text:
|New Revised Standard (NRS)
|New International Version (NIV)
|30 But by refusing to be baptized by him, the Pharisees and the lawyers rejected God's purpose for themselves.)
|30 But the Pharisees and experts in the law rejected God's purpose for themselves, because they had not been baptized by John.)
|31 "To what then will I compare the people of this generation, and what are they like?
|31 "To what, then, can I compare the people of this generation? What are they like?
|32 They are like children sitting in the marketplace and calling to one another, "We played the flute for you, and you did not dance; we wailed, and you did not weep.'
|32 They are like children sitting in the marketplace and calling out to each other: " 'We played the flute for you, and you did not dance; we sang a dirge, and you did not cry.'
|33 For John the Baptist has come eating no bread and drinking no wine, and you say, "He has a demon';
|33 For John the Baptist came neither eating bread nor drinking wine, and you say, 'He has a demon.'
|34 the Son of Man has come eating and drinking, and you say, "Look, a glutton and a drunkard, a friend of tax collectors and sinners!'
|34 The Son of Man came eating and drinking, and you say, 'Here is a glutton and a drunkard, a friend of tax collectors and "sinners." '
|35 Nevertheless, wisdom is vindicated by all her children."
|35 But wisdom is proved right by all her children."
|36 One of the Pharisees asked Jesus to eat with him, and he went into the Pharisee's house and took his place at the table.
|36 Now one of the Pharisees invited Jesus to have dinner with him, so he went to the Pharisee's house and reclined at the table.
|37 And a woman in the city, who was a sinner, having learned that he was eating in the Pharisee's house, brought an alabaster jar of ointment.
|37 When a woman who had lived a sinful life in that town learned that Jesus was eating at the Pharisee's house, she brought an alabaster jar of perfume,
|38 She stood behind him at his feet, weeping, and began to bathe his feet with her tears and to dry them with her hair. Then she continued kissing his feet and anointing them with the ointment.
|38 and as she stood behind him at his feet weeping, she began to wet his feet with her tears. Then she wiped them with her hair, kissed them and poured perfume on them.
|39 Now when the Pharisee who had invited him saw it, he said to himself, "If this man were a prophet, he would have known who and what kind of woman this is who is touching him—that she is a sinner."
|39 When the Pharisee who had invited him saw this, he said to himself, "If this man were a prophet, he would know who is touching him and what kind of woman she is--that she is a sinner."
|40 Jesus spoke up and said to him, "Simon, I have something to say to you." "Teacher," he replied, "speak."
|40 Jesus answered him, "Simon, I have something to tell you." "Tell me, teacher," he said.
|New Revised Standard Version Bible, copyright 1989, Division of Christian Education of the National Council of the Churches of Christ in the United States of America. Used by permission. All rights reserved. (New Revised Standard Bible Version Online)
|Scripture quoted by permission. Quotations designated (NIV) are from THE HOLY BIBLE: NEW INTERNATIONAL VERSION®. NIV®. Copyright © 1973, 1978, 1984 by Biblica. All rights reserved worldwide. (New International Version Bible Online)


text:
The 2011 MTV Video Music Awards are underway!
Before any Moon Man statues are handed out, the stars have to brave the heat and walk the red carpet at the Nokia Theater L.A. Live in downtown Los Angeles.
The cast of the "Jersey Shore" just hit the red carpet, including a svelte Snooki and Jwoww.
We can't wait to see what Lady Gaga, Nicki Minaj and Katy Perry will wear. Click on the "Launch Gallery" button to see photos of the early arrivals:
Relive some of the wildest past VMA fashions here and be sure to vote for who you think should win at this year's awards, here!
Runway worthy jewelry: http://www.etsy.com/shop/FancySchmancyMe
I just paid $22.87 for an iPad2-64GB and my girlfriend loves her Panasonic Lumix GF 1 Camera that we got for $38.76 there arriving tomorrow by UPS. I will never pay such expensive retail prices in stores again. Especially when I also sold a 40 inch LED TV to my boss for $675 which only cost me $62.81 to buy. Here is the website we use to get it all from, BidsOut.com
Visit www.b4pink.com and show your support for early detection and breast cancer awareness.
© 2014 EHM Productions, Inc. All rights reserved. Reproduction in whole or in part without permission is prohibited.
In partnership with TMZ.com | Privacy Policy

subset: commoncrawl


text:
Over at Reason's Hit and Run blog, Radley Balko has a roundup of five more instances of wrongly convicted people finally getting released from prison after being proven innocent. The five men spent a collective 89 years in prison. Four out of five were convicted on the basis of false eyewitness testimony. Our criminal justice system is broken from top to bottom.
Dispatches from the Creation Wars
The site is currently under maintenance and will be back shortly. New comments have been disabled during this time, please check back soon.


text:
SA News • Mon, Mar. 31
SA News • Sep. 9, 2013
From other sites
at MarketWatch.com (Sep 1, 2014)
at MarketWatch.com (Jul 14, 2014)
at MarketWatch.com (Jun 26, 2014)
at MarketWatch.com (Jan 31, 2014)
at MarketWatch.com (Jan 7, 2014)
at MarketWatch.com (Oct 24, 2013)
China's Q3 Real GDP Growth Is Likely To Exceed 7.4%PopperTech • Fri, Jun. 27
Wall Street Breakfast: Must-Know NewsSA Editor Yigal Grayeff • Aug. 22, 2011 • 23 Comments
Chinese Banks' Illusory EarningsPatrick Chovanec • Apr. 1, 2011 • 29 Comments
The 10 Largest Banks in AsiaDavid Hunkar • Jan. 1, 2011 • 1 Comment
4 ETFs Impacted by China's Bank Reserve RequirementsKevin Grewal • Dec. 10, 2010
2010 Banker Awards: The Best Banks by CountryDavid Hunkar • Dec. 6, 2010 • 2 Comments
The Best Asian Banks by CountryDavid Hunkar • Sep. 5, 2010
A Look at the FXI and the HSI IndicesL. Desjardins • Aug. 30, 2010
China's 10 Most Profitable CompaniesJim Trippon • Aug. 25, 2010 • 1 Comment
Red Flags From ChinaStock Traders Daily • Jul. 16, 2010 • 12 Comments
China's Bank Plans Make Markets NervousPatrick Chovanec • Jun. 20, 2010
The 10 Most Profitable Chinese CompaniesDavid Hunkar • May. 17, 2010 • 7 Comments
China's Economy: Growing and Facing ChallengesEcon Grapher • Apr. 15, 2010 • 2 Comments
Top 15 Global Bank Stocks Ranked by Price-to-Book ValueDavid Hunkar • Jan. 14, 2010 • 3 Comments
Gripping Reality: Sorkin's Too Big to FailWade Slome, CFA • Dec. 28, 2009 • 2 Comments
10 Emerging Market Financial TitansDavid Hunkar • Dec. 27, 2009 • 6 Comments
10 Leading Chinese StocksDavid Hunkar • Dec. 22, 2009 • 1 Comment
China's 10 Most Profitable BanksDavid Hunkar • Nov. 11, 2009
The Top 10 Chinese Banks by AssetsDavid Hunkar • Nov. 10, 2009
There are no Transcripts on CICHF.
Mon, Mar. 31, 12:47 PM
- Industrial & Commercial Bank of China, China Construction Bank (CICHY, CICHF), Agricultural Bank of China (ACGBY, ACGBF), Bank of China (BACHF, BACHY), and Bank of Communications (BKFCF, BCMXY) together shed nearly ¥64B ($10.5B) of bad loans last year, two and one-half times the amount in 2012, and the pace isn't expected to slow in 2014. A number of high-profile defaults in recent weeks remind of the slowing economy and deteriorating financial health in a number of key sectors.
- Still, four of the five posted double-digit profit growth last year (the other grew profit at 7%), giving the lenders room to take write-offs.
- "Industries with overcapacity problems were and will be the main sources of nonperforming loans," says S&P analyst Liao Qiang. "These industries including the steel sector will witness a large increase in bad loans in the next two to three years."
- The Global X China Financials ETF (CHIX) is off 9% YTD.
Sep. 9, 2013, 7:58 AM
- A gauge of financial companies soared 6.7% on rumors Chinese banks will be allowed to issue preferred stock to boost capital levels. Shanghai Pudong and Agricultural Bank each jumped 10% on speculation they will be the first to participate in a trial offering.
- Separately, Ping An Bank gained 10% after announcing plans to raise $2.4B by selling 1.32B shares to parent Ping An Insurance Group. The purchase will raise the parent's stake to 59% from 52.4%.
- Previous: China also boosted by favorable import data.
- China financial ETF: CHIX.
- China ETFs: FXI, GXC, PGJ, YAO, FCHI, PEK, CAF, YXI, XPP, FXP, MCHI, YINN, YANG, TCHI, CHXF, KFYP.
- Chinese banks: BACHY.PK, CICHF.PK, IDCBF.PK, CIHHF.PK.
Aug. 27, 2012, 7:14 AMInvestors are having nothing of China Construction Bank's "beat" of earnings expectations, instead more concerned with where non-performing loans are headed. The ratio fell to 1% in Q2 from 1.4% in March, but the bank says its "unrealistic" to expect further declines. You think? Of 47 business owners disappearing this year, 17 were CCB customers. | 1 Comment
Jul. 2, 2012, 4:15 AMChinese banks accounted for almost a third of global bank profit last year, up from just 4% in 2007. Much of the gains came at the expense of European peers who bled marketshare. Leading the profit tables: ICBC with pretax earnings of $43.2B, China Construction Bank with $34.8B, and Bank of China with $26.8B. JPMorgan (JPM) and HSBC (HBC) took fourth and fifth place. | 1 Comment
Jun. 13, 2012, 9:55 AMLast week's PBOC rate cut looks like a step to ending Chinese banks' comfy 3-6-3 arrangement (borrow at 3%, lend at 6%, golf course by 3). A major step towards a market-oriented interest rate regime, the central bank now allows lenders to offer up to a 20% discount from the state-mandated rate, a move expected to shave cushy profit margins. | Comment!
Jun. 7, 2012, 2:35 AMChina delays tightening bank capital rules until next year, with new draft rules from the China Banking Regulatory Commission that seek to set "reasonable" schedules for banks to meet capital targets in a way that helps "maintain appropriate credit growth." Shares of Chinese banks climbed. | Comment!
Apr. 12, 2012, 8:45 AMJim Chanos brushes off chatter about the large Chinese banks being broken up, calling them "arms of state policy. They loan because the local party official ... tells them we need a new stadium ... I really doubt the party is going to give up a lever of power." (Chanos earlier on "the party.") | Comment!
Apr. 5, 2012, 11:10 AM"China's banks (aren't) really the villains here," writes Patrick Chovanec, responding to Premier Wen's comments about their monopoly power. "They are creatures of the State; they do what they are told and incentivized to do," - that is lend, without counting the cost, for projects that "carry the imprimatur (and implicit guarantee) of the Mother State." | 1 Comment
Apr. 4, 2012, 7:54 AM"The Chinese government has said similar things for many, many years," without following up with action, says Victor Shih, reacting to yesterday's comments from Premier Wen about breaking up the big bank cartel (there, not here) and liberalizing the financial sector. | Comment!
Apr. 3, 2012, 12:21 PMChina's large banks are able to make profits "too easily," says Premier Wen Jiabao, calling for the monopoly posed by the country's giant lenders to be broken. | Comment!
Mar. 21, 2012, 9:31 AMChina's biggest banks are expected to post solid profits when they report Q4 income later this month, but will also higher non-performing loans for the first time in 3 years. "It's the beginning of a worrisome trend," says an analyst urging investors to cash in profits following a 42% rise in bank shares over the last 5 months. | Comment!
Feb. 21, 2012, 8:03 AM"The notion that Chinese banks have 1% non-performing loans is patently ridiculous," writes Patrick Chovanec of the record annual profits posted by the lenders. "That provisions for 2.5X this amount are somehow 'generous' are equally absurd." Based on the banks' valuations - Industrial Bank (IDCBF.PK) trades at a PE of 6 - investors don't buy it either. | Comment!
Oct. 28, 2011, 10:54 AMChina Construction Bank joins the country's other major lenders, reporting increasing profits in Q3 with strong loan demand and a falling bad debt ratio. Time will tell, but the reports don't square with anecdotal evidence of a lending slowdown and an increase in non-performing loans. China financial ETF: CHIX +26% this month. | Comment!
Oct. 12, 2011, 3:31 PMLate to the party, but still of interest, Sanjay Jain of Credit Suisse is bearish on Chinese banks, figuring their non-performing loans may rise to 8-12% in coming years - completely eradicating their equity. While the banks may look attractive at current P/B ratios, Jain thinks 2012 earnings could be wiped out, making the "cheap" valuation not so. | Comment!
Oct. 11, 2011, 11:30 AM"The government stepping in to shore up the banks, when two months ago people thought there was nothing wrong with the Chinese banks, should tell you just how seriously this situation is deteriorating," says Jim Chanos. "The property market is what investors ought to be watching ... (and it's in the) first parts of a very serious pullback." | 2 Comments
Oct. 11, 2011, 10:16 AMPatrick Chovanec sees China's buying of bank shares as a "head fake," a preemptive move to stop a crash and make it easier for the lenders to raise capital. He quotes Vitaliy Katsenelson: "China's SWF is not Warren Buffett... when he's buying BRK.A, he actually thinks it's undervalued. China (is) just trying to create confidence." | Comment!
CICHF vs. ETF Alternatives
Company Description
Currently, there's no company description for CICHF.
Sector: Financial
Industry: Money Center Banks
Country: China
Other News & PR
See More »


