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We recently wrote about a couple of news items that suggested that the "Chupa-Chupa" – meaning "Suck-Suck", alleged balls of light that burned and sucked blood – had returned to terrorize northern Brazilians. Two young girls were even hospitalized with "serious burns", and we noted how "a confirmed contemporary case of burn victims of the Chupa-Chupa would be something relevant".
Good news, everyone! Contrary to my pessimism, we have some news, and it seems the case has been solved. José Medeiros and a friend followed the clues and did the basic thing: they contacted the local authorities, including the health secretary of the city of Belterra, Ana Cláudia Tavares.
The secretary informed them that the news was just a rumor. She visited the hospital after reading about the news, and the staff there also confirmed it was only a tall tale. Well, not only: they also found that behind this tale about the return of the Chupa-Chupa are attacks from real suckers… known as bats.
Apparently, the two girls in question were actually attacked by bats. Those kind of attacks are becoming more common recently, as the habitat of the creatures is being destroyed by heavier tourism and expanding urbanization.
I also spoke by phone, on a lead from Medeiros, with a local from Maguari who confirmed there is not anything like a panic going on. Actually, the local told there was nothing happening up there.
This was, all suggests, just a hoax circulated by a free lance journalist to the local newspapers, including Diário do Pará, that just published the story without checking anything.
If a confirmed, contemporary case of Chupa-Chupa victims would be intriguing and warrant a more worried look at the original 1977-78 wave, what does a confirmed, contemporary hoax case of Chupa-Chupa panic warrants?
It does, at least, evidence once more that the phenomenon has a lot to do with psychosocial elements. Even if there were anomalous things happening back then, we already knew that the panic was also fueled by heavy sensationalist media exploitation. Hundreds of news items about the panic, including even several reported deaths, even when published on local newspapers, weren't necessarily even close to the truth.
In fact, there's no confirmed case of "death by Chupa-Chupa", neither back then, nor nowadays.
[With thanks to José Medeiros]
Popularity: 1% [?]Posted in Fortean,Skepticism,UFOs | 1 comment
1 Comment so far
Carlos Magno November 13th, 2008 12:35 pm
Uau! What a good new, Mori!
I was really frightened about the coming of a true wave of suck-suck attacks. Old videos showing false images about those genetic products of aliens and the interviews with liar witnesses should be destroyed for ever!
But now I'm soothed and I can finally sleep well.
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Q: A storage location from different plant can be assigned to the warehouse of any Plant. But different storage location within the same plant cannot be assigned to the same warehouse number. Why ?
A: Different storage locations from different plants can be assigned to the same warehouse. But different storage locations within the same plant can not be assigned to the same warehouse number. These storage locations may be defined as storage types or storage sections.
Q: We are using only fixed bins and do not want to use automatic bin creation nor any strategy for removing/loading goods to the storage? In what way Ware Housing helps me?
A: You may go for Ware House module if, you have materials in more than one bin
you manage several different types of storage (high rack, block ...)-
you need a very flexible control for printouts
Q: Can number of Datasource has one Infosource?
A: Yes ofcourse.For example, for loading text and hierarchies we use different data sources but the same infosource.
Get More Questions and Answers with Explanation related to Storage Locations at SAP BW Forum.

subset: commoncrawl


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GraphicRiver Set of 10 Logo Mock-ups 6593464
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Learn about this topic in these articles:
description of Arabian Desert
The first important modern work on the geography of Arabia, Travels in Arabia Deserta (1888), was written by English traveler Charles M. Doughty. At the turn of the 20th century, Czech explorer Alois Musil traveled through northern Hejaz and Najd, mapping topography as he went. In 1917 H. St. John Philby, an official of the British Foreign Office who paid a visit to the sultan of Najd...
discussed in biography
In 1888 he published Travels in Arabia Deserta, which won little recognition at the time. Eventually, however, the book came to be regarded as a masterpiece of travel writing, and it was still being published in the early 21st century. In it he was more concerned with producing a monument of what he considered to be pure English prose than with recording information. The Elizabethan...
reissue by Cape
...the two became friends, decided to set up a business on their own, and on January 1, 1921, opened Jonathan Cape, Publishers. Their first publication was a reissue of C.M. Doughty's 1888 classic, Travels in Arabia Deserta; the partners persuaded T.E. Lawrence ("Lawrence of Arabia") to write an introduction to the volume, which helped make it a success.


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Criminal law solicitors have redoubled their attacks on the Law Society – ramping up calls for senior resignations – after slapping the organisation's leadership with a vote of no confidence earlier this week.
Liverpool-based lawyer James Parry – who led the revolt against Chancery Lane – said the society failed to meet its immediate post-vote promise to set out and communicate a revised approach to dealing with the Government over its proposed legal aid rate cuts.
Parry told The Lawyer that despite saying they would "reach out" to him in the aftermath of the special general meeting (SGM) last Tuesday (17 December 2013), Chancery Lane officials had not been in touch. The society had also not responded to an open letter from Parry setting out his views of the ramifications of the no-confidence motion.
In the letter to society president Nick Fluck and chief executive Des Hudson, Parry said: "The anger and disappointment of many of those present was made clear and was reflected in the vote."
The name partner of Liverpool firm Parry Welch Lacey went on to tell senior Chancery Lane officials that it was "clear that the Law Society has some bridges to build with many criminal practitioners if it is to regain their confidence and to effectively resist all that is proposed … [I]t would be helpful if the Law Society were to set out in detail how it intends to respond to the views expressed at that meeting to avoid the possibility for rumour and misunderstanding and to demonstrate that the Law Society has listened and learned from what was said."
The society said it had responded to Parry today. A spokesman commented: "We have told him that we will fight the cuts, campaign more publicly, more vehemently and continue to push for more concessions for the benefit of our members." He went on to say "in response to the views of members at the SGM, we are taking a hard look at how the society engages and communicates with its members".
The one point on which the solicitor and Chancery Lane appear to agree is on the need of a profession-wide vote on the no-confidence motion. Chancery Lane has dismissed the move on cost grounds, saying it would add £80,000 to the £120,000 the body has already spent on the SGM. Chancery Lane said the £120,000 expenditure included catering, loss of revenue from commercial room hire bookings, audio-visual equipment and operating an electronic voting system.
For his part, Parry maintained there would be "no point" in polling all solicitors, as "it is obvious that a profession-wide vote would simply reflect the vote at the meeting". Indeed, Parry suggested a profession-wide poll would be likely to result in an even bigger margin in favour of the no-confidence motion.
Immediately following the meeting, Hudson suggested that criminal law specialist solicitors were not overwhelmingly opposed to Chancery Lane's approach to the Ministry of Justice. He claimed that larger criminal law legal aid firms supported the society's stance of "engagement" with ministers.
However, Parry responded by pointing out that the only speakers against the no-confidence motion at the SGM were either Law Society council members or those affiliated closely to the Chancery Lane establishment.
"The society leadership might well take the view that the big firms do not agree with my position," said Parry. "But if that is the case they certainly didn't express it at the SGM and there were senior members of the Big Firms Group at the meeting."
Comments on The Lawyer website following the vote reflected mounting pressure on Fluck and Hudson to stand down as, according to many, they fail to maintain the confidence of a significant section of the profession.
Wrote one commentator: "There are … few who have any confidence in the senior management of the Law Society at all. If the president of a rugby or cricket club suffered such a defeat, I have no doubt that their resignation would follow by return; have we now sunk to such depths that a no-confidence motion can be brushed off with such insouciance?"
Another sent a simple message to the leadership: "Resign."
Despite the loud cries for heads to roll, grassroot voices suggested Fluck and Hudson would resist calls to fall on their swords. Bill Waddington, chairman of the Criminal Law Solicitors Association said it was "unlikely" the two would resign.
"It is very difficult to get an absolute consensus across the entire criminal law profession," he said. "They will always be able to claim that they have at reasonable support from some of that group."
The Law Society's 100-strong council issued a general statement following the no-confidence vote, saying: "We must increase our engagement with members at the same time as putting maximum pressure on the government so that the Lord Chancellor can be in no doubt of the damage his proposals will cause."
It continued: "There are lessons to be learned from [the SGM] debate and we will reflect on these developments. Ultimately, everyone at [the] SGM is seeking the same outcome in terms of securing a functioning, high-quality criminal justice system with a sustainable body of criminal law solicitors."


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All 5 game Reviews
Snowman snowball fighting
Rated 2.5 / 5 stars
its a decent game, but that music or whatever it is, just done ever use it again.
Madness game(maze)
Rated 4 / 5 stars
Pretty good
maan this is pretty cool, but the elovators are kinda buged out O_o like wen i jup on them sumtimes they are transparent and i fall thro, also the zombies are a bit too fast :S anyway good game overall
Albert the Alien
Rated 2.5 / 5 stars
was ok
pretty good :P not the best game ive ever played but hey it kept me entertained for 8 mins and 59 secs :D
Flash tuts
Rated 2.5 / 5 stars
Its not that bad, EVERYONE: YOU MUST PRESS SPACE TO DO STUFF. just keep taping it, not too fast tho. Author: WRITE IT SUMWHERE THAT U NEED TO PRESS SPACE! :D still decent tho! once u know how
Hammer a nail
Rated 4 / 5 stars
Its cool! although it was hard to get past the first round at my first try! then i got it and its easy, but really cool i just got back from austria a few weeks ago and this nail game was in every restarant! (but u use the thin end in that game)


