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The Yangtze river dolphin was thought to be extinct, a victim of China's explosive economic growth and environmental negligence, but one of the baiji, as the animal is known, was just caught on tape—alive and well.
The Washington Post has obtained a draft of the Government Accountability Office's "progress" report—quite the euphemism in this case—about Iraq. The 69-page draft, which the paper describes as "strikingly negative," was apparently passed along by a government official worried that the final draft would be altered to lessen its detrimental impact.
Bruce Willis will star in an Oliver Stone film about the My Lai massacre, perhaps the most infamous atrocity to emerge from the Vietnam War. In other Stone news, Iranian President Mahmoud Ahmadinejad says he has "no objection, generally speaking," to the director's rumored desire to make a biopic about him but that Stone would need to "let me know what are the frameworks."
Not to be deterred by new developments in digital technology, the FBI laid the groundwork for its current DCSNet (Digital Collection System Network) wiretapping system during the Clinton years, allowing agents to just point 'n' click their way into the nation's land lines, cell phones and Internet telephony networks.
AP Photo / Douglas C. Pizac
The GOP is undergoing a bit of an ethical crisis following the recent string of scandals involving prominent Republicans—the most recent being, of course, the media hullabaloo surrounding Sen. Larry Craig's run-in with an undercover policeman in a Minneapolis airport men's room. Oh, and then there's that whole Iraq war issue.
Who knew that eating a donkey's, er ... member is good for the skin? Or that women should refrain from consuming animal testicles? These could be trumped-up claims, but the proprietor and employees of China's Guolizhuang restaurant, a self-described "penis emporium," stand by them, as brave BBC reporter Andrew Harding discovered on a recent culinary adventure.
The White House plans to ask for an additional $50 billion to fund the troop "surge" in Iraq. That may seem like peanuts when you consider the $607 billion in annual Defense Department and Iraq/Afghanistan supplemental funds, but it's a sign that the administration is politically confident it can extend the surge through next spring. Plus, it's money that could be used for something silly, like building schools.
Beijing Public Security Ministry
Web users in Beijing will soon have to deal with a new annoyance as part of China's endless effort to control the Internet. By the end of the year, all websites registered with the government will feature animated Internet cops that will warn users to avoid forbidden content and offer friendly (if obnoxious) Internet security tips.
If you're caught up financially in the housing bubble (who isn't these days?), you might want to skip this item. Home prices have fallen by 3.2 percent—the sharpest drop in 20 years, while the median price for homes has gone down for the 12th consecutive month—another record. That's not good news for a market eager to return to the good ol' days of easy loans and overpriced homes.
President Bush has once again accused Iran of supplying militants in Iraq, colorfully referring to "Tehran's murderous activities" in a speech Tuesday. The heated rhetoric, including references to Iran's supposed nuclear ambitions and mysterious evidence of unsavory behavior, bears an uncomfortable resemblance to the administration's push for war with Iraq.
Posted on Mar 30, 2015
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DK Eyewitness Travel Guide: JapanDK Publishing 2015; US$ 28.00
DK Eyewitness Travel Guide: Japan is your indispensable guide to this beautiful part of the world. The fully updated guide includes unique illustrated cutaways, floor plans, and reconstructions of the must-see sights, plus street-by-street maps of key cities and towns. This uniquely visual DK Eyewitness Travel Guide is packed with photographs... more...
DK Eyewitness Travel Guide: TokyoDK Publishing 2015; US$ 20.00
DK Eyewitness Travel Guide: Tokyo will lead you straight to the best attractions this city has to offer. The guide includes unique illustrated cutaways, floor plans, and reconstructions of Tokyo's stunning architecture, along with 3-D aerial views of the key districts to explore on foot. You'll find detailed listings of the best hotels,... more...
Roger Dahl's Comic JapanTuttle Publishing 2015; US$ 15.95
Roger Dahl's Zero Gravity cartoon strip has been a popular feature of Japan's leading English-language daily newspaper, The Japan Times , since 1991. Now, for the first time, Roger Dahl's Comic Japan brings together the best of Zero Gravity in book form. Offering a Western artist's take on Japan, the strip stars Larry and Lily, a young American... more...
Travel Tokyo, JapanMobileReference.com 2007; US$ 4.99
An illustrated travel guide, phrasebook, and maps. Indulge Yourself with a personal tour guide on Your PDA. Fully illustrated. Historical overviews. Interesting facts. City Attractions. Comprehensive Phrasebook. Landmark and Street maps, Metro map, and more. Museums address, telephone, hours and admission information. The guide is loaded into the device... more...
DK Eyewitness Travel Guide: TokyoDorling Kindersley Ltd 2013; Not Available
The DK Eyewitness Tokyo Travel Guide will lead you straight to the best attractions Tokyo has to offer. The guide includes unique cutaways, floorplans and reconstructions of the city's stunning architecture, plus 3D aerial views of the key districts to explore on foot. You'll find detailed listings of the best hotels, restaurants, bars and... more...
A Gaijin's Guide to Japan: An alternative look at Japanese life, history and cultureHarperCollins Publishers 2009; Not Available
An alternative look at Japanese life, history and culture more...
Tokyo Pink GuideTuttle Publishing 2013; US$ 12.95
There are other books about Tokyo's exotic night life, but for the first time ever the Tokyo Pink Guide gives a hands-on account of Tokyo's vast array of "Pink" pleasures. Whether you are male or female, straight or gay, this book has something for every dedicated pleasure seeker, and includes: Host and Hostess bars Peep, strip and sex shows "Fashion"... more...
Kyoto & Nara The Soul of JapanTuttle Publishing 2013; US$ 24.95
The cities of Kyoto and Nara are known throughout the world for their extraordinary beauty. In Kyoto and Nara: The Soul of Japan , their modern state of serenity is well illustrated with depth and distinction in the photographs of Toshitaka Morita. Commentary by Philip Sandoz provides essential background information about the two historic cities.... more...
A Gaijin's Guide to Japan: An alternative look at Japanese life, history and cultureHarperCollins Publishers 2009; Not Available
An alternative look at Japanese life, history and culture more...
Speed TribesHarperCollins 2010; Not Available
This foray into the often violent subcultures of Japan dramatically debunks the Western perception of a seemingly controlled and orderly society. more...


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|Reviews for Wild Child
| SILVERLINING67 chapter 37 . 9/22/2013
In addition to that, I am a United Airlines employee working at Newark International Airport were those aircrafts departed from. Again thank you for remembering us from across the pond. Honesty, some americans from the midwest and west coast forget about it until they have to remove their shoes and have their 7oz perfumes taken away at the security here you are apologizing. Silly woman.
| SILVERLINING67 chapter 39 . 9/22/2013
Lovely story. Thanks again!
| SILVERLINING67 chapter 38 . 9/22/2013
Absolutely no offense taken to your mention of the 9/11 attacks on the World Trade Center. More of a thank you, in fact. I live in New Jersey right across the river from the World Trade Center. My eldest cousin was actually in a bookstore inside the second building at the time the airplane hit and was lucky and blessed enough to escape unharmed. I thank you for recognizing that day for us from across the pond.
I love your story. I am sorry I have not reviewed until now.
| Vampfan1 chapter 39 . 9/14/2013
Great story! Love, love, loved it!
The wedding vows in this last chapter were spectacular. just beautifully written!
The only question that I felt was left unanswered was the issue of Tanya. I would have loved to see a little more about how she found out that E & B were married. Call me bitchy but I would have loved to see a scene in which Tanya was acting all superior to Bella and Bella sat there listening and then with a smirk, dropped the bomb on her effectively crushing Tanya in a hahaha I win scenario. But other than that its all good. Can't wait to see what else you have written out there in the fandom. until next time...
| Vampfan1 chapter 26 . 9/12/2013
I don't think I have ever said this in a FF story before and usually I am all over Edward for various reasons and I know this is my first review/ response to this story, but I have to say...I'm pretty sure I hate Edward right now and he deserves some serious fuckery coming his way. At this point if he doesn't get his shit together and figure out his feeling for Bella and soon, well then I hope she takes him for all he's worth and dumps his ass out of the company leaving him to the vapid, heartless bitches he seems to think are more appropriate for him and I hope they make his life a living hell and he realizes that Bella was the way to go and that its too late and she has someone else and he has to stew forever knowing what a dumbass he is. YEP you can tell I'm really really pissed at him right now!
| Guest chapter 30 . 9/12/2013
My grandparents where from England. Just love the story and the familiar words. When I was little my Grams use to tell me to get out of the road if I was standing in front of her, and blocking her view of the TV . I use to think she was so funny. TY for bringing back sweet memories.
| Jaygm chapter 39 . 9/5/2013
This really was a fantastic story. I sort of failed on my reviews - gave you several many chapters ago. Loved this- could read this again and again. Thank you so much for putting this here for us to read. You are a pretty awesome writer.
| Jaygm chapter 35 . 9/3/2013
Nice and sweet.
| Jaygm chapter 31 . 9/3/2013
Maybe it wasn't an accident?
| Jaygm chapter 30 . 9/3/2013
Oh, Bella! Come on, you are truly wearing me out here.
| Jaygm chapter 28 . 9/3/2013
Not too smart, Edward! She now thinks you want to take the company from her. Sort of like Tanya- showing your hand.
| Jaygm chapter 26 . 9/3/2013
Geez, Edward!
| Jaygm chapter 25 . 9/3/2013
Oh My!
| Jaygm chapter 24 . 9/3/2013
Kinda sad.
| Jaygm chapter 23 . 9/3/2013
Well, this chapter ended on a down note.


