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|"Carsten Ziegeler" <cziege...@s-und-n.de>
|RE: [RT] New Input for woody
|Thu, 31 Jul 2003 14:10:15 GMT
Antonio Gallardo wrote: > > The idea looks great. A business oriented framework! > > What can we also use to use to send mails under this framework? Sometimes > there is a need to send a automatic email notifications of some changes. > But of course we can use other approach to do this maybe encapsulated into > the business objects. > You can either use one of the existing other approaches or you can send the mail from within your java code. > Are you thinking in persistence? How you mean this will be done? I will be > glad if we can exchange some ideas between this. > Yes, persistence is the key feature. Now currently you can use whatever you want, hibernate, ojb etc. I don't want to create a layer inbetween and I don't want to force others to use one over the other. I just started to look at those two and currently I like ojb more. I guess I will have to throw my ideas for some improvements into the ojb list and see what happens. Persistence is a separate concern so I don't want to solve this in Cocoon. If you or me or anyone else has specific requirements for persistence than we/you/he should try to get in contact with one of the persistence development teams. > I am currenlty spending my time trying to find a new way. The idea of > create business objects. Maybe we can create a more generalized interface > to do that. I am also facing the raping changes in the Woody arena. But it > is OK. I am glad Woody that woody runs too fast! > > Currently I am starting to try Woody with Beans (or may we can call it > ValueObjects)? Ok, I'm interested to see the results. > > You can also download the lastest CVS of OJB because there is a very nice > presentation that was posted 2 or 3 days ago. I think it is a worth to see > it. At the end it show how we can abstract the Data Access Tier. > I donwloaded the latest rc and it took me some hours yesterday night to get it running. I ported my test app from hibernate to ojb and it wasn't that easy because hibernate has some nice features ojb does not have and vice versa. Carsten
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ED Magedson – Founder
Ripoff Report
Amtrol1400 Division Road, West Warwick, RI , Select State/Province USA
Amtrol Lack of warranty West Warwick Rhode Island
Does your business have a bad reputation?
Fix it the right way.
Corporate Advocacy Program™
We purchased our original Amtrol indirect fire water tank back in 1998. Since then they fail every 2 years. The seal/bolts on the bottom give out. The last one lasted only 2 years (as they all have) but the difference is this time no one in the area is willing to exchange the item without us paying for the tank up front and waiting for the paperwork to be completed for refund. After so many times of this happening we are done jumping through hoops and called Amtrol directly. They tell us that we must not have an expansion tank on the heating system (we do per code) and we have to pay 125.00 shipping to get the unit to us.
Again, we have been paying money up front every 2 years and if Amtrol cared they would do a few things, they would (1) make a product without inferior bolts and (2) ship a replacement free of charge especially after so many times of having to change out the unit.
We have even gone and added a water softener system tin case the water is too hard.
We are in the northeast in the winter and had to relocate to a hotel until this is solved.
This report was posted on Ripoff Report on 03/04/2014 04:07 PM and is a permanent record located here: http://www.ripoffreport.com/reports/amtrol/select-stateprovince/amtrol-lack-of-warranty-west-warwick-rhode-island-1128291. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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subset: commoncrawl


text:
Pipedreams Live! in Rochester, Part 1
Audio not yet available
Recorded live, this week's Pipedreams features performances by students and faculty of the Eastman School of Music during a remarkably popular and successful weekend organ festival.
Program details:
CHARLES-MARIE WIDOR: Finale, from Organ Symphony Number 6 in g, Opus 42, number 2 –Benton Blasingame.
GASTON LITAIZE: Lied, from Douze Pieces –Lars Gjerde.
J.S. BACH: Fugue in D, BWV 532 –Amanda Mole.
STEPHEN KENNEDY: 3-3-33 –Hans Davidsson, David Higgs, and William Porter.
STEVEN SEIGART: Improvisation March –Steven Seigart.
JOHANN CHRISTIAN HEINRICH RINCK: Flute Concerto, 1st movement –Annie Laver.
COLE PORTER: "It's d 'Lovely" –Jonathan Ortloff, organ; Allan Ward, drums.


text:
NEWS: Kanye West, Drake, OutKast, Pharrell and More To Play Wireless Festival 2014
Posted In Featured,Hip-Hop,LDN LIFE,News by Speeakz
It has become quite clear over the past few years that Wireless has become one of the hypest London festival of the calendar year.
This year they've done it again and secured headliners Kanye West, Drake, Bruno Mars, as well as Outkast and Pharrell. Not to mention countless other acts like Azealia Banks, A$AP Ferg and others who have yet to be announced. Oh yea, did we mention Salt N Pepa too? Yah.
And it was hard to imagine Wireless topping last year. Not only did they lock in headliners Justin Timberlake & Jay Z but they also put on one of the most progressive hip hop lineups I think we've ever seen in a mainstream UK festival. I mean – they had A Tribe Called Quest there!
This year they'll help tick another life box with Outkast (!!). Although not billed as a headliner (however strange that may feel, it's actually not that unusual when you think about it), Andre and Big Boi, as promised, will for the first time in over 10 years perform live.
Moreover this years show will not take place at the Olympic Village as it did last year, but instead will happen in North London's Finsbury Park. And as a North Londoner, that's pretty much the icing on the cake. Moreover, the festival will also be heading to Birmingham for the very first time.
For more information and for tickets head to wirelessfestival.co.uk. We'll keep you updated on new announcements to come.


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Victim 38
My helicopter hovered above the road. Canadian soldiers were in a line, gunshots going of every few seconds. My helicopter touched down and I jumped out. A colonel ran towards me, looked at my rank and yelled "lieutenant! Colonel Drouin sir. Sir, command said that we would be getting reinforcments." I shrugged "sorry colonel, i'm it. Everything else is either being used in evacuating citizens or other ops." The colonel's eyes opened wide and his hand waved me towards the line. As we walked, he exclaimed "I was told that Charlie company was drawing them towards us! Sixty soldiers don't have the potential or ammo to deal with half the population of Toronto! Even with Charlie company, I was depending on more men sir! Not only that, but we have to somehow get civilians through the line while we're pegging the freaks of!" We walked to a jeep. The corporeal laid a map out and yelled "mines are all around us and we've salvaged a daisy cutter from a downed bomber and laiden it with C4. That's about 200 meters out. Hopefully, our fox holes by the road will give us enough cover if we have to detonate it." I nodded as I heard over the gunfire screams.
The corpereal screamed "HAVE THEY BREACHED OUR LINE?!" I patted him on the shoulder and yelled "no, Corporeal. The main waves coming." The ground started to shake and in the distance, tens of thousands of zombies sprinting down the road. I yelled "Corporeal, I am hereby assuming command. Tell your men to deploy mortars and fire a kilometer ahead, there is no way in hell that anyone is still alive in that crowd." The corporeal nodded and yelled. Soldiers set up mortars and started firing as fast as possible. In the distance, blood and body parts showered. I walked to each person in the line and ordered "put your mask on before you swallow any blood!" Soldiers put on cloth facemasks, meant for keeping dust out. I walked back to the corporeal and yelled "in eight minutes, we are blowing that daisy cutter or we aren't going to live through this." The corporeal shook his head "bravo is coming in. I can't detonate now when we're getting reinforcements ridding on the top of the tanks." I nodded.
Six minutes later, tanks and APCs were rolling up to the fenceline, with the soldiers on top clinging to the hatches. Suddenly, they were ten meters away and I could see that they were drooling blood. I raised my rifle and opened fire as they jumped over the barbwire fence. They ran through the line and started wreaking havoc. Soldiers turned to face the threat in their line as the main wave got within 100 meters of the fenceline. The a private ran and jumped on a jeeps 50 cal machine gun. He tore through the zombified soldiers bodyarmour and anihilated half of them. The rest were soon dispatched with bayonets or bullets. I yelled into everyone's radio "they are 60 meters away, switch to underbarrel grenade launchers now!"The twenty two soldiers still alive raised their guns and fired. Two hundred zombies were blown apart, but they still kept coming. I yelled into the com "keep firing!" I ran to the colonel and yelled "detonate that bomb now, or we are all dead!" I looked at his hand to see the detonater. He clicked it and yelled "it isn't working!" I groaned and yelled into my com "everyone, switch to bullets including mortars. I repeat, switch to bullets only!" Gunfire resumed as I screamed into my radio" Bravo 1, I'm jumping on your tank! Carve a path through those zombies on the road until I say stop, not a moment before!" I ran to the tank and jumped on the top, screaming into my com "BRAVO ONE, GO, GO, GO!" I shielded my face as the tank lurched forwards, crushing bodies and spraying blood over the tank. Sickening thuds rocked the tank and small bits of bodies hit me. An impossibly long time passed by until I looked up. The bomb was just a little further, wedged inbetween two cars. Twelve sticks of C4 sat next to it. I could taste blood through my facemask. I yelled into my com "Corporeal, you're in charge now, make me proud! Bravo one, stop the tank and then run!" The tank slowly stopped a meter away from the bomb. I jumped of and rolled onto the bomb. Zombies converged on me as I pressed the sync button on the C4 and on my detonator. I fired my rifle with one hand as they ripped of my helmet and tore into my neck, legs and chest. My left hand kept clicking the detonator. Everything went white as the C4 blew up with the daisy cutter and set of every cars gas tank along the road.