text:
Finally Some Real Evolution
I was reading the latest issue of Shonen Jump (May 2009), and though I may despise it, I do read …Read the Rest
I was reading the latest issue of Shonen Jump (May 2009), and though I may despise it, I do read …Read the Rest
John Jakala found the Inuyasha VizBig Edition on Amazon and noticed something that I didn't see on Simon and Schuster; …Read the Rest
Wizard has announced that it's ending the publication of its Anime magazine, Anime Insider. This neither surprises me nor bothers …Read the Rest
Viz has been a great supporter of manga in the US. They were among the first companies to bring translated …Read the Rest
Yes the economy is bad, but tax refunds are going out (got my Fed already), so Bookcloseouts.com is ready with …Read the Rest
Anime News Network has an article about Viz Media having to restructure and layoff some employees in this difficult economy. …Read the Rest
A week or so ago, I wrote about trading manga and the website Mangatude. While, as some have mentioned, this …Read the Rest
Found via AiCN. Gia of Anime Vice has put together a collection of fanart pictures of the Doctor, manga style. …Read the Rest
Just a few comments about this month's Previews catalog: Marvel/Del Rey collaboration: I have two words for the Wolverine manga; …Read the Rest
Want to know why the Japanese model of selling anthologies without back issues won't work in the US? This ebay …Read the Rest
I guess Viz has faith in their chapter books line. In the Naruto line, they already have 4 books out …Read the Rest
I'm glad Yen Press chose to go the anthology route and put out a magazine. Anthologies are probably the best …Read the Rest


text:
Welcome to the Lake of Ill Omen. Would you like an Iksar-kabob?
Lots of Conan Love.
With the San Francisco event out of the way, there is a horde of Conan love being thrown around the Internet. This time around, CVG has dropped their Age of Conan preview onto their site for all to see. Although many general facts are displayed, their are a number of interesting elements that can be drawn from the CVG preview, including some facts on player vs. character skill.
Disemboweling and beheadings are only months away.
A brief preview of AoC has gone live at 1up.com. Although short, the preview does include the previewers initial thoughts on the Age of Conan combat system and the gritty, hands-on feeling that they were left with.
Enjoyed in French or English!
EQ2 Mondes Persistants, the French-speaking EQ2 fansite, has posted an interview with Emily Taylor, one of the newest tradeskill developers at SOE. While she may be new, Emily certainly isn't without her fair share of knowledge about the game or the tradeskill that she is currently working on.
By Crom!
IGN.com has whipped up a preview of Funcom's upcoming MMOG, Age of Conan: Hyborian Adventures, and they've relayed a bit of information regarding the first few levels of play and their thoughts on the aggressive combat system. Get your Crom on and enjoy some AoC info!
City of Heroes/Villains Lead Designer Matt Miller Interviewed at Cryptic Studios
As the team behind City of Heroes / City of Villains prepares to launch its tenth free expansion, we spoke with Lead Designer Matt Miller and a handful of the crew on-site at Cryptic Studios in Los Gatos, California last week about Issue 10: Invasion and, in general, what it takes to keep a subscription game fresh and compelling long after the release date.
WarCry: The complication and difficulty of getting keyed and attuned for many instances has risen quite a bit. What is the reason for increasing the complication for attunements and keys?
© Copyright 2000 - 2014 Master Games International. All other trademarks are the property of their respective owners.
Contact Us | Advertise With Us | About Us | Privacy Policy | Legal


text:
I am excited to share with you our Interior Trends talk from this years May Design Series, featuring myself, Heart Home Magazine and Kate Watson-Smyth. Make yourself a coffee, grab a pen and take note as you find out what's hot and what's not…!
I am excited to share with you our Interior Trends talk from this years May Design Series, featuring myself, Heart Home Magazine and Kate Watson-Smyth. Make yourself a coffee, grab a pen and take note as you find out what's hot and what's not…!
On June 16th, 2011 by Pippa Jameson.
Hi Pippa,
Wow, what a great service, thanks!
we are knocking a wall down between our tiny kitchen and dining room. we are doing a white kitchen with a light grey tile floor and there will be a peninsula between the kitchen and dining room. We have decided to install bifold doors in the dining room that open up onto our deck. It has an oak floor. I am trying to decide what colour to choose for the doors. I like white windows because I love how they fade out when the sun shines in but in all the pictures I have seen of the doors in white aluminum look kind of cheap. You can still see some of the darker coloured hardware showing through. I also don't want white on the outside of the house since the brick is mostly brown and black. I can do two different colours. I was thinking of black on the inside frame but I am worried it will close the room in. It is about 3mx4m. The doors will be about 2.5 m high. Do you have any recommendations on colour? also do you think there should be a transom?
Here is the room now. the doors will be where the window is:
Hi Jane,
Thanks for your email.
The dining room looks very pretty and I think the doors will look great.
With regards to the colour, I am not sure that black would be the right option; I think it would look too strong and harsh against the clean white units. I appreciate that the doors need to work tonely inside and out and so taking into consideration the colours of the brick on the outside of your house, I would opt for slate grey doors.
Slate Grey is a smart, striking and sophisticated colour that works fantastically well within a neutral colour scheme. From the inside, the colour will tone with your white modern units and contemporary decor and create a beautiful framed picture of the garden. I would recommend you buy a few coordinating accessories to sync the look even more such as a slate grey vase for your flowers/plant or perhaps a table runner that incorporates the colour as visually, this would sit in the centre of the doors.
From the outside, the colour will balance well against the natural earthy tones of the brick. You can then introduce a few accessories for outside such as large slate or aluminium planters to match the door colour and marry all of the elements. UK based paint company Farrow & Ball sell a beautiful range that should inspire you.
I have created a little moodboard for you to look at (below)
I hope this helps!
Best wishes,
Thank you so much Pippa! I think the rich grey is a wonderful solution, the mood board is fabulous. Your new service is great and I will be sure to check in with my next design dilemma! I am off to have a look at the colour samples.
For all of your interior design questions, please email: email@example.com