text:
Digital Home & Smartphones Help
It's free to register, to post a question or to start / join a discussion
iPhone4- rings but no sound!
Likes # 0
Posted June 6, 2012 at 2:44PM
Please help me!
I have had an iPhone4 for a while (so basically out of warranty!)
It is in working order part from the ring - there is no sound. However, when you go into settings to change the ringtone/volume it works. All other aspects of sound work incl radio and music.
Also, the toggle buttons do not work on the side - i.e. cannot turn onto silent or turn volume up/down. So using it on vibrate which is fine.
I have restored the software to no avail.
Don't really want to buy another - please help! Thanks muchly
Likes # 1
Posted June 9, 2012 at 10:25PM
Google has many answers for this, the most popular is to check the button on the top of the phone which should be up (towards the screen). If it's already up then move it down and back up again. That seems to fix things for most people.
If not, then do a reset. If still wrong then go to an Apple dealer.
Likes # 0
Posted June 21, 2012 at 10:07AM
In that case you have to go to the service center of iphone.
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Apr 26, 2012; Eden Prairie, MN, USA; Minnesota Vikings 1st round draft pick Xavier Rhodes (29) answers questions from the media at the 2013 1st round draft picks press conference at Winter Park. Mandatory Credit: Bruce Kluckhohn-USA TODAY Sports
68 remain, click here
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1500 ESPN Twin Cities is giving away the ultimate Chicago Pro Draft experience.
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Frank Oz Totally Looks Like David Cross as Tobias Funke
David Cross Totally Looks Like E.T.
Alan Ginsberg Totally Looks Like David Cross
The 10 Commandments of RPGs
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text: this was a very nice hotel staff is very friendly and helpful. be careful at the entrance, when we was there they had some very big pot holes and we had to go very slow so as not to damage our car. This is a new hotel just opened up in September of 2015.


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Telecom moves to flat mobile roaming fee
Relevant offers
Telecom will offer flat-rate data roaming prices from Friday next week that will let customers with post-paid smartphones surf the web in Australia for $6 day.
A flat rate of $10 a day will apply in eight other countries, including Britain, the United States and China.
Elsewhere, Telecom will slash its post-paid data roaming pricing by between 83 per cent and 92 per cent but charges will remain based on the amount of data customers consume, rather than a flat rate.
Telecom said it would review its "specially reduced" $6 Australian flat rate in the middle of next year, implying that might prove a short-term offer.
Telecom will also slash its data roaming charges for pre-pay customers by up to 88 per cent - the rate falls from $4 per megabyte to $1 per megabyte in Australia - and cut the cost of making phone calls from its phones overseas by up to 45 per cent. The price of pre-pay mobile phone calls in Australia will fall from 89 cents per minute to 49c.
However, Vodafone still offers a cheaper casual rate to pre-pay customers roaming in Australia- at 50 cents a megabyte - while 2degrees' pricing is 95c.
Telecom chief executive Simon Moutter said offering flat-rate prices for internet access overseas carried some financial risks for the company, but he thought it a risk worth taking.
"Currently, around two-thirds of our business customers switch off their data when in Australia. A flat fee provides 'certainty' and puts an end to concerns about nasty bill shocks on your return home.
"We know data roaming charges have been a pain-point for customers. Personally, it was a real bugbear of mine as a customer before I joined Telecom earlier this year," he said.
The new rates also apply to people who surf the web overseas using Telecom data sticks connected to their laptops.
Xero founder Rod Drury endorsed Telecom's pricing strategy.
"Flat rate pricing takes the cost of connecting back to New Zealand and all over the world out of the equation – and that's just great for business," he said.
- BusinessDay.co.nz
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Charles-H. Schulz Joins Mandriva's Recovery TeamSubmitted by srlinuxx on Thursday 31st of May 2012 09:44:35 PM Filed under
ostatic.com: Today Charles-H. Schulz posted a short message on Mandriva's official blog stating that he will be joining the Mandriva team to help them come back to life.
Mandriva has become a jokeSubmitted by srlinuxx on Saturday 19th of May 2012 02:41:58 AM Filed under
itwire.com: Mandriva SA, the French company that used to control development of the Mandriva GNU/Linux distribution, has become something of a joke.
Mandriva Returning to CommunitySubmitted by srlinuxx on Friday 18th of May 2012 03:54:21 AM Filed under
ostatic.com: In a blog post today Mandriva COO Jean-Manuel Croset announced that the new strategy going forward will be to let "the distribution evolve in and under the caring responsibility of the community."
ROSALabs Releases New DistributionSubmitted by srlinuxx on Wednesday 16th of May 2012 03:35:50 AM Filed under
ostatic.com: ROSALabs, Mandriva's partner on their last desktop, has been working on their own Linux distribution and have recently announced their latest release. If you liked Mandriva 2011, then you'll probably like ROSA Marathon 2012.
Mandriva Community Planning Next ReleaseSubmitted by srlinuxx on Tuesday 15th of May 2012 03:33:42 AM Filed under
ostatic.com: While waiting for the Mandriva management to decide the future direction of the distribution, the community is taking matters into their own hands and beginning the planning stages for the next release, assumed to be Mandriva Linux 2012.
Mandriva Receives Reprieve, Future Still UncertainSubmitted by srlinuxx on Tuesday 1st of May 2012 10:23:45 PM Filed under
ostatic.com: Today Jean-Manuel Croset, Mandriva COO, announced that enough funds have been secured to allow Mandriva to keep its doors open and continue development. With Croset saying little else, users at least have a nugget of good news to sustain them.
Mandriva – Customization With StyleSubmitted by srlinuxx on Saturday 28th of April 2012 07:26:04 PM Filed under
techzed.net: It took me literally hours to figure out which Linux distributions I would want to download and test. In this little article I will try to go over some of the basic features of one of my favorites, Mandriva.
Mandriva: A Call to ArmsSubmitted by srlinuxx on Thursday 19th of April 2012 08:17:59 PM Filed under
unsolicitedbutoffered.blogspot: News regarding the fate of Mandriva has not been coming hard and fast despite the failing fortunes of this once popular Linux distribution. However, a recent corporate blog post by current Mandriva COO Jean-Manuel Croset reveals the uncertain future of Mandriva Linux.
Mandriva's Alive!Submitted by srlinuxx on Saturday 14th of April 2012 03:23:49 AM Filed under
- Mandriva's Alive!
- Mageia 2 Default Wallpapers Chosen
- ROSA 2012 Marathon
- ROSA Desktop 2012 beta review
- ROMP: Media player with built-in desktop recorder
Ahoy Mandriva! Are you still out there?Submitted by srlinuxx on Tuesday 3rd of April 2012 06:17:50 AM Filed under
itwire.com: What exactly is happening at Mandriva, the French company that markets a well-known GNU/Linux distribution but seems unable to communicate its position to its users and the public at large?
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Ubuntu 15.04 Vivid Vervet Final Beta Available For Download
Ubuntu 15.04 Vivid Vervet final beta was released today, bringing quite a few changes, like locally integrated menus (LIM) by default, upstart was replaced with systemd by default as well as various other improvements and fixes. Let's take a look at what's new! Also: Kubuntu Vivid Beta 2
The Changing Cost of Open Source
At one time higher ed wanted community-built software because of the $0 price tag; now many universities are paying somebody else to keep open source projects moving forward.
Allwinner Continues Jerking Around The Open-Source Community
While Allwinner has been caught violating the (L)GPL and resulted in obfuscating their code and playing around with their advertised licenses, now this ARM vendor is taking things a step further. Also: Allwinner Plays Around With Licenses On Its Media Codec
OS X 10.10 vs. Ubuntu 15.04 vs. Fedora 21 Tests: Linux Sweeps The Board
With having a new Apple Mac Mini in our testing labs this week, I ran some basic benchmarks comparing Mac OS X 10.10.2 to Ubuntu 15.04 to Fedora 21 in a few different configurations.


