avec l'usage, en été notament
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text:
American University of Sharjah hosts 3D Printing expo
SHARJAH, May 5, 2018
The American University of Sharjah (AUS) recently hosted the 'Robotics and 3D Printing in the Construction Industry Showtime,' which concluded the series of workshops focused on the promotion of the 'Sharjah Construction Industry Innovation Challenge Program.'
The programme is a co-operation project of the AUS, Sharjah Research Technology and Innovation Park (SRTIP) and the Oulu University of Applied Sciences, aimed at developing a world-class innovation system in Sharjah.
The exhibition highlighted the technological innovations that accelerate the development of the construction sector in line with the requirements of the 21st century and the national directive to increase economic diversification in Sharjah and the UAE, said the organisers.
Hussain Al Mahmoudi, CEO of AUS Enterprises (AUSE) and SRTIP highlighted the significance of the exhibition in determining the success of the sessions in introducing the 'Sharjah Construction Industry Innovation Challenge Program'.
The program is important as it focused on exploring the best ways to apply 3D printing techniques within the construction sector locally and regionally, he stated.
Al Mahmoudi emphasized that the success of this initiative is an important addition to the efforts aimed at enhancing Sharjah's leadership on the global innovation, development and knowledge landscape, in line with the directives of HH Sheikh Dr. Sultan bin Muhammad Al Qasimi, Member of the UAE Supreme Council, Ruler of Sharjah, in making scientific research and innovation an everlasting culture in the emirate.
"The collaboration between the AUS, Sharjah Research Technology and Innovation Park and the Oulu University of Applied Sciences has produced remarkable results in enriching knowledge and sharing of expertise in the 3D printing industry, which is expected to contribute $300 billion to the global economy by 2025," noted Al Mahmoudi.
"We look forward to our international partnerships and initiatives to enhance the role of Sharjah as a leading hub for robotics and 3D printing in the construction sector. We will continue to consolidate channels of effective communication with Oulu University to transform our aspirations into developing a world-class ecosystem that supports innovation in construction field and 3D printing in UAE," he added.


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- 1.Costco: (Membership Required) Samsung 65" Class - 710D Series - 4K UHD LED LCD TV for $449.99. Free Shipping.(57 minutes ago) more like this*Costco* [costco.com] is offering the Samsung 65" Class - 710D Series - 4K UHD LED LCD TV for *$449.99. Free Shipping. (Membership Required). *$450
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- 14.BJ's Members: Samsung UN75NU6950 75" 4K UHD Smart LED TV with White Glove Delivery and 3-Year Warranty $799.99BJ's Wholesale has for their Members: Samsung UN75NU6950 75" 4K UHD Smart LED TV with White Glove Delivery and 3-Year Warranty Note: log into your BJ's Account to see price ...$800
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- 18.Amazon has Samsung The Frame QN49LS03RAFXZA 49" 4K Ultra HD HDR Smart QLED TV with Alexa Compatibility (2019 model) for?$743?with free shipping.
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Exynos 9810 Octa-Core CPU, 4GB RAM, 64GB storage
The rear fingerprint sensor is now positioned centrally under the camera.
5.8" AMOLED (2960 x 1440), 12MP cam, 802.11ac, Android 8.0 Oreo$235
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3840 x 2160 (4K UHD), HDR10, HDR10+, HLG Support, Motion Rate 240Built-in Wi-Fi, Ethernet, Bixby, Google Assistant, Alexa Support, 4 x HDMI$919
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- 28.Ends tomorrow. eBay with vipoutlet has the seller refurbished Samsung Galaxy Watch Active 40mm Smartwatch, U.S. Version (Black, SM-R500NZKAXAR) for $125 - 15% off automatically in cart [Exp 4/1] = $106?with free shipping.
