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Mindless Budget Reporting: Fooling Some of the People All of the Time
Filed Under Greenberg's Law of The Media
The PBS story, Mindless Budget Reporting: Fooling Some of the People All of the Time by Dean Baker talks about an example of Greenberg's Law of The Media. Baker is castigating a report in The New York Times.
"A plan by House leaders to cut $40 billion from the food stamp program — twice the amount of cuts proposed in a House bill that failed in June — threatens to derail efforts by the House and Senate to work together to complete a farm bill before agriculture programs expire on Sept. 30."
The problem with this description of the Republican plan is that the proposed cut of $40 billion is supposed to be over a 10-year budget window, not a single year. (The Republicans want to cut the food stamp budget by 5 percent, not 50 percent.) This information is not reported anywhere in the article. As a result, even a very intelligent and extremely knowledgeable person like Krugman could read through the piece and be off by a factor of 10 in his understanding of the size of the proposed cuts.
One of the ways Greenberg's Law is demonstrated is to give us a number out of context. You are obviously supposed to infer that the number illustrates some point that the reporter is implying, but you are never given the context to judge whether the desired inference is correct. It is unlikely that the reporter knows whether the desired inference is correct.
Baker is correct that all you know is that it is a large number. If you don't know whether it is over 1 year or 10, or what fraction it is of the budget, or how this government spending compares to the spending of the corporate sector under similar circumstances, then you have no idea if the number is too large, too small, or just about right. However, your thinking about the matter has been prejudiced by the report. Because of this, you might come away from reading or hearing the story with less knowledge than you started with.
Sort of like all of Faux Noise, the more you watch, the less you know.
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Charter schools in Boston score higher on key tests
Filed Under Greenberg's Law of The Media, SteveG's Posts
The Boston Globe has the article Charter schools in Boston score higher on key tests. If you are not a Globe subscriber, the only text you get to see is:
Boston charter schools outperform other public schools on three popular barometers of achievement — the MCAS, the SAT, and the Advanced Placement exams — but tend to have lower four-year graduation rates, according to a study being released Wednesday.
If you read the newspaper or have full access to the site, you will see the following about half way through the article:
In Boston, there are 25 charter schools.
The study examined 3,400 students who sought admission to one of the six charter high schools in Boston between fall 2002 and 2008. (The study excluded two charter high schools that closed during that period because of low performance.)
I commented on the article which reported on a study done at MIT.
If there had been more room, the headline might have said "Charter schools score higher on key tests except for the ones that don't" It is convenient how two schools that would have lowered the averages for the Charter schools were taken out of the study. Perhaps the people conducting the study and doing the statistical analysis could have excluded a similar proportion of low performing public schools from the study.
With MIT accepting huge amounts of funds to build buildings named after the infamous Koch brothers and then this story, perhaps it is true that MIT is selling its soul to the devil in order to raise funds. Now when MIT calls me for an alumnus donation, I just tell them to put it on the Koch brothers' tab.
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State Fails To Measure Effect Of Voter ID Law
Filed Under Greenberg's Law of The Media
The Boston Globe story State reports few problems with voter ID law is a good example of Greenberg's Law of the Media.
The overwhelming majority of voters who cast ballots this year in Rhode Island had no problems complying with a new voter identification law. Secretary of State Ralph Mollis's office reported Friday that of 560,000 ballots cast in this year's elections fewer than 190 provisional ballots were submitted because the voter failed to present a driver's license, bus pass, or other form of ID. Lawmakers passed the law last year to prevent voter fraud.
This proves that 190 people who had no ID still attempted to vote despite the law. It does not tell you how many people decided not to vote because they did not have the required ID. If these people without ID who did not vote were otherwise legally eligible to vote, then I would say that these were problems. We have no idea of how many such people there were. So while the story appears to be true that the state reported few problems, that does not mean that there were only a few problems. In fact there is no report of the state trying to measure how many problems there were. It is very likely that you will not find what you do not seek.
I predict that the "information" published in this article will be used as a means to justify the continuation of the voter ID law. Perhaps a better headline would be the one I used for this article.
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More Wisdom from the Guy Who Brought You "Rape Can't Get You Pregnant"
Filed Under Greenberg's Law of The Media
The New Republic has the article More Wisdom from the Guy Who Brought You "Rape Can't Get You Pregnant".
It's fine for magazines to debunk the pseudo-science of people in the news, but they shouldn't use pseudo-science in one of their arguments.
In the section titled "Legalizing abortion didn't make abortion safer" they quoted Dr. Willke as saying:
"If, in fact, the elimination of illegal abortion eliminated back alleys, there should have been a perceptible drop in the number of women dying. That didn't happen. The line didn't even blip from 1967 to 1973 and 1974. … It just kept going down at the same slow rate. There was no evidence of a decline in mortality from legalization."
Then to disprove what he said the article posits:
In any event, evidence that his claim was totally bunk was readily available by 1989. In March of 1987, the American Journal of Obstetrics & Gynecology published a study which read, in part, "Between 1972 and 1982 … [t]he overall death rate resulting from legal abortion dropped nearly fivefold, from 4.1 per 100,000 abortions in 1972 to 0.8 in 1982."
In one case, Dr. Willke talks about the number of women dying. In the other case they quote the death rate per 100,000 abortions. Now if the death rate went down, but the number of abortions went up, then it is quite possible that the total number of deaths of women did not go down.
I am not saying that this is true. I am just saying that people should not use arguments that are so easily ripped apart. The New Republic is trying to show that Dr. Willke doesn't know science, but they don't show a great grasp of science themselves, or at least not statistics, math, or even numbers.
Chalk up another example of Greenberg's Law of the Media – "If a news item has a number in it, then it is probably misleading."
You might find the rest of the article more enlightening. Too bad they had to spoil it with this blunder.
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Doctors dispute Akin's claim, but some supporters say it was misunderstood
Filed Under Greenberg's Law of The Media
The Kansas City Star has the generally good article Doctors dispute Akin's claim, but some supporters say it was misunderstood.
If you are wondering about the supporters' claims to a misunderstanding,
But Tim Wildmon, president of the American Family Association — a nonprofit that describes itself as a pro-family organization — told The Star on Monday that "fair-minded people" know what Akin really meant by his statement. Wildmon speculated that Akin was differentiating between forcible rape and statutory rape, which can be consensual.
"What I read from some medical sources, when a woman is raped, her body shuts down in some respects that may prevent her from getting pregnant," Wildmon said.
Wildmon adds a new wrinkle, but then goes back to repeat the same stupid statement that got Akin in trouble in the first place.
The part of the article that gets my goat is the statement:
A 1996 study in the American Journal of Obstetrics and Gynecology, generally considered one of the few peer-reviewed research efforts on this subject, estimated that 5 percent of rapes result in pregnancy.
The above statement tells you nothing about the truth or falsity of the claims of either side. To complete the above half a statistic, there would need to be a statement like, "and it is estimated that X percent of incidents of consensual intercourse result in pregnancy." If X is significantly higher than 5%, then there could conceivably (no pun intended) be some truth to Akin's claim. If X is significantly lower than 5%, then it might be true that rape has an enhanced rate of causing pregnancy. If X is not significantly different from 5%, then it might be tru that rape versus consensual sex has no affect on the rate of pregnancy after the act.
So the half statistic has shown that rape may lead to enhanced rates of pregnancy, or it might lead to lowered rates of pregnancy, or it might have no effect at all. In other words, you don't know anymore about the effect of rape on pregnancy than you did before you read that statistic. You don't even learn anything about the claim to rarity. Without knowing the number X, you can't say whether 5% means rare or frequent.
For this reason, I give the article a 5 star rating for proving Greenberg's Law of the Media – "If a news item has a number in it, then it is probably misleading."
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The CEO Plan to Steal Your Social Security and Medicare
Filed Under Greenberg's Law of The Media, SteveG's Posts
The Nation Of Change has the article The CEO Plan to Steal Your Social Security and Medicare.
Many of the same folks who brought the economy to ruin just a few years ago are now going to come up with a plan that is supposed to set the budget and the economy on a forward path. At the center of their proposal are big cuts in Social Security and Medicare.
It is an interesting article even if I do classify this as an example of Greenberg's Law of the Media. He talks about an 0.3% change per year in the COLA adjustment for Social Security, aggregates this to 3% over ten years and then compares this to the 3% change in upper income tax rate. 3% is 3%, right? Well 0.3% a year is not the same as 3% a year and 3% over 10 years is also not the same as 3% over 1 year. Putting this aside, the rest of the article might supply you with some information you didn't know.
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Fact-Checking the Fact-Checkers: The AP Releases Misleading Analysis of Obama's Tax Plan
Filed Under Greenberg's Law of The Media
Fact-Checking the Fact-Checkers: The AP Releases Misleading Analysis of Obama's Tax Plan says the following:
As Hanlon noted, "AP's 'fact check' misses the point of the Buffett rule. The point is not to ensure that rich people on average pay higher taxes than middle-class people on average," but "to ensure that all households with incomes above $1 million pay at least what middle-class families are paying."