text:
Today is a national holiday in France and everything is closed. We needed to top up our fuel before returning our rental car in Toulouse and during our drive from north of Sarlat we had seen no gas stations with human presence to take cash or swipe a US credit card. Finally, before getting on the A68 near Gaillac, we decided to try our card in a fuel pump behind the Leclerc store near exit 9 and it worked! It even asked us if we wanted to continue in French or change to English. No PIN was required. Maybe there's some hope out there for us card-challenged Americans. I was so happy and the gazole was cheap - 1.299/L.
My US Bank FlexPerks Visa with Chip worked in Leclerc Fuel Pump Today!!!
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Societe Generale's Albert Edwards sees a kindred spirit when Ray Dalio compares today's economy to 1937 Read more
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The San Diego Chargers are terrible at returning punts
The San Diego Chargers have a 4-7 record this season and there are many things wrong with this team.
San Diego is tied with the Pittsburgh Steelers for 24th in the NFL with 22 sacks and their offensive line has given up 32 sacks, which ranks sixth in sacks allowed.
Philip Rivers has thrown 14 interceptions, which ranks second in the NFL, and San Diego averages 3.8 yards per rushing attempt, which ranks 24th in the NFL.
The biggest problem with San Diego is their terrible job at returning punts. San Diego averages 6.1 yards per punt return–30th in the NFL.
Former Denver Broncos return man Eddie Royal was supposed to help San Diego improve at returning punts, because they averaged 8.5 yards per return last season, which ranked 22nd in the NFL.
This has obviously not been the case because he is averaging a career low 5.3 yards per return.
Royal leads San Diego with 12 punt returns this season. He averaged over 11 yards per return for his career heading into this season, which ranked third among active players.
I expected Royal to be better than he has been, but his 5.3 yards per punt return ranks last on San Diego's roster. Royal's longest punt return of the season was 14 yards against the Oakland Raiders.
Royal got a three year deal worth $13.5 million during the off-season. His average salary of $4.5 million is ninth on San Diego's roster, but he has not been close to matching this value.
San Diego needs to be better in their punt return game to take pressure away from their offense.
Chargers' Post-Free Agency 2015 NFL Mock Draft
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2 States Hits The Glorious 100cr Mark
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The blockbuster movie '2 States' continues to create quiet a buzz among the audiences, weeks after its release. It has now achieved another honour by entering into the prestigious 100cr club. This marks the talented actors Arjun Kapoor and Alia Bhatt's first 100cr film & also makes Alia the youngest actor to join the 100cr club. Watch the video to know more!
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JORDAN CARLYLE Nature In The Sky Framed Graphic Art
36" H x 48" W Size
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JORDAN CARLYLE Nature In The Sky Framed Graphic Art
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36" H x 48" W Size
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JORDAN CARLYLE Nature In The Sky Framed Graphic Art
About the ManufacturerJordan Carlyle is a modern and alluring visual artist making his name in the world of art. As an artist and designer, he continues to break the mold and surprise his collectors by engaging them with his bold, fresh, and captivating original pieces of artwork. Design, architecture and his educational background are the foundation that grounds his work. His innovative and inspired images continue to produce a loyal following of collectors and admirers of all different types. Jordan 's bold creativity, which he puts forth into each piece, is inspired by his profound love of travel and outdoor settings.
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Iacopo Petrini
National Cancer Institute (USA), Maryland, United States
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Total impact
Available from: PubMed Central
Mutations of epigenetic regulatory genes are common in thymic carcinomas
Yisong Wang
Anish Thomas
Christopher Lau
Arun Rajan
Yuelin Zhu
J Keith Killian
, Iacopo Petrini,
Trung Pham
Betsy Morrow
Xiaogang Zhong
Paul S Meltzer
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
Genetic alterations and etiology of thymic epithelial tumors (TETs) are largely unknown, hampering the development of effective targeted therapies for patients with TETs. Here TETs of advanced-stage patients enrolled in a clinical trial of molecularly-guided targeted therapies were employed for targeted sequencing of 197 cancer-associated genes. Comparative sequence analysis of 78 TET/blood paired samples obtained from 47 thymic carcinoma (TC) and 31 thymoma patients revealed a total of 86 somatic non-synonymous sequence variations across 39 different genes in 33 (42%) TETs. TCs (62%; 29/47) showed higher incidence of somatic non-synonymous mutations than thymomas (13%; 4/31; p < 0.0001). TP53 was the most frequently mutated gene in TETs (n = 13; 17%), especially in TCs (26%), and was associated with a poorer overall survival (p < 0.0001). Genes in histone modification [BAP1 (n = 6; 13%), SETD2 (n = 5; 11%), ASXL1 (n = 2; 4%)], chromatin remodeling [SMARCA4 (n = 2; 4%)], and DNA methylation [DNMT3A (n = 3; 7%), TET2 (n = 2; 4%), WT1 (n = 2; 4%)] pathways were recurrently mutated in TCs, but not in thymomas. Our results suggest a potential disruption of epigenetic homeostasis in TCs, and a substantial difference in genetic makeup between TCs and thymomas. Further investigation is warranted into the roles of epigenetic dysregulation in TC development and its potential for targeted therapy.
Scientific Reports 12/2014; 4:7336. DOI:10.1038/srep07336
· 5.08 Impact Factor
A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors
Iacopo Petrini,
Paul S Meltzer
In-Kyu Kim
Marco Lucchi
Kang-Seo Park
Gabriella Fontanini
James Gao
Paolo A Zucali
Fiorella Calabrese
Adolfo Favaretto
, [......],
Robert L Walker
Marbin Pineda
Yuelin J Zhu
Christopher Lau
Keith J Killian
Sven Bilke
Donna Voeller
Sivanesan Dakshanamurthy
Yisong Wang
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
We analyzed 28 thymic epithelial tumors (TETs) using next-generation sequencing and identified a missense mutation (chromosome 7 c.74146970T>A) in GTF2I at high frequency in type A thymomas, a relatively indolent subtype. In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified. Therefore, GTF2I mutation correlated with better survival. GTF2I β and δ isoforms were expressed in TETs, and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas carried a higher number of mutations than thymomas (average of 43.5 and 18.4, respectively). Notably, we identified recurrent mutations of known cancer genes, including TP53, CYLD, CDKN2A, BAP1 and PBRM1, in thymic carcinomas. These findings will complement the diagnostic assessment of these tumors and also facilitate development of a molecular classification and assessment of prognosis and treatment strategies.
Nature Genetics 06/2014; 46(8). DOI:10.1038/ng.3016
· 29.65 Impact Factor
Available from: Simone Pacini
Are MSCs angiogenic cells? New insights on human nestin-positive bone marrow-derived multipotent cells
Simone Pacini
, Iacopo Petrini
[Show abstract]
[Hide abstract]
Recent investigations have made considerable progress in the understanding of tissue regeneration driven by mesenchymal stromal cells (MSCs). Data indicate the anatomical location of MSC as residing in the "perivascular" space of blood vessels dispersed across the whole body. This histological localization suggests that MSCs contribute to the formation of new blood vessels in vivo. Indeed, MSCs can release angiogenic factors and protease to facilitate blood vessel formation and in vitro are able to promote/support angiogenesis. However, the direct differentiation of MCSs into endothelial cells is still matter of debate. Most of the conflicting data might arise from the presence of multiple subtypes of cells with heterogeneous morpho functional features within the MSC cultures. According to this scenario, we hypothesize that the presence of the recently described Mesodermal Progenitor Cells (MPCs) within the MSCs cultures is responsible for their variable angiogenic potential. Indeed, MPCs are Nestin-positive CD31-positive cells exhibiting angiogenic potential that differentiate in MSC upon proper stimuli. The ISCT criteria do not account for the presence of MPC within MSC culture generating confusion in the interpretation of MSC angiogenic potential. In conclusion, the discover y of MPC gives new insight in defining MSC ancestors in human bone marrow, and indicates the tunica intima as a further, and previously overlooked, possible additional source of MSC.
Frontiers in Cell and Developmental Biology 05/2014; 2. DOI:10.3389/fcell.2014.00020
Molecular analysis of cell-free circulating DNA for the diagnosis of somatic mutations associated with resistance to tyrosine kinase inhibitors in non-small-cell lung cancer.