Samsung Galaxy Watch Active 40mm Smartwatch w/ Bluetooth (Rose Gold, SM-R500NZDAXAR, Refurb)?for $132 - 15% off in cart = $112?with free shipping$106
- 29.(3 days ago) more like thisvipoutlet via eBay has select *Samsung Galaxy Smartwatches* (Refurbished) on sale at prices listed below (price shown in cart). *Shipping is free*. Thanks delz4stelz Prices below are shown in...$127


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Welcome to the WLC Library Media Center!
The WlC Library Media Center is at the heart of WLC -- literally at the cross roads of the school. The purpose of the Center is to guide students to be active seekers of knowledge, users of information, and life long learners. An appreciation of literature is also at the core of what we do.
Materials in the library are chosen to stimulate curiosity and enable students to become self-directed learners. The Librarian works with classroom teachers to teach skills to find, evaluate and use information and integrate technology and information literacy througout the curriculum.
WLC Catalog
The WLC Library Catalog can be accessed from any computer with internet access. Click on the icon to search the library's holdings, online resources, ebooks, and vetted websites that will help all student research.
Library HoursMonday 7:30 - 3:00*Tuesday 7:30 - 5:00*Wednesday 7:30 - 5:00*Thursday 7:30 - 5:00Friday 7:30 - 3:00* Extended hours offered on these days.
Circulation Policies
- Students may check out library books for two weeks.A book may be renewed if no one else has requested the book. Please be sure to check out books at the circulation desk before leaving the library.
- While the library does not fine students for overdue books, lost or damaged books will result in a bill to recover the replacement cost of the book.
- Teachers can put books on reserve at the circulation desk for in library use only.
- Reference books and current issues of periodicals do not circulate. They must stay in the library.


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Do you know what Monday, November 27 is? It is Cyber Monday!
Cyber Monday lands on the Monday after American Thanksgiving.
Think of the annual Black Friday craze with its in-store product sales without the crush of human in-store bargain hunters. Cyber Monday occurs online for software, Apps, websites, programs, subscriptions, and an array of royalty free photos and videos. On this day, much of that software will have promotions or deep discounts.
If you've been coveting something, this is the day to seek it out and purchase it.
Priority software to run your business, you buy as you need them, but Cyber Monday may put your 'want to have' items a little closer to your budget. This is your chance to own it.
We can all get a little crazy with purchases between Black Friday and Cyber Monday, but can find great value in the tools we need over the next year. As an author, the real value is preparing now for Cyber Monday/Black Friday for next year.
As a consumer…
Start next year's list of 'want to have' software and apps and keep it handy. (In fact, there's probably an app for that!) That way you won't miss it in case you do not see an ad for it.
As a seller …
Just look at Amazon's jump in sales this weekend and the big push they're doing for their Kindle Reads author promo. Consider adding this valuable boost to a new or existing book campaign next year. You'll want to have your promotion finalized by mid October, so be sure to include enough time to include this promotion.
Over to you – What great deals did you find this year?
My best find? I got 30% more off my upgrade to Final Draft.
See you online,
Catherine Saykaly-Stevens | The Networking Web
Community Growth and Fan Engagement – Social Media Consultant and Trainer
Website: http://www.theNetworkingWeb.com
Connect with me: LinkedIn | Twitter | Facebook | Instagram | Google
Are your social media accounts up-to-date and ready to impress? Take the FREE 21-Day Challenge!
Don't let Influencers, Media, and Potential Clients lose interest in your social media accounts before they've even read your content.
>> https://theNetworkingWeb.com/21DayChallengeGetReady/


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Energy for Prosperity
Energy for Prosperity
Matthew Cullinen
senior director, renewable energy
Richard Harrison
ceo, smart power myanmar
Changing rural agriculture businesses with electricity
January 10, 2020
Rural entrepreneurs without access to electricity rely on diesel generators to run their businesses. The average cost of power generation can be very high — up to MMK 1,200 (USD 0.80) per unit. This...
Quadrupling sales through reliable electricity access
December 12, 2019
Khin Cho Wint lives in a rural village in Myanmar with electricity access supplied through a decentralized mini-grid. She took an interest-free loan from Smart Power Myanmar's Energy Impact Fund and...