text:
Outsourcing Guide
Cont. Education
Training Courses
Web Seminars
Buyer's Guide
Home Page
Pharm Patents
Pharm News
Federal Register
Pharm Stocks
FDA Links
FDA Warning Letters
FDA Doc/cGMP
Pharm/Biotech Events
Newsletter Subscription
Web Links
Site Map
Title: cDNAs and proteins
involved in hypoxia, circadian and orphan signal transduction pathways,
and methods of use
United States Patent: 7,105,647
Issued: September 12, 2006
Inventors: Bradfield;
Christopher A. (Madison, WI), Gu; Yi Zhong (Sunnyvale, CA), Hogenesch;
John B. (San Diego, CA)
Assignee: Wisconsin Alumni
Research Foundation (Madison, WI)
Appl. No.:
Filed: November 27, 1998
PCT Filed: November 27,
PCT No.: PCT/US98/25314
371(c)(1),(2),(4) Date:
July 24, 2000
PCT Pub. No.: WO99/28464
PCT Pub. Date: June 10,
Woodbury College's
Master of Science in Law
The present invention provides isolated
nucleic acids and proteins that are new and distinct members of the bHLH-PAS
superfamily of transcription regulators. These "MOPs" (members of PAS) are
useful in a variety of research, diagnostic and therapeutic applications.
Several of the MOPs of the present invention are .alpha.-class
hypoxia-inducible factors. Several other of the MOPs of the invention are
involved in circadian signal transduction.
Characterization of MOPS 1 9
Our hypothesis in accordance with the present invention was that
additional bHLH-PAS proteins are encoded in the mammalian genome and that
some of these proteins are involved in mediating the pleiotropic response
to potent AHR agonists like TCDD. It has been observed that other bHLH
superfamilies employ multiple dimeric partnerships to control complex
biological processes, such as myogenesis (MyoD/myogenin), cellular
proliferation (Myc, Max, Mad) and neurogenesis (achaete-scute/daughterless).
The observation that bHLH proteins often restrict their dimerization to
within members of the same gene family (i.e., "homotypic interactions")
and that this restriction may occur as the result of constraints imposed
by both primary (e.g., bHLH) and secondary dimerization surfaces (e.g.,
leucine zippers and PAS), prompted us to screen for additional bHLH-PAS
proteins and test each protein for its capacity to interact with either
the AHR or ARNT. The ultimate objective was to identify MOPs that were
physiologically relevant partners of either the AHR or ARNT in vivo. Our
prediction was that such proteins might respond to or modulate the AHR
signaling pathway or other signaling pathways involving ARNT.
To rapidly identify expressed genes, the "expressed sequence tag" (EST)
approach was developed, whereby a cDNA library is constructed and randomly
selected clones are sequenced from both vector arms (Adams et al., Science
252: 1651 1656, 1991). These partial sequences, generally 200 400 bp, are
deposited in a number of computer databases that can be readily analyzed
using a variety of search algorithms. As of 1996, the I.M.A.G.E.
Consortium has deposited over 300,000 human ESTs, generated from different
tissues and developmental time periods into publicly accessible databases,
identifying approximately 40,000 unique cDNA clones (Lennon et al.,
Genomics 33: 151 152, 1996). The availability of these sequences and
plasmids harboring their corresponding cDNA clones provided a means by
which to identify novel members of the bHLH-PAS family by nucleotide
homology screening of available EST databases.
At the time this invention was initiated, the human AHR and ARNT and the
drosophila SIM and PER were the only PAS protein that had been described.
Therefore, we used the nucleotide sequences encoding their PAS domains as
query sequences in BLASTN searches of the available EST databases. Using
this strategy in an iterative fashion and confirming each hit with a
reverse BLASTX search, we have identified eight cDNAs referred to herein
as members of the PAS superfamily, or "MOPs". Using PCR, we were able to
obtain the complete ORFs of MOPs 1 4, and extensive but incomplete ORFs of
MOP5. We have also identified four more MOPs, MOPs 6, 7, 8 and 9, and
obtained their complete ORFs.
While MOPs 1 5 were being characterized, Wang and colleagues identified
two factors involved in cellular response to hypoxia, HIF1.alpha. and
HIF1.beta.. These proteins are identical to MOP1 and ARNT, respectively
(Wang et al., Proc. Natl. Acad. Sci. USA 92: 5510 5514, 1995). Thus, of
the nine MOPs we have cloned, seven have not been previously
characterized. For consistency herein, we describe MOP1 extensively, and
describe heretofore undisclosed methods of using MOP1.
The experimental approach taken in accordance with the present invention
has significantly expanded the number of known members of the emerging
bHLH-PAS superfamily of transcriptional regulators. Along with the MOPs
described herein, five additional mammalian bHLH-PAS proteins have been
identified, HIF1.alpha. (MOP1, as described above), SIM1, SIM2, ARNT2, and
SRC-1 (Wang et al., 1995, supra; Hirose et al., Mol. Cell. Biol. 16: 1706
1713, 1996; Fan et al., Mol. Cell. Neurosci. 7: 1 16, 1996; Ema et al.,
Mol. Cell. Biol. 16: 5865 5875, 1996; Chen et al., Nat. Genet. 10: 9 10,
1995; and Kamei et al., Cell 85: 403 414, 1996). To compare amino acid
sequences of these proteins, we performed a CLUSTAL alignment with the
bHLH-PAS domains of MOPs 1 5 and all the known family members using a
PAM250 residue weight table (Higgins & Sharp, Gene (Amst.) 73: 237 244,
1988). The two most related members were MOP1/HIF1.alpha. and MOP2, which
shared 66% identity in the PAS domain. A comparison of these two proteins
reveals only a single amino acid difference in the basic region and 83%
identity in the HLH region. This sequence similarity is in agreement with
our contention (discussed in Example 1) that MOP1/HIF1.alpha. and MOP2
function analogously, interacting with the same heterodimeric partners and
binding similar enhancer sequences in vivo. A comparison of MOP3 and ARNT
and a comparison of MOP5 and SIM reveal 40% and 38% identity in the PAS
domain, respectively. The basic regions of MOP3 and ARNT have only three
substitutions, while the HLH domains share 66% identity, again suggesting
that the two proteins may regulate similar or identical enhancer sequences
(half sites).
A CLUSTAL alignment of the C-termini of MOPs 1 5 and the previously
identified PAS members demonstrated that these regions are not well
conserved (data not shown) (Burbach et al., Proc. Natl. Acad. Sci. USA 89:
8185 8189, 1992). This lack of conservation may indicate that the
C-termini of these genes have divergent functions, or that the functions
harbored in the C-termini can be accomplished by a variety of different
sequences. For example, the C-termini of the AHR, ARNT, and SIM all harbor
potent transactivation domains, yet display little sequence homology.
To characterize the evolutionary and functional relationships of these
proteins, we performed a parsimony analysis to identify functionally
related subsets. A dendrogram representing the primary amino acid
relationship between the PAS domains of these proteins is illustrated in
FIG. 4 (see Original Patent). This schematic suggests that major groups
exist for eukaryotic PAS family members. The AHR, drSIMILAR,
MOP1/HIF1.alpha., MOP2, drTRACHEALESS, MOP5, and SIM exist in one group,
ARNT, muARNT2, MOP3, and MOP4 in another and PER and huSRC-1 exist in
their own groups. Interestingly, this pattern reflects what is known
functionally about the existing PAS members. The AHR, SIM,
MOP1/HIF1.alpha. and MOP2 have all been shown to heterodimerize with the
ARNT molecule and bind DNA. Additionally, the AHR and SIM are known to
interact with HSP90, a chaperonin protein necessary for the signaling of
the AHR and a number of steroid receptor family members in response to
ligand. Based on these groupings, MOP5 may also be an ARNT-interacting
protein and a candidate for interacting with Hsp90 and being activated by
small molecule ligands. The observation that ARNT has been shown to be
capable of forming DNA binding homodimers and as heterodimers with a
number of previously identified members of the bHLH-PAS family (at least
in vitro), suggests that it plays a role in a number of biological
processes. Based on their similarity with ARNT, MOP3 and MOP4 may be
candidates for binding DNA as homodimers, or for interacting with multiple
bHLH-PAS members, possibly from the AHR group.
In addition to the relevance of the above data to TCDD signaling, they
also reveal additional factors important to cellular responses to hypoxic
stress. HIF1.alpha./MOP1 and MOP2 appear to share a common dimeric
partner--ARNT, and are capable of regulating a common battery of genes.
This notion is supported by three lines of evidence: (1) both MOP1 and
MOP2 interact with ARNT as defined by coimmunoprecipitation or two-hybrid
assay; (2) they have similar DNA half-site specificities when complexed
with ARNT; and (3) they are both transcriptionally active from TACGTG
enhancers in vivo. The observation that HIF1.alpha./MOP1 and MOP2 have
markedly different tissue distributions suggests that these two proteins
may be regulating similar batteries of genes in response to different
environmental stimuli. Alternatively, these proteins may be involved in
restricting expression of certain groups of genes regulated by TACGTG-dependent
enhancers. Finally, it is now known that MOP2 and MOP7 are subunits of a
"HIF1-like" complex (i.e. a "HIF2.alpha." and a "HIF3.alpha.,
respectively) that regulates hypoxia responsive genes in distinct sets of
From the foregoing discussion, it can be seen that, while the MOPs share
certain common features among themselves and with other new members of the
bHLH-PAS superfamily, each of MOPs 2 9 is a distinctive and unique member
of that family. cDNA and deduced amino acid sequences for each of MOPs 1 9
is set forth at the end of this specification. General features of each
MOP are summarized below. In addition, MOPs 1 5 are described in great
detail in Example 1, MOP3 is specifically described in Example 2 and MOP 7
is described in Example 3.
MOP1: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP1 are set forth herein as SEQ ID NOS: 1 and 10, respectively. The cDNA
includes a complete coding sequence for MOP1. As discussed above, MOP1 is
known more commonly in the literature as HIF (Hypoxia-Inducible
Factor)-1.alpha. (Wang et al., 1995, supra). The factor is induced by low
oxygen. It interacts with HSP90 and with ARNT (AHR's binding partner). The
ARNT-dimerized factor regulates expression of erythropoietin, among other
MOP2: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP2 are set forth herein as SEQ ID NOS: 2 and 11, respectively. The cDNA
includes a complete coding sequence for MOP2. MOP2 appears to be related
structurally and functionally to MOP1. Similar to MOP1, MOP2 interacts
with ARNT, but not AHR, and drives transcription in its ARNT-dimerized
form. Unlike MOP1, MOP2 does not appear to interact significantly with
HSP90. MOP2 is induced by low oxygen and may be involved in hypoxia
responses in different cells and tissues than is MOP1. MOP2 is sometimes
referred to herein as HIF2.alpha..
MOP3: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP3 are set forth herein as SEQ ID NOS: 3 and 12, respectively. The cDNA
includes a complete coding sequence for MOP3. MOP 3 and MOP 4 are related
to each other as binding partners, analogous to ARNT and AHR,
respectively. As described in greater detail in Example 2, in addition to
being a specific partner for MOP4, MOP3 is a general dimerization partner
for a subset of the bHLH/PAS superfamily of transcriptional regulators.
MOP3 interacts with MOP4, CLOCK, HIF1.alpha. and HIF2.alpha.. The
MOP3-MOP4 heterodimer binds a CACGTGA-containing DNA element. Moreover,
MOP3-MOP4 and MOP3-CLOCK complexes bind this element in COS-1 cells and
drive transcription from a linked luciferase reporter gene. A
high-affinity DNA binding site has also been deduced for a
MOP3-HIF1.alpha. complex (TACGTGA). MOP3-HIF1.alpha. and MOP3-HIF2.alpha.
heterodimers bind this element, drive transcription, and respond to
cellular hypoxia.
MOP3 also binds HSP90, and may be conditionally activated (like AHR)
depending on whether it is bound to HSP90 (see Example 1) (of the
MOP3/MOP4 dimerization pair, one appears to be conditionally activated,
but as yet it is unclear which one). Evidence from Drosophila and rat
suggest that MOP3 (cycle/bMAL1b) is regulated in a circadian manner.
MOP3 expression appears to be controlled by alternate 5' promoter regions.
MOP3 mRNA expression overlaps in a number of tissues with each of its four
potential partner molecules in vivo.
MOP4: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP4 are set forth herein as SEQ ID NOS: 4 and 13, respectively. The cDNA
includes an apparently complete coding sequence for MOP4. MOP4 appears to
be a human ortholog of a recently identified murine gene called "Clock",
for its involvement in circadian rhythms (King et al., Cell 89: 641 653).
MOP4 also interacts with HSP90 and, as discussed above, is the
dimerization partner of MOP3, and may be conditionally activated. MOP4
appears to be localized in the cytoplasm.
MOP5: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP5 are set forth herein as SEQ ID NOS: 5 and 14, respectively. The cDNA
includes a partial coding sequence for MOP5; however a complete coding
sequence for MOP5 has become publicly available subsequent to the making
of the present invention (GenBank Accession No. U77968, submitted Nov. 11,
1996, published Jan. 21, 1997 by Zhou et al., Proc. Natl. Acad. Sci. USA
94: 713 718).
MOP6: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP6 (of human origin) are set forth herein as SEQ ID NOS: 6 and 15,
respectively. The cDNA includes a complete coding sequence for MOP6. The
nucleotide sequence of MOP6 is fairly unique. It is most similar in the 5'
region to the bHLH-PAS member trachealess, which suggests that MOP6 may be
a regulator (developmental or otherwise) of hypoxia. Functional data shows
that MOP6 forms a partnership with ARNT and drives a hypoxia responsive
MOP7: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP7 are set forth herein as SEQ ID NOS: 7 and 16, respectively. The cDNA
includes a complete coding sequence for MOP7. In accordance with this
invention, MOP7 has been characterized as a new hypoxia-inducible factor,
and therefore is sometimes referred to herein as HIF3.alpha.. The
expression profile of MOP7 is as follows: testis, thymus>[lung, brain,
heart, liver, skeletal muscle]>[skin, stomach, small intestine, kidney].
This expression profile is distinct from any of MOP1, MOP2, MOP3, AHR and
ARNT, suggesting a different functional role for MOP7. MOP7 is most
closely related to MOP1/HIF1.alpha. and MOP2 (HIF2.alpha.), as described
in greater detail in Example 3. Accordingly, MOP7 is likely to regulate
the same genes as does HIF1.alpha. and HIF2.alpha., as evidenced by its
dimerization with the same partners (ARNT, MOP3) and recognition of the
same core response element. This, combined with the unique tissue-specific
expression of MOP7 suggests that it may have a functional role associated
with response to low oxygen in the tissues in which it is expressed.
MOP8: The nucleotide and deduced amino acid sequences of a cDNA encoding
MOP8 are set forth herein as SEQ ID NOS: 8 and 17, respectively. The cDNA
includes a complete coding sequence for MOP8. Like MOP4 and MOP3, MOP8 may
be involved in regulation of circadian rhythm. MOP8 shows sequence
similarity to other genes involved in the circadian pathway (human PER,
Drosophila PER, human RIGUI).
MOP9: The nucleotide and deduced amino acid sequence of a cDNA encoding
MOP9 are set forth herein as SEQ ID NOS: 9 and 18, respectively. Two ESTs
(GenBank AA577389, AA576971) corresponding to a novel bHLH-PAS protein
homologous to MOP3/bMAL1 were identified by TBLASTN searches of the
Drosophila homolog of MOP3. Upon characterization, these clones were
revealed to be truncated, and one of which appeared to be a splice
variant. The cDNA was cloned from human brain mRNA, and alternative 5'
splicing was found probably reflecting multiple promoters. A BLASTX search
of the MOP 9 sequence reveals that it displays extended homology to MOP3
(E-154). These data suggest that MOP9 also pairs with CLOCK and MOP4 and
binds an E-box element with flanking region specificity.
Although specific MOP clones are described and exemplified herein, this
invention is intended to encompass nucleic acid sequences and proteins
from humans and other species that are sufficiently similar to be used
interchangeably with the exemplified MOP nucleic acids and proteins for
the purposes described below. It will be appreciated by those skilled in
the art that MOP-encoding nucleic acids from diverse species, and
particularly mammalian species, should possess a sufficient degree of
homology with human MOPs so as to be interchangeably useful in various
applications. The present invention, therefore, is drawn to MOP-encoding
nucleic acids and encoded proteins from any species in which they are
found, preferably to MOPs of mammalian origin, and most preferably to MOPs
of human origin. Additionally, in the same manner that structural homologs
of human MOPs are considered to be within the scope of this invention,
functional homologs are also considered to be within the scope of this
Allelic variants and natural mutants of SEQ ID NOS: 1 9 or 10 17 are
likely to exist within the human genome and within the genomes of other
species. Because such variants are expected to possess certain differences
in nucleotide and amino acid sequence, this invention provides isolated
MOP-encoding nucleic acid molecules having at least about 65% (and
preferably over 75%) sequence homology in the coding region with the
nucleotide sequences set forth as SEQ ID NOS: 1 9 (and, most preferably,
specifically comprising the coding regions of any of SEQ ID NOS: 1 9).
This invention also provides isolated MOPs having at least about 75%
(preferably 85% or greater) sequence homology with the amino acid sequence
of SEQ ID NOS: 10 18. Because of the natural sequence variation likely to
exist among the MOPs and nucleic acids encoding them, one skilled in the
art would expect to find up to about 25 35% nucleotide sequence variation,
while still maintaining the unique properties of the MOPs of the present
invention. Such an expectation is due in part to the degeneracy of the
genetic code, as well as to the known evolutionary success of conservative
amino acid sequence variations, which do not appreciably alter the nature
of the protein. Accordingly, such variants are considered substantially
the same as one another and are included within the scope of the present
For purposes of this invention, the term "substantially the same" refers
to nucleic acid or amino acid sequences having sequence variation that do
not materially affect the nature of the protein. With particular reference
to nucleic acid sequences, the term "substantially the same" is intended
to refer to the coding region and to conserved sequences governing
expression, and refers primarily to degenerate codons encoding the same
amino acid, or alternate codons encoding conservative substitute amino
acids in the encoded polypeptide. With reference to amino acid sequences,