Marzia Del Re
Enrico Vasile
Alfredo Falcone
Romano Danesi
, Iacopo Petrini
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[Hide abstract]
In non-small-cell lung cancer, the molecular diagnosis of somatic mutations is instrumental for the choice of the most appropriate treatment. However, despite an initial response, resistance to tyrosine kinase inhibitors occurs and thereafter tumors progress. For this reason, next generation inhibitors able to overcome acquired resistances are currently in development. Therefore, the identification of the molecular determinants of resistance is needed to adapt treatment accordingly. The analysis of circulating cell-free tumor DNA represents a powerful tool to monitor the somatic changes induced by treatment. This review focuses on the most recent advantages in the diagnosis of acquired resistance in circulating cell-free tumor DNA and underlines the strategies ready to be translated in the clinical practice.
Expert Review of Molecular Diagnostics 04/2014; DOI:10.1586/14737159.2014.908120
· 4.09 Impact Factor
Available from: Sean Davis
Whole genome and transcriptome sequencing of a b3 thymoma.
Iacopo Petrini,
Arun Rajan
Trung Pham
Donna Voeller
Sean Davis
James Gao
Yisong Wang
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
Molecular pathology of thymomas is poorly understood. Genomic aberrations are frequently identified in tumors but no extensive sequencing has been reported in thymomas. Here we present the first comprehensive view of a B3 thymoma at whole genome and transcriptome levels. A 55-year-old Caucasian female underwent complete resection of a stage IVA B3 thymoma. RNA and DNA were extracted from a snap frozen tumor sample with a fraction of cancer cells over 80%. We performed array comparative genomic hybridization using Agilent platform, transcriptome sequencing using HiSeq 2000 (Illumina) and whole genome sequencing using Complete Genomics Inc platform. Whole genome sequencing determined, in tumor and normal, the sequence of both alleles in more than 95% of the reference genome (NCBI Build 37). Copy number (CN) aberrations were comparable with those previously described for B3 thymomas, with CN gain of chromosome 1q, 5, 7 and X and CN loss of 3p, 6, 11q42.2-qter and q13. One translocation t(11;X) was identified by whole genome sequencing and confirmed by PCR and Sanger sequencing. Ten single nucleotide variations (SNVs) and 2 insertion/deletions (INDELs) were identified; these mutations resulted in non-synonymous amino acid changes or affected splicing sites. The lack of common cancer-associated mutations in this patient suggests that thymomas may evolve through mechanisms distinctive from other tumor types, and supports the rationale for additional high-throughput sequencing screens to better understand the somatic genetic architecture of thymoma.
PLoS ONE 04/2013; 8(4):e60572. DOI:10.1371/journal.pone.0060572
· 3.53 Impact Factor
Copy Number Aberrations of Genes Regulating Normal Thymus Development in Thymic Epithelial Tumors
Iacopo Petrini,
Yisong Wang
Paolo Andrea Zucali
Hye Seung Lee
Trung C Pham
Donna Voeller
Paul S Meltzer
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
Purposes: To determine if the deregulation of genes relevant for normal thymus development can contribute to the biology of thymic epithelial tumors. EXPERIMENTAL DESIGN: Using array comparative genomic hybridization, we evaluated the copy number aberrations of genes regulating thymus development. The expression of genes most commonly involved in copy number aberrations was evaluated by immunohistochemistry and correlated with patients' outcome. Correlation between FOXC1 copy number loss and gene expression was determined in a confirmation cohort. Cell lines were used to test the role of FOXC1 in tumors. RESULTS: Among 31 thymus development-related genes, PBX1 copy number gain and FOXC1 copy number loss were presented in 43.0% and 39.5% of the tumors respectively. Immunohistochemistry on a series of 132 thymic epithelial tumors including those evaluated by comparative genomic hybridization, revealed a correlation between protein expression and copy number status only for FOXC1 but not for PBX1. Patients with FOXC1-negative tumors had a shorter time to progression and a trend for a shorter disease related survival. The correlation between FOXC1 copy number loss and mRNA expression was confirmed in a separate cohort of 27 thymic epithelial tumors. Ectopic FOXC1 expression attenuated anchorage-independent cell growth and cell migration in vitro. CONCLUSION: Our data support a tumor suppressor role of FOXC1 in thymic epithelial tumors.
Clinical Cancer Research 02/2013; 19(8). DOI:10.1158/1078-0432.CCR-12-3260
· 8.19 Impact Factor
Reproducibility of the WHO classification of thymomas: Practical implications.
P A Zucali
L Di Tommaso
, I Petrini,
S Battista
H S Lee
M Merino
E Lorenzi
E Voulaz
F De Vincenzo
M Simonelli
M Roncalli
L Giordano
M Alloisio
A Santoro
G Giaccone
[Show abstract]
[Hide abstract]
BACKGROUND: The WHO-classification was shown to be an independent prognostic marker in some but not all retrospective studies possibly due to lack of reproducibility. We investigated the reproducibility of the WHO-classification and its prognostic implication using a large series of resected thymomas. METHODS: Four independent pathologists histologically classified a surgical series of 129 thymic tumors in a blinded fashion. Fleiss' kappa-coefficient was used to assess the pathologists' overall agreement, and Cohen-Kappa to assess the agreement between two observers. Disease-related-survival (DRS) and progression-free-survival (PFS) curves were generated by Kaplan-Meier method and compared by log-rank test. RESULTS: In 63/129 (48.8%) cases there was a complete agreement; in 43/129 (33.3%) cases 3/4 pathological diagnoses were identical; in 15/129 (11.6%) cases the diagnoses were identical by pair; in 8/129 (6.2%) cases three different pathological diagnoses were on record. The Kappa-correlation coefficient was only moderate (0.53). A following web review carried out on the 23 cases with at least two different diagnoses reached a complete consensus. The histotype showed a statistically significant impact on PFS and DRS in the classification provided by only two pathologists. CONCLUSIONS: In this study, the agreement on WHO classification of thymomas was only moderate and this impacted on patients management. Web consensus conference on the diagnosis, more stringent diagnostic criteria or the adoption of referral diagnostic centres may substantially reduce discrepancies.
Lung cancer (Amsterdam, Netherlands) 12/2012; DOI:10.1016/j.lungcan.2012.11.015
· 3.14 Impact Factor
Available from: Daniela maria Gioia
Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study.
Sara Galimberti
Francesca Guerrini
Flavia Salvi
, Iacopo Petrini,
Daniela Gioia
Emanuela Messa
Giuseppe A Palumbo
Daniela Cilloni
Mario Petrini
Alessandro Levis
[Show abstract]
[Hide abstract]
Arsenic Trioxide (ATO) is effective in about 20% of patients with myelodysplasia (MDS); its mechanisms of action have already been evaluated in vitro, but the in vivo activity is still not fully understood. Since ATO induces apoptosis in in vitro models, we compared the expression of 93 apoptotic genes in patients' bone marrow before and after ATO treatment. For this analysis, we selected 12 patients affected by MDS who received ATO in combination with Ascorbic Acid in the context of the Italian clinical trial NCT00803530, EudracT Number 2005-001321-28. Real-time PCR quantitative assays for genes involved in apoptosis were performed using TaqMan® Assays in 384-Well Microfluidic Cards "TaqMan® Human Apoptosis Array".Quantitative RT-PCR for expression of EVI1 and WT1 genes was also performed. Gene expression values (Ct) were normalized to the median expression of 3 housekeeping genes present in the card (18S, ACTB and GAPDH). ATO treatment induced up-regulation of some pro-apoptotic genes, such as HRK, BAK1, CASPASE-5, BAD, TNFRSF1A, and BCL2L14 and down-regulation of ICEBERG. In the majority of cases with stable disease, apoptotic gene expression profile did not change, whereas in cases with advanced MDS more frequently pro-apoptotic genes were up-regulated. Two patients achieved a major response: in the patient with refractory anemia the treatment down-regulated 69% of the pro-apoptotic genes, whereas 91% of the pro-apoptotic genes were up-regulated in the patient affected by refractory anemia with excess of blasts-1. Responsive patients showed a higher induction of BAD than those with stable disease. Finally, WT1 gene expression was down-regulated by the treatment in responsive cases. These results represent the basis for a possible association of ATO with other biological compounds able to modify the apoptotic pathways, such as inhibitors of the BCL2 family.