This is not the first time this month that the AP's "fact-checkers" have bungled the facts regarding Obama's economic plans. At this rate, they should think about opening a new division to fact-check the fact-checkers.
This is no surprise to me. When I saw the headline for the AP story, I didn't even bother to read the story. I knew that it would be a distortion.
After reading the exposé, I decided to follow the link to the AP story, FACT CHECK: Are rich taxed less than secretaries? Here is the red-flag.
On average, the wealthiest people in America pay a lot more taxes than the middle class or the poor, according to private and government data. They pay at a higher rate, and as a group, they contribute a much larger share of the overall taxes collected by the federal government.
What does that even mean? How did they take the average? Did they average the percentages of all the included taxpayers? Did they weight the averages by the amount of income earned by each tax payer? When the income of people making more than $1 million ranges from that $1 million to several billion dollars, then the average weighted by income is quite skewed from the average weighted by the numbers of taxpayers in each category.
When the article uses such imprecise terms, you know the article is an example covered by Greenberg's Law Of The Media.
Another of the many red flags in the article include:
The 10 percent of households with the highest incomes pay more than half of all federal taxes. They pay more than 70 percent of federal income taxes, according to the Congressional Budget Office.
That is what I call half a statistic. They don't say it, but they obviously want you to infer that 10% of the households paying 70% of the federal income taxes is too much taxation. To know if this inference is correct, you'd have to know what fraction of the income these 10% of households make, but they don't tell you that. Even if they did tell you about the declared income, they would be leaving out the unrealized capital gains of these wealthy people which may dwarf the income the IRS requires them to report as income. So to paraphrase Bill Clinton "It all depends on what the meaning of income is."
Of course the quote is not going to emphasize that paying only 50% of federal taxes while paying 70% of all federal income taxes means that there are other hefty federal taxes other than income taxes that the less wealthy pay in larger percentages than the wealthy.
To use these tricks in their article, you would almost have to conclude that the article is purposely distorting the facts or the authors are totally ignorant of how they are misusing the numbers. Personally, I don't need people to report the news who know less about it than I do. I certainly don't need reporters who tell lies in their reports.
Click on the link under categories at the right side of this window for Greenberg's Law Of The Media to see other articles in that category. In the set of articles that come up, you might notice Associated Press the Faux Noise of the Print Media.
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Republican's Refusal On Raising Taxes Costs The Wealthy $7.8 Trillion
Filed Under Greenberg's Law of The Media
The article Global Bonds Gain $132 Billion as Stock Rout Cuts $7.8 Trillion says (among other things),
… yesterday's stock rout wiped out about $2.5 trillion in global equity values, extending total losses since July 26 to $7.8 trillion.
Put this together with the words in the Standard & Poors downgrade of the US credit rating:
Compared with previous projections, our revised base case scenario now assumes that the 2001 and 2003 tax cuts, due to expire by the end of 2012, remain in place. We have changed our assumption on this because the majority of Republicans in Congress continue to resist any measure that would raise revenues, a position we believe Congress reinforced by passing the act.
I think that S & P is only looking for a couple of trillion dollars more of deficit reduction. Wouldn't it have been cheaper even for the wealthy to have raised their taxes instead of making them lose trillions of dollars in the stock market?
My friend JohnK said the following:
I think any increase in consumer interest rates as a result of the downgrade should be called the "Tea Party Tax Increase, or, in Washington parlance, the "TPTI".
I would just change that to say that this loss of wealth could be dubbed the TPTI.
Notice that I classify this post under the category of Greenberg's Law of The Media which states that "if a news item has a number in it, then it is probably misleading."
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S & P – Decide Answer, Then Look For Evidence
Filed Under Greenberg's Law of The Media, SteveG's Posts
I find the following from the Bloomberg News report as published in The Boston Globe article, Treasury official faults credit rating downgrade:
S&P made a $2 trillion calculating mistake and then changed the rationale for its decision, raising "fundamental questions about the credibility and integrity of S&P's ratings action,'' John Bellows, acting assistant secretary for economic policy, wrote in a Treasury blog post.
The dispute stems from how S&P used figures from the Congressional Budget Office. The discrepancy didn't change the downgrade decision, S&P officials said, because Treasury's $2 trillion figure was derived by calculating government debt over a 10-year period while S&P's ratings are determined using a three- to five-year timetable.
It appears that S & P may have come to the conclusion that it needed to downgrade the US credit rating and then went searching for the evidence that would justify the foregone conclusion.
In making hypotheses, I suppose there can be circumstances where your gut tells you what the hypothesis should be before you find the evidence to support it. However, especially in this case where the hypothesis came before a formal search for evidence, you must be extremely diligent to not look only for supporting evidence. You must be as diligent in searching for any evidence that would contradict your hypothesis.
As pointed out by Nassim Nicholas Taleb, The Black Swan: The Impact of the Highly Improbable, it doesn't make any difference how many swans that you see that are white, seeing just one black swan is enough to convince you that not all swans are white. Even before you see the black swan, you ought to be cautious about claiming all swans are white.
Yes, I know, if I am to follow my own logic, I should look for evidence that S & P did not make its decision to stick by its original conclusion because of confirmation bias. I'll leave that as an exercise for the reader. After all, I don't get paid millions of dollars for writing these blog posts. I would say millions of dollars may be at stake for S & P if they should lose their reputation, what reputation they have left, for making good calls on the creditworthiness of investments. Remember their investment grade rating of banks' mortgage backed securities.
August 8, 2011 9:00 AM
As mentioned in the post Resistance To Revenue Increase Causes S & P Downgrade, I was able to read the full S&P report.
I can't tell if I was reading the original report or the corrected one, but it does look to me as if the quote mentioned above from John Bellows on the Treasury blog may have been very self-serving.
Perhaps S & P didn't so much as make a mistake as they did use different assumptions from the CBO report from which they took their numbers. I don't know if this difference was mentioned in the original report, but it is very clearly stated in the report that I read.
I think this shows that you cannot trust what either political side has to say about the report. You have to read the report and decide for yourself what you think it says and what you think it means.
Here is the link where you can read the full 8 page S & P Report.
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Resistance To Revenue Increase Causes S & P Downgrade
Filed Under Greenberg's Law of The Media, SteveG's Posts
According to the article Mainstream Media Ignores S&P Attack On Republicans:
Page 4 of the official Standard & Poors "Research Update"
We have changed our assumption on this because the majority of Republicans in Congress continue to resist any measure that would raise revenues, a position we believe Congress reinforced by passing the act.
I did a Google search and could find no mention of this except in a comment on an article on one newspaper web site. Of course, I only checked the first few of the 33,600 entries from the search S & P Downgrade "raise revenue". I had hoped for a link to the actual report so I could read it myself.
See if you can do any better finding this information.
I did a Google search on Reason US Downgrade. Again I only found the reason in comments on news stories. One of the comments cited the same article as I cited above.
In the article from Bloomberg News that I read in The Boston Globe, Treasury official faults credit rating downgrade, I did find the following paragraphs:
S&P reduced the US rating one grade to AA+ while keeping the outlook at "negative,'' saying it was less confident that Congress would end Bush-era tax cuts or tackle spending on entitlements.
S&P was looking for $4 trillion in budget cuts over 10 years. The deal that passed Congress Tuesday would bring $2.1 trillion to $2.4 trillion in cuts over that time.It is concerned that lawmakers and the administration might fail to make those cuts because Democrats and Republicans are divided over how to implement them. Republicans are refusing to raise taxes in any deficit-cutting deal while Democrats are fighting to protect entitlement programs such as Social Security and Medicare.
August 7, 2011, 11:03 PM.
I have now read the full 8 page S & P Report as have millions of other investors.
The original article from which I quoted left out an important sentence that makes the quote even more damaging in my opinion. In the quote below, I put in the missing sentence along with the original.
Compared with previous projections, our revised base case scenario now assumes that the 2001 and 2003 tax cuts, due to expire by the end of 2012, remain in place. We have changed our assumption on this because the majority of Republicans in Congress continue to resist any measure that would raise revenues, a position we believe Congress reinforced by passing the act.
Putting the missing sentence together with the original extracted quote makes it clear that S & P does not believe that President Obama will be able to prevent the Republics from making the Bush tax cuts for the wealthy a permanent fixture of our tax laws. All Congressional Budget Office analyses assume a base line scenario that the Bush tax cuts will expire. The CBO analysis of any proposed congressional legislation only rates what that legislation will do when compared to existing law. The existing law says that the Bush tax cuts will expire in their entirety. Even President Obama wants to keep the tax cuts for the middle class.
I am not faulting the CBO for their assumptions. The job of the CBO is to make objective analyses without introducing any political speculations. So the best thing they can do is to to not second guess the political process and clearly state their assumptions. With the assumptions clearly stated, the reader can then make whatever different assumptions they want to make and then adjust the results as appropriate. This seems to be exactly what S & P did.