text:
Oxbridge Re's 2016 profits are dented by Hurricane Matthew
A sharp fall in net income and a drop in underwriting performance hit Oxbridge Re, a reinsurance provider for property/casualty insurers in the Gulf Coast, in the second quarter of 2016.However, its total revenues increased by two thirds.
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Oxbridge Re, Insurance, Reinsurance, Results, Cayman Islands


text:
Tainted Saint, Chapter Fifty-TwoMature
There were absolutely no words to describe the King's castle. The grandeur Cassandra had seen when she had come to Marcos' and Gabelle's anniversary celebration had only been a small glimpse of the glory of which King Amadeo was capable. Everything, from the tapestries to the floor designs to the lamp fixtures, was exquisite. But the best part was the ballroom.
Opening the door for Cassandra, the King watched with pleasure on his face as Cassandra surveyed the room. Jaw dropped in awe, she spun around to take in the full beauty of the place. Turning to the King, she smiled. "This is perfect," she said, voice trembling from how much she meant the words.
"Do you really like it?" the King asked, genuinely excited.
He is desperate for my affection and admiration, Cassandra realized. No, he doesn't need either my affection or my admiration, but...he wants it. The thought was enough to cause Cassandra's heart constrict in...in...
No. It couldn't be. There was no way that love could be involved in what was unfolding.
The King had watched the myriad of thoughts flicker in Cassandra's eyes. Stepping forward, he gently placed his hand on her shoulder. "Are you alright?"
Cassandra looked away. "I was just...I was just thinking..."
The King waited patiently, that beautiful face of his openly displaying his heart.
"You...you really want me to be here."
"Yes!" King Amadeo exclaimed, eyes filling with tears. He put his other hand on Cassandra's other shoulder and shook her ever so slightly - not out of frustration, but out of an excitement so pure and true that Cassandra couldn't help but laugh, delighted. "Yes!" he said again.
And then, something changed.
The smile slowly faded from the King's face as he searched Cassandra's eyes. As he brushed Cassandra's hair back, an expression of sadness filled his eyes. Cassandra wanted to ask him what was wrong, but she already knew.
"Do you want to stay here?" the King asked.
Cassandra began to nod, but then, she lowered her head. For even though she wanted to stay with the King and make him happy forever, she knew the truth. Something within her was already missing Hadrian's presence.
"What does he have that makes you want him so?" the King whispered.
"I don't know," Cassandra whispered. And it was true. In that moment, she honestly couldn't fathom why she still wanted Hadrian...she just did.
"Do you doubt me?"
Shaking her head vigorously, Cassandra immediately replied, "No! No, I don't doubt you at all, Amadeo, I just - "
In that moment, Amadeo's eyes brightened, and he gave a soft laugh of utter joy. He grasped Cassandra's hand and held it tightly in both of his own.
"What? What is it?" Cassandra asked, wondering what had occurred.
"Nothing. Nothing, it's just..." Amadeo laughed softly. "That's the first time you've called me 'Amadeo.'"


text:
You won't have a monitor large enough to properly watch them, nor the recording equipment to capture them, nor the broadband connection speed to stream them, but reality be damned - YouTube has announced it will support video of up to 4096 x 3072 pixel resolutions!
In an official blog post, YouTube engineer Ramesh Sarukkai explained this madness saying:
"We always want videos on YouTube to be available in the highest quality possible, as creators intend. In December of last year, we announced support for 1080p, or full HD. At 4096 x 2304 pixels, 4K is over four times the size of 1080p... We're excited about this latest step in the evolution of online video. We've been impressed by the 1080p videos you've uploaded over the last seven months and can't wait to see (in 4K!) what you do next."
Thankfully Sarukkai does acknowledge: "video cameras that shoot in 4K aren't cheap, and projectors that show videos in 4K are typically the size of a small refrigerator {while} watching these videos on YouTube will require super-fast broadband."
Why is YouTube doing this? It's not really anything more than a) a little bit of future proofing, b) showing off, and c) wanting to be the first streaming service to offer this - which is closely tied to point b). If you have the hardware to watch 4K videos pixel to pixel let us know how you find them. The fact we don't have that capability in the TR offices probably says everything...
Side rant: I've always hated the term 'Full HD' after all, what are we going to call 4K video when it takes off down the line: 'Really Full HD'? 'Full HD 2'? 'Fullest HD?'


text:
A Corporate Income Tax with many favourable rebates (IS)
The Corporate Income Tax general rate is 28% (25% for SMEs) and can be noticeably reduced when certain legally established tax benefits, such as those affecting R&D and innovation, are applied.
Take advantage of the Non-resident tax system
Available income of individuals is taxed according to a progressive rate scale ranging from 22% to 49%. Expatriate workers can choose between the general tax system or the non-resident tax system (IRNR) at the fixed rate of 20% for dividends, interest and capital gains. Income generated in other countries is not subject to the tax on this Spanish income.
Value Added Tax (VAT)
Three different rates are applied: 4%, 10% or 21%.


text:
Stud farm
A stud farm or stud in animal husbandry, is an establishment for selective breeding of livestock. The word "stud" comes from the Old English stod meaning "herd of horses, place where horses are kept for breeding"[1] Historically, documentation of the breedings that occur on a stud farm leads to the development of a stud book.
The word stud is often restricted to larger domesticated (especially farm) animals, such as cattle and horses. A specialized vocabulary exists for the studs of other animals, such as kennel (dog), cattery (cat) and aviary (birds).
Monastic stud farms
During the Middle Ages, stud farms were often managed as part of a monastery. At the time, few people apart from monks could read and write, and so they were charged with the responsibility of recording pedigrees. The Carthusian monks are famous for their role in breeding the Andalusian horse in Spain, while monasteries in Bavaria were responsible for the original Rottaler horse.
State stud farms
A state stud farm (German: Landgestüt,) is one that is owned by the government. The first state studs were ordered by Louis XIV of France in 1665. The purpose of the state studs was to make high-quality horses available to local breeders and farmers to accelerate the evolution of local horses. Stud farms which kept a herd of mares in addition to stallions were dubbed "Principal" Studs. State-owned stallions were made accessible with low or no stud fees. Germany is most famous for its Principal and State Studs, which have been instrumental in the shaping of the German riding horses and several breeds of German cold bloods. The Hanoverian is associated with the State Stud of Celle, the Rhinelander and Westphalian with the State Stud of Warendorf, the Brandenburger with the Principal Stud of Neustadt an der Dosse, and so on.[2]
Other European state studs include:
- Lipizza (1580) of Inner Austria (now Lipica, Slovenia), known for the Lipizzaner horse
- Kladrub (1579), another state stud established by Austria at Kladruby nad Labem, in what is now the Czech Republic, which breeds the Kladruber
- Mezőhegyes (1784) of Hungary
- Bábolna (1789) of Hungary, which breeds the Arabian horse, the Shagya Arabian and others
- Radautz (1792) of Austria (present day Romania)
- Piber (1798) of Austria, began as a military depot, since 1920 known for breeding the Lipizzaner horse
- Janów Podlaski (1817) in Poland, best known for breeding purebred Arabians.
- Kisbér (1853) of Hungary
- The Irish National Stud (1946), which breeds Thoroughbreds
- Michałów (1953) of Poland, which breeds Arabians.
- Marbach stud, (1477) also known as Weil-Marbach, Württemberg (present day Germany). Produces Arabians, Black Forest Horses, Haflingers, and warmbloods.
- Yeguada Militar, Spain
The German city of "Stuttgart" gets its name from stud farms.
See also
- ↑ Online Etymology Dictionary
- ↑ Eylers. "History and present day situation of the principal and state studs of Germany". State Studs of Germany. http://www.horse-gate.com/landgestuete/index_en.html. Retrieved 2008-02-05.
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text: Posted February 4, 2008 GRAND FORKS, N.D. – University of North Dakota co-acting athletic directors Betty Ralston and Steve Brekke announced today that UND head men's hockey coach Dave Hakstol has been suspended for its next two games for his actions during a men's hockey game Saturday at the University of Minnesota.Ralston said the disciplinary action was determined by the University of North Dakota and was made independent of any decision or action by the Western Collegiate Hockey Association."We hold all University of North Dakota coaches and student-athletes to the highest standards of sportsmanship, conduct and ethical behavior," Ralston said. "We expect our coaches to keep themselves and their teams in control at all times. Profane language and poor behavior on the part of our coaches and student-athletes is unacceptable." Share this post Link to post Share on other sites


text:
Ah ah ah .. okay please stop whining...
I don't see the meaning of your thread.. why did you make a thread posting " aah thor is so epic I'm a fanboy and in love with his haair hihi" It's not necessary! And it's my problem if I post something in your thread! You must respect that I respect that you opened a thread but I don't understand it...
The dildo poster isn't a friend of mine.. get your facts straight!
Unnecessary bad rep bro...
If you could explain how your thread could enrich this forum then I'm going to be quiet.
He certainly is! He only has 1 eye because his previous owners mistreated him, we adopted him from a rescue organisation. I'm from Australia. How about you?
hahaha... so cute. I have another dog, I named him Mr.Snuggles.
I know! I chose Taco cos it's mexican, and my dog is a chihuahua. Also cos he's not much bigger than a taco!
I feel bad that I probably wont be online for so much longer thought. =(
Listen there is no worries at all! I know the feeling of panic attacks, how your whole body just stops function the way you want to, how the panics increase and increase and how you can't control yourself even if you want to. You get full of energy but at the same time feel so powerless. Uff, no having panic attacks isn't something nice to have at all! I really feel for you, I really really and truly do.
It's a good thing thought that the attack that you had seems to start to go away now, that's good. But continue to take long breath and relaxing for a while more anyway, because panic attacks gets back easily even if you think that they have passed. So try to relax some more. You should, as I also mentioned before, think of taking away your number from that OP. Just click on the edit option in the right corner and then save. But it's your decision of course. Again, hope that the panic attack will go away completely soon.
Id segest highschool of the dead. Its about zombies
Im curentley re watching elfin lied. I watch death note,tri gun,cowboy bibop,famaley guy,american dad,clannad,fruits basket,fullmetal alchimsit,fullmetal panic,mad lax and black lagone. If you are in to supernatral anime i highley recomend elfin lied. Heads up it has nudity and a lot of. blood
Send an Instant Message to xMaTTx Using...
Senior Member
I Love him
¿Donde estás, papá?