Journal of Hematology & Oncology 09/2012; 5:53. DOI:10.1186/1756-8722-5-53
· 4.93 Impact Factor
Available from: PubMed Central
Copy number aberrations of BCL2 and CDKN2A/B identified by array-CGH in thymic epithelial tumors
I Petrini,
P S Meltzer
P A Zucali
J Luo
C Lee
A Santoro
H S Lee
K J Killian
Y Wang
M Tsokos
M Roncalli
S M Steinberg
G Giaccone
[Show abstract]
[Hide abstract]
The molecular pathology of thymic epithelial tumors (TETs) is largely unknown. Using array comparative genomic hybridization (CGH), we evaluated 59 TETs and identified recurrent patterns of copy number (CN) aberrations in different histotypes. GISTIC algorithm revealed the presence of 126 significant peaks of CN aberration, which included 13 cancer-related genes. Among these peaks, CN gain of BCL2 and CN loss of CDKN2A/B were the only genes in the respective regions of CN aberration and were associated with poor outcome. TET cell lines were sensitive to siRNA knockdown of the anti-apoptotic molecules BCL2 and MCL1. Gx15-070, a pan-BCL2 inhibitor, induced autophagy-dependent necroptosis in TET cells via a mechanism involving mTOR pathways, and inhibited TET xenograft growth. ABT263, an inhibitor of BCL2/BCL-XL/BCL-W, reduced proliferation in TET cells when administered in combination with sorafenib, a tyrosine kinase inhibitor able to downregulate MCL1. Immunohistochemistry on 132 TETs demonstrated that CN loss of CDKN2A correlated with lack of expression of its related protein p16(INK4) and identified tumors with poor prognosis. The molecular markers BCL2 and CDKN2A may be of potential value in diagnosis and prognosis of TETs. Our study provides the first preclinical evidence that deregulated anti-apoptotic BCL2 family proteins may represent suitable targets for TET treatment.
Cell Death & Disease 07/2012; 3(7):e351. DOI:10.1038/cddis.2012.92
· 5.18 Impact Factor
Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma.
Iacopo Petrini,
Monica Lencioni
Miriam Ricasoli
Mauro Iannopollo
Cinzia Orlandini
Filippo Oliveri
Carlo Bartolozzi
Sergio Ricci
[Show abstract]
[Hide abstract]
Sorafenib improves overall survival and time to progression of advanced hepatocellular (aHCC) patients such as demonstrated in 2 phase III trials. However, aHCC patients' outcome is still poor despite these results. In order to improve the efficacy of systemic treatment for aHCC, we evaluated the combination of sorafenib plus 5-fluorouacil infusion in a phase II trial. Patients with aHCC not eligible for loco-regional therapies, Child-Pugh A-B, ECOG-PS 0-1, and without history of anti-cancer systemic treatment were enrolled. Treatment schedule was: sorafenib 400 mg/bid continuously and continuum infusion of 5-fluorouracil 200 mg/sqm/daily day 1-14 every 3 weeks. Thirty-nine patients were enrolled: ECOG-PS 0-1: 29-10, Child-Pugh A-B: 36-3. Grade 3/4 (%) toxicities included: diarrhea 5.1/0, mucositis 20.5/2.6, hand foot skin reaction 20.5/0, skin rash 10.5/0, hypertension 10.3/0, hyperbilirubinemia 5.1/2.6, glutamic-oxaloacetic transaminase increase 10.3/0, glutamic-pyruvic transaminase increase 7.7/0, cardiac toxicity (one heart failure, two atrial fibrillation cases) 7.7/0, and bleeding (melena) in 2.6/0. One partial response was observed. Stable disease was obtained in 46.2% of patients with a median duration of 16.2 months. Median time to progression was 8 months (CI 95% = 5.7-10.4), and median overall survival was 13.7 months (CI 95% = 9.5-17.9). The results show an encouraging disease control rate, time to progression, and overall survival. The combination of sorafenib and 5-fluorouracil was feasible, and the side effects were manageable for patients carefully selected for liver function and performance status.
Cancer Chemotherapy and Pharmacology 03/2012; 69(3):773-80. DOI:10.1007/s00280-011-1753-2
· 2.80 Impact Factor
Available from: Niccola Funel
Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer
Jih-Hsiang Lee
Elisa Giovannetti
Jin-Hyeok Hwang
, Iacopo Petrini,
Qiuyan Wang
Johannes Voortman
Yonghong Wang
Seth M Steinberg
Niccola Funel
Paul S Meltzer
Yisong Wang
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted. Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells. We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G(1) accumulation. Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer.
Clinical Cancer Research 11/2011; 18(2):524-33. DOI:10.1158/1078-0432.CCR-11-1903
· 8.19 Impact Factor
Thymic Malignancies: From Clinical Management to Targeted Therapies
Ronan J Kelly
, Iacopo Petrini,
Arun Rajan
Yisong Wang
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
A key challenge in the treatment of thymoma and thymic carcinoma (TC) is in improving our understanding of the molecular biology of these relatively rare tumors. In recent years, significant efforts have been made to dissect the molecular pathways involved in their carcinogenesis. Here we discuss the results of large-scale genomic analyses conducted to date and review the most active chemotherapies and targeted treatments. We reviewed the literature for chemotherapeutic trials in the last 20 years and trials involving targeted therapies between 1999 and 2010. The search was supplemented by a review of abstracts presented at the annual meetings of the American Society of Clinical Oncology (from 1999 to 2010), at the first International Conference on Thymic Malignancies in 2009, and at a follow-up meeting of the newly formed International Thymic Malignancies Interest Group in 2010. Surgery remains the treatment of choice for operable tumors, whereas chemotherapy is standard in locally advanced and metastatic disease. Thus far, targeted therapies have been developed empirically. Histone deacetylase inhibitors have shown some activity in thymoma whereas sunitinib may be active in TC. There are no data to support the use of HER2- or EGFR-targeted therapies in thymic malignancies. Drug development for the treatment of thymic malignancies is difficult because of the rarity of these tumors. Ethnic differences are becoming apparent, with aggressive subtypes being observed in Asians and African Americans. Incremental improvements in our understanding of tumor biology suggest that molecular profiling-directed therapies may be the preferred route of investigation in the future.
Journal of Clinical Oncology 11/2011; 29(36):4820-7. DOI:10.1200/JCO.2011.36.0487
· 17.88 Impact Factor
Available from: Simone Pacini
Impaired function of gamma-delta lymphocytes in melanoma patients
Iacopo Petrini,
Simone Pacini
Sara Galimberti
Maria R Taddei
Antonella Romanini
Mario Petrini
[Show abstract]
[Hide abstract]
Melanoma is an immunogenic tumour but, despite the wide range of immunotherapies tested, only few promising results have been reported to date. Both in vitro and in xenograft models, γδ lymphocyte-mediated cytotoxicity against melanoma cells has been reported. IL-2/zoledronate treatment can expand γδ cells in vitro and in animal models. This could represent an immunotherapeutic strategy against melanoma. To evaluate the feasibility of this approach, we studied γδ lymphocyte phenotype from patients with melanoma, their ability to be expanded by IL-2/zoledronate and their cytotoxic activity against SK-MEL-30 cell line. Peripheral blood samples were collected from 30 patients with melanoma and 10 healthy donors. Percentage of γδ lymphocytes and CD45RO+CD27+, CD45RA+CD27-, CD57+, Vγ9Vδ2 subpopulations were evaluated by flow cytometry. IL-2/zoledronate γδ cell expansion rate and their cytotoxicity against SK-MEL-30 cell line were studied. A percentage decrease in circulating Vγ9Vδ2 and an increase in CD45RA+CD27- and CD57+ γδ lymphocytes were observed in melanoma. IL-2/zoledronate expansion rate did not differ between controls and patients with melanoma but cytotoxicity against SK-MEL-30 appeared reduced. Our results show that γδ cell function is impaired in patients with advanced melanoma and suggest a possible role in tumour progression.
European Journal of Clinical Investigation 11/2011; 41(11):1186-94. DOI:10.1111/j.1365-2362.2011.02524.x
· 3.37 Impact Factor
CD57 and γδ T-cell receptor expression in nodal metastatic spread of melanoma.
Iacopo Petrini,
Cristian Scatena
Antonio G Naccarato
Mario Petrini
[Show abstract]
[Hide abstract]
Eur J Clin Invest 2012; 42 (5): 575–576
European Journal of Clinical Investigation 10/2011; 42(5):575-6. DOI:10.1111/j.1365-2362.2011.02612.x
· 3.37 Impact Factor
Abstract LB-314: Array comparative genomic hybridization of thymic epithelial tumors identifies loss of CDKN2A as a prognostic factor and BCL2 family members as targets for therapy
I. Petrini,
P. A. Zucali
H. S. Lee
J. Luo
K. J. Killian
P. S. Melzer
Y. Wang
G. Giaccone
Cancer Research 07/2011; 71(8 Supplement):LB-314-LB-314. DOI:10.1158/1538-7445.AM2011-LB-314
· 9.28 Impact Factor
Available from: Maria J Merino
Insulin-like growth factor-1 receptor and phosphorylated AKT-serine 473 expression in 132 resected thymomas and thymic carcinomas.