No wonder the S & P is so upset with the prospects for our getting control of the budgeting process and appropriately adjusting the results of the CBO report.
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Apple to sell 75 million low-cost iPhones next year, says analyst
A low-cost iPhone could see unit sales of 75 million in 2014, projects Piper Jaffray analyst Gene Munster.
In an investors note released today, Munster said he expects Apple to sell a $300 non-subsidized iPhone starting in September. Such a device is likely to trigger a 30 percent cannibalization rate, which means that for every three low-cost iPhones sold, one full-price iPhone is cannibalized.
As such, Apple's share of the high-end smartphone market may dip to 37 percent next year from 43 percent last year. But its share of the low-end (under $400) market will rise to 11 percent … Read more

subset: commoncrawl


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Today weezer played a outdoor festival in downtown Cedar Rapids, the Rockin The Rapids Music Festival. We followed several other bands including Tonic, Fuel, Filter and Chevelle (they seemed to have a muscle car theme going on today, up till when weezer took the stage). It was a hot and windy day with the streets blocked off, lotsa port a potties in rows, barbeque huts, tents, folding chairs, drunk people getting rowdy, a PTSD meltdown or two, and a generally disorganized and unruly feel prevailing throughout the afternoon. Things seemed to settle down a bit in time for weezer's set, when the crowd coalesced into a unified music frenzy, including shoulder riding bikini clad rock chicks, little kids freaking out, and one shoe wearing crowdsurfers, both male and female. The rock was strong today.
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I was there. I was the guy wearing THIS shirt (in case you saw me)
Rockin' The Rapids 6-10-2012 was amazing! Lineup in order:Mint (from Des Moines)Issac James (from Des Moines, Missouri, their drummer was the original founding drummer for Stone Sour)TonicFilter (sound was terrible - they still rocked out hard!)FuelChevelle#Weezer (they read my mind and opened their set with the song 'Tired of Sex')Some might know that #Weezer has a touring 'band' adding well renound drummer Josh Freese and taking Pat from behind the drums and putting him on guitar and vocals. Well this was NOT the case. There were four (not the ORIGINAL four) but JUST four and it was good... :-)
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Demi Moore is 50!
The movie star, mother-of-three and ex-wife of Bruce Willis and Ashton Kutcher turns 50
Wire Image, Rex FeaturesShow Thumbnails
Demi Moore has just turned 50 years old but she looks as good as she did aged 20, pictured right!
The star of 'Ghost' and 'Indecent Proposal' has been in the limelight for nearly 30 years and in that time has experienced massive movie stardom (at one point she was the highest paid actress in the world), as well as collosal heartbreak, enduring high-profile splits from Bruce Willis and Ashton Kutcher.
Relive Demi's turbulent life in pictures...
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Quick Facts
- NAME: Justine Bateman
- OCCUPATION: Television Actress
- BIRTH DATE: February 19, 1966 (Age: 48)
- EDUCATION: Taft High School, University of California, Los Angeles
- PLACE OF BIRTH: Rye, New York
- Full Name: Justine Tanya Bateman
- AKA: Justine Bateman
- ZODIAC SIGN: Pisces
Best Known For
Justine Bateman is best known for her role as Mallory Keaton on the hit show Family Ties. She later appeared on Men Behaving Badly.
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Play NowJustine Tanya Bateman. (2014). The Biography Channel website. Retrieved 01:21, Mar 12, 2014, from http://www.biography.com/people/justine-bateman-21359113.
Justine Tanya Bateman. [Internet]. 2014. The Biography Channel website. Available from: http://www.biography.com/people/justine-bateman-21359113 [Accessed 12 Mar 2014].
"Justine Tanya Bateman." 2014. The Biography Channel website. Mar 12 2014, 01:21 http://www.biography.com/people/justine-bateman-21359113.
"Justine Tanya Bateman," The Biography Channel website, 2014, http://www.biography.com/people/justine-bateman-21359113 [accessed Mar 12, 2014].
"Justine Tanya Bateman," The Biography Channel website, http://www.biography.com/people/justine-bateman-21359113 (accessed Mar 12, 2014).
Justine Tanya Bateman [Internet]. The Biography Channel website; 2014 [cited 2014 Mar 12] Available from: http://www.biography.com/people/justine-bateman-21359113.
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Justine Tanya Bateman. The Biography Channel website. 2014. Available at: http://www.biography.com/people/justine-bateman-21359113. Accessed Mar 12, 2014.
Justine Bateman was born February 19, 1966, in Rye, New York. She became well known for her role as Mallory Keaton on the sitcom Family Ties, and then starred in Men Behaving Badly. In 2011, Bateman enrolled at UCLA to pursue a degree in computer science.
Early Years
Justine Tanya Bateman was born in Rye, New York, on February 19, 1966. Her father, Kent, was a film producer, and her mother, Victoria, was a flight attendant. She starred in a number of plays as a child, but was inspired to take on roles in commercials at the age of 15, after her younger brother, Jason, landed a spot on Little House on the Prairie. She graduated from Taft High School in Woodland Hills, California, in 1984.
Professional Success
Bateman was still in high school when she landed a big part on the television sitcom Family Ties, starring as Mallory Keaton, the spacey, underachieving younger sister of Alex Keaton (played by Michael J. Fox). The show ran from 1982 to 1989, and helped earn her nominations for two Emmys and one Golden Globe. Her fame and success hid a painful secret, however. In 1996, she revealed that her time on the set of Family Ties was beset with anorexia, bulimia and compulsive overeating.
In 1988, Bateman got a starring role in the motion picture Satisfaction, a summer romance film that—despite featuring Liam Neeson and Julia Roberts—was so poorly received that it prompted one critic to write: "Ms. Bateman's singing is so distant from any human voice that the sound engineers must have been the busiest people on the film." Despite her setback on the big screen, Bateman continued to appear on television, including recurring roles on Men Behaving Badly and Out of Order.
In 2000, the actress took a break from Hollywood and founded her own clothing company. In 2008, she wrote an episode of the sitcom Wizards of Waverly Place. In 2012, she enrolled at UCLA in order to pursue a degree in computer science.
Personal Life
Justine Bateman is married to Mark Fluent, a real-estate developer. They have a son, Duke, and a daughter, Olivia.
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Learn more about the cast of the incredibly popular 1980s sitcom Family Ties, including Meredith Baxter, Michael J. Fox, Tina Yothers, Brian Bonsall and Justine Bateman. Explore full biographies, photos and videos, only at Biography.com.
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If you like staying in larger hotels, Worldhotel Bel Air The Hague will be of your liking. Rated with 4 stars, this accommodation is certainly higher than average.
Dine at one of the 2 restaurants of Worldhotel Bel Air The Hague. A garden, a coffee shop/café and an exhibit space are located here as well. You can benefit from a doctor on call here, in addition to a luggage storage and an express check-in/out service. If you need a hotel with meeting facilities, this accommodation has 20 meeting rooms. Especially convenient for business guests is the presence of a conference space and a business center in addition to an audio-visual equipment set. You can select one of the 300 bedrooms. Paid parking can offer some convenience if you travel to the hotel by car. It is not needed to have a car here, a paid area shuttle bus belongs to the possibilities to get around in The Hague.
Thanks to the air conditioning at Worldhotel Bel Air The Hague you don't have to worry about the climate indoors. The standard room services here are enhanced by a wake-up service as well as a daily housekeeping service. Stay up to date with news, your friends, e-mail and more via wireless high-speed Internet access (surcharge). In the bathrooms at this hotel, a magnifying mirror is provided in combination with a complimentary toiletries set and a shower/bath combination. Rooms with a city view can be reserved in advance.
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Check-in: | From 14:00 Check-out: Until 12:00 |
Internet: | Wireless high-speed Internet access (complimentary), Free wired Internet, Internet Point, Computer Station |
Parking: | Paid parking, Paid Parking (Self-service) |
Airport shuttle: | Paid Area Shuttle Service |
Rooms: | 300 |
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North Carolina State 77, Notre Dame 70: T.J. Warren scored 17 points and Anthony Barber added 16 as the visiting Wolfpack edged the Fighting Irish.Desmond Lee and Ralston Turner added 12 points apiece for North Carolina State (11-4, 1-1 ACC), which never trailed in the second half and improved to 3-0 in ACC road openers under coach Mark Gottfried. Jordan Vandenberg gathered a team-high 11 rebounds.Garrick Sherman paced Notre Dame (10-5, 1-1) with 21 points and a career-high 18 rebounds while Pat Connaughton was 5-of-11 from 3-point range and finished with 15 points. The Fighting Irish lost for the first time in three games since leading scorer Jerian Grant was dismissed from the team for an academic violation.Barber's half-court shot at the halftime buzzer gave the Wolfpack a 3-point advantage, and the Fighting Irish trailed by six with five minutes remaining. Steve Vasturia hit a 3-pointer to cut the deficit to 69-66 with 1:29 left, but the Wolfpack scored their final eight points at the foul line to secure the win.Eric Atkins had 14 points for the Fighting Irish, who shot 7-of-24 from 3-point range and failed to capitalize on a 79-77 win over Duke on Saturday. North Carolina State, making its first visit to Notre Dame since 1982, was 25-for-32 from the foul line while the Fighting Irish were 9-for-12.GAME NOTEBOOK: Sherman has scored in double figures in each of the last 12 games. … Warren, who entered the game averaging a team-high 23.9 points, missed 11-of-17 shots and failed to convert his three attempts from beyond the arc. … Notre Dame dropped to 126-12 at home since the beginning of the 2006-07 season.