text:
- 1[countable, usually singular] a crowd of people pressed close together in a small space a big crush in the theater bar I couldn't find a way through the crush.
- 2[countable] crush (on somebody) a strong feeling of love that usually does not last very long and often is not expressed. It is usually young people that have crushes, especially on people they do not know very well a schoolgirl crush I had a huge crush on her.
Check pronunciation: crush


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text:
When I was looking at notebooks for college, my father, who ran a small computer consulting business at the time, encourage me to buy a Lenovo Thinkpad. Six years later, I still write many of my blog entries from the Lenovo 3000 N100 that has since traveled to three continents and absorbed many scrapes and bruises. It was the legacy of IBM that led my father to encourage me to buy the computer, a legacy of computer engineering that spans one hundred years almost exactly to this very day. IBM has a particularly fascinating, and not totally conflict-free, history in which they have re-invented themselves time and time again in order to not only provide the solutions to problems arising in our global information age, but to contribute largely in the framing of those very problems themselves so as to position themselves in such a way that their solutions remain ahead of the curve. Originally IBM, or what was then known as C-T-R, engineered tabulating machines for various information processing needs (punch cards serving as the primary mode of information storing), fostering a corporate culture and pride that largely involved their drive to create new cutting-edge technologies. Retrospectively, IBM's groundbreaking strategies to instill corporate culture that included singing the IBM rally song (http://www-03.ibm.com/ibm/history/multimedia/everonward_trans.html) in the workplace and insisting on a corporate uniform, leave a somewhat unappealing taste in my mouth, if only for former IBM CEO Thomas J. Watson's ambiguous role in making it possible for the National Socialist regime to systematically target Jews using IBM's tabulation machines.
Regardless of how dark a chapter of IBM�
39;s business dealings with Hitler really were, their commitment to R & D–always investing their profits back into the company–drawing on their punch card system, IBM invented calculators, electronic typewriters, and magnetic disks for data storage, all before introducing the System/360 (http://en.wikipedia.org/wiki/IBM_System/360) in 1964, a multifunctional computer that supported several applications at the same time. From then on IBM invented the magnetic strips featured in all credit cards, bar codes, floppy drives, and in 1981 the first personal computer. During the eighties however, IBM's clean-cut, blue suit business ethic took a nosedive when more free-thinking Silicon Valley companies such as Apple Macintosh and Microsoft picked up steam, and they had to cut out 100,000 jobs. According to many analysts, IBM's fall can be attributed to their spreading themselves too thin, an issue they have since addressed by dedicating themselves to developing new information architecture and infrastructure, having sold off their Thinkpad computer line to Lenovo in 2005. One of the largest investors in Open Source technology, IBM has maybe made its biggest headlines by providing two prototypes whose intelligence has outmatched its greatest human competitor: in 1997 Gary Kasparov, the reigning chess champion, was defeated by Deep Blue, an IBM chess-playing computer, and then, in 2011, Watson, a supercomputer constructed by IBM engineers, took down two previous champions in Jeopardy. All in all, IBM's active engagement with their markets and consumers, along with the range of flexibility they have demonstrated in taking on new challenges, has brought them the one hundred years of success we now attribute to them.


text: INDIANAPOLIS, Nov. 1, 2012 /PRNewswire/ -- Local and state government officials joined representatives from Eli Lilly and Company (NYSE: LLY) today to announce a $140 million expansion to the company's Indianapolis insulin manufacturing operations. The 80,000-square-foot expansion, which will enable the manufacturing of insulin cartridges to meet the growing diabetes demand in the U.S., represents one of the most significant investments in Lilly's U.S.-based manufacturing operations in the past decade. Construction will begin immediately with completion expected in March 2014. During this period, construction trade staffing will average 250, with peak employment at approximately 350 workers at the site. Once operational in 2015, more than 100 full-time, highly skilled, specialized technicians, scientists, and engineers will be needed to manage the operations. Diabetes care is a major segment of Lilly's pharmaceutical business with projections from health care experts – including the Centers for Disease Control and Prevention – indicating that as many as one in three U.S. adults could have diabetes by 2050. The rise in prevalence of the disease is due, in part, to an aging population more likely to develop type 2 diabetes, increases in minority populations that are at high risk for type 2 diabetes, and people with diabetes living longer. Diabetes afflicted 366 million people worldwide last year, according to the International Diabetes Federation. John C. Lechleiter, Ph.D., Lilly's chairman, president, and chief executive officer, said that Lilly's commitment to meeting the long-term needs of people with diabetes in the U.S., as well as its role as a biomedical leader in Indiana, drove the company's decision to build this state-of-the-art manufacturing facility in Indianapolis. "Lilly is committed to providing a full range of innovative treatment options for people with diabetes," said Lechleiter. "The need in our country is great – and it is growing. This investment will help us to better meet that need while expanding our advanced manufacturing footprint in our home state – helping to strengthen Indiana's bioscience industry." Lechleiter said the new facility will manufacture insulin cartridges for people with diabetes. It will be a first-of-its-kind facility for Lilly in the U.S.