the term "substantially the same" refers generally to conservative
substitutions and/or variations in regions of the polypeptide not involved
in determination of structure or function of the protein. The terms
"percent identity" and "percent similarity" are also used herein in
comparisons among amino acid sequences. These terms are intended to be
defined as they are in the UWGCG sequence analysis program (Devereaux et
al., Nucl. Acids Res. 12: 387 397, 1984), available from the University of
The following description sets forth the general procedures involved in
practicing the present invention. To the extent that specific materials
are mentioned, it is merely for purposes of illustration and is not
intended to limit the invention. Unless otherwise specified, general
cloning procedures, such as those set forth in Sambrook et al., Molecular
Cloning, Cold Spring Harbor Laboratory (1989) (hereinafter "Sambrook et
al.") or Ausubel et al. (eds) Current Protocols in Molecular Biology, John
Wiley & Sons (1998) (hereinafter "Ausubel et al.") are used.
III. Preparation of MOP Nucleic Acid Molecules, MOP Proteins and Anti-MOP
A. Nucleic Acid Molecules
Nucleic acid molecules encoding the MOPs of the invention may be prepared
by two general methods: (1) They may be synthesized from appropriate
nucleotide triphosphates, or (2) they may be isolated from biological
sources. Both methods utilize protocols well known in the art.
The availability of nucleotide sequence information, such as a full length
cDNA having any of SEQ ID NOS: 1 9, enables preparation of an isolated
nucleic acid molecule of the invention by oligonucleotide synthesis.
Synthetic oligonucleotides may be prepared by the phosphoramadite method
employed in the Applied Biosystems 38A DNA Synthesizer or similar devices.
The resultant construct may be purified according to methods known in the
art, such as high performance liquid chromatography (HPLC). Long,
double-stranded polynucleotides, such as a DNA molecule of the present
invention, must be synthesized in stages, due to the size limitations
inherent in current oligonucleotide synthetic methods. Thus, for example,
a several-kilobase double-stranded molecule may be synthesized as several
smaller segments of appropriate complementarity. Complementary segments
thus produced may be annealed such that each segment possesses appropriate
cohesive termini for attachment of an adjacent segment. Adjacent segments
may be ligated by annealing cohesive termini in the presence of DNA ligase
to construct an entire double-stranded molecule. A synthetic DNA molecule
so constructed may then be cloned and amplified in an appropriate vector.
Nucleic acid sequences encoding MOPs may be isolated from appropriate
biological sources using methods known in the art. In a preferred
embodiment, cDNA clones are isolated from libraries of human origin. In an
alternative embodiment, genomic clones encoding MOPs may be isolated.
Alternatively, cDNA or genomic clones encoding MOPs from other species,
preferably mammalian species, may be obtained.
In accordance with the present invention, nucleic acids having the
appropriate level sequence homology with the coding regions of any of
Sequence I.D. Nos. 1 9 may be identified by using hybridization and
washing conditions of appropriate stringency. For example, hybridizations
may be performed, according to the method of Sambrook et al., using a
hybridization solution comprising: 5.times.SSC, 5.times. Denhardt's
reagent, 1.0% SDS, 100 .mu.g/ml denatured, fragmented salmon sperm DNA,
0.05% sodium pyrophosphate and up to 50% formamide. Hybridization is
carried out at 37 42.degree. C. for at least six hours. Following
hybridization, filters are washed as follows: (1) 5 minutes at room
temperature in 2.times.SSC and 1% SDS; (2) 15 minutes at room temperature
in 2.times.SSC and 0.1% SDS; (3) 30 minutes 1 hour at 37.degree. C. in
1.times.SSC and 1% SDS; (4) 2 hours at 42 65.degree. in 1.times.SSC and 1%
SDS, changing the solution every 30 minutes.
One common formula for calculating the stringency conditions required to
achieve hybridization between nucleic acid molecules of a specified
sequence homology (Sambrook et al., 1989): T.sub.m=81.5.degree. C.+16.6Log
[Na+]+0.41(% G+C)-0.63 (% formamide)-600/#bp in duplex As an illustration
of the above formula, using [N+]=[0.368] and 50% formamide, with GC
content of 42% and an average probe size of 200 bases, the T.sub.m is
57.degree. C. The T.sub.m, of a DNA duplex decreases by 1 1.5.degree. C.
with every 1% decrease in homology. Thus, targets with greater than about
75% sequence identity would be observed using a hybridization temperature
of 42.degree. C.
Nucleic acids of the present invention may be maintained as DNA in any
convenient cloning vector. In a preferred embodiment, clones are
maintained in plasmid cloning/expression vector, such as pGEM-T (Promega
Biotech, Madison, Wis.) or pBluescript (Stratagene, La Jolla, Calif.),
either of which is propagated in a suitable E. coli host cell.
MOP nucleic acid molecules of the invention include cDNA, genomic DNA,
RNA, and fragments thereof which may be single- or double-stranded. Thus,
this invention provides oligonucleotides (sense or antisense strands of
DNA or RNA) having sequences capable of hybridizing with at least one
sequence of a nucleic acid molecule of the present invention, such as
selected segments of the cDNA having any of SEQ ID NOS: 1 9. Such
oligonucleotides are useful as probes for detecting MOP genes or mRNA in
test samples of cells, tissue or other biological sources, e.g. by PCR
amplification, or for the positive or negative regulation of expression of
MOP genes at or before translation of the mRNA into proteins.
B. Proteins
MOP proteins of the present invention may be prepared in a variety of
ways, according to known methods. The proteins may be purified from
appropriate sources, e.g., cultured or intact cells or tissues.
Alternatively, the availability of nucleic acids molecules encoding MOPs
enables production of the MOP proteins using in vitro expression methods
known in the art. For example, a cDNA or gene may be cloned into an
appropriate in vitro transcription vector, such a pSP64 or pSP65 for in
vitro transcription, followed by cell-free translation in a suitable
cell-free translation system, such as wheat germ or rabbit reticulocytes.
In vitro transcription and translation systems are commercially available,
e.g., from Promega Biotech, Madison, Wis. or BRL, Rockville, Md.
According to a preferred embodiment, larger quantities of MOP proteins may
be produced by expression in a suitable procaryotic or eucaryotic system.
For example, part or all of a DNA molecule, such as any of the cDNAs
having SEQ ID NOS: 1 9, may be inserted into a plasmid vector adapted for
expression in a bacterial cell (such as E. coli) or a yeast cell (such as
Saccharomyces cerevisiae), or into a baculovirus vector for expression in
an insect cell. Such vectors comprise the regulatory elements necessary
for expression of the DNA in the host cell, positioned in such a manner as
to permit expression of the DNA in the host cell. Such regulatory elements
required for expression include promoter sequences, transcription
initiation sequences and, optionally, enhancer sequences.
The MOPs produced by gene expression in a recombinant procaryotic or
eucyarotic system may be purified according to methods known in the art.
In a preferred embodiment, a commercially available expression/secretion
system can be used, whereby the recombinant protein is expressed and
thereafter secreted from the host cell, to be easily purified from the
surrounding medium. If expression/secretion vectors are not used, an
alternative approach involves purifying the recombinant protein by
affinity separation, such as by immunological interaction with antibodies
that bind specifically to the recombinant protein. Such methods are
commonly used by skilled practitioners. The MOP proteins of the invention,
prepared by the aforementioned methods, may be analyzed according to
standard procedures.
The present invention also provides antibodies capable of
immunospecifically binding to MOP proteins of the invention. Polyclonal or
monoclonal antibodies directed toward any of MOPs 1 9 may be prepared
according to standard methods. Monoclonal antibodies may be prepared
according to general methods of Kohler and Milstein, following standard
protocols. In a preferred embodiment, antibodies have been prepared, which
react immunospecifically with various epitopes of the MOPs.
Polyclonal or monoclonal antibodies that immunospecifically interact with
MOPs can be utilized for identifying and purifying such proteins. For
example, antibodies may be utilized for affinity separation of proteins
with which they immunospecifically interact. Antibodies may also be used
to immunoprecipitate proteins from a sample containing a mixture of
proteins and other biological molecules. Other uses of anti-MOP antibodies
are described below.
IV. Uses of MOP-Encoding Nucleic Acids, MOP Proteins and Anti-MOP
A. MOP-Encoding Nucleic Acids
MOP-encoding nucleic acids may be used for a variety of purposes in
accordance with the present invention. MOP-encoding DNA, RNA, or fragments
thereof may be used as probes to detect the presence of and/or expression
of genes encoding MOPs. Methods in which MOP-encoding nucleic acids may be
utilized as probes for such assays include, but are not limited to: (1) in
situ hybridization; (2) Southern hybridization (3) northern hybridization;
and (4) assorted amplification reactions such as polymerase chain
reactions (PCR). In addition, recombinant cellular assay systems to
examine signal transduction pathways in which the MOPs are involved are
described below.
The MOP-encoding nucleic acids of the invention may also be utilized as
probes to identify related genes either from humans or from other species.
As is well known in the art, hybridization stringencies may be adjusted to
allow hybridization of nucleic acid probes with complementary sequences of
varying degrees of homology. Thus, MOP-encoding nucleic acids may be used
to advantage to identify and characterize other genes of varying degrees
of relation to the respective MOPs, thereby enabling further
characterization the AHR or related signaling cascades. Additionally, they
may be used to identify genes encoding proteins that interact with MOPs
(e.g., by the "interaction trap" technique, or modifications thereof, as
described in Example 1), which should further accelerate elucidation of
these cellular signaling mechanisms.
Nucleic acid molecules, or fragments thereof, encoding MOPs may also be
utilized to control the production of the various MOPs, thereby regulating
the amount of protein available to participate in cellular signaling
pathways. In one embodiment, the nucleic acid molecules of the invention
may be used to decrease expression of certain MOPs in cells. In this
embodiment, full-length antisense molecules are employed which are
targeted to respective MOP genes or RNAs, or antisense oligonucleotides,
targeted to specific regions of MOP-encoding genes that are critical for
gene expression, are used. The use of antisense molecules to decrease
expression levels of a pre-determined gene is known in the art. In a
preferred embodiment, antisense oligonucleotides are modified in various
ways to increase their stability and membrane permeability, so as to
maximize their effective delivery to target cells in vitro and in vivo.
Such modifications include the preparation of phosphorothioate or
methylphosphonate derivatives, among many others, according to procedures
known in the art.
In another embodiment, the transcription regulation activity of bHLH-PAS
homodimers or heterodimers involving MOPs may be blocked by genetically
engineering a target cell to express a defective MOP--specifically one
that has been modified to be unable to bind DNA. When the defective MOP
dimerizes, the dimer is also unable to bind DNA, and therefore is unable
to carry out its transcriptional regulatory function.
In another embodiment, overexpression of various MOPs is induced, which
can lead to overproduction of a selected MOP. Overproduction of MOPs may
facilitate the isolation and characterization of other components involved
in protein--protein complex formation occurring during the MOP-related
signal transduction in cells.
As described above, MOP-encoding nucleic acids are also used to advantage
to produce large quantities of substantially pure MOP proteins, or
selected portions thereof.
B. MOP Proteins and Anti-MOP Antibodies
Purified MOPs, or fragments thereof, may be used to produce polyclonal or
monoclonal antibodies which also may serve as sensitive detection reagents
for the presence and accumulation of MOPs (or complexes containing the
MOPS) in cultured cells or tissues or in intact organisms. Recombinant
techniques enable expression of fusion proteins containing part or all of
a selected MOP protein. The full length protein or fragments of the
protein may be used to advantage to generate an array of monoclonal or
polyclonal antibodies specific for various epitopes of the protein,
thereby providing even greater sensitivity for detection of the protein in
cells or tissue.
Polyclonal or monoclonal antibodies immunologically specific for a MOP may
be used in a variety of assays designed to detect and quantitate the
protein. Such assays include, but are not limited to: (1) flow cytometric
analysis; (2) immunochemical localization of a MOP in cells or tissues;
and (3) immunoblot analysis (e.g., dot blot, Western blot) of extracts
from various cells and tissues. Additionally, as described above, anti-MOPs
can be used for purification of MOPs (e.g., affinity column purification,
C. Recombinant Cells and Assay Systems
Genetically engineered cells, such as yeast cells or mammalian cells, may
be produced to express any one, or a combination, of MOPs described
herein. Such cells can be used to evaluate the binding interactions
between MOPs, or between a MOP and another member of the bHLH-PAS
superfamily (e.g., AHR, ARNT), and the requirement for homodimerization or
heterodimerization of the MOPs for initiation of transcriptional control
of a reporter gene driven by appropriate enhancer elements. In addition,
such recombinant cells can be used to study the effect of external
stimuli, such as hypoxia or TCDD, on activation of a selected MOP, or they
can be used to screen panels of drugs for control of MOP-involved signal
transduction pathways. U.S. Pat. No. 5,650,283 to Bradfield et al., the
disclosure of which is incorporated herein by reference, describes
recombinant cellular systems and assays for detecting agonists to the AHR.
These materials and methods may be used similarly to design recombinant
systems for evaluating any of MOP1-MOP8, in the presence or absence of an
external stimulant.
Appropriate yeast cells for production of such recombinant systems include
Saccharomyces cerevisiae and Saccharomyces pombe. Yeast strains carrying
endogenous functional HSPs may be utilized (e.g., A303 obtained from Rick
Gaber, Northwestern University, or commercially available equivalents).
Yeast strains in which the genes encoding HSPs have been disrupted may
also be utilized (e.g., GRS4, obtained from Susan Lindquist, University of
Chicago), affording an opportunity to examine the relationship of various
MOPs to HSPs.
Appropriate mammalian cells for production of such recombinant systems
include COS, Hep3b, HepGr and Hepalclc7 cells, among others.
In one type of assay where the MOP signal transduction pathway is affected
by an external stimulus (i.e. an agonist such as TCDD in the AHR-ARNT
system, or cobalt chloride in the MOP1/HIF1.alpha.-ARNT system), an
appropriate cell can be transformed with an expression plasmid expressing
a full length agonist receptor MOP, along with its dimerization partner
(if the MOP forms heterodimers) and a reporter plasmid expressing a
reporter gene, such as LacZ or luciferin, which is driven by an
appropriate enhancer element. The presence or potency of a selected
agonist may be determined by its ability to activate transcription of the
reporter gene in the recombinant system.
In another embodiment, a recombinant system that does not rely on
heterodimerization can be constructed. In this case, a cell is transformed
with an expression plasmid expressing a chimeric agonist-sensitive MOP,
along with a reporter plasmid expressing a reporter gene driven by a
suitable promoter. The chimeric MOP is modified to replace the
heterodimerization domains (i.e. the bHLH-PAS domain) with a DNA binding
domain, such as LexA or Gal4. Such chimeras will homodimerize and activate
transcription of genes positioned downstream of LexA or Gal4 binding sites
engineered into the reporter plasmid.
In a preferred embodiment, described in detail in Example 1 (see Original Patent),
a modified yeast "two hybrid" system is used to assess binding
interactions between MOPs (and other bHLH-PAS proteins) and the subsequent
initiation of transcriptional control. For instance, as described in
Example 1, fusion proteins were constructed in which the DNA binding
domain of the bacterial repressor, LexA, was fused to the bHLH-PAS domains
of the MOP proteins. Interactions were tested by cotransformation of each
LexAMOP construct with either the full length AHR or ARNT into the L40
yeast strain, which harbors an integrated lacZ reporter gene driven by
multiple LexA operator sites. In this system, LexAMOP fusions which
interact with AHR or ARNT drive expression of the lacZ reporter gene. The
effect of various agonists on reporter gene expression can also be
evaluated using this system.
Any one or more of the aforementioned recombinant cell systems and assays
can be used to screen panels of drugs for their effect on specific signal
transduction pathways. For instance, recombinant systems employing any or
MOPs 1, 2, 6 or 7 may be used to screen for drugs that stimulate red blood
cell synthesis, angiogenesis or glucose metabolism.
Recombinant systems employing any of MOPs 3, 4, 8 or 9 may be used to
screen for drugs that modify circadian rhythms. In connection with this
embodiment, as described in greater detail in Example 2 (see Original Patent),
we have determined the binding sequence for the MOP3/MOP4 heterodimer, and
have constructed the following recombinant plasmids: PL833, a MOP3
expression vector for mammalian cells; PL834, a MOP4 expression vector for
mammalian cells; and PL880, a reporter plasmid (expressing luciferase)
driven by the MOP3/MOP4 consensus enhancer sequence GCA_CACGTG_ACC (SEQ ID
NO: 124). When the three plasmids are introduced into a mammalian cell,
the reporter gene responds to the presence of the MOP3/MOP4 dimer. This
system is used in a high throughput microwell assay to screen for
compounds that are specific activators or inhibitors of these
transcription factors. A similar system has been established for MOP7
(HIF3.alpha.), as set forth in Example 3 (see Original Patent).
Claim 1 of 10 Claims
1. An isolated nucleic acid
molecule having a sequence selected from the group consisting of: a) SEQ ID
NO:3; b) a sequence encoding a polypeptide having amino acid SEQ ID NO:12.
If you want to learn more
about this patent, please go directly to the U.S.
Patent and Trademark Office Web site to access the full