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Two years ago, my husband and I hired a personal assistant on a part-time basis. It was a great job: excellent hourly rate; lovely office at the bottom of the garden; one full-day a week (arriving after 10am in order to do school run) plus reasonable flexible hours spread across the week from their own home. Some of the work wasn't that exciting – filing receipts is no thrill-chase – but it was varied and I was genuinely happy to put money in the pocket of a working mum.
On top of the hours in which she had formal childcare, she also had freedom to put in hours (at her discretion) after the kids had gone to bed, when the toddler was having a nap or at weekends – whatever it took to get the tasks done at her convenience. She was allowed days off for kids' birthdays (and her own) and if the kids were ill, no problem: just prioritise the to-do list and let's discuss. It wasn't always convenient but I felt we had a moral obligation to employ a working mum, someone who shared the same juggling issues as my husband and I.
But recently, when the role demanded more time at our place (having a husband running as an MEP can do that to your life) she was unable to increase her hours. We let her go.
So it was with some sympathy that I learnt of Cherie Blair being exposed as a "hypocrite" by ex-employee, Louise Allain, one of five office staff who is now "utterly betrayed" after her receptionist job developed into a full-time position and she turned down the offer. "So am I being fired for not taking a full-time role?" asked Allain to which Cherie replied: "You are being made redundant as there is no longer a part-time role."
Last Autumn Cherie said: "Helping families, especially mothers, back into employment after having a baby has to be a priority," and "changing our society so our workplaces are truly open to the talents and life choices of women needs real leadership and effort". And she doesn't just talk the talk. Whatever you think of her politics, the way in which Cherie Booth continues to maintain her own identity, work as a barrister, accommodate her husband's workload, support charities and raise four kids is nothing short of mind-blowing.
Despite Miss Allain's best efforts, one sulky ex-employee telling her story to the press should not undermine the good work the ex-PM's wife does for professional women.
According to The Daily Mail, 41-year-old Allain now wishes she had never taken the job. "I am just washed up. Prospective employers see I worked for her for only a year before leaving and think that is suspect. If you explain what happened, they think, 'Mrs Blair would not have done that'."
Ah diddums. Prospective employers might actually be more wary of a woman who tells her story to a paper and then claims she is the one feeling "betrayed."
"I'd have been better off never taking the job," sniffs Allain. "Now I've got next month's bills coming up, loans to pay and I don't have another salary. I've had to sign on. I never wanted to see the inside of a job centre again. I thought she had pulled me away from that place, but now she has sent me back."
Perhaps that's true – but slagging off your influential old boss, even after she said in an email that she and her assistant would "do anything we can to get you another part-time job", is a great way to keep yourself in the very job centre you dread. It certainly won't help her find a new position of trust.
I cannot comment on Allain's day-day competence, but let's just say that when our own part-timer didn't want to go full-time, it was something of a relief. If a working mum is committed, loyal, self-motivated and competent, employers will make it work.
If they are petulant, self-pitying and lazy, threatening to increase the hours is a great way of waving them off. That is the harsh reality of being a working mum wanting to job-share or work part-time. You may struggle to feel as valuable as your full-time colleagues, but if you are good, you can still make yourself indispensable. Part-time workers but full-time whingers are the first to go.
Most working mums are spectacularly productive. If you can simultaneously fill a bath, load a washing machine, answer the phone, stir a pan, oversee homework and take a pile of clothes up the stairs all while carrying a baby on one hip, chances are you can breeze through any typical workplace requests in half the time of the non-parent at the desk beside you. Employers who don't tap into that ability to focus, graft and master a schedule are missing a trick.
Shadow childcare minister Lucy Powell recently agreed when she said that working mothers "are not sitting on Facebook or coming in with a hangover. When we are working we are on it – and making the most of every minute of every day because when you are at home with family you have got to be on it every minute as well."
We now have a new PA. She happens to be young and childless but that was in no way part of her appeal. Her intelligence, efficiency, initiative and technological know-how is such that we will make it work with her – no matter what happens to her womb in the future.
Obviously, it is worth saying with a yawn (as always) that this whole debate makes me nauseous because we use the word "mother" instead of "parent". But of course working dads are not ordinarily losing jobs because they are in the midst of an employment parent trap.
Women such as Cherie, myself and all the other thousands of female employers who want to support working mums will continue to do so – not just because it's politically correct but because it's a smart choice due to most mothers being so damn efficient.
But these worker-bees will have to be as good as – in some places, sadly better than – any childless candidate. Only when a politician's ex-wife is betrayed by a male employee wanting to spend more time with his kids will our work be done.


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7 RepliesJump to last post
I keep getting headhunter calls about Ameriprise. Can anyone give me the good, bad and ugly on the firm?
Used to be American Express Advisors. Got into a good bit of regulatory trouble a few years ago. Didn't really like them when I was looking to make a move.
AMP... great question.. you're going to get a lot of negs here...I think this is the 300th time someone's asked about AMP. Search for Ameriprise in this forum for more. I do know there's not one indy firm paying more dough to bring you in the fold. Just be aware the contract to cash those checks will take days to read and comprehend. Been there.. done that from a 'recruit' perspective. I like AMP.. one day they will have a great platform and they get closer by the month. They are NOT the same as the AMEX owned crap company that we all beat on here.. that's been vastly improved upon. HRB acquisition has brought a great deal of talent and open minds there and they have cash and dreams greater than most firms from NY to CA.
I heard they are on the opposite way. Everything is going down. Prioritary products galore.
I had some friends who met with them. They seemed to be pretty blown away with what was offered. Not quite sure of the details, but definately worth checking out.
I think you need to look pretty closely at the offer. Lots of smoke and mirrors on the one I saw. They are offering some up-front money to move the book.......a forgivable loan as they call it?? Looks like it is 7 years forgivable. I don't like to be tied for 7 years.
They have a lot of cash right now and are rumored to be on the prowl for a M Fund company to call their own. Not sure I like to sound of that, if it happens.
I'd put them in a category with the likes of WDR.
Good luck.
I was with HRBFA until this year. The platform under HRBFA was pretty good but since AMP took over, they are planning on reducing the number of VA companies to 3 or 4. This includes Riversource (proprietary) and if you don't do over 100k in insurance revenue annually, you can only write insurance biz through Riversource. How's that for open architecture? They do offer most MF's out there but the annuity and insurance changes as well as the horror stories of the past are what drove me away. I think it is very likely that many HRB reps will leave when their 5 year retention package is fully vested in November of 2013.


text: Good morning OTAP! Over the weekend my mom called me to say she found a camera lens at a yard sale in Montana. She went out there with my step dad to visit my brother after hitting up Sturgis. She found a canon mount Sigma APO 170-500mm DG lens at a yard sale. They originally wanted $200 but my mom haggled them down to $150. I'm hoping it's a somewhat decent lens but for $150 can't complain. My mom said it looks like it has never been used. Is this lens any good? http://www.sigmaphoto.com/lenses/lenses_all_details.asp?id=3276&navigator=3 Cliffs: Mom found a Sigma APO 170-500mm DG lens at a yard sale in Montana for $150.


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Roland Intros New X-Rite Color Management Tools
Wednesday, July 11, 2012
Press release from the issuing company
Roland DGA Corp. has expanded its line of inkjet printing accessories and supplies with i1Basic Pro 2 and i1Publish Pro 2, two powerful color management solutions from X-Rite, the global leader in color science and technology. Compatible with Roland's award-winning line of wide-format printers and printer/cutters, these proven solutions bring together the industry's most advanced color management hardware and software tools to ensure precision imaging across multiple devices and media.
"We are excited to offer these new advanced color management tools to our customers, which will help them achieve even better print quality across production environments both small and large," said Julie Gederos, product manager for Roland DGA Corp. "The new solutions extend the color management capabilities of our own VersaWorks RIP software by enabling users to simplify their color management workflow."
Designed for any application where color matching is critical, X-Rite's i1Basic Pro 2 allows professionals to calibrate their monitors to display accurate digital color while linearizing their Roland printers for consistent output. This solution includes X-Rite's new i1Pro 2 spectrophotometer, Pantone Color Manager software and the all-new, more robust i1 accessories package, including an ambient light measurement head, monitor holder, scanning ruler, backup board and spot color positioning target.
For a complete color management solution from design to finished print, users can upgrade to i1Publish Pro 2. This expanded solution includes the i1Basic Pro 2 package, as well as i1Profiler software, which allows users to develop their own custom media profiles based on the Roland printers in their production environment. As an added bonus, ColorChecker is included for users interested in camera calibration.
Priced at $1,199 and $2,098 respectively, i1Basic Pro 2 and i1Publish Pro 2 are available immediately from authorized Roland dealers and online at www.rolanddgastore.com/xrite. Other new Roland accessories for inkjet customers include a new line of anti-static kits from TAKK for users of any Roland 54-, 64- or 74-inch printer or printer/cutter. Additionally, a new Benes dryer line is now available for customers who purchase a VersaCAMM VS inkjet printer/cutter with a double white ink configuration.
For more information on Roland products, please call (800) 542-2307 or visit the Roland website at www.rolanddga.com.
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Joanna Robinson (Senior Writer, vanityfair.com) and David Chen (Editor-at-large, slashfilm.com) have been making TV recap podcasts for over five years, including "A Cast of Kings" and "Decoding Westworld". Together, their shows have been downloaded over 5 million times. But in all that time, they've always wondered: Isn't there more stuff to talk about than just television? The answer is an unequivocal yes, and thus, Gen Pop was born -- a new pop culture podcast that covers the major events and writings of each week.
Gen Pop is a new podcast experiment we're trying, and we hope that if you've enjoyed our content in the past, you'll check out the show and consider supporting our Patreon!