text:
How Sydney can keep its power during heatwaves
The Berejiklian government will issue warnings of potential threats to electricity supplies from this summer after its review of February's heatwave found the power sector to be vulnerable.
Peter Hannam is Environment Editor at The Sydney Morning Herald. He covers broad environmental issues ranging from climate change to renewable energy for Fairfax Media.
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Developmental mechanisms directing early anterior forebrain specification in vertebrates
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DOI: 10.1007/s00018-013-1269-5
- Cite this article as:
- Andoniadou, C.L. & Martinez-Barbera, J.P. Cell. Mol. Life Sci. (2013) 70: 3739. doi:10.1007/s00018-013-1269-5
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Research from the last 15 years has provided a working model for how the anterior forebrain is induced and specified during the early stages of embryogenesis. This model relies on three basic processes: (1) induction of the neural plate from naive ectoderm requires the inhibition of BMP/TGFβ signaling; (2) induced neural tissue initially acquires an anterior identity (i.e., anterior forebrain); (3) maintenance and expansion of the anterior forebrain depends on the antagonism of posteriorizing signals that would otherwise transform this tissue into posterior neural fates. In this review, we present a historical perspective examining some of the significant experiments that have helped to delineate this molecular model. In addition, we discuss the function of the relevant tissues that act prior to and during gastrulation to ensure proper anterior forebrain formation. Finally, we elaborate data, mainly obtained from the analyses of mouse mutants, supporting a role for transcriptional repressors in the regulation of cell competence within the anterior forebrain. The aim of this review is to provide the reader with a general overview of the signals as well as the signaling centers that control the development of the anterior neural plate.
KeywordsAnterior forebrain Neural induction AVE Hesx1 Six3 Tcf3
The overall anatomical structure of the mature vertebrate brain has been highly preserved throughout evolution, although the degree of development of particular domains can vary enormously between species. From fish to mammals, the brain can be divided into three main areas according to their position along the antero-posterior axis: the fore-, mid-, and hindbrain. The anterior forebrain includes the telencephalon (cortex, hippocampus, and basal ganglia), hypothalamus, prethalamus as well as the eyes and visual tracts (optic chiasm). The posterior forebrain comprises the thalamus, epithalamus, and pretectum [59, 128, 129]. The entire brain has a common origin during early embryonic development in a single-layered pseudostratified epithelium called the neural plate (NP). The NP becomes molecularly distinct to surface ectoderm (destined to form the skin) soon after gastrulation when neural induction takes place. Subsequently, it is divided into domains along the antero-posterior and medio-lateral axes characterized by specific gene expression patterns, which will eventually give rise to brain structures at later stages of development [121, 130]. Using embryological techniques such as single cell labeling and cell transplantations or genetic approaches (i.e., genetic tracing using mouse lines expressing Cre recombinase), the origins of the distinct components of the mature brain have been mapped in the early NP [25, 27, 28, 29, 63, 123, 159]. Such studies have also demonstrated a remarkable degree of conservation between species at early embryonic stages, despite the considerable differences in the shape and size of their mature brain structures.
The focus of this article is to revise the major findings that have contributed in the generation of a model of how the forebrain is formed during the early stages of development and in particular, the mechanisms underlying anterior forebrain formation. We have attempted to provide a historical perspective of the milestones that provided the foundations to this model and to link these with more recent discoveries. We aim to discuss findings obtained from studies in different animal models, often first describing the results obtained from the initial experiments regardless of the species and commenting on the degree of conservation in other experimental models. We will discuss the relevance of essential signaling centers as well as critical signals involved in the process of anterior forebrain formation, paying special attention to the WNT/β-catenin pathway. To learn about the numerous intrinsic factors that are also essential for normal anterior forebrain development we refer the readers to other published review articles [9, 59, 76].
Neural induction and antero-posterior axis formation: a historical perspective
Some basic principles derived from these experiments have survived to date. Structures with similar activities to the amphibian organizer were identified in other vertebrate species including chick (Hensen's node), zebrafish (embryonic shield), and mouse (node). In these, the transplantation of the organizer led to similar results to those in amphibians [124, 138, 153]. However, it came as a surprise that transplantation of the mouse node gave rise to an incomplete axis lacking the anterior forebrain [10, 145]. The possibility existed that the difficulty of such transplantations in the small mouse embryo may affect the results and so, the inability of inducing a full axis may be a "technical flaw". Even in Xenopus, where these experiments are easier due to the larger embryo size, only a small proportion develop a full neural axis upon dorsal blastopore lip transplantation. An alternative explanation may be that the transplanting node only contained the posterior inducing activity, as does the late or trunk organizer of the amphibian embryo. However, even the transplantation of cells from the "tip of the primitive streak" at early streak stages (early gastrula organizer, EGO), which contains precursors of the node, failed to induce a full axis [145].
The influence of extrinsic signals in anterior neural induction
It is broadly accepted that anterior neural induction requires the inhibition of the BMP, TGFβ, and WNT/β-catenin pathways. This model has been built from a bulk of evidence based on gene expression, loss- and gain-of-function experiments, chimeric analyses, and embryological data in Xenopus, zebrafish, chick, and mouse.
Historically, experiments in Xenopus had a major impact on the origin of this model. Animal caps that are cultured as intact explants become surface ectoderm, but if cells are disaggregated, hence released of extrinsic cues, they become neural ectoderm of anterior identity [55]. This has been one of the pillars sustaining the "default" model of neural induction, which suggests that at pre-gastrula stages, the default fate of naive ectoderm is usually neural (i.e., brain) rather than surface (i.e., skin) ectoderm [86]. In fact, treatment of dispersed animal cap cells with BMPs could convert them into epidermis [155]. These initial findings have been confirmed in different experimental models, including zebrafish [15, 44] and mice. Mouse embryos deficient for the BMP receptor 1A (Bmpr1a−/−), the main receptor for BMP2 and 4, exhibit premature neural induction at pre-gastrula stages with expression of anterior markers Hesx1 and Six3 [35]. This is a similar phenotype to that observed in Nodal−/− mutants, and indeed Bmpr1a−/− embryos show no expression of Nodal [21, 35]. These findings fit well with the concept that inhibition of BMP/TGFβ signaling is a prerequisite for neural induction. BMP inhibitors such as noggin and chordin are expressed in the vertebrate organizers and play a role in neural induction by preventing BMP signaling [6, 118, 162]. This is beautifully exemplified in Xenopus, where the simultaneous depletion of noggin, chordin, and follistatin function by means of specific morpholinos, prevents the acquisition of neural fates demonstrating the critical role of BMP signaling inhibition during normal neural induction [66]. In addition, this research shows that there is a significant degree of functional redundancy, which may complicate the interpretation of data obtained in different animal models when addressing the requirement of specific signaling pathways [105].
Despite the robust evidence supporting the inhibition of BMP signaling for neural induction to occur, it was shown that this is not sufficient to induce an entire ectopic neural axis containing anterior and posterior components. The ability of Cerberus, a secreted inhibitor of nodal, BMP, and WNT molecules to induce an ectopic full axis when over-expressed in Xenopus confirmed the necessity to repress the BMP/TGFβ and WNT pathways for head formation to occur [16, 51, 64, 115]. WNT molecules were found to exert caudalizing activity on neural tissue. For instance, treatment of chick ectodermal explants fated to become anterior forebrain could be transformed into posterior neural tissue by exposure to WNT molecules [108] and Wnt8c over-expression in mouse embryos caused an expansion of midbrain markers at the expense of anterior forebrain [116]. These data suggest that once neural tissue has been induced, it must be protected from caudalizing activities that would bestow posterior identity, as proposed by Nieuwkoop.
Other molecules, such as retinoic acid (RA), were also shown to act as caudalizing factors, by promoting posterior fates in the neural plate [39]. In vivo, retinoic acid is synthesized from vitamin A (retinol) by the action of retinol dehydrogenases, which are expressed in the posterior regions of the embryo, but not in the anterior neural plate at the time of neural induction. In contrast, enzymes such as CYP26, a cytochrome P450 enzyme that degrades RA, is expressed at high levels in the anterior neural plate [56, 78]. This differential expression of synthesis and degradation enzymes is thought to create a RA signaling gradient along the AP axis (high-anterior and low-posterior) [90]. Fibroblast growth factors (FGFs) have also been shown to have caudalizing action on neural tissue in chick and Xenopus [97] and in mouse, exposure of prospective anterior forebrain tissue to FGF4 resulted in lack of expression of anterior forebrain markers and expansion of posterior markers [33].
FGF signaling has also been involved in the initiation of neural induction. Activation of FGF signaling has been proposed to be required prior to or independent to the inhibition of BMP signaling [43, 77, 88, 140]. Likewise, WNT signals have also been proposed to be required for neural induction in chick embryos [7, 112, 156]. However, there is also evidence suggesting that FGF signals are dispensable for the process of neural induction [154]. FGF signaling plays multiple and often contrasting roles in the early embryo as well as in pluripotent stem cells, and conclusions may vary depending on the particular experimental conditions and the assays used [81, 152]. Reconciling, at least partially, these discrepancies, elegant experiments have led to propose a model by which the activation of the FGF and WNT signaling pathways inhibits BMP signaling by promoting phosphorylation of Smad1 in a region of the molecule leading to its degradation and reduced nuclear localization [7, 40, 48, 113]. These findings are in line with experiments showing that inhibition of Smad1 and Smad2 is sufficient to induce neural character [23]. Together, these studies suggest that the activation of both the FGF and WNT pathways converge with the inhibition of BMP signaling at the levels of Smad1 and reinforces the idea that BMP signaling inhibition may be a conserved requirement for neural induction. They also suggest that there may be some species-specific differences regarding the temporal requirement of FGF signaling for neural induction. It will be important in the future to delineate the role of these specific pathways (e.g., retinoic acid, TGFβ, BMP, FGF, and WNT) and we anticipate that in vitro neural differentiation experiments using mouse embryonic and epiblast stem cells may provide important insights [26, 41, 54, 84, 102, 104, 131, 137, 142].
Signals from both the AVE and gastrula organizers are required for normal anterior neural induction
The experiments described above led to a working model and identified major molecular players deployed during anterior neural induction. It is now clear that there is an involvement of at least two signaling centers for normal anterior neural induction, the AVE and the gastrula organizers. Relevant questions to further comprehend anterior neural induction are when during normal development, is the inhibition of the BMP/TGFβ and WNT pathways required? And which tissues do signals responsible for their inhibition derive from?
The visceral endoderm (VE) derives from a few cells lining the inner cell mass and the blastocoel cavity of the implanting 4.5 dpc mouse embryo (Fig. 2). At 5.0 dpc, VE is a single cell epithelial sheet surrounding the naive epiblast, fated to give rise to the embryo proper and the extraembryonic ectoderm. At this stage, the precursors of the AVE are molecularly identifiable at the distal tip of the conceptus (distal visceral endoderm, DVE) by the expression of genes such as Hex, Lefty1 (a secreted inhibitor of Nodal) and Cer1 (an inhibitor of Nodal as well as WNT and BMP molecules) [11]. They are induced at the distal tip of the egg cylinder through the co-operative inductive action of the Nodal and MAPK signaling pathways, whose action is restricted to the distal tip by repressive signals from the extra-embryonic ectoderm [19, 24, 119]. Recent elegant lineage tracing experiments have demonstrated that the AVE is derived from specific primitive endoderm cells of the pre-implantation blastocyst [144]. At the onset of gastrulation (6.5 dpc in the mouse), the AVE is located in the antero-proximal region of the embryo underneath the embryonic/extraembryonic border. This final location of the AVE requires the antero-proximal movement of the DVE cells by cell intercalation into the VE cell layer [149, 150]. Therefore, it is clear that prior to the onset of gastrulation, the AVE has had ample opportunity to affect the patterning of the overlying anterior epiblast. However, it seems unlikely that the AVE can induce permanent neural character on its own; mouse embryos deficient for either Wnt3 or Ctnnb1 (encoding β-catenin), express AVE markers, but there is no activation of neural markers in the epiblast and therefore, no neural induction [62, 89, 94]. Corroborating these genetic data, ectopic transplantation of chick hypoblast can induce naïve ectoderm to express transient expression of neural markers, suggesting a priming effect during neural induction, but the stabilization of neural character requires BMP inhibitors and/or organizer activities [2].
Cell intermingling in the epiblast of the pregastrula mouse embryo is very high [49] and fate map analyses have shown that the most antero-proximal region of the epiblast overlying the AVE at these stages is not fated to give rise to the anterior neural plate. Rather, the prospective neural plate precursors are located in the antero-distal region of the embryo [85]. It is likely that the function of the AVE at these pre-gastrula stages is not only to "prime" the epiblast for anterior neural induction, but also to position the primitive streak, hence for the establishment of the AP axis. Genetic evidence from mouse mutants supports this idea. For example, embryos lacking Cer1 and Lefty1 show abnormal AVE patterning concomitant with the formation of multiple ectopic primitive streaks [114]. In addition, embryological studies have shown that removal of the chick hypoblast also leads to the appearance of multiple primitive streaks [14].