text:
|Contact this shelter/rescue group to see their pets for adoption.
Our Featured Washington, IA Partner:
Paws and More Animal Shelter
Dog adoption and cat adoption saves lives. Adopt a dog or adopt a cat and you'll have a friend for life! Contact us, or contact another local humane society, animal shelter or SPCA.
1004 1/2 W. Madison
Washington, IA 52353
(319) 653-6713
Pets at Our Shelter:
Cities, Towns, and/or Counties We Serve:PAWS & More Animal Shelter primarily serves the city of Washington, Iowa, and the rural area surrounding it. The shelter also frequently takes in stray and abandoned animals from the rest of Washington County and counties bordering it, including nearby communities such as Ainsworth, Crawfordsville, Kalona, Richland, Riverside, Wellman, and West Chester.
About Our Shelter:The shelter was established as the Washington County Humane Society Animal Shelter in 1993 as a caring alternative to the local city dog pound. The shelters first home was a small building on the east side of Washington. In July of 1998, the shelter was moved to a much bigger building on the west side of town thanks to a generous donation from a local patron and matching funds raised by local Humane Society members and supporters. The name PAWS & More was chosen in 1999. PAWS & More Animal Shelter is a private, no-kill shelter located in Washington, Iowa. PAWS stands for Providing Animals With Shelter, while More stands for the loving care and treatment we give to every animal who passes through our doors.
Come Meet our Pets:Join us the second Saturday of every month from 11am - 2pm at Petco at 1450 Twixt Town Road (across Collins Road from Lindale Mall) in Marion, IA.
Join us the first Saturday of every month from 11-2 at PetSmart Cedar Rapids (near Lindale/Bed Bath & Beyond) we'll bring some of our wonderful animals.