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IRAs aren't just retirementtools, they are also significant tools for estate planning. This is especiallytrue when it comes to Roth IRAs.
One specific application forRoth IRAs is in the context of inheritance planning for grandchildren. Unlike"regular IRAs,†there will be no future "income taxation†on withdrawals fromRoth IRAs. MarketWatch recentlyexplored this issue in a Q&A titled "How to leave your Roth IRA to a minor.â€
Is it possible to leave a RothIRA to grandchildren for educational purposes or, failing that, to a trust fortheir benefit? The short answer: yes. The Roth IRA (or other IRA) can be leftas part of the inheritance simply by naming one or more individuals as thebeneficiary or beneficiaries under the plan. In addition, you can name a trustas a beneficiary, thereby allowing a single IRA to either work overtime for ahost of beneficiaries or to more carefully manage it.
Of course there is a long answerto this question, too. Naming a minor as a direct beneficiary to an accountwill require a legal guardian, which is a court-appointed role. Problem: thelegal guardian appointed may not be the person you would have selected.Moreover, the IRA will not be skirting the court system as you may haveintended by passing free of the courthouse.
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SimCity Buildit is one of one of the most popular mobile approach video games by EA. Similar to any other Sims game, right here also, your main purpose is to develop a city and then run it correctly. Nonetheless, EA has included some brand-new features to this game. Below are some SimCity Buildit cheats as well as suggestions, which will aid you gain more gold:
Raise your Populace: Your success in Simcity Buildit is judged by the population in your area. When the population increases, you reach gather tax gold from your residents. In order to enhance the populace, you need to construct lots of structures, to make sure that people can come there and also live. It is also very important to keep the Sims pleased, otherwise they will just leave your city. To maintain them satisfied, you have to frequently upgrade the homes as well as develop a few parks. If the Sims are happy, you will certainly have the ability to earn lots of coins regularly.
Strategy your city intelligently: It is additionally crucial to have an approach while developing your city. You should make an industrial park and a separate suburb. Ensure that the enterprise zone is far away from the house. Or else, it could pollute the location and also your Sims might decide to leave. You ought to also ensure that you have a police headquarters and also a fire station near the houses. You can removal the buildings later as well, but you need to have a strategy first. To make sure that, you don't lose out on any kind of profits.
Make your manufacturing facilities working from all times: It is extremely important to develop some factories, which produces some raw materials like woods, metal or plastic. When you start playing the game, you initially task need to be to begin production in all your manufacturing facilities. Your stores will just have the ability to function, when the manufacturing facilities generate the raw materials. While the production is going on, you could take care of the residential areas and the other aspects of the game.
make coins and cash
Look out for bargains: This is an excellent and also simple means making coins. While playing the video game, often you will have the ability to find the coin icon on top of some structures or parks. When you tap the sign, you will certainly be asked to give away some of your materials and in return, you will certainly obtain coins. You must constantly take the offer. You could make the products once again, however generating income is not easy, but you can use methods from popular games blogs like http://sbhackguide.com/. It's all from my about simcity buildit hints, feel free to enjoy the game with top tips.