In the mouse, at 6.5 dpc the PS forms in the posterior proximal region of the epiblast and will elongate during gastrulation so that by 7.5 dpc it reaches the distal tip of the embryo, where the node will form. Neural induction is thought to take place in the early/mid-streak stage embryo, when Otx2 expression starts to be restricted to the anterior region of the epiblast. A few hours later, expression of anterior neural markers such as Hesx1 and Six3 becomes evident. The inducing activities of the tip of the PS and the gastrula organizers have been extensively studied in several species, including the mouse, and the evidence strongly suggests that the AVE and the gastrula organizers act together to induce anterior neural character. For instance, the EGO cannot induce anterior forebrain marker expression when transplanted to the lateral side of a host mouse embryo, but does so when combined with the AVE [145]. In agreement with the need for signaling activity from the AVE, the Otx2−/−, Foxa2−/−, and Lhx1−/− mutants have a molecularly identifiable EGO, but the AVE is not specified, resulting in an absence of anterior neural plate development [1, 5, 73, 117, 126]. However, the EGO activity is also required; as previously discussed, mouse embryos deficient for either Wnt3 or Ctnnb1, express AVE markers at pre-gastrula stages, but do not form a PS and so do not express the molecular activities typical of the gastrula organizers, resulting in failure to undergo neural induction [62, 89]. The EGO/node and its derivatives express many common genes, among them inhibitors of the TGFβ and WNT pathways such as Cer1, Dkk1, Nog (noggin), and Chrd (chordin), reinforcing the idea that they act synergistically during anterior neural induction. Of note, the activities required for anterior neural induction may still be present in the absence of discernible anatomical structures. This is exemplified in the Cripto−/− mutants, which fail to gastrulate and so, neither the primitive streak or gastrula organizer are formed. However, genes normally expressed in the primitive streak and organizers are detected in the proximal region of the embryo. The AVE is also specified and typical AVE marker expression is observed at the distal tip of the mutant embryo. Despite this atypical arrangement of the AVE and organizer activities, anterior neural induction and patterning of the neural plate takes place in these mutants, although this is along the proximo-distal rather than AP axis [36].
Some experiments, however, have shown that the AVE and the mid-gastrula organizer (MGO, located at the distal tip of the primitive streak at mid-streak stage) can in isolation induce neural character. For instance, rabbit AVE is able to induce anterior neural character to naïve avian epiblast [74] and conversely, the MGO also appears to induce neural tissue in the absence of AVE [72]. There are several possible explanations for these findings, one being that the AVE or MGO may have the potential to induce anterior neural character when the experimental conditions are permissive. However, during normal development of the embryo both signaling centers are required. This is conceptually similar to the differences between regenerative and physiological potential of somatic stem cells when assessed in either transplantations or in lineage tracing experiments [132].
Axial mesendoderm (AME) as a signaling center that maintains anterior neural character
Once the anterior neural plate has been induced, evidenced by the expression of anterior neural markers such as Hesx1 and Six3 at early neural fold stages, it is important to ensure the maintenance of this character and prevent its posteriorization. As with AVE at earlier stages, anterior axial mesendoderm (AME) tissue underlying the neural plate, plays a critical role in performing this function. The AME is a mixed population comprised of (1) anterior definitive endoderm (ADE), which is fated to give rise to the anterior foregut and its derivatives (e.g., liver, stomach, pancreas) [147]; (2) prechordal plate, which refers to endodermal and mesenchymal cells underlying the anterior region of the neural plate, which will form the anterior hypothalamus, telencephalon, and eyes; (3) notochordal plate, which gives rise to the notochord, underlying the developing neural plate caudal to the anterior hypothalamus (Fig. 2). The term AME in mouse is usually used to refer to the ADE and mesodermal component of the prechordal plate underlying the anterior neural plate. The origin of the AME is the gastrula organizers and the node. From the tip of the PS and subsequently from the node, a population of ADE cells expressing Cer1 and Hex move anteriorly within the VE to underlie the rostral neural epithelium [13, 147]. Notochordal plate cells derive from the node and will follow the ADE and prechordal plate, but its location is more restricted to the midline of the neural plate. Of note, within the mouse ADE, endoderm cells from the prechordal plate and notochordal plate initially move within the existing layer of VE and not underneath, therefore they need to intercalate with VE cells in their migration [141]. This causes part of the VE to become displaced into the extraembryonic region, mainly in the anterior portion of the embryo, but VE cells also become trapped and contribute to the endodermal lining of the adult gut [79]. The notochord will form a rod before somitogenesis and will be situated between the endoderm and neuroectoderm as in other vertebrates.
The inducing activities of the anterior AME are well established [20]. Explant experiments have shown the capacity of these cells to induce and/or maintain anterior character (i.e., Otx2 expression) in the vertebrate embryo [45]. In chick, the specific ablation of the ADE results in forebrain abnormalities with lack of telencephalic and eye development [158]. Likewise, absence of Hex, a transcription factor expressed in the ADE as it is formed from the tip of the PS, leads to patterning defects of the ADE and subsequent loss of anterior character (i.e., Hesx1 and Six3 expression) in the initially induced anterior neural plate [93]. The transcription factor Lhx1, and its co-factors Ssdp1 and Ldb1 are also necessary for normal brain development [42, 107, 126] and chimeric analyses have demonstrated its requirement in both the AVE and the AME [127]. The molecular activity of the anterior AME is thought to be similar to those of the AVE and gastrula organizers: to secrete inhibitors of the BMP/TGFβ and WNT pathways, hence protecting the anterior neural plate from posteriorizing signals. Supporting this notion, the AME expresses Dkk1, Cer1, Nog, and Chrd [34, 103, 163] and lack of these inhibitors, either single or in combination, is associated with defects in anterior AME and anterior forebrain specification [6, 34, 103, 162].
The role of the AME in protecting the ANP from caudalizing signals is also important for the establishment of other signaling centers within the neural plate responsible for the expansion and further patterning of forebrain tissue. For further detail on the relevance of these local signaling centers within the ANP, we refer the reader to other reviews [96, 122, 157]. One such center was initially discovered from elegant experiments in zebrafish, whereby the removal of the most anterior neural plate cells (anterior neural border, ANB) caused severe forebrain truncations [61]. The relevance for the ANB was also demonstrated in mouse embryos by means of ablation experiments where FGF8 was found to act as an essential signal for normal development of the anterior forebrain [130], which was further confirmed in several genetic studies [100, 110, 111, 139]. In the Hex−/− mutants, which show severe forebrain defects including lack of the telencephalon and eyes, Fgf8 expression in the ANB is reduced or absent [93], and this appears to be caused by primary defects in ADE patterning. Corroborating this notion, removal of anterior definitive endoderm in chick leads to reduced Fgf8 expression in the ANB and forebrain, including eye defects [158]. Neural crest cells have been shown to play a critical role in the maintenance of Fgf8 expression in the ANR and expansion of the forebrain region [30, 31]. Another important signaling center in the forebrain is the zona limitants intrathalamica (zli), which is required for diencephalic development and is delineated by the expression of Shh [67, 82, 125]. It develops within the neural tube, specifically between the prethalamus and thalamus (ventral and dorsal thalamus, respectively), but its position coincides with the boundary between the prechordal and notochordal plates [96, 122], suggesting that underlying tissues may also play a role in its formation.
In summary, the induction of the anterior neural plate and specification of the AP axis require the continued inhibition of signals that would bestow the naïve epiblast of the pregastrula embryo with a non-neural or caudal neural character. AVE, gastrula organizers and anterior AME are sources of secreted inhibitors that ensure the protection of a population of epiblast cells from these signals. In addition, the AME is required for the proper positioning of local signaling centers within the anterior neural plate that are responsible for further growth and development of the area.
Intrinsic regulation of cell competence: an additional level of protection of anterior neural character
In the previous section, we summarized a great deal of research pointing at the requirement for the anterior neural plate to be protected from signals that would transform it into posterior neural tissue. The activities of the AVE and gastrula organizers grant the epiblast anterior neural character, while the anterior AME acts to prevent its posterior transformation and refined patterning. This is achieved by the synergistic action of several secreted inhibitors. However, there are additional levels of protection within the neural plate itself, which prevent a posterior transformation of the ANP at stages when diffusion of secreted inhibitors from underlying tissues may be unable to reach this expanding region of the developing embryo.
Among the studied posteriorizing signals, it is the WNT/β-catenin pathway that appears to be critical in preventing anterior neural character. In Xenopus embryos there is a high-caudal to low-rostral gradient of activated WNT pathway, consistent with observations in other vertebrates [68]. For instance, in transgenic mouse lines expressing lacZ under the control of TCF/LEF binding sites, it has been shown that the anterior neural plate is initially devoid of X-gal staining, demonstrating that the WNT/β-catenin pathway is not activated in anterior neural precursors [4, 92]. Likewise, expression of the WNT/β-catenin target genes Axin2 and Sp5 is detected in posterior regions but not in the anterior-most part of the neural plate [3]. The necessity of the suppression of this pathway has been further analyzed in vitro and in vivo. As previously discussed, WNT molecules can transform cells initially fated to be anterior to acquire a caudal neural character [108]. In mouse embryos, genetic studies have demonstrated the need to negatively modulate the levels of WNT signaling for normal head formation [46, 47, 87, 116]. In zebrafish, mutations resulting in over-activation of the WNT pathway lead to posterior transformation of telencephalon and eye tissues in favour of diencephalic fates [57]. The expression of several secreted inhibitors able to bind either WNT molecules or their receptors is high in the anterior neural plate and AME. For instance, the anterior neural border of the zebrafish embryo is the source of a secreted WNT inhibitor, tlc, which is required for normal telencephalic development [60, 61]. However, the presence of these inhibitors is not the only way to ensure low levels of WNT signaling in the anterior neural plate.
Very similar forebrain defects are observed in the Hesx1−/− mutants. Telencephalic vesicles and eyes are reduced or absent at early somite stages, but Six3 expression is unaffected at neural plate stages [32, 95]. The lack of anterior forebrain is caused by a posterior transformation of the anterior neural plate, which was evidenced by the rostral expansion of posterior markers such as Wnt1 and Pax3. In addition, and confirming the change of fate of the ANP, genetic fate mapping studies on Hesx1Cre/−;R26YFP/+ (Hesx1 null-mutants) and Hesx1Cre/+;R26YFP/+ (normal) embryos have demonstrated that descendants of neural precursors initially fated to colonize the telencephalon and eyes end up populating posterior regions of the neural plate such as the thalamus, epithalamus, and pretectum [3]. In Hesx1−/− embryos, ectopic activation of the Wnt/β-catenin signaling pathway, evidenced by Axin2 and Sp5 expression, is detectable at early somite stages prior to the onset of Wnt1 expression in the prospective midbrain/posterior forebrain region of the neural plate or Fgf8 expression in the ANR. This suggests that the observed reduction of the Fgf8 expression domain in the ANR and the expansion of the Wnt1 expression domain are a consequence of the ectopic activation of the WNT/β-catenin pathway in the ANP. At the molecular level, gene profiling of isolated anterior forebrain precursors has demonstrated the ectopic activation of the WNT pathway in Hesx1-deficient embryos relative to controls [4]. Therefore, HESX1, as well as SIX3, may regulate the competence of the ANP making it unresponsive to the WNT molecules that are secreted at posterior levels (WNT1 and WNT3a). The regulation of cell competence, i.e., the ability of a cell to either respond or not to a given signal, is an important factor in cell fate specification that usually attracts less attention than the function of the inductive signals themselves [91, 133, 148]. For example, the expression domains of Six3 and Irx3 (a member of the Iroquois family of homeoproteins with a role in neural induction and patterning) have been proposed to confer distinct competence to inducing signals to specify anterior versus posterior neural plate identity [52, 53, 75, 120]. Analysis of the Tcf7l1 (Tcf3) mutants supports the hypothesis that SIX3 and HESX1 may regulate cell competence within the anterior neural plate.
In conclusion, research over the last years has revealed the principles that regulate the development of the anterior forebrain at early stages of embryogenesis. There is a perfect interplay of signaling centers during normal morphogenesis of the embryo to ensure that the anterior forebrain is protected from caudalizing factors. This is initiated by the AVE, embellished by the ADE/AME, and reinforced by transcriptional repressors regulating cell competence within the anterior forebrain itself.
The authors wish to apologize for any omission as we may have inadvertently left some relevant work un-cited. We are grateful to Shankar Srinivas, Tristan Rodriguez, and Paul Le Tissier, for comments and suggestions. The authors are funded by the Wellcome Trust grant 084361.
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Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.