Paolo A Zucali
, Iacopo Petrini,
Elena Lorenzi
Maria Merino
Liang Cao
Luca Di Tommaso
Hye Seung Lee
Matteo Incarbone
Beatriz A Walter
Matteo Simonelli
Massimo Roncalli
Armando Santoro
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
Thymic malignancies are rare tumors. The insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) system is involved in the development of the thymus. IGF-1R expression in thymic epithelial malignancies is unknown. The authors investigated the expression of IGF-1R and phosphorylated AKT serine 473 (p-AKT) by using immunohistochemistry and examined the clinicopathologic correlations in a retrospective, single-institution surgical series of 132 patients with thymic epithelial malignancies. Earlier disease stage, less aggressive histologic types, and complete resection were significant positive prognostic factors for disease-related survival and progression-free survival, and being a woman was a better prognostic factor for disease-related survival. IGF-1R and p-AKT protein levels were expressed in 20% and 36% of thymic tumors, respectively. Both markers were expressed more commonly in recurrent disease than in primary tumors, in more aggressive subtypes, and in more advanced disease stages. There was a trend toward better survival and progression-free survival in patients who were negative for IGF-1R or p-AKT expression in the whole series. When only the 91 primary tumors, IGF1R expression was associated with worse progression-free survival (P < .001). The current retrospective analysis demonstrated that disease stage, tumor histology, sex, and resection type were major prognostic factors in the survival of patients with thymic malignancies. The expression levels of IGF-1R and p-AKT in thymic tumors suggested that IGF-1R is a potential target for treatment.
Cancer 10/2010; 116(20):4686-95. DOI:10.1002/cncr.25367
· 4.90 Impact Factor
Available from: Helmut H Popper
MicroRNA Expression and Clinical Outcomes in Patients Treated with Adjuvant Chemotherapy after Complete Resection of Non-Small Cell Lung Carcinoma
Johannes Voortman
Akiteru Goto
Jean Mendiboure
Jane J Sohn
Aaron J Schetter
Motonobu Saito
Ariane Dunant
Trung C Pham
, Iacopo Petrini,
Alan Lee
Mohammed A Khan
Pierre Hainaut
Jean-Pierre Pignon
Elisabeth Brambilla
Helmut H Popper
Martin Filipits
Curtis C Harris
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
This study determined whether expression levels of a panel of biologically relevant microRNAs can be used as prognostic or predictive biomarkers in patients who participated in the International Adjuvant Lung Cancer Trial (IALT), the largest randomized study conducted to date of adjuvant chemotherapy in patients with radically resected non-small cell lung carcinoma (NSCLC). Expression of miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a was determined by quantitative real-time PCR in formalin-fixed paraffin-embedded tumor specimens from 639 IALT patients. The prognostic and predictive values of microRNA expression for survival were studied using a Cox model, which included every factor used in the stratified randomization, clinicopathologic prognostic factors, and other factors statistically related to microRNA expression. Investigation of the expression pattern of microRNAs in situ was performed. We also analyzed the association of TP53 mutation status and miR-34a/b/c expression, epidermal growth factor receptor and KRAS mutation status, and miR-21 and Let-7a expression. Finally, the association of p16 and miR-29b expression was assessed. Overall, no significant association was found between any of the tested microRNAs and survival, with the exception of miR-21 for which a deleterious prognostic effect of lowered expression was suggested. Otherwise, no single or combinatorial microRNA expression profile predicted response to adjuvant cisplatin-based chemotherapy. Together, our results indicate that the microRNA expression patterns examined were neither predictive nor prognostic in a large patient cohort with radically resected NSCLC, randomized to receive adjuvant cisplatin-based chemotherapy versus follow-up only.
Cancer Research 10/2010; 70(21):8288-98. DOI:10.1158/0008-5472.CAN-10-1348
· 9.28 Impact Factor
Expression and mutational status of c-kit in thymic epithelial tumors.
Iacopo Petrini,
Paolo A Zucali
Hye Seung Lee
Marbin A Pineda
Paul S Meltzer
Beatriz Walter-Rodriguez
Massimo Roncalli
Armando Santoro
Yisong Wang
Giuseppe Giaccone
[Show abstract]
[Hide abstract]
Overexpression of c-kit, a tyrosine kinase receptor protein encoded by the protooncogene kit, has been previously reported in thymic epithelial tumors and in other neoplasms such as gastrointestinal stromal tumors, myeloproliferative disorders, melanoma, and seminoma. Mutations in the kit gene have been related to response to imatinib in gastrointestinal stromal tumor and one case report of thymic carcinoma. We studied expression of c-kit in a large retrospective series of thymic epithelial malignancies and sequenced the whole gene in a subset of patients. Thymic epithelial tumors from 120 patients (13 thymic carcinomas and 107 thymomas) were examined. Immunohistochemical staining with an antic-kit polyclonal antibody was performed on a tissue microarray. Mutation analyses of exons 1 to 20 were conducted by direct DNA sequencing of polymerase chain reaction products in eight thymic carcinomas, five thymomas, and one thymic carcinoma cell line. The percentage of c-kit positive cells was significantly higher in thymic carcinoma (46%) than in thymoma (4%). Decreased disease-related survival and progression-free survival were observed in c-kit positive tumors. No mutations were detected. c-kit expression is strongly but not exclusively related to thymic carcinoma histotype, and it is of prognostic value. Mutations are very rare.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2010; 5(9):1447-53. DOI:10.1097/JTO.0b013e3181e96e30
· 4.55 Impact Factor
Available from: Simone Pacini
Mesenchymal cells inhibit expansion but not cytotoxicity exerted by gamma-delta T cells.
I Petrini,
S Pacini
M Petrini
R Fazzi
L Trombi
S Galimberti
[Show abstract]
[Hide abstract]
Multipotent mesenchymal stromal cells (MSCs) exert a relevant immunosuppressive activity by inhibiting T- and B-lymphocytes, natural killer (NK) cells and dendritic cell expansion. Nevertheless, a possible activity on gamma/delta T cells has still not been evaluated. Gamma-delta T lymphocytes play an important role in the control of cancer and they have been shown to be implicated in graft-vs.-host disease. Thus, modulation of activation and proliferation of these cells could be relevant for therapeutic purposes. Peripheral blood mononuclear cells from 21 healthy donors were used as source for gamma-delta T cells, expanded in presence of 10 IU mL(-1) interleukin-2 (IL-2) and 1 microM zoledronate. MSCs were recovered from patients undergoing routine total hip replacement surgery, and characterised by flow cytometry. Cytotoxicity on multiple myeloma and melanoma cell lines was assessed by measuring dilution of the carboxyfluorescein diacetate succinimydylester dye (CFSE). Gamma-delta T cells were then incubated with MSCs in contact cultures, and with addition of MSC-conditioned medium. In this article we confirmed that (1) in vitro expanded gamma-delta T cells play a significant anti-proliferative effect on multiple myeloma and melanoma cells and (2) multipotent mesenchymal stromal cells effectively suppress the ex vivo expansion of T cells carrying a specific T-cell receptor gene (TCR) rearrangement, Vgamma9/Vdelta2, induced by the combination of IL-2 and zoledronate, without interfering with their cytotoxic activity. These findings contribute to explain the activity of ex vivo expanded mesenchymal cells, suggesting that MSCs would interact with gamma-delta T lymphocytes. This effect could be relevant in separating graft-vs.-host from the graft-vs.-tumour effect, especially considering the possibility of modulating T-lymphocytes activity by the immunomodulating drugs now available.
European Journal of Clinical Investigation 07/2009; 39(9):813-8. DOI:10.1111/j.1365-2362.2009.02171.x
· 3.37 Impact Factor
Available from: Domenico Amoroso
A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer.
E Vasile
G Masi
L Fornaro
S Cupini
F Loupakis
S Bursi
, I Petrini,
S Di Donato
I M Brunetti
S Ricci
A Antonuzzo
S Chiara
D Amoroso
M Andreuccetti
A Falcone
[Show abstract]
[Hide abstract]
The triple drug combination consisting of irinotecan, oxaliplatin and 5-fluorouracil (FOLFOXIRI) has demonstrated higher activity and efficacy compared to the doublet FOLFIRI. 5-Fluorouracil could be substituted in FOLFOXIRI regimen by capecitabine, an oral fluoropyrimidine with similar efficacy. Recently, a dose-finding trial has demonstrated the feasibility of the combination of irinotecan, oxaliplatin and capecitabine (XELOXIRI) and established their recommended doses. The aim of this study was to evaluate the activity of XELOXIRI. A total of 36 patients with unresectable metastatic colorectal cancer received irinotecan 165 mg m(-2) and oxaliplatin 85 mg m(-2) on day 1 plus capecitabine 2000 mg m(-2) per day orally in two doses from day 1 to day 7, every 2 weeks. Grade 3-4 toxicities were infrequent, expect for neutropenia and diarrhoea, which were each observed in 30% of patients. Two complete and twenty-two partial responses were obtained, corresponding to an overall response rate of 67% (95% CI 51.4-82%). After a median follow-up of 17.7 months, the median progression-free and overall survival were 10.1 and 17.9 months, respectively. The substitution of 5-fluorouracil with capecitabine, in combination with irinotecan and oxaliplatin, is feasible and does not impair the activity of the regimen. However, the XELOXIRI combination is associated with a high incidence of diarrhoea and, therefore, should be considered as a not preferable alternative to FOLFOXIRI.