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Trang, a coastal southern province with picturesque beaches and castaway islands, has emerged as a destination for travellers in search of seclusion. Si Kao and Koh Kradan are increasingly popular, though both remain pleasant and peaceful. Accommodation choices range from affordable city hotels to luxurious spa resorts with pool villas and suites set on the beach.
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This study reports for the first time the effects of retinoid-related orphan receptors [RORβ; receptor gene deletion RORβ(C3H)−/−] in C3H/HeN mice on behavioral and circadian phenotypes. Pineal melatonin levels showed a robust diurnal rhythm with high levels at night in wild-type (+/+), heterozygous (+/−), and knockout (−/−) mice. The RORβ(C3H)−/− mice displayed motor ("duck gait," hind paw clasping reflex) and olfactory deficits, and reduced anxiety and learned helplessness-related behaviors. Circadian rhythms of wheel-running activity in all genotypes showed entrainment to the light-dark (LD) cycle, and free running in constant dark, with RORβ(C3H)−/− mice showing a significant increase in circadian period (tau). Melatonin administration (90 μg/mouse sc for 3 days) at circadian time (CT) 10 induced phase advances, while exposure to a light pulse (300 lux) at CT 14 induced phase delays of circadian activity rhythms of the same magnitude in all genotypes. In RORβ(C3H)−/− mice a light pulse at CT 22 elicited a larger phase advance in activity rhythms and a slower rate of reentrainment after a 6-h advance in the LD cycle compared with (+/+) mice. Yet, the rate of reentrainment was significantly advanced by melatonin administration at the new dark onset in both (+/+) and (−/−) mice. We conclude that the RORβ nuclear receptor is not involved in either the rhythmic production of pineal melatonin or in mediating phase shifts of circadian rhythms by melatonin, but it may regulate clock responses to photic stimuli at certain time domains.
- retinoid-related orphan receptors β gene
- circadian activity rhythms
- melatonin receptors
- suprachiasmatic nucleus
retinoid-related orphan receptors (ROR) belong to a superfamily of nuclear hormone receptors comprising more than 40 transcription factors (7, 24). Members of this superfamily share a common modular structure consisting of a transactivation domain, a DNA-binding domain, and a ligand-binding domain (24). The family of ROR receptors is a subfamily of orphan receptors comprising RORα, RORβ, and RORγ (21). RORβ is a nuclear receptor expressed in areas related to processing of sensory information, as well as circadian rhythmicity (27, 33). Recently, structural data and structure-function analysis identified all-trans retinoic acid as a bona fide ligand for the RORβ nuclear receptor (37).
Circadian oscillations of the mammalian biological clock within the suprachiasmatic nucleus (SCN) are driven by a main transcriptional/translational feedback loop of clock gene products. The negative arm of the loop involves the circadian oscillation of three period (Per) genes and two cryptochrome (Cry) genes, potent repressors of CLOCK/BAML1-induced transcription. The positive loop is driven by the transcription factors CLOCK and BMAL1 positively influencing Per and Cry rhythmic transcription (16). Recently, Hogenesch and colleagues (32) demonstrated a second, stabilizing feedback loop, in which the nuclear receptors Rev-Erbα and RORα are repressors and activators, respectively, on the same RORE element of the Bmal1 promoter, generating the rhythms of Bmal1 transcription. This is an elegant demonstration that RORα, a member of the family of retinoid-related orphan receptor element (RORE) orphan receptors, is a necessary component of the core circadian function.
RORβ receptor mRNA oscillates with a circadian rhythm in the retina (1, 33). In the pineal gland, RORβ receptor expression exhibits a robust daily rhythm under photoneural regulation involving an adrenergic/cAMP mechanism (1, 3), which suggests its involvement in the daily rhythm of melatonin production (3). Disruption of the RORβ receptor leads to behavioral phenotypes (i.e., duck-like gait, delayed onset of male fertility, blindness due to retinal degeneration) (1) resembling the spontaneous mouse mutation vacillans described in 1956 (35). C57BL/6 mice lacking the RORβ receptor entrain to a light-dark (LD) cycle, in spite of the retinal degeneration that causes blindness (1). When running in constant dark, however, the period of activity (tau) is longer than in wild-type mice (1). In assessing involvement of the RORβ gene product as a component of the biological clock, the response to any agent that phase shifts the clock may be altered in mice lacking the RORβ receptor. Here, we studied the response of RORβ knockout mice with a C3H/HeN background to the phase-shifting effect of light during the night.
Melatonin, a hormone synthesized primarily in the retina and the pineal gland following a circadian rhythm with high levels at night, modulates neuronal activity and phase shifts circadian rhythms (10, 20, 23). In the suprachiasmatic nucleus, inhibition of neuronal activity is mediated through activation of MT1 melatonin receptors (23), while phase shifts of neuronal firing rhythms in vitro require activation of the MT2 melatonin receptors (9, 19, 20). However, paradoxically, phase shift of overt circadian rhythms of activity in vivo requires activation of MT1 receptors, as this effect is absent in MT1 knockout mice (9, 19). Initially, melatonin was suggested as the natural ligand of retinoid orphan receptor β (RORβ); however, further research did not confirm this finding (4). The MT1 melatonin receptor and RORβ gene are both localized on AVP containing neurons in the Siberian hamster suprachiasmatic nucleus (36). However, it is not known whether RORβ receptor activation participates in melatonin-mediated phase shifts of circadian rhythms or affects photic phase shifts. The goal of this study was to investigate the role of the RORβ nuclear receptor in various behavioral domains, in the diurnal rhythm of pineal melatonin levels, or in melatonin- and light-mediated circadian phase shifts and acceleration of reentrainment.
Experimental Animals
The RORβ gene knockout was initially generated in the 129/Sv mouse and was made congenic with the C57BL/6J mice (1). The RORβ gene was disrupted downstream of the exon encoding the DNA-binding domain via insertion of and in-frame fusion with the lacZ gene. RORβ (C57BL/6J) knockout mice were then backcrossed with C3H/HeN (rd/rd) mice at Glaxo-Wellcome (Geneva, Switzerland). RORβ(C3H) mice used for experiments reported here were at least of the F6-F7 generation. All animals were genotyped at the time of weaning and at the time of death by PCR using DNA obtained from a tail sample. Genomic DNA (0.1–0.5 μg) was subjected to PCR using the following primer pair: the upstream primer derived from the RORβ gene GGAGCCAGCAGAACAATG, and the downstream primer was derived from the lacZ gene CCTCTTCGCTATTACGCCAG. All mice were bred under a 12:12-h LD cycle (250 lux at the level of the cage). Mice were group housed under controlled lighting conditions with food and water available ad libitum. All animal care and procedures were performed according to institutional guidelines and to the National Institutes of Health standards and were approved by the Institutional Animal Care and Use Committee of Northwestern University.
Behavioral Phenotyping of RORβ(C3H) Mice
Basic behavioral screening.
All behavioral screening was performed according to the methods described by Crawley (8). RORβ (C3H)+/+ mice (male: n = 14, female: n = 2, 6.3 ± 1.0 mo old) and RORβ(C3H)−/− mice (male: n = 8, female: n = 10, 6.5 ± 0.8 mo old) were kept in a 14:10-h LD cycle. All testing was performed between zeitgeber time (ZT) 3 and ZT 7 (ZT 0 = lights on). All mice underwent an examination of basic physical characteristics [weight, piloerection (%), whiskers (%), bald patches (%) and palpebral closure (%)], and general behaviors (sniffing, licking, rearing, jumping, moving around the cage, and wild running). Mouse behaviors were observed and quantified individually in a clean cage. Results were expressed as % of animals displaying each behavior during a 1-min period.
Neurological reflexes, muscle strength, and coordination.
Reflexes observed included righting, eye blink, ear twitch, whisker orienting, and smell. Muscle strength was assessed using the hanging wire test and motor coordination using the vertical pole test (8).
Emotional behavior.
Behaviors in the emotional domain used methods previously developed (8, 28) and included a 5-min open-field test (anxiety) (48 × 48 × 10 cm with a total of 64 squares each 6 × 6 cm), a 5-min elevated plus maze (anxiety) (two open arms 30 × 6 cm crossed with two closed arms 30 × 5 × 15 cm elevated to a height at 60 cm), and a 6-min forced swimming test (learned helplessness) (11.5 cm in diameter ×14 cm in height). For the tests in the emotional domains, the mice were exposed to the three tests in the order of less stressful to most stressful: the open-field, then the elevated plus maze, and lastly the forced swimming test.
Quantification of Pineal Melatonin Levels
Melatonin levels in pineal glands from male and female mice were determined by radioimmunoassay using the Buhlmann-saliva direct kit (ALPCO, Windham, NH), based on the Kennaway G280 melatonin antibody (40). Briefly, pineal glands were homogenized in assay buffer and spun at 12,000 rpm. Aliquots of the supernatant were incubated with the antimelatonin antibody and 2-[125I]-labeled iodomelatonin for 20 h. The antibody-bound fraction was precipitated by solid-phase second antibody and counted. The concentration of melatonin in the samples was interpolated from a standard curve. The intra-assay precision at 3.56 expressed as the coefficient of variance was 4.1%, while the interassay precision at 3.39 pg/ml expressed as the coefficient of variance was 7.5%. The assay limit of analytical sensitivity was 0.2 pg/ml and the functional sensitivity was 0.9 pg/ml.
Circadian Activity Rhythms
Circadian activity rhythms were determined in mice housed in individual cages (18 × 30 × 12 cm) equipped with activity wheels. Circadian activity rhythms were measured with a magnetic microswitch that detected wheel rotations online with a personal computer. Data were collected and analyzed using Clock Lab (Actimetrics, Evanston, IL). Circadian time (CT) 12 was defined as the onset of running wheel activity.
Circadian phase shifts.
Male and female RORβ(C3H)−/−, RORβ(C3H)+/−, and RORβ(C3H)+/+ wild-type mice (2–15 mo) were maintained in a 12:12-h LD cycle (300 lux at the level of the cage) for 2 wk and then transferred to constant and complete darkness. Once a stable free-running activity pattern was established, mice received either vehicle (3% ethanol/saline) or melatonin (90 μg sc in vehicle) at CT 10 for three consecutive days. Each mouse was treated with vehicle or melatonin using a crossover design 3 wk apart. Light pulses (300 lux, 15 min) were given at either CT 14 or at CT 22 to animals free running in constant dark. All treatments were performed under dim red light (15 watt, GE soft light with red 1A Safe Light Kodak filter). The time of the treatment was predicted using Clock Lab software. Steady-state onsets of free-running activity were determined over a period of 7–10 days, both before and after the treatment. Transient shifts in activity during the 3 days of melatonin treatment or during the 3 days that followed the light pulse were not included in the steady-state onsets. The magnitude of phase shifts was calculated as the difference between the pre- and postpulse activity onset.
Reentrainment to a 6-h advance to the LD cycle.
Mice were kept in a 12:12-h LD cycle (40–60 lux at the level of the cage) for at least 3 wk. Following this entrainment, the onset of darkness was advanced by 6 h. Vehicle (3% ethanol/saline sc) or melatonin (90 μg/mouse in vehicle sc) or were injected at dark onset for three consecutive days. Daily advances (hours) in running wheel activity onsets were recorded every day for 10 days.
Statistical Analysis
Statistical analysis was conducted using SPSS (Windows, release 10.0, Chicago, IL) or Graph Pad Prism 4.3 for Windows (GraphPad Software, San Diego, CA) software packages. Student's t-test for comparisons between two groups or one- or two-way ANOVA with the Bonferroni post hoc test for multiple comparison were applied. All analyses were considered statistically significant with P values ≤ 0.05.
Behavioral Phenotypic Characterization of ROR(C3H)+/+ and ROR(C3H)−/− Mice
Table 1 shows the physical characteristics, general behavior, and neurological reflexes of RORβ(C3H)+/+ mice and mice with genetic deletion of the RORβ gene. No differences were observed in basic physical characteristics between RORβ(C3H)+/+ and RORβ(C3H)−/− mice with the exception of palpebral closure. Over 60% of the RORβ(C3H)−/− group showed at least one nonfunctional eyelid (Table 1). RORβ(C3H)+/+ and RORβ(C3H)−/− mice showed identical general behaviors while in their home environment with the exception of grooming, which was greater in the RORβ(C3H)−/− group (Table 1).
RORβ(C3H)−/− mice showed several impaired neurological reflexes (Tables 1 and 2). Neural reflexes that appear to be impaired in RORβ(C3H)−/− mice were the ear twitch, the eye blink, and the whisker-orienting reflexes (Table 1). RORβ(C3H)−/− mice took almost four times longer to advance to the smell target compared with their RORβ(C3H)+/+ counterparts (Table 2).
All RORβ(C3H)−/− mice exhibited the prominent and obvious phenotypic "duck-like gait" and hind paw-clasping reflex when suspended by the tail (1). Motor coordination was similar in the RORβ(C3H)−/− mouse compared with the RORβ(C3H)+/+, as shown in the vertical pole test (Table 2). However, the RORβ(C3H)−/− mouse exhibited less muscle strength compared with the RORβ(C3H)+/+ group in the hanging wire test (Table 2).
In the emotional domain, RORβ(C3H)−/− mice showed a high level of approach behavior in the open-field paradigm, as they transversed over three times more square grids compared with the RORβ(C3H)+/+ group (Fig. 1A). They also showed more exploratory behavior as determined by their number of rearing and assisted rearing, which was almost five times the level of the wild-type group (Fig. 1A). No differences in transfer latency or number of defecations were shown (not shown).
In the elevated plus maze paradigm, RORβ(C3H)−/− mice exhibited similar behavior to that of the RORβ(C3H)+/+ in the total number of arm entries, number of entries into open and closed arms; RORβ(C3H)−/− mice, however, spent considerably more time in the open arms (Table 3), indicating less anxiety-related behavior. Additionally, RORβ(C3H) −/− mice spent less time with risk-related behaviors, showing less apprehension compared with their RORβ(C3H)+/+ counterparts.
In the forced swimming test, we assessed whether the duck gait abnormality affected the ability of the RORβ(C3H)−/− mice to swim. Interestingly, RORβ(C3H)−/− mice exhibited a more pronounced swim behavior and hence spent significantly less time in the state of immobility compared with the RORβ(C3H)+/+ group (Fig. 1B).
Circadian phenotypic characteristics.
Figure 2, A and B shows actograms from male and female mice maintained in a 12:12-h LD cycle showing circadian rhythms of wheel-running activity with higher levels at night. Although the circadian rhythm is maintained across genotypes, the RORβ(C3H)−/− mice showed significantly reduced wheel revolutions/min [total: 6,384 ± 2,195, P < 0.01; day (Rho): 790 ± 239, P < 0.01; night (alpha): 5,593 ± 1,986, P < 0.01; n = 12] when compared with the RORβ(C3H)+/+ mice [total: 36,092 ± 3,032; day (Rho): 5,115 ± 597; night (alpha): 30,977 ± 2,721, n = 15], respectively, or RORβ(C3H)+/− mice (not shown). The amplitude of the rhythm determined by χ2-periodogram shows a main effect for genotype [F(2,32) = 5.11, P < 0.05] being more robust in the RORβ(C3H)+/+ (1,926 ± 127, n = 15; P < 0.05) and RORβ(C3H)+/− (2,189 ± 64, n = 4, P < 0.05) mice than in the RORβ(C3H)−/− (806 ± 104, n = 12) mice (Fig. 2, A and B). No main effect for gender or group interaction was observed.
Mice of either genotype or gender entrained to the 12:12-h LD cycle (Figs. 2 and 3). Although the RORβ(C3H)−/− mice are visually blind (1), they stably entrain to the LD cycle in a similar fashion as the RORβ(C3H)+/+ counterpart (Fig. 2, A and C, Fig. 3, A–C), suggesting that the RORβ(C3H)−/− mutation did not affect light perception by the circadian system. When released in constant dark, RORβ(C3H)−/− mice free ran (Fig. 3, A–C) with a period significantly longer than RORβ(C3H)+/+ or RORβ(C3H)+/− mice [tau: RORβ(C3H)+/+: 23.59 ± 0.04 h, n = 29; RORβ(C3H)+/−: 23.58 ± 0.03 h, n = 36; RORβ(C3H)−/−: 23.98 ± 0.07 h, n = 21] (P < 0.001) (Fig. 3D).
Pineal Melatonin Levels During Day and Night
Pineal melatonin levels were determined in pineals collected from the three genotypes, RORβ(C3H)+/+, RORβ(C3H)+/−, and RORβ(C3H)−/− during the day (ZT 9–11) and during the night (ZT 20–22) (Fig. 4). A robust and significant diurnal rhythm of pineal melatonin with low levels during the day and high levels during the night was observed (F1,103 = 30.08, P < 0.001). For all genotypes, pineal melatonin levels were significantly higher during the night [RORβ(C3H)+/+ (P < 0.05), RORβ(C3H)+/− (P < 0.001), and RORβ(C3H)−/− (P < 0.05)].
Light-Induced Phase Shifts of Circadian Activity Rhythms
Figure 5 shows representative wheel-running activity records from RORβ(C3H)+/+, RORβ(C3H)+/−, and RORβ(C3H)−/− mice kept in constant dark and exposed to a light pulse (300 lux, 15 min) at CT 14 (Fig. 5, A–C) or CT 22 (Fig. 5, D–F). Light pulses administered during either the early or the late subjective night produced phase shifts of locomotor activity of similar direction and magnitude in all three genotypes (Fig. 6B). When administered at the beginning of the subjective night phase (CT 14–18), light-induced phase delays [−2.10 ± 0.08 h, n = 14 for RORβ(C3H)+/+; −1.87 + 0.07 h, n = 14, for RORβ(C3H)+/−; and −2.01 ± 0.13 h, n = 14, for RORβ(C3H)−/−]. Following exposure to light during the late subjective night (CT 20–24), all three groups phase advanced. However, the magnitude of the shifts was significantly larger than for mice lacking the RORβ gene (F2,43 = 73.09, P < 0.0001) [0.72 ± 0.11 h, n = 10 for RORβ(C3H)+/+; 0.86 + 0.05 h, n = 17, for RORβ(C3H)+/−; and 1.80 ± 0.07 h, n = 17, for RORβ(C3H)−/−].
Melatonin-Mediated Phase Shifts
Mice free-running in constant dark were injected with vehicle or melatonin (90 μg/mouse) for three consecutive days, at the melatonin window of sensitivity: CT 9–11. Figure 7 shows representative actograms of circadian rhythms of wheel-running activity obtained in all three genotypes free-running in constant dark and their response to vehicle (Fig. 7, A, C, E) or melatonin (Fig. 7, B, D, F) at CT 10. Mice lacking the RORβ receptor responded to melatonin with a phase advance of similar magnitude (1.00 ± 0.22 h, n = 8) as the heterozygous (0.90 ± 0.11 h, n = 15) or the wild-type (1.26 ± 0.26 h, n = 11) (Fig. 7G) mouse. Melatonin did not affect the tau of circadian activity in either genotype [tau change: ROR(C3H)+/+: −0.02 ± 0.03, n = 11; RORβ(C3H)+/−: −0.01 ± 0.02, n = 15; RORβ(C3H)−/−: −0.02 ± 0.04, n = 8].
Rate of Reentrainment After Phase Advance of the LD Cycle
The rate of reentrainment of RORβ(C3H)−/− mice after a 6-h phase advance was slower than the rate of wild-type mice (F1,260 = 42.31, P < 0.0001) (compare Fig. 8, A and B). RORβ(C3H)+/+ mice needed ∼7 days to complete the 6 h advance in the wheel-running activity onset, while RORβ(C3H)−/− mice needed more than 10 days to complete the advance. Melatonin administration facilitated the rate of reentrainment in both the wild-type and RORβ(C3H)−/− mice (Fig. 8), indicating that RORβ(C3H)−/− mice respond to melatonin with the same efficacy as their wild-type counterpart.
Results from this study show that the RORβ nuclear receptor is involved in sensory processing and that its absence leads to specific behavioral changes. The prolonged circadian period (tau) and the reduced rate of reentrainment to a phase advance of the LD cycle in the RORβ(C3H) knockout mice confirm the involvement of the RORβ nuclear receptor in circadian rhythm regulation. In response to melatonin administration RORβ(C3H), knockout mice phase advance the onset of circadian activity rhythms as their wild-type counterparts. These results suggest that the RORβ nuclear orphan receptor is not involved in melatonin-mediated phase shifts of running wheel activity. Moreover, in the pineal gland of the C3H mouse, the transcription factor RORβ appears not to be necessary for the circadian production of melatonin, despite the cyclic nature of this gene's activity.
RORβ(C3H) knockout mice have the same behavioral phenotype as previously reported for RORβ(C57) knockout mice (1), in that they display a duck-like gait, male inability to reproduce until 6–9 mo of age, retinal degeneration, and an increased free-running period in constant darkness. As with RORβ(C57) knockout mice, the phenotype of RORβ(C3H)−/− mice are very similar to that reported for the vacillans mutant mouse 50 years ago (35). The pattern of expression of the RORβ mRNA in the central nervous system suggests a role for RORβ in the processing of sensory information, as well as in circadian rhythm (27, 33). Our results show a deficit in the RORβ(C3H)−/− mice's ability to perceive and process sensory information, including smell and touch (ear and whisker reflex). Furthermore, the eye blink response was also altered in the RORβ(C3H)−/− mice, which may represent an additional sensory deficiency. However, because the RORβ(C3H)−/− mice showed a high incidence of palpebral closure, motor dysfunction cannot be ruled out as a contributing factor for the lack of responsiveness to the eye blink test. Interestingly, RORβ(C3H)−/− mice showed reduced muscular strength contrary to a previous report (1), demonstrating normal muscular strength in adult C57 mice lacking the RORβ receptor.
Our results show a deficit in the ability to perceive and process sensory stimuli, including smell and touch (ear and eye blink twitch reflex) in the RORβ(C3H)−/− mouse, and provides corroborating behavioral data to the already reported expression of the RORβ mRNA in such areas as the anterior olfactory nucleus posterior (33) and sensory cortices (thalamus and cerebellum) (1, 26, 33, 38).
We report for the first time that RORβ(C3H)−/− mice are less prone to anxiety-related behaviors, as evidenced in their performance in the open-field test and the elevated plus maze. In the open-field paradigm, the animals were placed in a novel and unfamiliar environment to create conflict by evoking both approach and avoidance behaviors. As such, this test has been cited as inducing moderate anxiety in the animal (11). Our data suggest the RORβ(C3H)−/− mouse to be less inhibited, more curious, and more responsive to the novel environment, thus showing less anxiety-related behavior compared with the wild-type mouse. Similarly, in the elevated plus maze, RORβ(C3H)−/−, mice appear to exhibit less anxiety-related behaviors; thus they are more receptive to novel situations and environments, despite their visual deficits.
RORβ−/−(C3H) mice exhibited less depressive-like behavior as they appeared to show a resistance to learned helplessness induced by the forced swimming test compared with the RORβ(C3H)+/+. Taken together, these animals appear to have above-average emotional behavioral characteristics. Numerous mutant animal models show altered anxiety and depression-related behaviors; for example, the mouse knockout for the μ-opioid receptor (41) or for the tac1 gene encoding substance P and neurokinin A (6), and the most remarkable, the Clock mutant mouse, carrying a mutation of the circadian gene clock (12). Behavioral changes in clock mice are very similar to the ones reported here, including increased exploratory behavior and less depressive-like behavior. These results suggest a potential interaction of RORβ with the clock or other clock genes that may be involved in the modulation of behaviors in the emotional domain.
Disruption of the RORβ orphan receptor does not affect rhythmic synthesis of pineal melatonin in mice with a C3H/HeN background, one of the few melatonin-producing mouse strains. The rhythmic expression of RORβ mRNA coincides with melatonin production in both the retina and pineal gland (1–3), which originally suggested that this nuclear receptor may somehow be involved in the regulation of melatonin production. However, the absence of ROR response elements in the promoter of the arylalkylamine N-acetyltransferase gene suggests that the RORβ receptor may not influence melatonin synthesis. Indeed, our results showed a robust rhythm of melatonin synthesis for the wild-type, heterozygous, as well as the RORβ(C3H) knockout mice, arguing against the involvement of the RORβ receptor in the production of pineal melatonin.
RORβ(C3H)−/− mice perceive light signals to entrain physiological rhythms to the 24-h LD cycle and phase shift circadian activity rhythms in response to a light pulse when running in constant dark. The running-wheel activity patterns of RORβ(C3H)−/− mice, however, is significantly less robust than in RORβ(C3H)+/+mice, showing only small bursts of activity during the subjective night. RORβ(C3H)−/− mice have genetically abnormal retinas due to the lack of the RORβ receptor gene, as well as the rd/rd mutation of the C3H background (1, 13). As demonstrated for the RORβ knockout mouse in a C57 background (1) or for the rd/rd C3H mouse (13), the massive loss of cones and rods does not impair the circadian responses, suggesting that in RORβ(C3H)−/− mice, the elements in the visual system mediating circadian responses are intact. In a similar way, RORβ(C3H)−/− mice respond to light with phase shifts in the same direction as the wild-type and the heterozygous mice, supporting the concept that despite the abnormality of the retinal visual system, C3H mice lacking the RORβ receptor still conserve the elements of the retinal circadian system. These elements may include the melanopsin-containing retinal ganglion cells (17) that may account for the nonvisual retinal functions as pupil reflex and photoentrainment of circadian rhythms in rod- and cone-deficient mice (18).
The expression of RORβ mRNA in areas related to circadian physiology (pineal gland, SCN, retina) (1, 33) and the longer free-running period (Ref. 1 and present results), point toward a role of this nuclear receptor in circadian biology. The nature of that involvement and the targets of RORβ, however, remain to be elucidated. It is conceivable that the endogenous rhythm of activation of RORβ regulates transcriptional activation of clock genes in the SCN. In fact, all-trans retinoic acid activation of RAR (retinoic acid receptor) or RXR (retinoid X receptor) nuclear receptors phase shifts the rhythmic expression of the per2 gene in smooth muscle cells in vitro and in the vasculature in vivo (25). Both the staggerer mutant mouse, lacking a functional RORα receptor, as well as the Rev-erb α knockout line, have a shorter free-running period (32). These transcription factors seem to compete for the same response element on the Bmal1 gene promoter forming part of a positive stabilizing loop (32). On the contrary, RORβ knockout mice show a longer tau, suggesting that this gene product may bind to a different response element or be part of another stabilizing loop. One interesting finding is the larger phase advances observed in ROR(C3H)−/− mice after light pulses administered during late subjective night. This finding suggests that the RORβ nuclear receptor negatively modulates the light-induced phase advance. Whether the potentiation in light-mediated phase shifts in the C3H mouse strain with genetic deletion of the RORβ gene is related to the expression of a circadian period larger than 24 h is not known. Indeed, several studies reported that light-mediated phase advances are positively correlated with the length of the circadian period (29, 34), while others did not observe this correlation (30).
The ability of melatonin to phase advance wheel-running activity rhythms in mice lacking the RORβ gene suggests that this nuclear receptor does not affect the melatonin-mediated phase shifts. In mice, activation of MT1 or MT2 melatonin receptors mediate two distinct responses: inhibition of neuronal firing (MT1) and phase shifts of neuronal firing rhythms in the SCN in vitro (MT2) (9, 20, 23). However, phase shift of overt activity rhythms in vivo appears to require activation of MT1 receptors (9). Here, we demonstrated that the orphan receptor RORβ does not contribute to the phase shift of circadian rhythm of activity by melatonin. Activation of the RORβ receptor was postulated to be the mechanism by which melatonin may transmit photic information from the circadian pacemaker to peripheral tissues, that is, GnRH mRNA rhythm in the GT1-7 neurons depends on the circadian effect of melatonin on an enhancer region of the GnRH gene containing consensus sequences for the RORβ response elements (31). Recently, however, the transcription factor involved in melatonin-mediated repression of GnRH gene expression was shown to be COUP-TFI and not RORβ (14).
Taken together, these results show that RORβ does not seem to be involved in the relay of photic information by melatonin and may not be a nuclear melatonin receptor (4, 15, 39). However, AVP neurons in the Siberian hamster SCN coexpress the MT1 melatonin receptor and the RORβ nuclear receptor mRNAs (36). Similarly, TSH cells of the rat pars tuberalis coexpress the MT1 melatonin receptor and the RORβ orphan receptor (22). Although it is unlikely that RORβ nuclear receptor is involved in melatonin-mediated phase shifts, we cannot exclude the possibility that other MT1 melatonin receptor-mediated responses may require the presence of a functional RORβ receptor.
The rate of reentrainment following a phase advance of the LD cycle is slower in the RORβ(C3H)−/− mouse. This phenotypical characteristic of the RORβ(C3H)−/− correlates with a longer free-running period of the RORβ(C3H)−/− compared with wild-type mouse (Ref. 1 and this study). RORβ(C3H)−/− mice showed the longest free-running period compared with both wild-type and heterozygous mice and the slowest rate of reentrainment. The longer circadian period in the RORβ knockout mice, and therefore the natural tendency to delay, may counteract the advance imposed by the LD cycle and therefore slow down the reentrainment process compared with that of wild-type mice possessing a circadian period shorter than 24 h. Melatonin accelerates the rate of reentrainment in the RORβ(C3H)−/− mouse, demonstrating again that the RORβ receptor does not mediate melatonin's effects on circadian rhythms.
Here, we demonstrate that melatonin-mediated effects on circadian activity rhythms are not mediated by activation of the nuclear receptor RORβ. Similarly, the synthesis of melatonin is not affected in mice lacking the RORβ receptor. The role of the nuclear RORβ receptor in circadian rhythms is demonstrated by extended tau and reduced rate of reentrainment in mice lacking this receptor, underpinning RORβ as one of the numerous molecules that may be part of the fine-tuned structure of the circadian biological clock.
This research was supported by U.S. Public Health Service Grants MH52685 and MH42922 (to M. L. Dubocovich).
We thank Dr. Stephanie Hauge for her participation in early experiments and Kenneth Yun, Elizabeth Manna, Iwona Stepien, and Paula Ginter for expert technical assistance. RORβ(C3H)−/− mice were created by Dr. Michael Becker-Andre (Glaxo-Wellcome, Geneva, Switzerland) and kindly provided to us by Glaxo-Smith-Kline (Stevenage, UK). Our thanks go to Jeremy M. Davies for editorial assistance.
A preliminary version of this work was presented at the International Congress on Chronobiology, Washington, DC, August 28–September 1, 1999.
Current addresses: Isabel C. Sumaya Dept. of Psychology, California State University, Bakersfield, 9001 Stockdale Highway, Bakersfield, 93311-1099, CA; and Michael Becker-Andre, Ludwig Maximilian University Munich, Institute for Biometry and Epidemiology, Marchioninistrasse 15, 81377 Munich, Germany.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2007 the American Physiological Society