To electrify Myanmar, build the grid from the outside in
June 19, 2019
In this Forbes article, learn how Smart Power Myanmar, implemented by Pact, is rethinking rural electrification in Myanmar to end energy poverty.
New market analysis shows high potential for sustainable, successful mini-grid solutions for electrifying Myanmar
June 3, 2019
As part of ongoing efforts to bring electricity to every household and business in Myanmar, Smart Power Myanmar, a national platform with a mandate to advance a modern energy ecosystem in country,...
Ahlin Yaung: Lighting a path to prosperity and development
December 6, 2018
U Kyaw Htay, a villager in Myanmar's Myeik township, Tanintharyi Region, used to only do business when the sun was up. With his wife, he runs a small café shop that caters to his neighbors in Ashae...
Ending energy poverty: An interview with Pact's Matthew Cullinen
August 21, 2018
For years, Pact has worked with rural communities in Myanmar to improve their lives. With its partners, the organization has helped villages make dramatic change in areas including health, water and...
The next phase of rural electrification in Myanmar
June 26, 2018
How do you provide a service when neither the provider nor the customer has a good sense of the demand? This is one of the main challenges facing the off-grid energy industry in Myanmar, a country...
Pact launches Energy for Prosperity, a global initiative to improve energy access in developing communities
May 2, 2018
Today, Pact announced the launch of a new global initiative called Energy for Prosperity (E4P) to improve energy access in low- and middle-income communities as part of the organization's integrated...
With renewable energy, building prosperity in rural Myanmar
April 29, 2018
Sein Win May has spent more than her share of time in the dark. At 51, she has lived her whole life in Shin Hla, a remote village of about 600 people in Myanmar's Dry Zone that is accessible only by...


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London, UK, August 31st 2007: PURE Digital is making an on-going commitment to the environment with EcoPlus™, a radical change to the way PURE's leading DAB products are designed, manufactured and presented. The initiative is being launched at the IFA show in Berlin from August 31st 2007.
EcoPlus sets standards within PURE for: reduced power consumption; use of materials from recycled and sustainable sources; packaging size; and use of components with minimised environmental impact.
PURE's Siesta was the first EcoPlus product to be launched. Since then EVOKE-1S, TEMPUS-1S and Chronos iDock have all been added to the EcoPlus family. PURE has also made a significant commitment to reduce the power consumption of its existing products, and will have reengineered all of the following products to be part of the EcoPlus range in time for Christmas: EVOKE-3; EVOKE-2XT; Oasis; ONE; PocketDAB 1500; Move; Chronos CD; Élan DX-40 and Élan RV-40.
All EcoPlus product packaging shares a consistent look and feel with a memorable EcoPlus logo and an eye-catching tree motif. They also clearly show in a graphical form, the product's standby and operational power compared to the industry average.
Products within the EcoPlus range have reduced power consumption both in use and in standby. Standby and active power consumption have been made significantly lower than the industry average*.
EcoPlus products are packaged using cardboard produced with a minimum of 70% recycled material, and finished using water-based varnish. Internal pulp trays are 100% recycled, and the user documentation is printed on 100% recycled paper using soya-based inks. Packaging size has also been optimised to reduce materials used and minimise the environmental cost of transport.
All current PURE battery operated radios now use the unique, innovative ChargePAK rechargeable battery packs. These are not only more cost-effective and convenient for the consumer, but also avoid the need for alkaline batteries to be put in landfill sites.
PURE products also conform to the RoHS (Restriction of Hazardous Substances) standard.
PURE General Manager, Paul Smith says: "With EcoPlus, we are proud to be leading the way in reducing environmental impact in the consumer electronics sector. We will ensure that EcoPlus continues to evolve to further decrease our impact on the environment. Any thoughts or suggestions are welcomed and can be emailed to firstname.lastname@example.com."
For more information log onto www.pure.com/ecoplus or call 01923 277 488.