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Re: Deep Sky Fishing
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Actress/singer Hilary Duff is returning to the world of music, having signed with RCA Records for her upcoming fifth album, due out this fall. Duff releases a new single, "Chasing The Sun," on July 29. Its video will debut that day as well. Duff said in a statement, "I couldn't be more excited to join the RCA family! I love my team there and feel so lucky to be in the company of their talented artists. I came to them with my vision for the album and it has been a real labor of love, but something I am so proud of. 'Chasing The Sun' is just a peek into my new album. I've worked very hard and the album is a great representation of the experiences I've had in my life and where I want to go from here!" "We are thrilled to welcome Hilary Duff to the RCA Records family," said RCA Chairman/CEO Peter Edge. "She is a supremely talented young woman, who after achieving massive success at a young age, continues to be an extraordinarily creative, relevant and cutting edge performer with a enduring appeal." "Hilary Duff is a global superstar, a talented singer, actress and performer and we are thrilled to welcome her to RCA Records," added RCA President/COO Tom Corson.
Pharrell has released the video for "Come Get It Bae," his latest single. The track features Miley Cyrus, who appears in the clip, hanging around with Pharrell, who is filming a bevy of dancing models. THe song can also be heard in a recent Red Bull ad. Check out the video below:
Jack White is expanding his Third Man Records empire with a book imprint, naturally called Third Man Books. The first release from Third Man Books is due out August 5 and is a 321-page hardcover book of poetry, prose, and art called Language Lessons: Volume I, which will of course be accompanied by a two record set.
Singer/songwriter Ryan Adams has announced a new fall tour, in support of his upcoming eponymous album, due out September 9. Adams' new dates begin in Santa Barbara on October 1, with shows announced up to October 20 in Kansas City.
Mudvayne guitarist Greg Tribbett is turning his attention to his work as a producer. Tribbett has inked a deal with Strong Management under its producer/songwriter roster, and he's looking to expand his resume after co-producing all of the Mudvayne albums, the first three Hellyeah records, Nonpoint's Miracle and Man Made Machine's Become. Meanwhile, Mudvayne remains on temporary hiatus. The band recently posted a note on Facebook explaining: "With respect to all the band members, we are all doing something in music that satisfies our appetite right now. When the time is right, Mudvayne WILL be back in action. In no shape or form is this a disrespect to our fans. We Love our Fans and will give them all they can handle when it is time."
Nicki Farag, SVP of Promotion, Def Jam Recordings
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Livro online Livro Figure Drawing For Fashion Design – Drudi, Elisabetta – ISBN: 9054961503 para você comprar em loja virtual. Confira preço, ofertas e descontos.
This book offers a topic by topic guide to acquiring and perfecting the skills of visualising ideas and concepts in costume and fashion design, concentrating on the female form. Realism and anatomical precision are the chief values, whereas for costume and fashion, stylisation and exaggeration are ways of adding individuality and verve to a plate, and of focusing attention on specific elements.