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"Best of Times" vinyl w/ handwritten lyric sheets
THIS ITEM IS NO LONGER AVAILABLE. WE SOLD OUT OF IT IN UNDER AN HOUR! I'm really glad that these pieces found nice homes. Thank you! We have another extremely rare item we're about to announce at http://StrangeFamousRecords.com soon, so stay tuned.
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SIDE B: 1) Love the Lie, 2) Love the Lie instrumental
The music for "The Best of Times" is written by French composer Yann Tiersen. The music for "Love the Lie" is written by Mark Linkous (Sparklehorse.)
*When the LI(F)E album dropped in 2010, two hundred of these 12″ singles were pressed and distributed as a promo item to DJs in the UK. When Sage Francis toured the UK he was given a short stack of these vinyl singles to bring home, at which point he discovered a great error occurred at the manufacturing plant. Instead of having the Best of Times instrumental on the B side (as listed on the 12″ label,) the instrumental for a song that was scrapped from the LI(F)E album was there in its place. You will not recognize this music as the original version of this song has still not been released, but it should be very clear that this 12″ does NOT feature the Best of Times instrumental. This is the music industry's version of the "error card" and another reason why this particular 12″ will never see another re-pressing.
During the Best of Times video shoot, Sage Francis used a black marker to write the lyrics of the song on music sheets which were then hung on a clothing line. These are the same exact lyric sheets we are offering as part of this package deal (one lyric sheet per purchase.) We definitely don't want is for these items to end up in the hands of an eBay seller. For a song that has resonated so strongly with our listeners, we'd really like to know that these 13 pieces are going into the right homes.
Leave a Reply
Jesse says
i really really hope to get me a copt of the vinyl as well as lyric sheet, your music has made me the person i am today and would mean so so so much to me if i got one of these copys so pray for me Sage ! i shall pray 20 times over that i get one according to some programs if i pray that many times it will come true right?
gilberto gomez says
please come to guadalajara, jalisco, mexico
your music is amazing, inspiring, and it hits me, were it hurts the most.