British Journal of Cancer 06/2009; 100(11):1720-4. DOI:10.1038/sj.bjc.6605075
· 5.08 Impact Factor
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Yisong Wang
National Institutes of Health
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Alfredo Falcone
Università di Pisa
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Gianluca Masi
Azienda Ospedaliero-Universitaria Pisana
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Università di Pisa
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Università di Pisa
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text:
Likud negotiator says Bayit Yehudi central to any coalition
Unity threat looms over coalition talks
New education minister will have to hit the books
Joint Arab List launches march on Jerusalem
Health Ministry: Watch those eggs
Elusive answer to length of Saturn's day reached with TAU, Weizmann team
Yad Sarah prints large-font Haggada
Science, Technology and Space Ministry names Arab chemical engineer its deputy chief scientist
Eco Wave Power to establish its first Chinese power station
Watch: Technion students recreate Passover story with robots
Noble Energy walks away from Ruth C exploration license
Cyber Chief: 8% of ministry budgets should go to cyber security
Texas artists exhibit in Israel
The man behind 'The Missing Picture'
Concert Review: Mark Lanegan
The blizzard is over
Scuffling Maccabi must dig deep on road at group leader Real
Preview: Unbeaten Israel in for tough tests at home
Similar starting lineup expected for Israel
Ga'ash teams up with Cigar for 9-hole event
IDF passes reform to W. Bank laws dealing with Palestinians
Serry: Time to replace 242 with new 'peace architecture'
Dalya Lemkus' terrorist murderer sentenced to 2 life prison terms
Terror attack thwarted after bomb found near Hebron's Cave of the Patriarchs
Amnesty International charges Palestinians with war crimes during Gaza conflict
French company quits Jerusalem cable car project
German party's petition to recognize Palestinian state 'won't pass'
Spain close to granting citizenship to relatives of Jews expelled in 1492
Movie mogul Harvey Weinstein urges Jews to kick anti-Semites 'in the ass'
Reporter's Notebook: In Mariupol, a war only minutes away
Lauder criticizes US efforts against 'new anti-Semitism' in Europe
Turkey unveils Great Synagogue as Jewish population fades
Saudi Arabian military action in Yemen kept quiet from US until last minute
Analysis: Sunni-Shi'ite wars going global
Amidror: Yemen fighting unlikely to affect US position in Iran nuclear talks
Regional war in Yemen challenges Iran talks
Turkey's Erdogan says can't tolerate Iran bidding to dominate Middle East
Into the Fray: It's Arab enmity – not Arab ethnicity
My Word: Safe and unsound
Parting Shot: Tentative steps
Restarting the US-Israel relationship depends on Palestinians too
Column One: Managing Obama's war against Israel
The blood libel Haggada
The turning point
Travel tech start-ups
On wings of carbon
Veterans: On target
Fusing modern and traditional in the kitchen
Book Review: Perceptive Haggada
Hot off the Arab press
Let's cooperate
Shabbat screenings
Passover perspective
On the field and in court
Happily Eva After: Times, they are a-interestin'
Music and the mamaloshen
What's the catch?
Kayaking for gold on the Kinneret
Palestine – words matter but their meaning matters more
A nuclear deal with Iran – would it stick?
When words matter and when they don't
Countering Iran and IS – Muslims take action
'מְלָגוֹת 'צוּק אֵיתָן
עוֹלִים חֲדָשִים
כּוּלָם רוֹצִים לִחְיוֹת
יִשְׂרָאֵל בְּמַבָּט פָּנוֹרָמִי
Getting a young start
A culinary festival starring the women next door
Global girl power
Apartheid South Africa: Israel edition
Sa'ar says national unity government is 'still on the table'
Israeli parties prepare legislative demands for Netanyahu's new coalition
With full term possible, Netanyahu may outlast Ben-Gurion (and Obama)
Arab sector turnout for recent elections reached 63.5%, polling data shows
Joubran: Polls have to include parties that don't pass threshold
Unconvincing ISIS video shows Assyrian captive converting to Islam
'Those who hate Jews hate Christians': A closer look at US Presidential hopeful Ted Cruz
WATCH: Pope Francis receives a pizz-a Naples cuisine
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Scenic Lookout in Memory of Lt-Gen. Amnon Lipkin Shahak
Following in the Footsteps of Meir Har-Zion
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French Students Get to Know the Real Israel
Serbian PM Plants a Tree in the Grove of Nations
Sharing and Learning - German Forestry Students Intern with KKL-JNF
Israel and Finland Connect through the Environment
New Bio-filters Purify Surface Runoff Water for Reuse
Future Tour Guides Discover the Negev with KKL-JNF
The Shamir Drilling Project
Graduation Ceremony for Rosh HaAyin's Volunteer Firefighters
From Sunny Israel to Cold Canada
Walking for Water with KKL France in the Mountains of Eilat
JNF Ontario Community Mission Tours the Western Negev
Celebrating 50 Years of German-Israeli Diplomatic Relations
The Negev Conference on Agricultural Research and Development
Arava Open Day: Food Security for Israel and the Entire World
Living Green in Israel: the Contest and the Winners
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From Think Tank to Environmental Consultant
Award Winning Designer Launches Career as Wedding Dressmaker
Outdoor Fitness Israel: An Innovative Fitness Program Developed By UK Olim
The Burstein Brothers: 3 Oleh Siblings in the IDF
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Starting Your Own Business in Israel: Real Life Examples
5 Strategies for Finding Your Professional Place in Israel
PetBNB:An Olah's Unusual Canine Startup
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Thanks to Aliyah video
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Starting Over in Israel
VIDEO: Are you ready for the South?
Sovev Tel Aviv, Israel's Largest Biking Event
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Formula 1 Racecars Zip Through Jerusalem
Make yourself at home… in Israel
NBN Announces Bonei Zion Prize Recipients for 2015
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Over 1,000 IDF 'lone soldiers' attend personal errand day in Tel Aviv
03.27.2015 | 7 Nisan, 5775
Into the Fray: It's Arab enmity – not Arab ethnicity
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Restarting the US-Israel relationship depends on Palestinians too
Column One: Managing Obama's war against Israel
March 27: Spy vs spy
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Parshat Tzav: Distinguishing between the important and the unimportant
J Street U's 'March on Hillel'
Sinai Today: Heaven's ambassador
Yael's Corner: Welcoming a flight to freedom
We need electoral reform now
08/11/2014 23:10
President Reuven Rivlin. .