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December didn't bring many presents this year. Typically, things stay active for a few weeks before the holidays but in this case 2012 was an early wrap.
There were 6 IPO deals priced but one was a just a "blank check" company. The others were Sprott Physical Platinum (commodity fund), Silver Bay Realty (Real Estate), SolarCity (solar), PBF Energy (oil refiner), and Western Gas Equity (midstream energy LP).
Seven deals were officially withdrawn, including Safety-Kleen, Singulex, Bluestem Brands, Glori Energy, Era Group, Planet Payment and Rib_X Pharmaceuticals. Safety-Kleen was acquired by Clean Harbors (CLH) back in October.
It's worth noting that the market overall has been in a slow drift down for the past few months. The Nasdaq declined 3% in Q4 and 1% in December.
The deal that caught our attention last month, Ruckus Wireless (RKUS), had a major rally after dropping below $15. The shares exited the year at just over $22 as investors came to appreciate their leading market position in "carrier Wi-Fi" equipment.
Heading into 2013 it's hard to see any clear IPO market trends. The market faces what looks to be a mild recovery in the US economy and real estate market, along with substantial uncertainty in terms of changes in tax regulations and government spending. On the regulatory front, the turmoil at the SEC has delayed new initiatives related to the JOBS act.
Ecosystem Performance
The ecosystem was a positive 2% in December. The top 10 names were up 43% and the bottom 10 were down 32%.
Top December Performers
BCD Semiconductors (BCDS) was acquired at a big premium by Diodes Incorporated (DIOD), a profitable mid-sized ($635M in revenue) semiconductor company based in Plano, Texas.
We noted Ruckus Wireless earlier as an IPO that managed to come out quietly in a difficult market and offered investors an attractive opportunity in the aftermarket. Carrier-grade Wi-Fi should be a strong growth area for the next few years.
Intercept Pharma (ICPT) moved up in concert with the progress of one of their leading drugs for treating liver disease moving into Phase III trials.
Velti (VELT) is a bit of a broken story in online advertising that received some interest from bottom fishers.
One of our favorite development stage biotechnology names, Verastem (VSTM), started to generate some institutional interest after presenting at a major conference mid-month. There are quite a few cancer-focused biotech names out there, but Verastem is one of the better small cap opportunities.
Worst Performers in December
We can credit tax-loss related selling for the major losers in December. Some of these may be dropped from our coverage list as they may or may not remain going concerns in 2013.
December IPO Performance And New Filings
The few deals priced in December did fairly well as a group but it should be noted that many didn't make it out and some that did were priced below the range.
SolarCity popped 49% after being priced below the filing range. Energy deals like Western Gas and PBF Energy did well. Investors were drawn to Silver Bay as a play on a recovering US residential real estate market. Silver Bay is basically buying up houses cheap, fixing them up and turning them into rental properties.
Looking at filings, we can see the trend towards US residential real estate continuing with new offerings planned from two home builders: Taylor Morrison and TRI-Point, and a residential mortgage company called Five Oaks Investment.
Many were happy to see a new filing from SeaWorld Entertainment, which promises some fun as a roadshow and offers another way to play an improving US consumer economy.
IPO Candy Folio Update
For the month of December the IPO Candy Folio was up 3.36%, which beat the average for both the S&P (+0.91%) and the Russell 2000 (+2.91%).
For the year, the IPO candy Folio was up 7.4% but underperformed both the S&P 500 (up 16%) and the Russell 2000 (+14%).
As we begin 2013 we decided to "clean house" and eliminate a number of holdings. In particular, we removed companies from the portfolio that have not managed well enough post-IPO in our view.
So, we eliminated our positions in Active Network (ACTV), Ceres (CERE), RPX Corporation (RPXC), and Yandex (YNDX).
We still have a position in Teavana Holding (TEA), which is being acquired by Starbucks (SBUX) but we are not allowed to trade the shares now. That position will be closed when the deal is completed.
These actions give us a 26% cash level to use to add new positions and/or increase our stakes in existing ones.
More information and disclosures regarding the IPO Candy Folio can be found here.
The Pipeline of Deals and Events
The deal pipeline that we can see is about 120. Between pricings and withdrawn deals the "book-to-bill" ratio has been below parity for a couple of months. One factor is the new confidential disclosure rule that the JOBS act ushered in. The other may be some slackening of demand that was "pent-up" by the weak market of 2009.
Coverage And Lockup Expirations
There's no new coverage scheduled for January but there are plenty of lockups coming off. A few stocks that could be particularly vulnerable to lockup expiration include: Northern Tier Energy (NTI), Chuy's Holdings (CHUY), Palo Alto Networks (PANW) and Five Below (FIVE).


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Dr. Deren's Background
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Initially it was believed that DeForest was not working under a formal contract. He had worked under only a term sheet his first season, one which stipulated that DeForest's "appointment is made at the will and pleasure of the Director of Athletics, and your service in this position or termination from it is at the discretion of the Director of Athletics.'' Nowhere in the letter, dated Jan. 12, 2012, was there a specific length of term mentioned.
However, WVU sources said Saturday night that between January and now DeForest has signed a formal contract. The details aren't known except that he still makes $500,000. The term of the contract and any buyouts are likely included.
The WVU source also confirmed that DeForest is no longer the only WVU assistant coach making half a million dollars annually. Patterson, the new defensive coordinator, was apparently bumped up to that figure as well, although the university never mentioned it publicly.
The Sports Illustrated project alleges that both coaches and boosters paid athletes at Oklahoma State, including paying them for jobs not performed or overpaying them, in addition to the pay-for-plays accusations.
It also alleges academic fraud, drug use and that hostesses in the Orange Pride program provided sex to recruits.
Oklahoma State president Burns Hargis issued a statement calling the accusations "deeply troubling.''
Reach Dave Hickman at 304-348-1734 or dphickm...@aol.com or follow him at Twitter.com/dphickman1.


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NXP/Philips TDA182xx
From LinuxTVWiki
TDA182xx are a family of tuner ICs from NXP/Philips. They appear to be in the process of being superceded by newer devices such as the NXP/Philips CX24109.
Contents |
A tuner IC for DVB-T, targetted at STB.
A tuner IC.
A tuner IC targetted at STB.
The TDA18271HD is a Tuner IC by NXP designed mainly for terrestrial analog and digital TV reception and targetted at PC-TV. The TDA18271HD integrates the overall tuning function, including selectivity.
The TDA18271HD is compatible with all analog and digital TV standards and delivers a low IF signal to a demodulator (for analog TV) and/or channel decoder (for digital TV).
Fortunately documentation useful for writing a driver is available.
A tuner IC covering DVB-T and DVB-H.
A tuner IC covering DVB-T, DVB-H, DVB-SH, T-DMB and ISDB-T, targeted at low power applications such as notebooks, handheld devices, USB sticks.


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Krämer, Bernhard K. and Ritthaler, T. and Ackermann, M. and Holmer, S. and Schricker, K. and Riegger, G. A. and Kurtz, Armin (1994) Endothelium-mediated regulation of renin secretion. Kidney international 46 (6), pp. 1577-1579.
Krämer, Bernhard K. and Ackermann, M. and Kohler, S. M. and Riegger, G. A. (1994) Role of endothelin in hypertension. The Clinical investigator 72 (2), pp. 88-93.


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Premier League - 1 year ago
Watching: Following on from a timely return to form in the Premier League, Newcastle switch their attentions to the knock-out stage of the Europa League.
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Wild Country: Wild Wire Carabiner
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Leaflet showing how the ICRC's Advisory Service functions. The purpose of the service is to assist civilian and military authorities in implementing international humanitarian law. International humanitarian
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Thursday, 26 May 2011
Bishops are not the Focus for Unity
I am absolutely furious this morning with Rowan Williams and with the Church of England. I don't trust myself right now to write anything about the power abuses and the blatant injustices within the organisation I work for. (Read Andrew Brown). So I just want to concentrate on the phrase about bishops being the "focus for unity"
Apparently a Bishop can only be appointed if they can be a "focus of unity" in the diocese. But how many objectors does it take to stop a bishop? And who decides? Are there any priests who could carry the whole of a diocese with them before appointment? And suppose a bishop loses the support of his diocese – should he then resign? (I can't possibly imagine Rowan thinks that for one moment, not at present!)