Editor's Notes
* source: Engineers at PURE Digital measured the active and standby power consumption of the top ten best-selling portable and clock radios of 2006, and showed their average power consumption alongside the EcoPlus products. An illustration of this can be found on the PURE website – www.pure.com/ecoplus
About PURE Digital
PURE Digital is the world's leading manufacturer of DAB digital radios, the number one supplier of radios in the UK, and the creator of EVOKE-1XT, the world's most popular DAB radio. A UK business using UK technology, PURE Digital offers the widest range of award-winning DAB radios. PURE Digital is a division of Imagination Technologies Group plc. See www.pure.com.
Vicky Deacon
e-mail: email@example.com
tel +44 (0)1923 260 511
fax +44 (0)1923 270 188
PURE Digital
Imagination Technologies
Home Park Estate
Kings Langley
Herts WD4 8LZ


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About The Sunny Florida Team
The Sunny Florida TeamSales Professionals
Email: firstname.lastname@example.com
Direct Office: 239-390-4000 Ext:4099
Mobile: 239-223-8955
Languages: English, Polish
Office:Bonita Springs
24880-1 Tamiami Tr. Ste. 1
Bonita Springs, FL 34134
Team Members:
Jack Rynkiewicz
Sales Professionals
Sylwia Kochanowska
Sales Professionals
Jack and Sylwia know the importance of finding the right home for you. Both born and raised in Poland after receiving BA and MA degree Jack and Sylwia moved to beautiful Southwest Florida in 2002. They have lived in Lee and Collier County for over 15 years and just love it. They know all the neighborhoods inside and out, and can help you select the best one for your needs. Jack and Sylwia are currently members of the Naples Area Board of Realtors (NABOR). They are fully committed to providing you with a noticeably higher level of service that will make your real estate experience as easy and as stress-free as possible. What you can expect from Jack and Sylwia: Personal and knowledgeable service that is genuinely responsive to your needs A "Neighborhood Specialist", familiarity with local communities, home values, and price trends Top professional skills continually refined through training programs respected industry wide Advice and guidance throughout the entire process Commitment to help you leverage many resources that can save you valuable time and effort in securing home financing, insurance, and home connections. As a bilingual agents (Polish/English) they exhibits professionalism and close attention to details. They also use the latest Internet marketing tools to present your property to the widest possible range of qualified buyers.


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Who to Write a StoryWho's writing a story?
Should/Should You Write One Story A Day? No. Here is what I have learnt from the last two month.
Really I didn't want to write another article about "writing one story a day". A lot of folks have done that before me. However, I chose to write about it this mornings because I think my opinions differ from most others, and I state my own advantages and disadvantages.
I' ve been fighting for the last two week to write something real. It' s just tough to write one real story a full 24/7, no matter what your surroundings or your routines. When I replied to her story, I referred to a story I had recently written: From the story above, I realize that high-caliber, "original" contents can be produced on the basis of genuineness, which I strive for in all my histories.
However, even then it is difficult to be genuine every single second. I spent two month doing one story a days, but I limited myself to 40-60 mins. This involved locating a subject, typing the heading, locating at least one picture and locating pertinent quotations (in no particular order).
Although it only took me 40-60 mins to write the story every single working days, I was possessed by looking at the statistics and reacting to most of the answers I got. And, let me say, typing 750-1,000 words in 40-60 min is QUICK and TIG! They don't always release my tales.
The majority of the tales they don't release don't get many opinions. They' re popular with the folks who trip over them. And I think I had one story that wasn't released at first and had good tractive power. You were gonna release it later. If I write things that are more story-based, I usually mail them to The Ascent because it's better for that.
Popular news really makes a big impact when it comes to getting more people into your story. It is preferable for me to be republished where my story finds more resonance with the reader of this work. When you write one story a days, you will end up fighting to find the creativeness to write something useful.