(photo credit:MARC ISRAEL SELLEM/THE JERUSALEM POST)
In the midst of the war in Gaza, a quiet revolution has been taking place in the office of Israel's president.Shimon Peres's recent retirement as the nation's ninth president marked not only the conclusion of his illustrious seven-decade political career, but also the end of an era for the nation's head of state.The position that has attained unprecedented prominence over the last seven years has already begun receding into the background under Peres's successor, Reuven Rivlin.From David Ben-Gurion's young aide to Israel's elder statesman, Peres utilized his many positions over the years to exploit opportunities and advance ambitious goals. For better or worse, he never allowed himself to be constrained by anyone or by any position. True to form, Peres did not fit the mold of a conventional president. He transformed this largely obscure, ceremonial institution into a highly visible and relevant post that became a vehicle for advancing his policy goals and which served, at times, as the de facto opposition to the Netanyahu government.To be sure, Peres deftly assumed the role of head of state, picking up numerous awards, crisscrossing the globe at a frenetic pace, and hosting myriad foreign dignitaries and celebrities who had come to Israel at his behest. The nonagenarian even embraced social media, becoming an active presence on Facebook, Twitter and YouTube.Peres expanded the limits of his post, however, to push his forward- looking agenda. He was a key backer, for example, of advancing neuroscience research in the hopes of finding cures for Alzheimer's and Parkinson's diseases, mental illnesses, and potentially hundreds of other neurological disorders. He also utilized his clout to promote and raise funds for the controversial $10 billion Red Sea-Dead Sea "Peace Canal," aimed at reversing the effects of the evaporating Dead Sea while generating electricity and desalinating water for Jordan, Israel and the Palestinian Authority.Most significantly, though, Peres accorded the presidency a new role as a check on the government. In the absence of a strong parliamentary opposition that could serve as an effective counterbalance to Netanyahu's right-wing coalition, Peres took it upon himself to put the brakes on some of Netanyahu's more aggressive plans and worked behind the scenes to pursue policies that were not supported by the government but which he felt were vital to Israel's interests. At times, he even intervened in Israeli domestic affairs.Peres grew increasingly concerned with a slew of bills introduced in the Knesset that many civil society actors have viewed as undemocratic.The legislation included attempts to restrict foreign funding of left-wing NGOs critical of Israeli policies, a ban on the Muslim call to prayer via loudspeakers at mosques across Israel, and an amendment to the Defamation Law, which would increase maximum compensation paid for libel violations regardless of proof of damage.Despite the support this legislation received from the prime minister and many of his ministers, Peres spoke out against the bills, saying he was personally "ashamed" that the Knesset was considering these laws.Convinced that Netanyahu and his former defense minister, Ehud Barak, were planning a reckless military adventure in Iran aimed at preventing it from becoming a nuclear weapon state, Peres took it upon himself to thwart such an attack.Despite Netanyahu's and Barak's entreaties to Peres that he remain silent on the matter, he refused and publicly warned against a strike in the absence of coordination with the United States, effectively quashing the government's plans.On the issue dearest to Peres's heart – Israeli-Palestinian peacemaking – Peres initially gave Netanyahu the benefit of the doubt, believing the prime minister had finally come around on this issue after his Bar-Ilan speech in which he publicly endorsed a Palestinian state for the first time. When Peres eventually became disillusioned with Netanyahu and concluded he was not serious about reaching a deal with the Palestinians, he broke his silence, challenging the government's hard-line approach on the Palestinian issue.Opposing the government's policy of rapid settlement construction, Peres warned that settlements threatened Israel's Jewish majority by creating a demographic shift. He challenged the majority opinion in Netanyahu's government that opposed a two-state solution, arguing that in its absence Israel would cease to exist as a Jewish state. And he dismissed Netanyahu's demand that Palestinians recognize Israel as a Jewish state – a demand not made of the Palestinian leadership in previous negotiations, nor of the Egyptians or Jordanians in their peace agreements with Israel – calling it unnecessary.Peres's greatest public challenge to Netanyahu concerned the question of whether Palestinian Authority President Mahmoud Abbas was a real partner for peace. While Netanyahu and senior members of his governing coalition have repeatedly cast doubt on Abbas's suitability to reach a deal with Israel, Peres has been outspoken in his belief that Abbas is a worthy peace partner.In 2011, Netanyahu gave Peres the green light to pursue a back-channel dialogue with Abbas. Peres recently revealed that he and Abbas had reached a framework for a peace agreement during these talks, claiming that Netanyahu torpedoed it.In the race to succeed Peres, Netanyahu unsuccessfully tried to stymie the candidacy of frontrunner Rivlin, with whom he has had strained relations. Netanyahu was needlessly preoccupied with the prospect of another president who would make his life difficult. In all likelihood, however, the Rivlin presidency will revert to the institution's traditionally symbolic, apolitical role. What may keep Netanyahu up at night is the role Peres will be carving out for himself in his retirement.
The author is an assistant professor of international relations at American University's School of International Service. His forthcoming book, Why Hawks Become Doves: Shimon Peres and Foreign Policy Change in Israel, will be published by SUNY Press this year.
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text:
Style Watch PollLast Night's Look: Hit or Miss?
Vote on this week's styles including Heidi, Reese and more stars! You decide – are they fashionistas or flops?
Credit: Dario Cantatore/Getty
Updated: Saturday Apr 30, 2011 | 06:00 AM EDT
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text:
Trinity's Podkowa all-time leader in points, rebounds, blocks
By Brad Spencer
The Trinity basketball team's Megan Podkowa is now the school's all-time leader in career points, rebounds and block shots.
Podkowa, a 6-foot-1 forward for the 28-1 Blazers, has thus far tallied 2,023 points, 1,152 rebounds and 304 blocked shots in her career playing for Trinity.
The senior, who with 18 points helped lead the Blazers to a 56-16 thrashing of Argo in the opening round of the Class 4A Trinity Regional on Tuesday night, will play for DePaul University next season.
The Blazers host area-rival OPRF on Thursday night in the regional title game (7:30 p.m.).
Email: firstname.lastname@example.com Twitter: OakParkSports
Reader Comments
1 Comment - Add Your Comment
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Andrea Lamacki from River Forest
Posted: February 17th, 2012 6:07 AM
We are so proud of Megan, and the entire team for an amazing season. Megan is an amazing young woman who is not only athletically talented but kind and smart too!
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Gloucester In Potential Fixture 'Madness'
18 March 2015 by Mark Tilley
Gloucester's hunt for a spot in next season's European Rugby Champions Cup could take on a strange twist with the news that their Kingsholm stadium is already booked for the date of one of the play-of...
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11 March 2015 by Mark Tilley
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Ireland Launch Women's RWC2017 Bid
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The Irish Rugby Football Union has announced that it has submitted a bid to host the Women's Rugby World Cup in August 2017 at locations in both Dublin and Belfast. University College Dublin is the in...
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text:
Discover a selection of top forums development fish on the internet. Come to share your passion on forums development fish and meet other fans of development fish. Then, why don't you create your own forum of development fish ?
Unity 3D Game Developer Forum : In MisterNinjaBoy's official community forum, you get more than just the youtube channel, you can join the Unity3D game developer community, were questions are answered, where you meet ot
unity, forum, game, developer, unityninja, unity3d, #development, community
FM Design aims to provide Forumotion users with tutorials, graphics, and promotion of their free forums!
Kent's Match Site, Live Match Calender, Up to Date Results, Local Club News. Sea Fishing Chat.
fishing, match, kent, clubs, results, anglers, #fish, coast, boatbeach, tackle, shops, angling, dungenees, hythe, folkestone, deal
A social network and Community resource for the Aquarium Hobby in Central Virginia!
virginia, #fish, club, cvas, central, aquarium, local, richmond, group
The forum for the development team of Project: Smash Bros. X. The forum is split and private, only the devs will be able to see anything of importance.
project, smash, bros, developer, forums, #development, team, split, private, devs, anythin
Free forum : An Oregon based pet forum for people interested in aquatics, small mammals, herps and invertabrates.
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Dedicated to the keeping of North American native fish.
forum, native, #fish, keepers, north, american, united, states, keeping, darters, dace, madtoms, sunfish, minnows, suckers, aquarium, lamprey, pickerel, pike, bass, catfish, bullhead, carp
Free forum : ETAK is a group of people that share the same interest in Reef, Freshwater, Saltwater, Brackish, Planted, Pond..keeping
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A place of Mediumistic discussion
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This is the official site for the StarCraft map Ultimate Boss Battles. It's shown as "In Development" in battle.net at the moment.
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All about Sabah, tourist heaven The Land Below The Wind, marketing, web development and it's smiling people, progressing Sabah.
sabah, borneo, forum, malaysia, lowyat, marketing, #development, tourism, kota, kinabalu, mount, akademi, fantasia, 1malaysia
Europa Barbarorum Late Campaign Development Forum
eb_late, europa, barbarorum, late, campaign, #development, forum
The official Forum for Augustine: Despondent and other projects like Slender: Darkplaces and Zombie Shootout. Other projects and developers welcome!
free, forum, augustine, official, zombie, shootout, game, #development, revamped, halo, inspired, mexicouger, tevin, dahl, supermario641996, coding, quake, darkplaces, help, community
Free forum : This is a site for ALL home fish keepers. If you've a 1 gallon beta tank to 1, 000's of gallons of fish under your care, you'll find someone sharing your passion and interest
freshwater, aquarium, angelfish, cichlids, pleco, discus, plecos, african, cichlids., betta, fishtank, #fish, marine, saltwater, tank, lights, metal, halide, light
A (non-official) role playing forum based in the Mass Effect canon. Still a work in development!
dark, space, mass, (non-official), role, playing, based, canon, work, development!
Welcome to the right place ! If it swims its awesome ! We Welcome all aquatic hobbyist to our site, to be a member of our community.
african, cichlid's, #fish, bowfront, livebearer, aquarium, light, free, forum, aquatics, freshwater, saltwater, hobbyist, snails, algae, filter
Incorporating anatomy & nutrition into skill development.
danse, time, diploma, incorporating, anatomy, nutrition, skill, #development