"Focus for unity" may appear to be a reasonable phrase, but in fact it is meaningless; it allows the blocking of anyone as a bishop because someone doesn't like the look of them, with no definition of who is and isn't acceptable. All rather like the Anglican Covenant, the offence is in upsetting someone else, not in any objective and predefined behaviour.
Given that "offence" is the basis of the blocking, then perhaps we will see no more Conservative Evangelical or Anglo Catholic bishops. We can certainly be assured that if the Women Bishops legislation gets through General Synod then it will be utterly useless - because surely there will be one parish in each diocese who would claim that a woman would not be a "focus for unity".
Or perhaps we can be sensible and decide that "focus of unity" is not a job description for the bishop, but for the diocese; that it is incumbent upon all of us in a diocese to gather round and support our bishops, which doesn't mean unthinking obedience, whether we agree with them or not.
Of all the rotten excuses for discrimination that I have heard this is by far the worst. It guarantees the status quo and the grounds for discriminating is "someone doesn't like your face".
Jesus is our "focus for unity", not the bishops! No wonder we are suffering power abuses if the Bishops have decided to put themselves in the place of God.
14 comments:
- UKViewer said...
What a sad commentary on the state of the preferment system that it can descend to such measures to actively pursue a discriminatory policy, which has caused candidates like Jeffrey John and Nick Holtom from being appointed.
It's time we adopted the system in use in USEC of elections for Bishops, whether suffragan or diocesan. - 26 May 2011 09:29
- Battersea Boy said...
Now, Lesley, don't hold back: tell us what you really think.
Actually, reading Thinking Anglicans and Pluralist this morning brought back to me some words spoken by my bishop, who said (and I do hope I'm recalling his words correctly), "Bishops can't actually DO anything. They have no real power to get things done and can only achieve lasting results by persuasion. Except in one way; they can STOP things." - 26 May 2011 09:35
Brilliant piece on the bishops - as you say, Jesus is the only one capable of being a 'focus for unity', which are just weasel words in the context the CofE hierarchy apparently use them. Colin Slee's last word has really triggered a tsunami reaction among Anglicans worldwide - with good reason. Drop the Covenant, Roll on the appointment of women bishops and hey, while you are about it, recognise the ministry of the laity like the Episcopalians!
Laura Sykes - 26 May 2011 09:42
- Mr CatOLick said...
These are the facts as I see them and experience them and hear about from others
Our church is being run, too often, by a network of people who are either pompus and believe thier own hype or are too scared of their reputation to stand up and do good. the ameturishness and bullying that goes on in so many diocese is appaling and it is no surprise that it happens at the top! This will be tollerated as long as secrecy continues (Confidentiality agreements to suppress scandal) and the people in the pew refuse to think the unthinkable.
It is essential to the work of the church that we stand alongside people like Johns who are determined for the truth to come out. Bullies do not thrive in the open unless we allow them to. Wake up! - 26 May 2011 10:42
- rev-org said...
Blimey, what a mess. Again.
The situation, rather than your blog piece that is.
If events occurred in the manner the dear late Dean describes then that is truly a disgrace, but 2 things occur to me:
1- We need to be careful about accepting one source's reflections on a meeting as a completely accurate report (& that goes for ++R's recollection of events too of course). As I know from experience, people experience the same events in very different ways sometimes, and come away with very different impressions of events.
2- "Focus of unity" has always been part of the job description, imperfect as that focus will always be. But there are always going to be particular 'red rag' issues that will really mess up unity at a particular time in the life of the church, and homosexuality is currently one of them.
I hate the fact that that is the case. I would love to see gay men and women valued equally by the church in the way that I'm sure God does. But we're being blind to the facts if we think that appointing a gay man as bishop (even a man as gifted and talented as I know JJ to be) is not going to cause serious rifts (far beyond those caused by other issues) when it comes to unity at the moment. Soon may that time come to an end, but we ain't there yet when it comes to winning over hearts and minds to accept homosexuality. - 26 May 2011 10:49
- Lesley said...
The problem is "Focus of Unity" can be horribly abused. Best to ditch it methinks...
- 26 May 2011 11:07
rev org
and if those who would suppport gay people if only it was a little easier to do so, less likely to cause arguments and more likely to be successful.... if they just got up and did it, they'd stop being the silent majority that actually allows the status quo to continue.
I'm getting seriously tired of all this liberal hand-wringing. Right-on opinions without the courage the back them up is worse than useless.
Erika - 26 May 2011 12:42
- Bishop Alan Wilson said...
For me (and I can only speak for me, not being a member of the house of bishops) I try to be as much of a focus of unity as possible of course, because who wants to go around stirring up strife? However, I have to watch within myself the gnawing desire to for peace at any price, real or pretended. If I want to be a focus of unity I have to be accountable to the people I am trying to unite (who? how?), including those who are on the margins, left and right. This cuts every way, most painfully. As some commenters have helpfully pointed out all of us who serve in episcopal ministry have to cope with our own purple haze.
Perhaps "focus for unity" is a functional emergent output from anyone's ministry, that has to emerge from the quality of our relationships with the people around us, rather than something any of us can impose by diktat from the Peacock Throne. - 26 May 2011 13:36
- Gurdur said...
Well, yes, Lesley, in view of the news in the scoop that Andrew Brown of the Guardian brought out, well, yes. I have to agree with you.
By the way, for Bishop Alan Wilson: I know well the gnawing feeling that one should sacrifice tons for unity (hey, you would be surprised how much this in my own world involves and affects me in real problems, but I assure you, it does); the Germans have a very useful word for this:
Where it's prnounced "harmony-be-darf", where 'harmony' is pronounced in the English way, 'be' as in 'bed', the 'a' in 'darf' as in 'carp'. Composed of two German words, "Harmonie" obviously meaning the English word "harmony" as in consensus agreement, and "bedarf" here as in "need".
Harmoniebedarf can grow to become an all-consuming anxious need. - 26 May 2011 13:44
- Lesley said...
Mmmm... re-reading my post it is a bit of a rant!!!
I watched a film last night - 'Made In Dagenham' - it was about 187 women machinists who worked for Ford in the late 1960s and turned a discriminatory organisation into one that offered equality. The whole time I watched it my heart bled for the Church of England - it isn't just women we discriminate against - it is gay people and divorced people and probably people of colour and people from working classes. And the way we do it is so sly - we call sexism 'legitimate theological difference', we discriminate against gay people or people with divorced wives by saying they have to be 'the focus for unity'.
And then we dress it all up and say we are obeying Christ's call for us to be one, therefore we mustn't upset anyone. It is as if, as an organisation, we are morbidly codependent. - 26 May 2011 13:58
- Erika Baker said...
Isn't the real problem that the systematic exclusion of one group of people for the sake of unity is a contradiction in itself?
A genuine attempt to unite would be precisely the opposite and would, as you say, include people at the margins of left and right. - 26 May 2011 14:02
- Bishop Alan Wilson said...
Thanks, Tim for German. The things is, you can only be a source of unity with someone you connect with. (Disconnection = disunity) If you treat any group of people as though they were in themselves the problem, you disconnect radically from them. What kind of focus for what sort of unity is a homophobic bishop (if such a thing has ever exsted) with gay people? This all leads to the fatal result that the only way you can have unity with one group is to treat some other group as subhuman or nonexistent. The result is not unity but anarchy and a situaton where the bullies seem unstoppable. They never wanted unity in the first place. the problem is similar in form to the old political chestnut about how you deal with fascists in a democracy.
- 26 May 2011 14:08
- Bishop Alan Wilson said...
Opps, our comments crossed in the ether, Erika! yes I agree entirely, for the reason you give.
- 26 May 2011 14:09
- Edward Green said...
"Lesley rightly points out that the whole idea of Focus of Unity is problematic. Theologically the Church of England is far too diverse, as are expectations of personality and character. The candidate from the working background, been in a few nasty fights, said the wrong thing in public, mishandled spiritual experiences, spoken the words of satan, with strange marital arrangements and a confused theology of legalism just won't do any more.
A pity he was the first Pope. Sancte Petre Ora pro nobis." - 26 May 2011 19:14


text:
Monoclonal antibody
Monoclonal antibodies (mAb or moAb) are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell, in contrast to polyclonal antibodies which are made from several different immune cells. Monoclonal antibodies have monovalent affinity, in that they bind to the same epitope.
Given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology and medicine. When used as medications, the non-proprietary drug name ends in -mab (see "Nomenclature of monoclonal antibodies").
The idea of a "magic bullet" was first proposed by Paul Ehrlich, who, at the beginning of the 20th century, postulated that, if a compound could be made that selectively targeted against a disease-causing organism, then a toxin for that organism could be delivered along with the agent of selectivity. He and Élie Metchnikoff received the 1908 Nobel Prize for Physiology or Medicine for this work, which led to an effective syphilis treatment by 1910.