I wanted to write every single working-day just to enhance my typing abilities. Genuineness in your letter makes the distinction. Sometimes I write my story and reread it, and I know it's not. All I want to do is to bury it and either give up or write another play.
Usually I'm right that my tales are poor. A good author can write evil things. But I don't necessarily suggest that you publish your own poor tales. It is not an inventive tip/lesson, but I think it is important to get it, especially for new authors here. Here is what the collapse looks like for my own stories:
You know, I like it when I write things a bunch of folks applaud. Several of my top stars have about 2 readings for 1 fans. It' not missilery, but if someone fully covers a long story, there' s a good chance they were actually influenced by what you have written. Every time I read a good story, I used to clapped.
Has the story affected me in any way? If someone will take the liberty to answer my tales authentically, I will give him 50 gossips. Please do not hesitate to write a remark about your thoughts on this topic. This is why I did not do it at first, and I think it is reflected in my previous histories.
This is because you have learnt things in your own lives that you think other human beings could use. When you haven't seen much in your lifetime, you probably don't have enough to write once a days over a longer amount of years. If you write every single working days, you will expand your lexicon, make fewer errors and become more effective.
It' a good enough excuse to want to write every single one. They can' t draw a thousand people, but that's not the point either. Also, please be aware that you don't have to post a story that you don't think will bring value to your reader. If you write every single pen, you'll be a better story teller.
The typing first enhances your narrative abilities and allows you to tell your tales personally after better. As above, if you don't think your story has added value for your reader, you don't have to post it. It' not that you have to write once a week to become popular.
At the most he types once a weeks, but what he types is really good. It' precious to a great many folks. Once a days write helps with your exposure, but more importantly, it helps: If you' re great, you probably don't even have to write a letter a single letter a single time.
Once a days write to be great, then begin to think about making your own cash, but before that it makes no sense. I, for one, don't write for cash. Indeed, with the volume I'm releasing this months, I intend to donate to a good cause and make my wizard payment so that I can write more, better things!
When it' s not about adding value to others, it becomes more difficult for the reader to find what they can do. You write for your reader, you know. Nobody should write every single one. The majority of humans cannot create high-quality contents on a regular base.
For my part, if you have a mission to the rest of the planet, write about it, no matter how many times. When it happens that you have so much to say that you can influence someone with your letter every single working days, then do it. I' m going to begin to write less this time.
I' ve nothing real left to write about every day. I also want to focus more on my real work, because as I have already said in my classes above, it takes a long day of work! Type contents that are important to you. You write things from your own personal experiences.
Don't just write the same thing in other words. So if you enjoyed this story, please contact (Up to 50 serious ) a few more time at ??? Come with me or my firm for more similar story! To learn more about my letter, my forthcoming poem and my audiobook and more, take a look:
Here you can sign up for our top news.


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We report a self–accelerating wave packets eigenmode solution of a two-dimensional (2D) nonlocal nonlinear Schrödinger equation (NNLSE) with an Airy–beam time–dependence, and present their spatiotemporal profiles. The behaviours of such Airy–Laguerre–Gaussian light bullets, as propagated in a strongly nonlocal nonlinear medium (SNNM), are investigated both analytically and numerically. We found that the generation, control, and manipulation of the NL spatiotemporal light bullets are affected by the radial mode number and the azimuthal mode number, as well as the modulation depth. Our scheme is quite different from the linear light bullets, in which the wave propagates in a NL medium and is an eigenmode of NLSE.
© 2017 Optical Society of America under the terms of the OSA Open Access Publishing AgreementFull Article | PDF Article
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J. Opt. Soc. Am. B 34(4) 808-813 (2017)
Wei-Ping Zhong, Milivoj Belić, and Yiqi Zhang
Opt. Express 23(18) 23867-23876 (2015)


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Advanced Mobile Platform Allows OneGold Customers to Buy, Sell and Redeem Precious Metals at the Touch of a Button from Anywhere at Anytime
OKLAHOMA CITY, OK / ACCESSWIRE / January 13, 2020 / OneGold, a marketplace to securely and conveniently buy, sell and redeem gold and other precious metals founded by APMEX and Sprott today announced the launch of their state-of-the-art mobile app with best in class security features. The app, now available for download on Android and iOS, is designed for customers to effortlessly buy, sell or redeem precious metals 24/7 on any device.