text:
My Profile
Member since Oct 2012
Flag This ProfileFlag as Inappropriate
Reviewed Horchata
Oct 13, 2012 in Food Network Community Toolbox on FoodNetwork.com
"This is a very easy recipe to make however in the future i would hold or greatly lessen the almond extract. it overpowered the whole drink and anything i tasted for the rest of the day had a strong almond taste to it. ""


text:
- Home
- Magazine
- Historic Sites
- Collections
- Travel
- Authors
- About
- Advertise
Home » Magazine » Contributors » Thomas Fleming
Thomas Fleming
Thomas Fleming, a longtime contributor and former president of the Society of American Historians, recently published the 50th anniversary edition of his Now We Are Enemies: The Story of Bunker Hill (American History Press 2010). Born in Jersey City, NJ, Fleming served in the United States Navy before graduating with honors from Fordham University. He was admitted as an honorary member of The Society of the Cincinnati, and has also appeared on C-SPAN, the History Channel, A&E, and PBS. Thomas Fleming's most recently published book is A Disease in the Public Mind, A New Understanding of Why We Fought the Civil War, to be published by Da Capo Press in May, 2013. He is currently writing Washington Vs Jefferson: The Conflict That Changed America's History.
Articles by this Contributor
September 2001
February/March 2006
How a lying poseur gave America its army
Fall 2008
Steely determination enabled Eddie Rickenbacker, the World I ace pilot and president of Eastern Airlines, to survive drifting across the Pacific in a life raft.
Fall 2009
The Vivacious Sally Fairfax stole the young man's heart long before he met Martha
Winter 2009
Speculators caused a stock market crash in 1792, forcing the federal government to bail out New York bankers— and the nation
Spring 2010
The 70-year-old statesman lived the high life in Paris and pulled off a diplomatic miracle
Fall 2010
An impetuous and sometimes corrupt Congress has often hamstrung the efforts of the president since the earliest days of the Republic
Summer 2009
Spring 2011
Strict codes of conduct marked the relationships of early American Politicians, often leading to duels, brawls, and other—sometimes fatal—violence
- « first
- ‹ previous
- 1
- 2
- 3
- 4
American Heritage is proud to host the
National Portal to
Historic Collections
Recently added:
- American Revolution Center
- National Museum of Civil War Medicine
- National Museum of the U.S. Navy
- Manassas National Battlefield
- Maryland State House
In association with the
American Association for State and Local History
Why do we need a national nonprofit membership society for American history?
"Save America's Treasures" has been totally eliminated—the largest Federal program supporting preservation of such treasures as the original Star Spangled Banner and George Washington's tent.
65% of Americans don't know what happened at the Constitutional Convention, according to a recent survey by Newsweek.
The "Teaching American History" grants—the largest Federal program supporting history education—have been completely eliminated.
Visits to the Top 20 Civil War battlefields have dropped in half from 1970 to 2009 according to official National Park Service statistics.
40% of Americans can't identify whom we fought in World War II, according to a recent survey by Newsweek.
A quarter of Americans believe Congress shares power over U.S. foreign policy with the United Nations, according to a recent Annenberg survey.
"There is little that is more important for an American citizen to know than the history and traditions of his country," John F. Kennedy wrote in American Heritage.
The "We the People Program," which touched some 30 million students and 90,000 teachers over 25 years, has been completely eliminated.
Two-thirds of Americans could not correctly name Yorktown as the last major military action of the American Revolution, according to a recent national Gallup survey.
The National Heritage Areas and Scenic Byways program, the only major Federal program encouraging visits to historic places, has been completely eliminated in Congressional committee.


text:
Kevin reviews Animal Kingdom's annual passholder special event... Discuss it here...
DIRECT ARTICLE LINK: Extra Everest - MiceAge.com
Printable View
Kevin reviews Animal Kingdom's annual passholder special event... Discuss it here...
DIRECT ARTICLE LINK: Extra Everest - MiceAge.com
I am normally a huge fan of Kevin's work. However, this time i must offer a huge "Bad Job". In this day and age, for any company to spend thousands of dollars for a free evening for customers, it is just plain rude to complain that you did not get enough for your free event.
Be thankful that they gave you extra ride time. I know that living here in Texas I would love to have a few free hours of Everest.
I think special thank you to WDW is in order. And Kevin, don't be greedy. It is not becoming.
Otherwise, i love Kevin and his commentary!
Criticism noted, and all due apologies. I was aiming for a balanced reaction here, but it was apparently harder than I thought to simultaneously say thank you and also suggest they could have improved it, too.
I did consider saying merely "thank you" and not offering the feedback they requested. But wouldn't that send the message that they need NOT do more than this in future such events? I do think the event could have been improved (and made profitable, in fact), so I was hoping to find a gentle balance in the review.
I agree with everything that Kevin stated. I could tell he enjoyed the event. He just wants to improve it with minor changes that would increase the guest experience as well as make Disney some money.
Kevin – Thanks for another great article.
We last visit WDW in 2005, so Everest was being build then. But the one thing I never figured out is why do they close DAK so early? Even during the summer months?
When I asked that of a cast member they said it was because of the animals – once it got dark they would be hard so see. Even the San Diego Wild Animal Park (now called San Diego Zoo Safari Park) stays open until at least 7pm, and offers the special over-night experiences for families.
But the animals aside, DAK has plenty more to do in the way of attractions, shows, restaurants, shopping, entertainment, etc…So at least to me they could easily stay open until 9pm or so with evening events not offered during the day. And additionally maybe offer special over-night "experiences" as the SD Safari Park does.
What are your thoughts on this?
Ken Goldenberg
Rancho Santa Margarita, CA
Compared to what Disneyland often offers the special EE 5th Anniversary AP event was lackluster. Of course, it is better than nothing. Adding special pins and t-shirts for the event would up it a notch in terms of specialness for APers at Disneyland East.
However, one big goal of the event was to garner publicity for EE and AK, the story about the special event splashed all over the web and Disney got their $20,000 worth in terms of advertising. After all, EE must be a fantastic ride if APers, who can ride the attraction whenever they want, lined up to ride it during a special event! I don't think that the main goal of the event was to offer APers a reward for buying an annual pass (which is worth it if you are a big Disney fan living within 200 miles of WDW IMHO).
I think WDW management is testing the waters to see if they can whip up enthusiasm among APers and see if they can free advertising in the mix. When they are competing against Harry and friends in Orlando they could use all the attention they can get, even if it is over a 5 year old ride with a broken AA.
The costs from labor are marginal. I would not be concerned about it. The cost for DJs are extra and I don't think it costs much. So Disney didn't do much for this event, whether cost, labor, effort, and any other criteria. It seems to be a do-it-yourself type party.
This is totally wrong. If it is billed as a party to appreciate the passholders, merchandise should be offered for free as a gift. It would be similar to a party favor. They could have offered additional perks like a free photopass. In other words, a party should be treated as a party. At least have some free cake and coffee or juice.Quote:
and offer something for sale.
Agreed on all the constructive criticism you gave at the gate.
However, experiencing these rides in the dark is not ALL that uncommon - remember all of the hotel guests who (until recently) got EMH at night. I for one always made it a point to visit DAK when it was open for that as it takes on a wonderful new personality at night.
Even with the loss of those EMHs at night, I see a ton of 8pm regular closings coming up this Spring - so perhaps all guests will see the park at night very soon.
After reading Kevin's article, maybe Disney should just not do anything.
Last thing WDW needs is to sell more AP's.
WDW should simply absorb the cost of not catering to JKR's demands, and wait out this HP storm (probably about three years). Oh, and improve the parks in the meantime.
While I may disagree with some of Kevin's complaints (burnt out bulb in Canada pavilion), I think that he makes a good point that when Disney goes half-way with a special event it hurts the brand, such as the apparent "declining by degrees" of Mickey's Not So Scary Halloween Party.
Regarding Expedition Everest articles, isn't Kevin going to do a part 2 looking at perhaps the broken Yeti or the poorly disguised backside of EE which greets everybody entering AK's parking lot from a certain angle?
Personally, EE will never be "special" for me like Pirates in Disneyland or even the Matterhorn. The best part is the queue, but the mountain looks unfinished, the back side looks weird, the train track juts up to the top of the mountain at an unatural angle and there aren't any plants on the mountain. I love the Matterhorn with the small pine trees and greenery, . . . Everest just plain looks fake. (Minus when it is seen when approaching it from a certain angle).
Plus, when you get to the top and see Epcot, well, it pretty much ruins the illusion for me.
I think that part of the reason that team Orlando went with a half-baked anniversary party is because how can they celebrate (with a straight face) an "E-Ticket" which has its star actor broken and which has an unifinished look?
I look forward to Kevin's second Everest column (if there is one?)
The Everest photo collection was sent in all at once; I have no idea when/if Al will run the rest. The point to that series wasn't to say Everest is bad; it was to point out that it still has a lot going for it.
The Canada bulb was actually an example of a thing that WASN'T a decline. It was invoked when I was saying that there are lot of maintenance problems I see that I don't report on, because they *do* get fixed.
There are, however, lots of maintenance problems that *are* declines :)
Ban FastPass on Disney rides?
Yes, this would be better for everyone... not just the privileged few (or those in the know).
I think I attended all the AP parties at Disneyland in Anaheim. They were always a $25.00 or so hard ticket event, with special foods, backstage tours (the projection rooms of Circle-Vision!), and chats with Imagineers. I'm surprised that the Everest event was free, it's hard to imagine Disneyland in Anaheim ever offering a free AP party. Frankly, it's hard to imagine them offering an AP party ever again after the Light Magic fiasco. I'd love to have the annual parties back, instead of the disorganized merchandise events that seem to have replaced them.
Great article! I wish they would do something like that here at Disneyland. The closest recent event like this that I can remember is the Haunted Mansion one, but one had to pay to attend. Unfortunately, I didn't get to. I liked this article just for the pictures and description of the event alone, especially since I'm in California and love any Walt Disney World news. I actually liked your criticism. I think criticism is important to building up and maintaining Walt Disney's amazing parks and company to what it once was or what it should be at right now. I think a lot of people have been disappointed by Disney many times in more recent years that they take anything and everything they can get from them and are afraid to criticize and think about or say what could be better. An example of this is with the recent "Princess" movies, Disney's Princess and the Frog and Disney's Tangled. People are just so happy Disney is attempting a classic, fairy-tale type animated movie that they don't point out or get mad at those who do mention that the films aren't as good as Walt Disney's classics, like Walt Disney's Snow White and the Seven Dwarfs or Walt Disney's Sleeping Beauty.