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Travel & Expenses Analyst - French
Location : Birmingham
Post Date : 14 March 2017
Employment Type : Permanent
Job Order Number : 469837
Line of Business : Accounting and Finance
Description :
The Company
Robert Half Finance & Accounting are currently recruiting for a French-speaking Travel & Expenses Analyst to join a manufacturing organisation based in South Birmingham.
Your Profile
This is an exciting opportunity that will suit someone who is seeking a new challenge, and is looking forward to an exciting career opportunity within an fast-paced and diverse work environment. Working within busy finance team, the successful candidate will be dedicated, enthusiastic and driven, with the desire to progress in a prestigious company. Fluency in French is a must in this role, and excellent communication skills are required to maintain good relationships with internal and external customers.
The Role
This role will have links to areas of the business so excellent interpersonal skills are essential to building relationships. Responsibilities:
- Daily audit of expenses
- Resolve any expense queries
- Review weekly payment report and resolve any unpaid expenses
- Support the independent review process
- Support month-end processes by delivering accrual information
- Assist with strengthening internal controls by complying with internal and external regulations
This is a hands on role and the ideal candidate will be competent, have excellent attention to details and good organisation skills to ensure all month end deadlines are complete.
Salary & Benefits
Salary is £19-£22k with additional company benefits such as health-care and pension plans.
Robert Half Ltd acts as an employment business for temporary positions and an employment agency for permanent positions. Robert Half is committed to equal opportunity and diversity. Suitable candidates with equivalent qualifications and more or less experience can apply.
20 Colmore Circus, Queensway,
B4 6AT Birmingham


text: PLDA introduced their QuickUDP, which is a 10Gb UDP Hardware stack IP core for FPGA devices. The QuickUDP IP solution is a 100% RTL-designed IP, compliant with the IEEE802.3 specification and supports the ARP, IPv4, ICMP, IGMP, and UDP protocols. The PLDA QuickUDP 10G UDP Hardware Stack IP is available now from PLDA. The PLDA QuickUDP can be integrated into Altera-based and Xilinx-based FPGA designs.


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Two Sicily's Bakerié is your destination for authentic Italian cuisine that you can enjoy any time at home. Our products are made with premium, fresh ingredients and deliver great taste from your freezer to the table in minutes. Our menu includes these Bistro favorites:
- Pizza
- Panini Classics
- Flatbread Melts
- 5-Cheese & Garlic Italian Bread


text: "Pichon Lalande's new owner, the Roederer champagne firm, appears to have produced one of the finest Pichon Lalandes made in recent years. Administrator Thomas Do-Chi-Nam, assisted in 2006 by consultant Hubert de Bouard, declared only 41% of the production as the grand vin, resulting in a wine that should rival both the 2003 and 2000. The final blend of 64% Cabernet Sauvignon and 36% Merlot was cropped at 41 hectoliters per hectare. This gorgeous wine represents an updated version of the 1996. It boasts a dense purple color as well as a beautiful nose of espresso roast, chocolate, creme de cassis, cedar, and spice. Full-bodied and powerful with high tannin, an attractive mouthfeel, and a multilayered texture, it will be a backward-styled Pichon Lalande, but it is significantly better than the 2005, recalling some of the finest vintages produced over the last 20-35 years." – RP


text: Human Rights Observatory HRW: Egypt's Trial of Morsi 'Badly Flawed' The trial of former Egyptian President Mohamed Morsi, deposed by the army and sentenced to 20 years in jail, was "badly flawed" and appears to have been politically motivated, Human Rights Watch said on Sunday. A court on April 21 convicted Morsi and 12 other Muslim Brotherhood members of violence, kidnapping and torture over the deaths of protesters in 2012. They were acquitted of murder, which carries the death sentence. The rise to power of the Brotherhood, a decades-old...Read complete article© Voice of America - Sunday, April 26, 2015


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Online about 1 year ago
Rent budget
Preferred stay length
Move date
My name is Marwa and i am 21 years old. I came from the Netherlands. I came to Sydney to do my internship here at the company WorknHoliday. I am a very social, friendly and funny girl. I love a clean house, so i'll do as much as possible in the housecleaning. I like to achieve things and I am very adventurious.


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Chemical Eye Burns (cont.)
Self-Care at Home
For all chemical injuries, the first thing you should do is immediately irrigate the eye copiously. Ideally, specific eye irrigating solutions should be used for this, but if none are available regular tap water will do just fine.
Medical Author:
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Burns to the sclera, conjunctiva, cornea, and eyelid are considered ocular burns.