In the 1970s, the B-cell cancer multiple myeloma was known, and it was understood that these cancerous B-cells all produce a single type of antibody (a paraprotein). This was used to study the structure of antibodies, but it was not yet possible to produce identical antibodies specific to a given antigen.
Production of monoclonal antibodies involving human–mouse hybrid cells was described by Jerrold Schwaber in 1973[1] and remains widely cited among those using human-derived hybridomas,[2] but claims of priority have been controversial. A science history paper on the subject gave some credit to Schwaber for inventing a technique that was widely cited, but stopped short of suggesting that he had been cheated.[3] Schwaber's work was only used for fusing human and mouse cells with the goal of eliminating chromosomes to identify genetic markers. Dr. Pieczenik suggested to Cotton what became the Cotton-Milstein experiment where the Kohler Milstein experiment was the control. This is all documented in the MRC, Cambridge, Archives and with letters from witnesses who later won the Nobel prize i.e. John Sedat and his wife Elizabeth Blackburn. The invention was reduced to practice by Cotton and Milstein, and then by Kohler and Milstein. Georges Köhler, César Milstein, and Niels Kaj Jerne in 1975;[4] who shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery. The key idea was to use a line of myeloma cells that had lost their ability to secrete antibodies, come up with a technique to fuse these cells with healthy antibody-producing B-cells, and be able to select for the successfully fused cells. This was put into practice by Milstein and Köhler in their search for a laboratory tool to investigate antibody diversity.[5]
In 1988, Greg Winter and his team pioneered the techniques to humanize monoclonal antibodies,[6] removing the reactions that many monoclonal antibodies caused in some patients.
Hybridoma cell production[edit]
Monoclonal antibodies are typically made by fusing myeloma cells with the spleen cells from a mouse that has been immunized with the desired antigen. However, recent advances have allowed the use of rabbit B-cells to form a rabbit hybridoma. Polyethylene glycol is used to fuse adjacent plasma membranes, but the success rate is low so a selective medium in which only fused cells can grow is used. This is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase (HGPRT), an enzyme necessary for the salvage synthesis of nucleic acids. The absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is also disrupted. By exposing cells to aminopterin (a folic acid analogue, which inhibits dihydrofolate reductase, DHFR), they are unable to use the de novo pathway and become fully auxotrophic for nucleic acids requiring supplementation to survive.
The selective culture medium is called HAT medium because it contains hypoxanthine, aminopterin, and thymidine. This medium is selective for fused (hybridoma) cells. Unfused myeloma cells cannot grow because they lack HGPRT, and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their limited life span. Only fused hybrid cells, referred to as hybridomas, are able to grow indefinitely in the media because the spleen cell partner supplies HGPRT and the myeloma partner has traits that make it immortal (similar to a cancer cell).
This mixture of cells is then diluted and clones are grown from single parent cells on microtitre wells. The antibodies secreted by the different clones are then assayed for their ability to bind to the antigen (with a test such as ELISA or Antigen Microarray Assay) or immuno-dot blot. The most productive and stable clone is then selected for future use.
The hybridomas can be grown indefinitely in a suitable cell culture medium. They can also be injected into mice (in the peritoneal cavity, surrounding the gut). There, they produce tumors secreting an antibody-rich fluid called ascites fluid.
The medium must be enriched during in-vitro selection to further favour hybridoma growth. This can be achieved by the use of a layer of feeder fibrocyte cells or supplement medium such as briclone. Culture-medium conditioned by macrophages can also be used. Production in cell culture is usually preferred as the ascites technique is painful to the animal. Where alternate techniques exist, this method (ascites) is considered unethical.
Purification of monoclonal antibodies[edit]
After obtaining either a media sample of cultured hybridomas or a sample of ascites fluid, the desired antibodies must be extracted. The contaminants in the cell culture sample would consist primarily of media components such as growth factors, hormones, and transferrins. In contrast, the in vivo sample is likely to have host antibodies, proteases, nucleases, nucleic acids, and viruses. In both cases, other secretions by the hybridomas such as cytokines may be present. There may also be bacterial contamination and, as a result, endotoxins that are secreted by the bacteria. Depending on the complexity of the media required in cell culture, and thus the contaminants in question, one method (in vivo or in vitro) may be preferable to the other.
The sample is first conditioned, or prepared for purification. Cells, cell debris, lipids, and clotted material are first removed, typically by centrifugation followed by filtration with a 0.45 µm filter. These large particles can cause a phenomenon called membrane fouling in later purification steps. In addition, the concentration of product in the sample may not be sufficient, especially in cases where the desired antibody is one produced by a low-secreting cell line. The sample is therefore condensed by ultrafiltration or dialysis.
Most of the charged impurities are usually anions such as nucleic acids and endotoxins. These are often separated by ion exchange chromatography.[7] Either cation exchange chromatography is used at a low enough pH that the desired antibody binds to the column while anions flow through, or anion exchange chromatography is used at a high enough pH that the desired antibody flows through the column while anions bind to it. Various proteins can also be separated out along with the anions based on their isoelectric point (pI). For example, albumin has a pI of 4.8, which is significantly lower than that of most monoclonal antibodies, which have a pI of 6.1. In other words, at a given pH, the average charge of albumin molecules is likely to be more negative. Transferrin, on the other hand, has a pI of 5.9, so it cannot easily be separated out by this method. A difference in pI of at least 1 is necessary for a good separation.
Transferrin can instead be removed by size exclusion chromatography. The advantage of this purification method is that it is one of the more reliable chromatography techniques. Since we are dealing with proteins, properties such as charge and affinity are not consistent and vary with pH as molecules are protonated and deprotonated, while size stays relatively constant. Nonetheless, it has drawbacks such as low resolution, low capacity and low elution times.
A much quicker, single-step method of separation is Protein A/G affinity chromatography. The antibody selectively binds to Protein A/G, so a high level of purity (generally >80%) is obtained. However, this method may be problematic for antibodies that are easily damaged, as harsh conditions are generally used. A low pH can break the bonds to remove the antibody from the column. In addition to possibly affecting the product, low pH can cause Protein A/G itself to leak off the column and appear in the eluted sample. Gentle elution buffer systems that employ high salt concentrations are also available to avoid exposing sensitive antibodies to low pH. Cost is also an important consideration with this method because immobilized Protein A/G is a more expensive resin.
To achieve maximum purity in a single step, affinity purification can be performed, using the antigen to provide exquisite specificity for the antibody. In this method, the antigen used to generate the antibody is covalently attached to an agarose support. If the antigen is a peptide, it is commonly synthesized with a terminal cysteine, which allows selective attachment to a carrier protein, such as KLH during development and to the support for purification. The antibody-containing media is then incubated with the immobilized antigen, either in batch or as the antibody is passed through a column, where it selectively binds and can be retained while impurities are washed away. An elution with a low pH buffer or a more gentle, high salt elution buffer is then used to recover purified antibody from the support.
To further select for antibodies, the antibodies can be precipitated out using sodium sulfate or ammonium sulfate. Antibodies precipitate at low concentrations of the salt, while most other proteins precipitate at higher concentrations. The appropriate level of salt is added in order to achieve the best separation. Excess salt must then be removed by a desalting method such as dialysis.
The final purity can be analyzed using a chromatogram. Any impurities will produce peaks, and the volume under the peak indicates the amount of the impurity. Alternatively, gel electrophoresis and capillary electrophoresis can be carried out. Impurities will produce bands of varying intensity, depending on how much of the impurity is present.
Antibody heterogeneity[edit]
Product heterogeneity is common to monoclonal antibody and other recombinant biological production and is typically introduced either upstream during expression or downstream during manufacturing.
These variants are typically aggregates, deamidation products, glycosylation variants, oxidized amino acid side chains, as well as amino and carboxyl terminal amino acid additions.[8] These seemingly minute changes in a monoclonal antibody's structure can have a profound effect on preclinical stability and process optimization as well as therapeutic product potency, bioavailability, and immunogenicity. The generally accepted method of purification of process streams for monoclonal antibodies includes capture of the product target with Protein A, elution, acidification to inactivate potential Mammalian viruses, followed by cation exchange chromatography, and finally anion exchange chromatography.
Displacement chromatography has been used to identify and characterize these often unseen variants in quantities that are suitable for subsequent preclinical evaluation regimens such as animal pharmacokinetic studies.[9][10] Knowledge gained during the preclinical development phase is critical for enhanced understanding of product quality and provides a basis for risk management and increased regulatory flexibility. The recent Food and Drug Administration's Quality by Design initiative attempts to provide guidance on development and to facilitate design of products and processes that maximizes efficacy and safety profile while enhancing product manufacturability.[11]
The production of recombinant monoclonal antibodies involves technologies, referred to as repertoire cloning or phage display/yeast display. Recombinant antibody engineering involves the use of viruses or yeast to create antibodies, rather than mice. These techniques rely on rapid cloning of immunoglobulin gene segments to create libraries of antibodies with slightly different amino acid sequences from which antibodies with desired specificities can be selected.[12] The phage antibody libraries are a variant of the phage antigen libraries first invented by George Pieczenik[13] These techniques can be used to enhance the specificity with which antibodies recognize antigens, their stability in various environmental conditions, their therapeutic efficacy, and their detectability in diagnostic applications.[14] Fermentation chambers have been used to produce these antibodies on a large scale.