text:
December 19, 2014
PORTLAND, Ore. (AP) - A University of Oregon student who says she was sexually assaulted by three members of the men's basketball team is making her first public statement since the controversy erupted on the Eugene campus.
The unidentified woman, through an attorney, sent an open letter to the Daily Emerald campus newspaper saying the athletic department prioritizes winning over student safety.
The alleged assault happened at the end of the regular season, and university officials allowed two of the players to compete in the NCAA tournament.
Prosecutors ultimately decided there was not enough evidence to charge the players. The players said the sexual contact was consensual.
Copyright 2014 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
Click Here to access the online Public Inspection File
Viewers with disabilities can get assistance accessing this station's FCC Public Inspection File by contacting the station with the information listed below. Questions or concerns relating to the accessibility of the FCC's online public file system should be directed to the FCC at 888-225-5322, 888-835-5322 (TTY), or email@example.com.


text:
Start: 10:00 am
Learning to ride a bike is one of the most important milestones of childhood, and no one captures the emotional ups and downs of the experience better than Chris Raschka, who won the 2012 Caldecott Medal for A Ball for Daisy. In Everyone Can Learn to Ride a Bicycle ($16.99), a simple yet emotionally rich work, a father takes his daughter through all the steps in the process — from choosing the perfect bicycle to that triumphant first successful ride. Using very few words and lots of expressive pictures, here is a picture book that not only shows kids how to learn to ride, but captures what it feels like to fall . . . get up . . . fall again . . . and finally "by luck, grace, and determination" ride a bicycle.Chris Raschka, the 2012 Caldecott Medalist, is an avid bike rider and wrote a 2010 New York Times op-ed piece, "Braking Away," about the importance of obeying the rules of the road while on a bicycle. He has written and/or illustrated over 30 books for children, including the 2012 Caldecott Medal winner A Ball for Daisy, which was also a New York Times Best Illustrated Book and described byThe Horn Book in a starred review as "noteworthy for both its artistry and its child appeal." His other books include the 2006 Caldecott Medal winner, The Hello, Goodbye Window by Norton Juster; the Caldecott Honor Book Yo? Yes!, and the ALA-ALSC Notable Children's Book Good Sports.
Start: 7:00 pm
Priority Seating with Purchase of Why Not? from Book Passage On August 7, 1974, Philippe Petit stepped out on a wire illegally rigged between the New York World Trade Center's twin towers, where he performed for nearly an hour. During this history-making walk, and many others throughout his celebrated career, knots have always been indispensable components--the guardian angels protecting his life in the sky.After years of hands-on research, Philippe presents Why Knot?: How to Tie More Than Sixty Ingenious, Useful, Beautiful, Lifesaving, and Secure Knots! ($19.95), a guide to tying his essential knots. Philippe's own practical sketches illustrate original methods and clear, clever tying instructions. Photographs in which special knots were used during spectacular high-wire walks, quirky knot trivia, personal anecdotes, helpful tips, magic tricks, and special tying challenges ensure that, if you're not already nuts for knots, Petit will transform you into a knot aficionado.


text:
See your orange on these designs right now!
Enter your colors here, then click the icon below any design to preview it in your colors.
Recommended Just For You
Customer Raves & Reviews
Wonderful Invites!
Sunset Silhouette Rectangle Invitations After looking for several weeks I finally found these invites for my destination wedding and they are perfect. I loved how I was able to preview the invite with my wording and colors without having to purchase a sample product first. My mom and I were very pleased with the quality of the paper and how accurate the online color pallet was. My colors are Key Lime, Tropical Blue & Tropical Orange. I used Lime, Ocean & Carrot on the invite and the colors matched perfectly. I've received so many compliments and I couldn't be happier. I would definitely refer magnetStreet to a friend.
Love these!
Hawaiian Sea Turtle Rectangle Invitations I love these invitations! We are getting married in Hawaii, and they are just the right combination of "island" and sophistication. We stuck with the original color combination, and they look great.
Starfish Foldover Pockets The invitations we ordered for our wedding were absolutely perfect. We did not have time to order a sample, so I was really nervous about the quality. The paper is thick and of great quality, and the printing is bright and beautiful! I loved the convenience of being able to work on the invitations and save my work. This allowed me to work on them at my convenience and order them when I was ready. I also had a great customer service experience. I had a small computer problem when ordering the invitations and I called the customer service line and the friendly rep was able to help me right away. I would definitely recommend the pocketfold invitations!
Excellent Wedding Invitations
Starfish Foldover Pockets Our wedding invitations were all that we could ever want. We absolutely love them! The fact that we could make any changes we wanted (including creating our own colour) to our invitations was a great service that magnet street offered. I would encourage any bride or anyone at all that is looking for this type of stationery to choose magnet street..
Stunning Invitations
Starfish Rectangle Invitations I am so happy with the invitations we chose for our wedding. We just received them and I can not wait to show them off. The choices of fonts and colors definitely let us personalize our invitations the way we wanted. We also ordered our RSVP cards, guest information cards, bands, and initial stickers. Our invitation suite is stunning thanks to MagnetStreet!!!


text:
ecoAmerica holds annual leadership summits — one-day, invitation-only conferences — that bring together the brightest and most innovative leaders from diverse sectors within and beyond the movement.
These leaders share their own research, thinking and best practices. They discuss, collaborate and prioritize solutions for the myriad of aspects for connecting with Americans on climate change.
These summits inspire new strategies, plans, and levels of collaboration, and forge fresh alliances with new sectors to engage the hearts and minds of Americans on climate solutions.


text:
WPLG Crew Threatened, Equipment Damaged by Knife Wielding Man
WPLG reporter Ross Palombo and a photographer Shane Walker had a bit of a scare last night while getting ready to go live on Local 10 News at 11. They had set up their live shot right in front of the gated house, on a public street, of a homeowner who had allegedly failed to pay his taxes on time and who became very agitated when he saw the TV crew in front of his house.
It was all caught on camera as the man walked out and threatened Palombo and Walker
Homeowner: I'm gonna ask you to take the camera off me once.
Palombo: Are you threatening me?
Homeowner: I am promising you, that I will rip that thing off your shoulder so quick and beat you down with it.
According to the arrest report Louis Paolino pointed a knife at photojournalist Shane Walker and "threatened to cut his throat". On camera Paolino can be seen damaging equipment with the knife – hitting the spot lights while they were still powered (!) and cutting the camera cables.
Police made no arrests at the time of the incident but Paolino arrived with his lawyer this morning at Fort Lauderdale Police Deparment to turn himself in. He taken into custody and charged with aggravated assault, criminal mischief and grand theft. Damage was estimated to be in excess of $1,400
Check out the video WPLG aired this morning:
Wow! If the guy only knew how few people still watch news on this station he would not even bothered coming out of the house.
He's just mad because 10 demoted Scott and Trent to the weekends.
Channel 10 has improved on their newscast. Did you notice the new music? after twenty years the one and only music has officially retired! I really like that theme and going to miss it but the new music is more miami/south beach which is good. All they need now is a new set and graphics. Like Betty Davis too she has the personality and shows realness with her viewers. Forget about comparing her with Trent this lady knows how to deliver a forecast and is professional. STOP WITH THE HATE!!! So far so good with the changes. They are the best team in this market very strong reporting like wsbtv in atlanta. And impressed with Ross and the new investigates team!
Local 10 is like a Hostess Twinkie, pretty, sweet and fluffy, full of sugar and cream, carbs and fat. No substance or nutritional value.
I think you just described about 90% of local newscasts.
You must have gotten your check in the mail from channel 10 management.
The music doesn't fit, the graphics doesn't fit. Yes it fits Miami, but it doesnt fit the reality of everyone else. It just feels off.
SOUTH FLORIDA must be Betty Davis. She is the only one who thinks " she has the personality and shows realness with her viewers. Forget about comparing her with Trent this lady knows how to deliver a forecast and is professional." Trent Aric dances circles around you and your goofiness. He is a true professional weathercaster that many have trusted for years.


text:
Added May 18, 2013
by Feenambulle
Paris, France
Dark purple gathered skirt with a gold metal zip back.
May 18, 2013, 07.18 PMby Slotaby
So cute! I love the color!
May 18, 2013, 06.12 PMby liliarike
tres jolie!
Add to Favorites 6 people added it
Pattern of the Week
The oversized shape has a cool bell shaped silhouette with a wide body and fitted sleeves
Editor's Pick
Stock up on our favorite BurdaStyle patterns sewn in white!
Web Seminar
Learn How to Sew Knits Successfully With a Sewing Machine
Online Course
Join Meg Healy in this 6 Week Course, we have just re-opened enrollment for a limited time!
Meg's Magazine Mash Up 2014
Take a look at Meg's 2014 Mash Ups, and get the special pattern bundle that includes them all
You must allow our "request for permission" request to login to Burdastyle with Facebook.


text:
Abu Dhabi-based Waha Capital plans to raise a $700m loan mainly to refinance existing debt, Reuters has reported, citing three banking sources aware of the matter. The investment firm, in which Abu Dhabi government investment fund Mubadala owns 16%, has selected HSBC Holdings and First Gulf Bank to help arrange the five-year loan, the sources said. Most of the cash will be used to refinance a $505m debt facility maturing in June, with the remainder to be used by the company for corporate purposes, two of the sources said.
All News Jan 30 2014
Thursday, January 30- 2014 @ 8:52 UAE local time (GMT+4) Replication or redistribution in whole or in part is expressly prohibited without the prior written consent of Mediaquest FZ LLC.


text:
Sunday, December 21, 2014
Follow us:
A police spokesperson said around 8 a.m.a caller reported finding a dead body in a wooded area off of Braker Lane, just east of Interstate 35.
The Austin Police Search and Rescue Team, a team made of volunteers, were called to the scene and found the body of an elderly man.
APD's Homicide unit is investigating, as is the standard procedure when dead bodies are found in public.
The police spokesperson said no other details were available at this time.
Reproduction in whole or in part without permission is prohibited.
© 1999-2014 Time Warner Cable Enterprises LLC. All Rights Reserved.
Web design and web development by Tipit.


text:
im a teenager and i really love to bake.i'd like to make some cute cupcakes and sell them at local craft shows or maybe have it where people can order them for parties or something.can i do this without a license or certificate from the health dept. or do i need one?thanks in advance!!
post #1 of 2
10/8/08 at 2:02pm
Thread Starter


text:
Guaranteed by Christmas Eve, just choose NEXT DAY AIR when checking out!
Maglite Flashlights
Maglite is a name synonymous with contemporary design and excellence in use. A known brand in the USA and across the world, Maglite stands for innovation and old fashioned American values. Add to that our expert laser etching technology and you know you have a winner. Enjoy the artfully engraved messages across your Maglite products and stand out from the crowd. Be it the Mini Mags, LED or the ever popular Maglite gifts set, you know you can�t go wrong with a Maglite!