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We all have body issues, real or imagined. We all have some body parts that we'd like to play up – like our beautiful eyes, and some we'd like to play down, like our bellies or larger bustlines. Here are some tips for dressing up or down your cleavage.
Tip 1: Buy a bra that fits. If you don't wear one, you probably should. Your girls have changed, especially if you've had a baby. You can get fitted for a new bra at the lingerie section of any big department store – free of charge, but you'll probably feel obligated to buy a bra or two. A real bra fitting session will help you find your true size plus help you find different styles – like padded, push up or minimizer.
Tip 2: To make a smaller bust look bigger – This actually isn't a problem. Just ask any large busted woman who is relatively petite all over. Clothes are designed for the flat chested. So the small busted woman just needs to engage in a few small sleight of hand tricks to make the girls pop. Start withe he right bra to push them up and give you wow cleavage. Tops with decorative flourish in front – like cascading ruffles, and shirring to give an illusion of breasts by obscuring their size. Halter tops, off the shoulder tops and jewel and bateau necklines – like Audrey Hepburn's classic necklines will all pump up the volume.
Tip3: To make a bigger bust look smaller – Woe to the poor big busted woman, especially if the rest of your frame is petite. Instead of being an asset, a large bust makes you look heavier than you are, makes it difficult to find clothes that fit and if not handled properly can send the wrong message. So to dress a large bust up with class, stay away from boxy or double breasted jackets that will make you look like a large sailed frigate ship gliding into port. Look instead for fitted jackets with a deep v and small lapels. Go for v-necks or sweetheart necks look great – if you're worried about exposing too much, wear a camisole to provide some color contrast or a little more coverage. Scoop and jewel necks will make big busts appear even bigger. Bulky knits make you look bulky so stay away. Details like shirring should be under the bust is better than on the bust.
Beware of button shirts as they can often pull. Wear a camisole and leave the shirt unbuttoned, or have buy your shirts a size larger and have a tailor insert darts or seams to shape it softly under your bustline.
A belted waist will make you appear top heavy so stay away. Instead for for a fitted waist with and open neckline.
Skinny pants and narrow skirts will also make you appear top heavy so go instead for full pants and those that flare becasue they will counterbalanxe larger busts. A line or softly draped shirts and dresses are better. And of course going for darker colors on top will visually diminish larger bustlines, especially if you wear brighter colors or patterns below.
Tip 3 – Wrap tops and dresses flatter both small and large busts because they give an illusion of a waist which creates balance. Fabrics should caress the bust and too tight or too loose tops are not flattering. Fabrics with a slight stretch will give you a better fit.


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Spa break takes F1 racing to the Max
After a lengthy lay-off the natural place to head off to is Spa and that was the case as Formula One returned from its summer recess to resume battle at the Belgian circuit.
This was one of Channel Four's live races, although the opening felt as if I'd stumbled onto Discovery or the History channel by mistake.
"The deep forests of the Ardennes, one of the cradles of the Industrial Revolution, a landscape torn apart by two World Wars, but a place too of healing - Spa - a small city of water that gave its name to all the spa towns of the world," it began, and there was me thinking it was outside Ballynahinch.
Presenter Steve Jones was quick to tell us this was a special place, and asked David Coulthard and Mark Webber was this because of the "high speed, the elevation, the pine trees, the fans or the waffle truck just up the road?"
The problem with F1 is that there is usually far too much waffle and not enough action, but Coulthard promised us this was "the scariest roller-coaster you've ever been on".
He wasn't wrong, as we only had to wait until the first turn for near disaster as Sebastien Vettel, Kimi Raikkonen and Max Verstappen had a bit of a to-do, meaning that a Max hasn't figured so centrally on a Sunday show since Hart to Hart was in its pomp.
Hard to imagine that Kimi and Max will be having too many heart to hearts anytime soon as the young whipper-snapper kept annoying the oldest man on the grid but before they really got started or finished, a man called Magnussen introduced us to the very scary Eau Rouge stretch of the track at high speed.
He failed to pass it with commentator Ben Edwards saying he would be "a little bit sore" but not as damaged as his car being shovelled onto the back of a lorry.
"They'll not be saving many bits from that, it's to be scraped off the back of the truck and into a skip," said Coulthard, where there is bound to be an old mattress.
The red flag for Magnussen's crash meant we had some time to fill and we were literally left scraping the you know what with Coulthard.
"Once in Malaysia I ended up, and I guess this isn't the most pleasant conversation, with a blister on my rear because the car was low to the ground, quite an unpleasant experience." And for us too, David, and why were you driving Fred Flintsone's motor?
Back to racing and Kimi and Max were getting along famously, the furious Finn hinting that the flying Dutchman's "only interest is in pushing me off the circuit completely" as he then proceeded to try it again.
"If Raikkonen's already frustrated he may have just upped that to angry level," said Coulthard and they really do think of everything in these cars, but Kimi's thoughts were more industrial, suggesting over the radio that "this is f****** ridiculous".
"I'll just apologise for any language there, Kimi Raikkonen getting a little hot under the collar," he added but it was catching, Fernando Alonso and Nico Hulkenberg locking horns, with the latter not just as fuming as the Finn.
"Did Alonso hit you?" he was asked by his team.
"Yes," came the whimpering reply, thus ruining a perfectly good chance to cram in a joke about him getting angry, tearing off his overalls and banging Fernando like a drum. Incredible.
What was more incredible was that Lewis Hamilton somehow managed to finish third having started last on the grid, with Nico Rosberg winning the race and Max, as Edwards told us, "didn't make it to the podium" which was maybe just as well as he'd probably have mowed it down.
"He has electrified Formula One this season," he added, as if he isn't dangerous enough, but even he couldn't overshadow the podium show from runner-up Daniel Ricciardo who enjoyed some Aussie banter with interviewer Webber, handing him a racing shoe filled with champagne.
And he drank it. Then again, he who races Australian, drinks Australian, and there was us thinking that XXXX stood for something else when in fact it stands for shoe.
What Kimi may do with his shoe when he sees Max was not shown, but at least Coulthard had a theory as to what happened to Magnussen.
"He's not spinning his tyres, it's almost like he's had an aero drop out," he said.
The same happened me once when I pranged into a feisty Finnish tourist when I dropped my Wispa. Careless of me, I know. I think I'll nip down to the Spar in Spa to pick up another one, a wee lad called Max has offered me a lift.
The good, the bad and the ugly
The good: For those of you with an interest in battered confectionery, Irn Bru and the Krankies, a small heads up for a very good football documentary on BBC Scotland. Scotland's Game is a three-part series exploring the history of fitba amongst our Caledonian cousins and part one focused heavily on Graeme Souness' moustache and if that isn't enough to watch, then I don't know what is.
The bad: Talking of Scottish icons, Charlie Nicholas had a little moment which he shared with the nation, whether they wanted it or not, on Sky's Soccer Saturday, his passionate moans of ecstasy filling the studio and leaving Jeff Stelling to utter "Charlie doing his best Meg Ryan impression". Let's just pray that he never has to use the words "Phil Thompson doing his best Sharon Stone impression".
The ugly: Saturday morning and there was nothing on UTV. No, I literally mean nothing as possibly one of the most hair-brained initiatives ever, entitled 'I am Team GB', filled the airwaves with nothing so that we could all go out and do some exercise. Bizarrely, 60,000 people decided to stay in and watch a blank screen, which augurs well for Tokyo 2020.
Belfast Telegraph


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President Barack Obama has nominated James Comey, a former George W. Bush administration official, to replace outgoing FBI director Robert Mueller and lead the agency for the next ten years.
Comey, a registered Republican, gained public notoriety in 2004, when he stopped Chief of Staff Andrew Card and Bush White House counsel Alberto Gonzales from reauthorizing a controversial program on warrantless wiretaps.
Obama, in a speech on Friday, referenced the incident, saying Comey "was prepared to give up a job he loved rather than be part of something he felt was fundamentally wrong."
Obama also mentioned Comey's other career highlights:
"As a young prosecutor in the US attorney's office in Manhattan he helped bring down the Gambino crime family; as a federal prosecutor in Virginia he led an aggressive effort to combat gun violence that reduced homicide rates and saved lives," Obama said.
After Comey left the Justice Department, he worked for Lockheed Martin, a defense contractor. In 2010, he worked for Bridgewater Associates, a hedge fund, and has served as a nonexecutive director of the UK bank HSBC.
Comey, who still needs to be confirmed by the Senate, said he was eager to get to work.
"They are men and women who have devoted their lives to serving and protecting others and I simply can't wait to be their colleague," he said.
Watch Obama talk about Comey here:


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Albertsons Companies Inc.
Morning Agenda: A Fight North of the Border for Pickens
Trading Slump Hurts Goldman Earnings | Y Combinator to Fund Later-Stage Companies | Morgan Stanley Deal Maker Leaves for BDT & Co.
October 16, 2015, Friday
Morning Agenda: Companies Test Inhospitable Market for Public Offerings
A Radical Plan for Puerto Rico | Rabobank Traders on Trial for Rigging Libor
October 15, 2015, Thursday
Copyright © 2008. Quotes and other information supplied by independent providers identified on the vendor disclosures page.
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There are all kinds of information and data that you can use when evaluating housing markets for homebuilding and real estate purposes.
A Washington Post article provided some interesting insight about where the highest earning citizens live in our country. You can use the related color-coded map tool to quickly identify the wealthiest US Counties based on the most recent Census data, and also to search by county to see the breakdown of high income households in each county. Click here for the Map Search Tool. We like it because it is easy to use and a very visual way to compare this information across large geographic areas.
Household income can be useful information for builders, developers, brokers and other real estate professionals when evaluating the housing markets in which they already focus, as well as new markets that they are considering. Of course these decisions are very individual and depend on many factors like geography, market conditions, your product, etc. — everyone has their own formula and uses different data sources to thelp them make these decisions. And while wealth alone may not be the primary indicator for your business decisions, wealth can help you understand more about your housing markets, particularly if you are building or selling homes that are targeted at high income households.
Just another tool for you to use, because it's always good to have as much useful information as possible when making these market-targeting and evaluation decisions. What kind of information do you like to use when evaluating housing markets?
- Lots and Land Development: How do you know when the market is ready? (lotnetwork.com)