Chimeric antibodies[edit]
Early on, a major problem for the therapeutic use of monoclonal antibodies in medicine was that initial methods used to produce them yielded mouse, not human antibodies. While structurally similar, differences between the two were sufficient to invoke an immune response when murine monoclonal antibodies were injected into humans, resulting in their rapid removal from the blood, as well as systemic inflammatory effects, and the production of human anti-mouse antibodies (HAMA).[citation needed]
In an effort to overcome this obstacle, approaches using recombinant DNA have been explored since the late 1980s. In one approach, mouse DNA encoding the binding portion of a monoclonal antibody was merged with human antibody-producing DNA in living cells. The expression of this chimeric DNA through cell culture yielded partially mouse, partially human monoclonal antibodies. For this product, the descriptive terms "chimeric" and "humanised" monoclonal antibody have been used to reflect the combination of mouse and human DNA sources used in the recombinant process.[15]
'Fully' human monoclonal antibodies[edit]
Ever since the discovery that monoclonal antibodies could be generated, scientists have targeted the creation of 'fully' human antibodies to avoid some of the side effects of humanised or chimeric antibodies. Two successful approaches have been identified: transgenic mice[16] and phage display.
Transgenic mice technology is by far the most successful approach to making 'fully' human monoclonal antibody therapeutics: 7 of the 9 'fully' human monoclonal antibody therapeutics on the market were derived in this manner.[17]
Transgenic mice have been exploited by a number of commercial organisations:
- Medarex — who marketed their UltiMab platform. Medarex were acquired in July 2009 by Bristol Myers Squibb[18]
- Abgenix — who marketed their Xenomouse technology. Abgenix were acquired in April 2006 by Amgen.[19]
- Regeneron's VelocImmune technology.[20]
- Kymab - who market their Kymouse technology.[21]
- Open Monoclonal Technology's OmniRat™ and OmniMouse™ platform.[22]
One of the most successful commercial organisations using phage display technology was Cambridge Antibody Technology (CAT). Scientists at CAT demonstrated that phage display could be used such that variable antibody domains could be expressed on filamentous phage antibodies. This was reported in a key Nature publication.[23]
Other significant publications include:
- Marks JD, Hoogenboom HR, Bonnert TP, McCafferty J, Griffiths AD, Winter G (December 1991). "By-passing immunization. Human antibodies from V-gene libraries displayed on phage". J. Mol. Biol. 222 (3): 581–597. doi:10.1016/0022-2836(91)90498-U. PMID 1748994.
- Carmen S, Jermutus L (July 2002). "Concepts in antibody phage display". Brief Funct Genomic Proteomic 1 (2): 189–203. doi:10.1093/bfgp/1.2.189. PMID 15239904.
CAT developed their display technologies further into several, patented antibody discovery/functional genomics tools, which were named ProximolTM[24][25] and ProAbTM. ProAb was announced in December 1997[26] and involved high throughput screening of antibody libraries against diseased and non-diseased tissue, whilst Proximol used a free radical enzymatic reaction to label molecules in proximity to a given protein.[27][28]
Monoclonal antibodies have been generated and approved to treat cancer, cardiovascular disease, inflammatory diseases, macular degeneration, transplant rejection, multiple sclerosis, and viral infection (see monoclonal antibody therapy).
In August 2006 the Pharmaceutical Research and Manufacturers of America reported that U.S. companies had 160 different monoclonal antibodies in clinical trials or awaiting approval by the Food and Drug Administration.[29]
Diagnostic tests[edit]
Once monoclonal antibodies for a given substance have been produced, they can be used to detect the presence of this substance. The Western blot test and immuno dot blot tests detect the protein on a membrane. They are also very useful in immunohistochemistry, which detect antigen in fixed tissue sections and immunofluorescence test, which detect the substance in a frozen tissue section or in live cells.
Therapeutic treatment[edit]
Cancer treatment[edit]
One possible treatment for cancer involves monoclonal antibodies that bind only to cancer cell-specific antigens and induce an immunological response against the target cancer cell. Such mAb could also be modified for delivery of a toxin, radioisotope, cytokine or other active conjugate; it is also possible to design bispecific antibodies that can bind with their Fab regions both to target antigen and to a conjugate or effector cell. In fact, every intact antibody can bind to cell receptors or other proteins with its Fc region.
The illustration below shows all these possibilities:
MAbs approved by the FDA include[31]
Autoimmune diseases[edit]
Monoclonal antibodies used for autoimmune diseases include infliximab and adalimumab, which are effective in rheumatoid arthritis, Crohn's disease and ulcerative Colitis by their ability to bind to and inhibit TNF-α.[32] Basiliximab and daclizumab inhibit IL-2 on activated T cells and thereby help prevent acute rejection of kidney transplants.[32] Omalizumab inhibits human immunoglobulin E (IgE) and is useful in moderate-to-severe allergic asthma.
Examples of therapeutic monoclonal antibodies[edit]
Below are examples of clinically important monoclonal antibodies.
Main category | Type | Application | Mechanism/Target | Mode |
Anti- inflammatory |
infliximab[32] | inhibits TNF-α | chimeric | |
adalimumab | inhibits TNF-α | human | ||
basiliximab[32] |
inhibits IL-2 on activated T cells | chimeric | |
daclizumab[32] |
inhibits IL-2 on activated T cells | humanized | |
omalizumab |
inhibits human immunoglobulin E (IgE) | humanized | |
Anti-cancer | gemtuzumab[32] |
targets myeloid cell surface antigen CD33 on leukemia cells | humanized |
alemtuzumab[32] | targets an antigen CD52 on T- and B-lymphocytes | humanized | ||
rituximab[32] | targets phosphoprotein CD20 on B lymphocytes | chimeric | ||
trastuzumab |
targets the HER2/neu (erbB2) receptor | humanized | |
nimotuzumab |
EGFR inhibitor | Humanized | |
cetuximab |
EGFR inhibitor | Chimeric | |
bevacizumab |
inhibits VEGF | humanized | |
Other | palivizumab[32] |
inhibits an RSV fusion (F) protein | humanized |
abciximab[32] |
inhibits the receptor GpIIb/IIIa on platelets | chimeric |
See also[edit]
- Antibody mimetic
- Immunotoxins, which sometimes use monoclonal antibodies as the targeting mechanism
- List of monoclonal antibodies
- Monoclonal antibody therapy
- Nomenclature of monoclonal antibodies
- Polyclonal antibodies
- Queen Mab Small mythological figure symbolizing hope (popular culture, used as biotech pun).
- ^ Schwaber, J.; Cohen, E. P. (1973). "Human x mouse somatic cell hybrid clone secreting immunoglobulins of both parental types". Nature 244 (5416): 444–447. Bibcode:1973Natur.244..444S. doi:10.1038/244444a0. PMID 4200460.
- ^ Science Citation Index
- ^ Cambrosio, A.; Keating, P. (1992). "Between fact and technique: the beginnings of hybridoma technology". Journal of the History of Biology 25 (2): 175–230. doi:10.1007/BF00162840. PMID 11623041.
- ^ Köhler, G.; Milstein, C. (1975). "Continuous cultures of fused cells secreting antibody of predefined specificity". Nature 256 (5517): 495–497. Bibcode:1975Natur.256..495K. doi:10.1038/256495a0. PMID 1172191.
- ^ The Story of César Milstein and Monoclonal Antibodies.
- ^ Riechmann L, Clark M, Waldmann H, Winter G (March 1988). "Reshaping human antibodies for therapy". Nature 332 (6162): 323–327. Bibcode:1988Natur.332..323R. doi:10.1038/332323a0. PMID 3127726.
- ^ Vlasek J, Ionescu R (2008). "Hetergeneity of Monoclonal Antibodies Revealed by Charge-Sensitive Methods". Current Pharmaceutical Biotechnology 9 (6): 468–481. doi:10.2174/138920108786786402. PMID 19075686.
- ^ Beck A, Wurch T, Bailly C, Corvaia N (May 2010). "Strategies and challenges for the next generation of therapeutic antibodies". Nat. Rev. Immunol. 10 (5): 345–52. doi:10.1038/nri2747. PMID 20414207.
- ^ Khawli LA, Goswami S, Hutchinson R, et al. (2010). "Charge variants in IgG1: Isolation, characterization, in vitro binding properties and pharmacokinetics in rats". MAbs 2 (6): 613–24. doi:10.4161/mabs.2.6.13333. PMC 3011216. PMID 20818176.