text:
Comment: Re:What? (Score 3, Informative) 428
Anything not forbidden to the Federal Government by the Constitution is allowed, assuming the appropriate laws are passed.
Uhh, no. Rather it is quite the opposite.
"The powers not delegated to the United States by the Constitution, nor prohibited by it to the states, are reserved to the states respectively, or to the people." http://www.law.cornell.edu/con...
Limited government, and explicitly so at the Federal level


text:
Showing 1-24 of 35 items found in Events
Paddock Hills Equestrian Center
Imagine a golden ball of Midwestern sun breaking on the horizon. As the night dew still clings to the vines and the grass in the pastures, a farm comes to life with the sights and sounds of morning. Hot coffee steeps in the pot. Hard-working farm-hands begin the daily chores. Horses whinny as the cool rush of morning air fills their lungs. The gently rolling hills are aglow with another new day. This is the beauty of horses and the magic of a vineyard. Paddock Hills Equestrian Center is located with Prairie Orchard Farm vineyard in the majestic countryside of Union, IL, and is minutes from the I-90 expressway, but miles away from the hustle and bustle of the city and suburbs. Whether, attending one of our many horse shows, riding lessons, clinics, or programs, we are sure that your time with us will be well spent.
CITY: Union
Vernon Hills Summer Celebration 2015
Join us for 4 days of food, fun, carnival rides and free entertainment and a huge beer tent. There will also be children's activities, bingo, live bands every night and fireworks on Thursday. Friday night enjoy Modern Day Romeos and Mike & Joe. Saturday Bella Cain and headliner Lonestar will perform along with a car show from 9am-2pm. Sunday enjoy a bags tourny and the music of Kaleidoscope Eyes. Please visit the website for updated entertainment schedule. Bring a blanket but leave the coolers home; no alcohol can be brought into the park.
CITY: Vernon Hills
Tough Mudder
Tough Mudder events are hardcore obstacle courses designed to test your all around strength, stamina, mental grit and camaraderie. With the most innovative courses, over one million inspiring participants worldwide to date, and more than $5 million raised for the Wounded Warrior Project, Tough Mudder is the premier adventure challenge series in the world. But Tough Mudder is more than an event; it's a way of thinking. By running a Tough Mudder challenge, you'll unlock a true sense of accomplishment, have a great time and discover camaraderie with your fellow participants that's experienced all too rarely these days.
CITY: Richmond
Winter Wonderland Holiday Light Show
A Lake County holiday tradition. Visit Northern Illinois' largest drive-through Holiday Light Festival, held at the Cuneo Mansion, and view thousands of twinkling lights, animated displays and holiday decorations. While visiting the light show, the Cuneo Mansion & Gardens invites you to walk through the museum for a magical view of Christmas' past. Please visit the website for more information.
CITY: Vernon Hills
Tempel Lipizzan's 2015 Performances
Witness artistry and history come to life as the Tempel Lipizzan stallions enchant audiences with their power, intelligence and grace. From the play of newborn foals to the leaps of athletic stallions, the Tempel Lipizzans are an experience for the entire family. This unique performance set to music has become a Lake County favorite. Save and buy tickets in advance. Come early and enjoy a lunch or dinner in the cafe. Please visit the website for performance schedule.
CITY: Wadsworth
87th Annual Lake County Fair
Come out and enjoy 5 days of fun at the 87th Annual Lake County Fair. Events at the fair include live entertainment, food vendors, carnival rides and games, live animals, motor crossing, banana derby, demolition derby, flower show, expo hall and so much more. Please visit the website for updated information.
CITY: Grayslake
Woodstock Groundhog Days
In 1992, something astonishing happened in the historic city of Woodstock, Illinois. People came to town and roped off the picturesque city square, moved all sorts of equipment into the park and started playing the Pennsylvania Polka, over and over and over again. They were filming a movie that has become a favorite of young and old for more than 20 years, and the city gathers each year to remember the fun and celebrate the special community that Woodstock has always been. There are events for everyone during this celebration: Groundhog trivia, free viewing of "Groundhog Day" at the movie theater, walking tours of the film sites, a Chili cook-off, a dinner and dance, bowling, and pancake breakfasts. The main event for Groundhog Day is the annual prognostication. Gather on the Woodstock Square to see Woodstock Willie emerge from his tree trunk home. If he sees his shadow, it means there will be 6 more weeks of winter and if he doesn't see his shadow, it means we will have an early Spring.
CITY: Woodstock
Dicken's Holiday Village
Olde England comes alive in Historic Downtown Antioch with lifelike figures representing scenes from the Dickens Era. Experience this public art exhibit while strolling among the delight streets of Antioch. Enjoy the charm of Dickens among the many boutiques, gift shops and eateries. Also enjoy special Saturday Dickens activities.
CITY: Antioch
Antioch's Taste of Summer Festival
4 Days of fun in Downtown Antioch. Carnival rides, delectable foods, and top entertainment. Enjoy live music, Antioch IDOL and kids activities. Enjoy the sidewalk sales and find craft booths too. Visit AntiochChamber.org for an updated entertainment schedule.
CITY: Antioch
Volo Bog's WinterFest
Looking for a great combination of indoor and outdoor fun in mid January? WinterFest is a long-standing event at Volo Bog featuring live music and storytelling, photo contest awards, and winter-theme and other crafts indoors, while outdoors winter bog hikes, and snow permitting - snow sculpting contests and cross-country skiing, may be enjoyed throughout the afternoon. There will also be cookies, hot cocoa & coffee for sale by the Friends of Volo Bog. Visit the website for a complete agenda. Donations accepted.
CITY: Ingleside
Barrington Art Festival
Celebrate Memorial Day Weekend at the Barrington Art Festival. The festival offers the work of 125 juried artists from around the country in a variety of mediums, including ceramics, fiber, glass, jewelry, metal, photography, watercolors and wood. Live music, great food and fun activities for kids make the Barrington Art Festival a perfect family experience!
CITY: Barrington
Antioch's Gingerbread Walk & Scavenger Hunt
Bring the family and friends to Downtown Antioch to hunt for Gingerbread! Find delightful Gingerbread Sculptures of Houses and other unique creations. Fill out a contest entry form and track down the different Gingerbread Clues throughout Downtown. Turn in the completed entry form for a chance to win exciting prizes and vote for the best one. Enjoy strolling musicians and carolers on Saturdays while finishing all the holiday shopping.
CITY: Antioch
Michael Londra's Celtic Yuletide
Described as one of the greatest Irish singers of the time, Michael Londra creates an Irish Christmas with world class dancers and classic stories from his homeland. He sings traditional heartwarming carols like Winter, Fire and Snow, The Maiden's Lullaby and Gaelic pieces like Oiche Ciuin (Silent Night), plus many sing-along carols the audience will know and love!
CITY: Grayslake
The Golden Dragon Acrobats Present: Cirque Ziva
Cirque Ziva is a fast-paced, technically innovative and beautifully presented new show, featuring the elite members of the Golden Dragon Acrobats. Enjoy an unique cirque spectacular showcases traditional Chinese acrobats who dazzle with amazing feats of athleticism, daring heart-stopping stunts and the grace of their centuries-old art form.
CITY: Grayslake
The Second City Hits Home
Come out for a night of laughter as The Second City takes on all the news that's fit to twist. The biggest headlines! The hot-button issues! All served up with a side of that famous Chicago-style improv. Don't miss this chance to see the superstars of tomorrow live on stage now!
CITY: Grayslake
Superb songwriting, harmonies and with a repertoire ranging from sentimental ballads to blistering rockers, Brian FitzGerald and Martin McCormack draw on Americana and Celtic themes reflecting their Midwestern roots and Irish heritage.
CITY: Grayslake
I've Got A Little Twist
The New York Gilbert & Sullivan Players perform a comedic mash-up cabaret of musical hits. The Mikado meets The Music Man and HMS Pinafore sets sail for Brigadoon. A fresh and most heartfelt performance, not to be missed.
CITY: Grayslake
Broadway's Next H!T Musical
Every song is fresh. Every scene is new. Every night is different. It's all improvised and it's all funny! Master improvisers create an evening of music, humor and laughter gathered from made-up, hit song suggestions from the audience, turning it into a full-blown improvised musical.
CITY: Grayslake
Six Flags Great America & Hurricane Harbor 2015 Season
Six Flags Great America is fun for the whole family with 14 heart-pounding roller coasters, a free water park with over 30 heart pounding water slides, spectacular shows and parades, family rides and big pint-sized fun for the kids with children's areas and over 35 rides for the little ones. Don't miss Goliath, a triple record breaking roller coaster. It is the world's fastest wooden coaster with the tallest and steepest drop, plunging riders down 180 feet and rocketing through twists and turns at 72 miles per hour. Also enjoy Hurricane Harbor and Riptide Bay, the water park that boasts more slides and attractions. Catch a wave at the only place to surf on Lake Michigan.
CITY: Gurnee
38th Annual Guest Artist Concert Featuring Rufus Reid
Bassist and composer Rufus Reid. His major professional career began in Chicago and continues since 1976 in New York City. He has toured and recorded with Eddie Harris, Nancy Wilson, Harold Land and Bobby Hutcherson, Lee Konitz, and many more. He continues to record adding to his over 400 record discography, 18 of which are under his own name.
CITY: Grayslake
Engelbert Humperdinck at Genesee Theatre
Engelbert Humperdinck has been a legend in the international music industry for more than 40 years, with over 150 million records sold. He's recorded everything from the most romantic ballads to a recent platinum-selling contemporary theme song. Tickets $45-$65.
CITY: Waukegan
The BoDeans With Taylor Hicks at the Genesee Theatre
Since forming in Waukesha, Wisconsin in 1983, the BoDeans has been bringing American Rock music to fans across the nation and has recently taken new directions into country & soul. They have had several singles in the top 40 Mainstream Rock charts and two top 10 songs in the Adult Contemporary charts. Along with American Idol winner Taylor Hicks this should be a show not to be missed.
CITY: Waukegan
The President's Photographer: 50 Years Inside the Oval Office Exhibit
Visitors will be transported through presidential history, from photos made when the first official presidential photographer was hired in 1963, to today's unprecedented coverage of Barack Obama. This exhibit will showcase the power of the still image as a tool for understanding 50 years of president's history. Assembled by three-time Emmy Award-winner John Bredar, this exhibition features works by veteran presidential photographers David Hume Kennerly (Gerald Ford), David Valdez (George H.W. Bush), Bob McNeely (Bill Clinton), Eric Draper (George W. Bush), Pete Souza (Barack Obama) and many more.
CITY: Wauconda
Rodney Carrington at the Genesee Theatre
Rodney Carrington has been making audiences laugh for almost twenty years with his unique brand of stand-up comedy. The country singer-songwriter has recorded eight major label comedy albums which have sold more than two million copies, two of which have been certified Gold. VIP Meet & Greet packages available. For mature audiences.
CITY: Waukegan