"We strive to consistently lead the pack in innovation and customer experience," said Ken Lewis, Chief Executive Officer at OneGold. "This mobile app will further enable our mission to ensure wealth preservation is conveniently available to everyone at the lowest possible total cost of ownership available on the market today."
OneGold eliminates all traditional barriers to purchasing gold and brings the precious metals buying experience to anyone who would like to protect their wealth, immediately. It's an easy-to-use website and now mobile app, with no hidden fees, and transparent pricing. OneGold is an ideal resource for people who would like to passively save weekly, monthly or quarterly and dollar cost average the price of gold and silver over time. Then, when the customer is ready to take possession, they can convert their precious metal's holding into physical metal and APMEX will QuickShip® the same business day.
Anyone who registers through the new OneGold mobile app will receive $5 for each new registration and a 'refer a friend' bonus of an additional $5.
Through an established partnership with BitPay, the largest global blockchain payments provider, Bitcoin, Bitcoin Cash, Ethereum, and various stable coins are also accepted through the OneGold mobile platform. All BitPay customers will save 2%, when using BitPay at OneGold.com.
OneGold Quick Facts:
To learn more about OneGold visit, https://www.onegold.com/. To download the new mobile app via iOS, click here to download the app via Android, click here.
About OneGold, Inc
OneGold eliminates all traditional barriers to purchasing gold and silver, bringing the precious metals buying experience to anyone looking to protect their wealth immediately. It is a very easy to use website and mobile app with transparent pricing and no hidden fees.
OneGold is the partnership between precious metals leaders, APMEX, and Sprott.
For almost 20 years, APMEX has been one of the nation's largest precious metals e-retailers, boasting over $10 billion in transactions. For more information, please visit www.apmex.com.
Sprott Inc. is an alternative asset manager and a global leader in precious metal and real asset investments. Sprott is based in Toronto with offices in New York, Carlsbad and Vancouver, and its common shares are listed on the Toronto Stock Exchange under the symbol (SII). For more information, please visit www.sprott.com.
Media Contact: Jeff Davidson, Interdependence PR for OneGold
Email: [email protected]
SOURCE: OneGold


text:
This is a past event. Its details are archived for historical purposes.
The contact information may no longer be valid.
Please visit our current events listings to look for similar events by title, location, or venue.
Thursday, February 13, 2020 at 9:00am to 11:00am
120 Maple Ave, Training Room 150
This 2-hour session is meant to assist participants through the login and search process for both Skillsoft and LinkedIn Learning Online Learning platforms. Learn how to narrow your search to find the course, video, resource, or digital book that matches your interests and/or training needs. Once logged in, participants will have time to try out both resource platforms.
***All active Staff, Students, and Faculty have free access to utilize both platforms.***
*The login process will require you to have your 2-Step Log In device with you.*
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Cornell staff, faculty, and students.
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- Real Estate Consultancy
Real Estate Consultancy
Dear Guests,
Our agency was established in 1999. The founder of our agency has been engaged in tourism profession in Side for nearly 30 years.
The Side region offers attractive opportunities for foreign investors. Return on investment capital can be quite fast depending on the type of investment and location. The whole point here is to invest in the right business in the right place. You can contact us for support services for your investment plan in and around Side.
We know the area and the prices very well!
Since 2004, foreigners have intensively purchased houses, plots and villas in and around the Side region. Although relatively low in quantity, this still continues for both used and new buildings.
You can get support from us for your real estate purchases in Side. Please write to us now. You can be sure we will return to you immediately.
Our agency with a wide business network will give you valuable information about your real estate purchase in Side.
Sincerely yours,
Vigo Tours