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Bugatti Has Already Sold More Than 200 Chirons
With a list price of $2.6 million, a third of all Bugatti Chirons will find their homes in America.
Some say Americans prefer value for money over the latest in technology and refinement, but I guess that may only be true at the price point of a Dodge Challenger Hellcat. For a cool $2.6+ million, you can bet each customer will demand a 1500 horsepower W16 with a sequential quad-turbo system and the best leathers Volkswagen can find jammed in a car that will reach a limited top speed of 261 mph, no matter where they live.
To celebrate the fact that around one third of the Chiron's production run will be sold to American customers (and to sell a few more), Bugatti brought this nice blue pre-production Chiron to Monterey, providing you with enough new wallpapers for the following weeks in the process:
I'm planning to buy mine used from Ashley Schaeffer eight years from now.


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1. aberration
(n.) something that differs from the norm
Wally knew the plan was crazy and he knew Dick did too. The only one that didn't seem worried was Artemis and she was the one being sent into danger.
2. abhor
(v.) to hate, detest
Every single day that Dick lives and Wally is gone -not dead, he's not dead-a ball of anger in his stomach keeps growing and he knows that he'll have to let it out eventually. And he knows it'll most likely be at one of his weekly visits to Wally's memorial.
3. acquiesce
(v.) to agree without protesting
Whenever Batman's eyes thinned into slits, Wally knew he should just agree without protest to whatever plan Batman already had organized.
4. alacrity
(n.) eagerness, speed
As Bart ran around the cave for at least the fifth time, Wally thought of himself at that age and was surprised by the many similarities but more so by the differences. The eagerness and energy were there but there was always something more wary and haunted in Bart's eyes.
5. amiable
(adj.) friendly
Cassie always thought Jaime was really friendly but always wondered if he had a serious problem when he kept having side conversations with seemingly no one.
6. appease
(v.) to calm, satisfy
Dick's attempts to calm Wally down while he ranted about how Artemis was in danger and Dick's idea was horrible were fruitless.
7. arcane
(adj.) obscure, secret, known only by a few
"Dick, I think it might be time to let the others know your identity. They're already suspecting that I know something already but-"
"That's because you hint at it anytime anything having to do with the name Wayne or Grayson comes up!"
8. avarice
(n.) excessive greed
The robber snickered quietly to himself after he successfully stuffed the last of the money into his getaway van. He stopped and sighed in defeat right when he felt a gust of wind behind him and the click of handcuffs around his wrists. "Got greedy again, huh, buddy?"
9. brazen
(adj.) excessively bold, brash, clear and obvious
"Nightwing, everyone knows you have a great ass. Do you you have to make it all the more obvious with that costume?"
10. brusque
(adj.) short, abrupt, dismissive
And with a flip of Batman's hand in his direction, Robin was dismissed from the cave. As he headed back to the door, Robin glanced back at the cowled figure hunched over the keyboard of the computer but he only continued typing.
11. cajole
(v.) to urge, coax
"Come on, Rob, it'll be fun! A day at the beach. You, me, the babes. We'll have a great time; I haven't been able to hang out with my best friend in forever, please?"
Robin almost said no off offhandedly to Wally but then he made the terrible mistake of looking at his best friend. Specifically his bright green eyes. The puppy eyes of doom were out. They were even glistening this time. Dammit.
He sighed. "'Kay, Wally, I'll go. But only for a couple of hours! Batman gave me a ton of work to catch up on that I need finished by tonight and neither of us want the Wrath of the Bat upon us."
Wally didn't even seem to hear him after he agreed; he just hopped up and started zipping around with joy. Dick realized he really hadn't hung out with him in a while. Today would be good for them both.
12. callous
(adj.) harsh, cold, unfeeling
"Why does it always have to be mind control?"
Wally sent the off handed thought through the mind link they shared while the team split up, each to contain their respective mentors, who at the moment had blank, unfeeling faces as they ruthlessly attacked the kids that they'd trained for years.
13. candor
(n.) honesty, frankness
In Robin's mind the Flash family were the most trustworthy heroes in the business but also had the potential to be the most dangerous. With the power to tap into a speedforce they could do a multitude of damage to the world. But they don't. They have hearts of gold that are bent on protecting and helping others whether in the line of duty or not.
14. chide
(v.) to voice disapproval
The team observed the high speed conversation between the two speedsters with awe and a tinge of jealously. They knew that the Flash was chiding Kid Flash for his brash actions in the mission but it didn't look like he was criticizing him at all. Flash listened to Kid's side of the story and then explained what could have been done better and what to look for next time in a situation similar to what had happened. At least that was as much as they could assume from the speedy gestures and speaking from the two of them.
15. circumspect
(adj.) cautious
"Guys, this is just Rob's Bat paranoia kicking into overdrive. Don't worry too much." Kid Flash's reassurances were needed but they didn't lower any of their worry for their little bird.
16. clandestine
(adj.) secret
Zatanna and Artemis never really ended up telling anyone what happened on that one Halloween night years ago.
17. coerce
(v.) to make somebody do something by force or threat
M'gann never wanted her team- no her family to get hurt because of something she had kept from them for so long. So agreeing to be a mole for Queen Bee was the only logical solution to keep them all safe. Yes, that's why she was betraying- no protecting her family. (But in her heart she knew it was wrong not to ask for help).
18. coherent
(adj.) logically consistent, intelligible
"Kaldur! Kaldur, you gotta stay awake man. Come on, look me in the eyes, say something coherent, do something! Don't just lay there flopping like a fish- bad analogy I know- you're Aqualad, you gotta lead our team! A little bump to the head can't bring our leader down, right? Aqualad, Kaldur!"
Kid Flash's frantic babbling followed him into the darkness of his mind until he knew no more.
19. complacency
(n.) self-satisfied ignorance of danger
Kid Flash got cocky during some missions. He knew it was dangerous, but when you're the Fastest Boy Alive nothing can hit you, right?
20. confidant
(n.) a person entrusted with secrets
Bart cut himself off immediately after he registered the looks of surprise on his team's faces. He forgot he was a tourist in this time with too many secrets that no one could ever really know except him. He was alone.
21. connive
(v.) to plot, scheme
"They call themselves the Light."
"Oooh, how devious. I bet they plot their schemes underneath those gigantic interrogating light thingies-"
Robin interrupted with a hiss. "Dude, stop."
22. cumulative
(adj.) increasing, building upon itself
This ever increasing snowball effect of keeping secrets from one another was eventually going to either blow up in their faces or an explanation was going to happen. Today was the day for either one.
23. debase
(v.) to lower the quality or esteem of something
Despite how awesome Wally knew his life was with his powers and all, his father still put him down in the dumps with offhand comments about one thing or another that Wally was apparently always doing wrong in his life.
24. decry
(v.) to criticize openly
As much as Batman openly criticized the team, every time he gave them a compliment (or as much of a compliment as a Bat could give) the team felt ten times better about the work they were doing.
25. deferential
(adj.) showing respect for another's authority
Black Canary made sure on the very first day of teaching this rowdy group of teenagers that they knew who was in charge and mutual respect was also a thing earned, not given freely.
26. demure
(adj.) quiet, modest, reserved
Even though M'gann's bubbly personality helped her with being the only girl on the team, she was still a very reserved person until Artemis joined the team. They immediately became united and stronger as the ladies of the group.
27. deride
(v.) to laugh at mockingly, scorn
Of course the one night that Batman allows him and KF to patrol together they run into the Joker.
"Ah, Boy Blunder. Looks like you brought a playmate to join in with our fun! Who is it again? Flash Boy? Mini Flash? Speedy?" the Joker said with his familiar cackle.
Kid Flash bristled at the incorrect naming and unnatural smile stretching across the Joker's chalk white face.
28. despot
(n.) one who has total power and rules brutally
Lex Luthor twists others' words to suit his purposes in his business and in the villain world. Thus becoming one of the most powerful men in both.
29. diligent
(adj.) showing care in doing one's work
"Barry Allen, late again. Am I going to have to start calling you in the morning so that you actually get here on time for once?"
"Sorry, Betty! You know me, always late but always working my ass off for you guys anyways." Barry passed by her desk with a breeze (slower than his usual) and a wink on his way to the lab.
30. elated
(adj.) overjoyed, thrilled
The end of the school year was a time of mixed feelings for Bart Allen. He was extremely happy to be out of that slow paced thing they called school. In fact, he meant to ask Wally about how he survived it- but then here was where Bart felt horrible and remembered he couldn't ever ask Wally anything again. Not about school or Chicken Whizees or how to deal with a secretive best friend or about how weird living in the past was or a million other questions that ran though his head every day. Just after school ended, every year now, the anniversary of Wally's dea- no -his disappearance was just around the corner.
31. eloquent
(adj.) expressive, articulate, moving
After Bruce Wayne's eloquent speech appeared on the news, the camera was showing close ups of the other guests at the city meeting. It just so happened that Wally saw his best friend pop up on the television from the kitchen in Mount Justice and almost spit out his cereal onto the back of M'gann and Conner's heads. He managed to swallow the rest of his snack and almost succeeded in stifling his giggling. M'gann turned around with a confused look.
"Wally, are you choking or laughing? I can't really tell, either way your face is always red."
"No, no, I'm fine, beautiful. Just sometimes Gotham news makes me laugh, don't ask why, it just does."
32. embezzle
(v.) to steal money by falsifying records
Wally's voice floated over from the floor to the desk where Dick was working on his laptop in the hotel room that they... borrowed temporarily. Half of Wally's body was on the bed with his head resting on the floor upside down. It would have looked like an uncomfortable position to anyone who wasn't an acrobat's best friend.
"Dude, we should totally rob a bank since we're already making all these false records and identities."
Sigh. "No, Wally, we can't rob a bank. And that doesn't even make any sense anyways. You need to sleep. So lay on the bed the right way and actually sleep." Dick's voice was laced with a combination of a hinted threat and annoyed fondness that usually came with talking with Wally.
Wally shimmied himself under the covers and his mumbles about how Dick didn't even know how to sleep properly so why should he criticize him brought a smile to his laptop lit face.
33. empathy
(n.) sensitivity to another's feelings as if they were one's own
M'gann could feel the multitude of intense emotions flowing into her mind from someone on their team until that someone pulled down a wall over their thoughts as strong as any grand fortress. She was confused and wondered about the identity of the person until everyone else's thoughts brought her back to the mission at hand.
She was left wondering who it was for a long while until she felt those same emotions on another mission when it was necessary to link up. She hesitantly brushed up against the mind before the wall she knew would fall could close her off and immediately recognized the thoughts as Kaldur's. M'gann met Kaldur's eyes one spare moment in the mission and made a mental note to talk with him afterwards.
She never would want any of her team members to feel those negative emotions for such an extended amount of time when they could just talk with her.
34. enmity
(n.) ill will, hatred, hostility
Jason was a kid with a lot of problems with an ever growing ball of hatred and hostility inside himself and that worried Bruce. Enough that he wondered at what he might become without someone to set him on the right path. And definitely enough that he would take him in.
35. erudite
(adj.) learned
'FAILED' flashed in bright holographic blue letters underneath Robin for the first time in a long time. Black Canary offered a hand to her fallen opponent and gave him a few pointers on what to do better on next time but also what he did well.
36. extol
(v.) to praise, revere
The Flash ran past the people of his city with the appropriate air related sound effect and they shouted for him in thanks for protecting them, especially little old Mrs. Sunden. He had rescued her cat from a tree just that morning.
37. fabricate
(v.) to make up, invent
Wally knew if Rob had gone on the Kent Nelson mission he wouldn't have been such an ass about magic and pretended to believe just for M'gann. That little Robin kept him in line, despite his age and size.
38. feral
(adj.) wild, savage
"Mr. Savage, are we expected to do anything about this 'Young Justice' group that's been floating around everywhere, or are you going to take care of that issue?"
39. flabbergasted
(adj.) astounded
"Jason Todd's back! He's alive!"
Bart Allen sped throughout the mountain yelling at the top of his lungs until he ran straight into Nightwing's outstretched arm and a hand immediately covered his mouth, stifling his excessive yelling. He harshly whispered directly into Bart's cowled ear.
"What did you just say?"
40. forsake
(v.) to give up, renounce
"Wally and Artemis threw in their cowls, Kaldur's gone darkside, Ted, Jason, and Tula are dead, shall I go on?"
41. fractious
(adj.) troublesome or irritable
Once Bruce left the room after he chastened Tim for hacking into the corporation Dick wrapped his arm around his little brother for a noogie in congratulations for his improved skills.
42. furtive
(adj.) secretive, sly
"Wally, how did you ever stand having a Bat for a best friend?" Bart questioned the hologram in front of him from his spot sitting on the grass with a quizzical look on his face and a bag of Chicken Whizees in his hands. "I mean- yeah, Tim and the Bats are all awesome and everything with their gadgets, which are going to improve so much in the years to come by the way, and everything, but why do they always have to be so secretive? Is it a Bat characteristic? Was Dick like that much? I guess so 'cause he still is mostly..." Crunch. Crunch.
43. gluttony
(n.) overindulgence in food or drink
Artemis' face scrunched up in disgust as she watch Wally consume an entire table of food after a long mission.
44. gratuitous
(adj.) uncalled for, unwarranted
"Hey! That was uncalled for." Robin's face was a hilarious combination of a pout and an attempt at looking threatening. It didn't work on a ten year old.
45. haughty
(adj.) disdainfully proud
"Mercy, scan for those meddling kids." Lex Luthor glanced over at his glorious machine guard with the pride of a father. As Robin hid up in the rafters with the rest of the team he thought it was horribly sickening.
46. hypocrisy
(n.) pretending to believe what one does not
The whites of Nightwing's mask became slits as he glared at Batman and stated the older man's entirely not whelming hypocrisy.
47. impeccable
(adj.) exemplary, flawless
"Puh-lease, that was flawless. It was at least an eight, if not more!"
"Nope. Too airy. Three."
"Everyone's a critic."
48. impertinent
(adj.) rude, insolent
"You two are impertinent children. How I can stand to be in a room with you, I'll never know."
49. implacable
(adj.) incapable of being appeased or mitigated
"Despite everything we're doing to get this Godfry guy off our backs, he's never satisfied with any hero work we do! He highlights the very few mistakes we make and blows them out of proportion then negates the good work that we do. I really want to head to that studio of his and give him a piece of my mind."
50. impudent
(adj.) casually rude, insolent, impertinent
"The JustUs League seems to be nowhere in sight while these teenage /heroes/ are running rampant around our cities!"
51. incisive
(adj.) clear, sharp, direct
"¡Ay Dios mío, cuando hablas español, necesitas usar los acentos! It changes the entire meaning of the word if you don't sometimes." Jaime muttered under breathe about how teaching speedesters with short attention spans Spanish was a horrible idea.
"Hey, ¡puedo oírte! How was that for not listening, eh?"
52. indolent
(adj.) lazy
Kaldur walked into the living room of Mount Justice with the intention of heading to the Zeta beams but he saw something out of the corner of his eye on the couch and turned around to investigate.
"Oh, hey Kaldur! We're having a Superboy lazy day, wanna join us?" Robin asked with an enthusiastic Wally nodding in agreement next to him on the couch.
"I might. But may I ask, as to what makes this a 'Superboy' lazy day?"
Robin gestured toward the television, which was on the black and white fritz channel, and Kaldur nodded in understanding with a small smile gracing his lips. His trip outside could wait.
53. inept
(adj.) not suitable or capable, unqualified
"I will not stand for this! Sending inept children on my rescue mission; I can't believe it."
"I assure you, Senator, we are some of the most qualified heroes for this type of covert mission. We managed to retrieve you safely from the enemies' hands, did we not?"
The man sat gaping at Aqualad for a few moments before sputtering an apology and thank you in one quick mumble.
54. infamy
(n.) notoriety, extreme ill repute
"That was harsh, man. You could go easy on the new kid for once."
55. inhibit
(v.) to prevent, restrain, stop
"Let me go! Let me GO! I have to see if he's OK; let me pass!"
The crowd of people around the fallen body parted reluctantly after the police released their hold on the Boy Wonder.
56. innate
(adj.) inborn, native, inherent
Ever since Garfield's big sister saved his life, he had even more of an inherent affinity towards animals, how they work and lived, and how different from humans they were. They fascinated him.
57. insatiable
(adj.) incapable of being satisfied
Kid Flash kept talking through the mouthful of food. "I don't know why but I haven't been able to go an entire hour without eating recently! I mean, I know that's sort of normal for me, but we haven't been on any missions and I haven't been out running with Flash in a couple days. So I really don't know what's wrong with me, I shouldn't be any hungrier than a normal growing teenage boy right now, but I am..." He stuffed another chicken finger in his mouth before muttering something about stupid metabolisms and then pillowing his head in his arms on the kitchen counter.
58. insular
(adj.) separated and narrow-minded; tight-knit, closed off
"Everyone has their tight-knit little groupie things here at school, and then there's me, talking to a scarab. Attached to my spine. What is my life?"
"A combination of hero work, school work, food, and sleeping."
59. intrepid
(adj.) brave in the face of danger
At one point in the battle Cassie and Tim ended up fighting side by side until a inappropriately hilarious moment came up when both of them attempted to push the other behind them to protect each other and their arms got tangled.
60. inveterate
(adj.) stubbornly established by habit
Batgirl muttered to herself about stubborn Bats and passing that gene somehow onto other Bats while she walked back up to her room.