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Submitted by FrancisGuy on 0 Comment(s)
Experience the sound of rosewood and taste of rose wineWithin the framework of the open-air concert series at The Cyprus Wine Museum "Commandaria Orchestra and Friends" feature two remarkable young performers from Britain and Cyprus. Yuval Shalson (Flute) and Maria Kramvi (Marimba) will perform masterpieces from the rare repertoire of the rosewood instruments duet, flute and marimba.Can anyone find links between the fascinating sounds of rosewood instruments and rosé wine? Let's give it a try on Wednesday, July 12th 2017 at The Cyprus Wine Museum in Erimi for a magical night under the moonlight.- Price 10 euro (a taste of the Cyprus Wine Museum Senses Rose Wine is included).- Concert Starts at 21:00- Cyprus Wine Museum
Yuval ShalsonYuval began playing the flute at the age of ten. She is currently studying towards her Master of Music (MMus Performance) degree at the Royal Conservatoire of Scotland (RCS), with flute professors Ruth Morley and Katherine Bryan, and piccolo professor Janet Richardson.A keen performer, Yuval was principal flutist in the London City Orchestra, one of London's leading amateur orchestras, for 3 years, performing at various prestigious venues and with many international soloists. She has performed in various competitions and master classes with renowned flutists from across the globe; such as Ian Clarke, Wissam Boustany, Michael Cox, Matthias Ziegler, Ruth Morley, Clare Southworth and Philippa Davies. So far, during her time at RCS she has performed in various concerts with the RCS Symphony Orchestra, RCS Wind Orchestra, RCS Chamber Orchestra and in many chamber concerts, in prestigious venues including the City Hall in Glasgow. Yuval completed her undergraduate degree, with First Class Honours at the City University, London. Throughout this time, and for two years prior, she studied flute with London based flute professor Wissam Boustany, who previously taught at Trinity Laban Conservatoire of Music and Dance and at the Royal Northern College of Music.
Maria KramviThe percussionist Maria Kramvi is a graduate of the City University of London and holder of a master degree at Trinity Laban Conservatoire of Music and Dance - MA in Performance and Education. Her percussion studies include lessons and master classes by Louise Morgan, Mick Doran, Marney O'Sullivan, Gillian McDonagh and Randy Max.Maria did her first steps in orchestras with Cyprus Symphony Youth Orchestra at an early age and until today she has performed with various orchestras including the Cyprus Symphony Orchestra, Greek Opera House, Bloomsbury Chamber Orchestra, City Symphonic Winds, Covent Garden Chamber Orchestra, London City Orchestra, Les Voix Nouvelles and others; at concerts in many countries including the UK, Greece, Cyprus, Malta, Turkey, Slovakia and Czech Republic. Education has always been a passion for Maria, not only as a music teacher but as a researcher and creator of original materials as well. Her latest research findings are published at www.teach4mallets.com and mark the starting point of ongoing researches and publications. Maria works regularly with various companies, museums and theme parks in order to set and support their educational department. Maria is a dynamic and experienced workshop leader and World Voice trainer, accredited by the British Council. At the moment, she is mainly working on a freelance basis as educator and percussionist and she is employed by the Ministry of Education as percussion teacher in music schools. She is also the percussion coach of the Limassol Municipal Philharmonic and regular guest percussionist of the Cyprus Symphony Orchestra.


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There is much to learn from Britain's top nurserymen. Over the next few weeks, Sarah Raven visits the country's most inspirational nurseries, starting with Marchants Hardy Plants for tips on how to use late-summer colour
A pilgrimage to Marchants Hardy Plants near Lewes in East Sussex is a joy for any keen perennial gardener at this time of year.
In spring, the garden and the nursery are full of greens, different tones, textures and wonderful leaf shapes, but not much colour.
But now, as autumn approaches, the place is at its peak. I asked Graham Gough, Marchants' creator, why he concentrated so strongly on plants for this season.
"We are emotional creatures," he says, "and respond differently to different times of year.'
For Gough, who describes himself as melancholic, autumn - the season of collapse and decay - is the best time of year. It's partly the light, but he also loves the sense of things coming to a close in a cyclical and seasonal sense. He sees more beauty in this withdrawal as part of the regenerative process than in the buoyant, pert perfection of spring.
That emotional response moulds his choice of plants and he specialises in those that are at their best in the autumn. He has found that gardening fashions often charge ahead, picking up a few favoured plants and throwing them into almost every garden.
However, with each fad there are many more plants, just as good, that don't get noticed. These are often his stars and are given a second, third and even fourth chance to prove themselves before they get jettisoned to free up precious space if they still don't perform.
The result, in Gough's garden, is a woven combination of the best forms of the usual autumn trumpeters - velvety heleniums, crocosmias, aconitums, tall, richly coloured agapanthus and perovskias - but mixed with barely known and often newly bred or wild-discovered ornamental grasses, lythrums, sanguisorbas and persicarias.
Some have less blatant charms but their delicate beauty combined with a long, steady performance over many weeks or months makes them invaluable. It is really for these that you should visit the nursery.
Bang in the middle of the garden, I found a combination as beautiful as any I have ever seen. I am ashamed to say that I'm usually drawn to bold and brassy plants and respond to the strong voluptuous colours of autumn, not pale blues, pinks and whites. But too much noise and solidity would have felt all wrong in Gough's garden.
At the side of the brick path running down the centre of the first border was a group of five plants that had me rooted to the spot. The floweriest was the species Gaura lindheimeri, much taller than the hybrid 'The Bride' that I grow.
But the magnificence of this group was not based on flowers - it was about interwoven shapes and colours, all pale and washy, with a lightness of texture that was at its most incredible as the sun rose higher and the whole group was back-lit.
Threaded through the gaura was Persicaria amplexicaulis 'Alba', a plant I would normally walk straight past, but the vertical spikes lining up through the gaura froth - with a fringe of the dark-flowered airy grass, Molinia 'Transparent', behind - was marvellous.
On one side, a curtain of crimson globules hovered in the air (Sanguisorba sp. CDC 262, a new find yet to be properly named) with the chunkier, iridescent Pennisetum alopecuroides 'Black Beauty' on the other. There was none of the blobbing that you sometimes get with mixed borders of perennials and shrubs, but rather sprinkles and threads from one plant to the next.
This is easier to achieve with these late-flowering airy perennials than it is with stockier plants, but I felt the influence of Graham's wife, Lucy Goffin, a textile designer, in this lightness of touch. This was wispy beauty at its best and a combination you can enjoy for several months.
On the left was another good grouping. The best of all willows, Salix purpurea 'Nancy Saunders', a tumble of crimson and silver, sat on the corner, with a pink-purple Lythrum virgatum tucked in just behind. This contrasted with a tangerine Crocosmia 'Queen Alexandra' and was then calmed by the feathery silver mass of tamarisk and Eleaganus angustifolia 'Quicksilver'.
Gough says that whenever there's a gap, he just shoves something in. There's never a design on paper, all is done on the hoof, but, with his critical and yet visionary eye, his instincts seemed to me to be spot on.
Gough gave up a musical career 20 years ago and had become bored working as a jobbing gardener. One September, he walked through the arch into the first courtyard of the garden at Sissinghurst, saw the purple border and, at that moment, realised that gardening could also be art.
If you put a date in your diary for a visit to Marchants, do empty the boot of your car. I hadn't intended to buy any plants but left with almost a garden-full.
Graham Gough's favourite autumn plants are: Sporobolus airoides - a delicate, tussock-forming grass that flowers earlier than most in early summer. The fine flower spears then shoot through the foliage and break into a silvery-pink froth.
It maintains its stature and fine presence right through the summer and autumn and is an ideal plant to combine with tall, elegant perennials such as Lavandula pinnata, perovskias and Dianthus carthusianorum.
Sanguisorba 'Cangshan Cranberry' -a Dan Hinkley introduction with doses of rich colour suspended on elegant, almost invisible thin stems. It flowers late in mid-September and has a gentle and beautiful presence right through the autumn.
Lythrum virgatum - a native European plant in vibrant pink-purple with small flowers that form a beautiful haze rather than the more typical lythrum spire. There is a lovely balance between flower and bud, all interspersed with fine, fresh green foliage.
Once the petals drop, the stems also give a lovely rosy hue to any group. It's very long-lived, clump forming, doesn't run and doesn't need staking, so is the ideal long-season perennial.
Salix 'Nancy Saunders' - the silver leaves and crimson stems of this willow are a winning combination. The best stem colour is given by coppicing almost to the ground in February or March. You can use the withies in the border or create a delicate yet architectural fence.
Lucy Goffin has done this outside their cottage by sticking withies in the ground in March and interweaving them to add strength. This looks lovely all year round.


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Nicely finished street front office space available in Kitchener's Warehouse District at Duke St. and Victoria St. N. Good mix of private offices and meeting rooms. Located across the street from the future Regional Transit Hub at King/Victoria Street Downtown. 900 SF of basement space included free of charge. Close to many nearby amenities. Great signage opportunity. Sublease expiry 12/31/2017. Mailing address is B-241 Duke St W, Kitchener


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Keep asking me about stuff that don't change. What was that definition of madness, again?
I haven't had any problems with this app!
I like it so much specially selfi pro
I enjoy this time out from the daily grind!!
Awesome but you should update it
I love it :)
Love it!
This game is so cool and Tom is really cute
Love it so much hate the people who hate tom!!!!!!!
Nice App! Keep improving!
I love it so much.
Just exactly what I needed


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These enlightened and enlightening words of the great "Avadhoot" of India, Bhagawan Nityananda, were carefully recorded by his devoted devotee, Tulsi Amma, from 1920 to 1927. Nityananda's esoteric words are like arrows that guide the soul beyond mediocre obsessions and into the heart of self realization, the great space of supreme Consciousness that is Chidakash. Compiled by Swami Nirmalananda Giri into 61 topics from Ananda to Yogi, with teachings about desireless, faith, meditation, moksha, breath, bhakti, avadhuta, reality, peace, shakti, spiritual practice, spiritual experience, viveka, vairagya, silence, self knowledge, inner consciousness and much more, this audiobook is narrated by Sharon Kumuda Janis, author of Spirituality For Dummies, Secrets of Spiritual Happiness, and other works.
©2014 Night Lotus Productions (P)2014 Night Lotus Productions
"enjoyed the wisdom teachings"
great wisdom teachings that gives one much to reflect on. I found many statements of profundity given during this audible book and will listen to this many more times
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Stock Graphic >> Illustration - Man reads a news paper 329887 by studiostoks @ CreativeMarket
File Size: 4.74 MB; Tileable: Yes; Requirements: Adobe CS1+; Layered: Yes; DPI: 300 DPI; Vector: Yes; Dimensions: 6000 x 6000 px.
A man reads a news paper. Morning reading press information
Set contains.
- one JPG file 6000x6000 pixels
- one eps10 file
Buy Now ~ $14
Man reads a news paper
by studiostoks
Keywords: man, reading, newspaper, news, media, economy, politics, journalist, editor, publisher, mail, morning, people, glasses, information, halftone, style, pop, retro, vector.