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Complementary Health Approaches
Frequently Asked Questions
9. What is spinal manipulation?
Spinal manipulation is a technique performed primarily by chiropractors, but it may also be done by physical therapists or other health professionals. Practitioners use their hands or a device to apply a controlled force to a joint of the spine.


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Neighbourhood priorities
We asked, You Said, We did
We asked…
What concerns do you have about your neighbourhood?
You said...
Nuisance and persistent motorcycle disorder and damage caused by this disorder particularly around the Elemore Lane Golf Club and Airedale Gardens in Hetton le Hole and Easington Lane.
We did...
The police mounted a plain clothes operation at the golf club and in the surrounding streets over a number of weeks. During this time they were able to identify a number of persistent offenders who have had their bikes seized and crushed and one offender has been arrested. This operation has led to a decrease in reports of this type of behaviour in that area however the police will continue to monitor the situation and will deal robustly with anyone committing further offences.


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At Prairie House, our mission is simple: creating environments where moments of joy, independence, and wellness are the focus each and every day. We believe in the elder-directed philosophy of The Eden Alternative. To learn more, visit www.edenalt.org
Prairie House is the home of a unique, Balance Fitness program designed especially to strengthen the core muscles needed for improved balance...
To learn more about assisted living in La Pine visit Prairie House Assisted Living and Memory Cares website.
Welcome to Prairie House Assisted Living and Memory Care
La Pine Senior Living
Looking for retirement or senior Services? Are you a senior looking for a chance to give back to your community? We invite you to join us for a meal, activity, event, or respite stay to experience the joy and security a supportive living environment can really bring.
Whether you are a Boomer seeking the best for your...
Be the first OregonLive.com user to add photos or videos of Prairie House
Prairie House is a wonderful place for mom or dad. It really is like being a part of another family.
We were not very happy with the Prairie House. The facility wasn't kept very clean. The staff didn't seemed very professional. We had some problems with medication not having been given or the wrong medication being given. The food was terrible. There weren't many choices and most of the time they were very bland. So, my father-in-law most of time refused to eat down there and they ended up...
Prairie House Assisted Living and Memory Care is committed to providing excellent senior living in La Pine, Oregon; visit our website to learn more about our commitment to care and service.
Comfortable Homelike Studio & 1 Bedroom
Comfortable Homelike Studio & 1 Bedroom Apartments
Assisted Living and Memory Care
Elderly and Disabled Care
Scheduled Activities & Transportation
Convenient On-Site Transportation
24 Hour Long Term Staff Onsite
Convenient On Site Transportation
Life Enrichment With Balance Fitness Programs
Alzheimer and Dementia Care
Life Enrichment...


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Shoe Steel Pty Ltd
Ca$h in a fla$h for $crap
Bundaberg East QLD 4670
Are you looking to get rid of scrap metal for cash? Do you need aluminium supplies for a project? Shoe Steel Pty Ltd is the business that you are looking for. We recycle scrap metal and resell new and used steel and aluminium. We can also cut metal to size according to your needs.... More info
Shoe Steel Pty Ltd is 1.5 km from Bundaberg, QLD - Click here for Directions