- ^ Zhang T, Bourret J, Cano T (August 2011). "Isolation and characterization of therapeutic antibody charge variants using cation exchange displacement chromatography". J Chromatogr A 1218 (31): 5079–86. doi:10.1016/j.chroma.2011.05.061. PMID 21700290.
- ^ Rathore AS, Winkle H (January 2009). "Quality by design for biopharmaceuticals". Nat. Biotechnol. 27 (1): 26–34. doi:10.1038/nbt0109-26. PMID 19131992.
- ^ Siegel DL (2002). "Recombinant monoclonal antibody technology". Transfusion clinique et biologique : journal de la Société française de transfusion sanguine 9 (1): 15–22. doi:10.1016/S1246-7820(01)00210-5. PMID 11889896.
- ^ "Dr. George Pieczenik". LMB Alumni. MRC Laboratory of Molecular Biology (LMB). 17 September 2009.
- ^ Schmitz U, Versmold A, Kaufmann P, Frank HG (2000). "Phage display: a molecular tool for the generation of antibodies—a review". Placenta 21 (Suppl A): S106–S112. doi:10.1053/plac.1999.0511. PMID 10831134.
- ^ Chadd HE, Chamow SM (April 2001). "Therapeutic antibody expression technology". Curr. Opin. Biotechnol. 12 (2): 188–94. doi:10.1016/S0958-1669(00)00198-1. PMID 11287236.
- ^ Lonberg N, Huszar D (1995). "Human antibodies from transgenic mice". Int. Rev. Immunol. 13 (1): 65–93. doi:10.3109/08830189509061738. PMID 7494109.
- ^ Monoclonal antibody therapy
- ^ "Bristol-Myers Buys Medarex Drugmaker for $2.4 Billion (Update3)".
- ^ "Amgen Completes Acquisition of Abgenix; Acquisition Provides Amgen with Full Ownership of Panitumumab and Eliminates a Denosumab Royalty".
- ^ http://www.regeneron.com/velocimmune.html
- ^ "Proprietary antibody platform".
- ^ "Naturally optimized human antibodies".
- ^ McCafferty, J.; Griffiths, A.; Winter, G.; Chiswell, D. (1990). "Phage antibodies: filamentous phage displaying antibody variable domains". Nature 348 (6301): 552–554. Bibcode:1990Natur.348..552M. doi:10.1038/348552a0. PMID 2247164.
- ^ Osbourn JK (2002). "Proximity-guided (ProxiMol) antibody selection". Methods Mol. Biol. 178: 201–5. PMID 11968489.
- ^ Abeloff, MD; Armitage, JO; Niederhuber, JE; Kastan, MB; McKenna, G (2008). "Therapeutic Antibodies and Immunologic Conjugates". Abeloff's Clinical Oncology (4th ed.). Elsevier.
- ^ "Cambridge Antibody Technology".
- ^ Osbourn JK, Derbyshire EJ, Vaughan TJ, Field AW, Johnson KS (January 1998). "Pathfinder selection: in situ isolation of novel antibodies". Immunotechnology 3 (4): 293–302. doi:10.1016/S1380-2933(97)10007-0. PMID 9530562.
- ^ "The Current State of Proteomic Technology".
- ^ PhRMA Reports Identifies More than 400 Biotech Drugs in Development. Pharmaceutical Technology, August 24, 2006. Retrieved 2006-09-04.
- ^ Modified from Carter P (November 2001). "Improving the efficacy of antibody-based cancer therapies". Nat. Rev. Cancer 1 (2): 118–29. doi:10.1038/35101072. PMID 11905803.
- ^ Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management
- ^ a b c d e f g h i j Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. pp. 241, for the examples infliximab, basiliximab, abciximab, daclizumab, palivusamab, gemtuzumab, alemtuzumab and rituximab, and mechanism and mode. ISBN 0-443-07145-4.
External links[edit]
Library resources about Monoclonal antibody |
- Monoclonal Antibodies, from John W. Kimball's online biology textbook
- Monoclonal antibodies at the US National Library of Medicine Medical Subject Headings (MeSH)
- Antibodypedia, open-access virtual repository publishing data and commentary on any antibodies available to the scientific community.
- Antibody Purification Handbook


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Snake Plissken
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sf2k4 said...
Just saw on the news that UAB Medicine is going to start requiring that new employees take a nicotine test to prove they don't smoke before they'll be hired. Current employees who smoke will be "grandfathered in," so to speak. Now, I don't smoke and I don't particularly like when people smoke around me, but is this ethical? Tobacco, as bad as it is, isn't illegal. I could see someone banning smoking at work, but at all?
Maybe I'm weird, but I've heard a similar argument made against people that drink (IE: You should have to be alcohol free 100% to be hired, or companies should be allowed to require as such). IMO, what I do in my free, non-job time isn't my company's business when what I'm doing is legal (drugs, etc. are an argument for another topic).
Thoughts? Again, they're not saying you can't smoke at work, they're saying their new employees can't smoke. Ever. Period.
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CMXI said...
I don't see a problem with this being a pre-req for enrollment in a company-sponsored health-care plan, but no company should be able to mandate your behavior outside of work unless it affects your actual work product.
If the company doesn't want to hire smokers, I think it'd be much easier just to tell people up front that the company doesn't offer any smoke breaks at any point throughout the day. That'd probably weed enough people out in advance.
cuznchips28 ●
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captain brandon said...
I'm a smoke and I call BS. At my work place, we get two 15 minute breaks, 10 am and 3 pm. That's everyone, the front office people rotate so someone is always there to answer the phones and help customers. Yes, I go out back and "burn" one, but I don't take "smoke breaks".
I personally don't agree with this practice, not because I smoke, but the idea of a company telling me what I can and can't do in my personal life. I'm not your damn slave, when I'm off the clock and off company property, I will do what I damn well please. What's next, fat people, non-christains, companies not hiring because of political views, having a kid out of wedlock, where does it end?
Scored 4 touchdowns...in a single game. Polk High!
WillyDees said...
I disagree with it. Addiction is a physical illness, and smoking is no different. Would they turn down a diabetic if they were the most qualified? What about someone who struggles with bipolar disorder?
Who do you want delivering a high risk baby? The smoking obstetrician who has handled hundreds of similar cases or less qualified OB who was hired because he/she doesnt use nicotene?
Hospital stress management and EAPs are a joke. Healthcare is stressful as hell. The decisions, the hours, etc...
I suggest a happy medium. Viva could negotiate better rates by requiring new smokng employes to enroll in nicotene cessation programs. Tell UAB "The the better results, the bigger discount". Push this on.grandfathered employees as well. Give them incentives. Lower rates mean more $$$ for everyone.
Do not allow smoking on campus. Not sure how theyd enforce this at UAB...
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Celebrating Culture
January 23, 2013
Experiencing the Day of the Dead in Oaxaca is at once a step into the traditions of the past, as well as a welcome into a vibrant community with a rich cultural history. Take a private tour through the city in the midst of this festival (which is uniquely lavish in Oaxaca) and relish the once-in-a-lifetime sights and sounds! The smell of a bubbling traditional chocolate mole will wash over you as the aroma of fresh produce wafts from the local market, and just as soon as that has whetted your appetite, you'll come around the corner into view of a spectacular procession complete with a full brass band, flower-wearing costumers in a riot of colors, and life-sized marionette puppets of skeletons and ghosts. You'll watch the parade wind its way through the city streets toward the cemetery, where people have laid down a path of marigold petals, meant to lead the spirits of their loved ones to the intricate, detailed altars that have been erected at their resting places. Cap off your day with an elaborately prepared sumptuous feast of local flavor, including rich, slow-cooked rabbit mole, crunchy fried grasshoppers, and a drink of smoky yet spicy Mezcal, the only-made-in-Oaxaca tequila derivative. And if you're feeling brave, you can even eat the worm in the bottle that proves it's really Mezcal!
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Publisher: Ishi Press Author: I. A. HorowitzYear of Publication: 2009(2nd)
Pages: 200 Notation Type: Figurine (FAN)
International Master Al Horowitz goes through every major chess opening system and provides just one line of play for White, one line of play for Black, and the reason for each move by White or Black. This book will not show the reader how to win every game, but it will provide an easy route which will enable the player to get a reasonable, playable position out of the opening with good winning chances, even against the strongest opponents, without having to memorize a bunch of opening lines.
Because the reason for every move is given, it is entirely possible to learn every move in this book, simply by remembering the reason for the next move. Once the reason is remembered, then it is much easier to figure out what the next move is.
All of the lines in this book are still played at the top levels. None are obsolete. In addition, while some might consider them to be out of date, the average chess player does not need to know the latest theoretical variations. The old lines will do just as well, if not better.
This book is recommended for any tournament player rated below 1700. Players rated higher than that will probably already know most of the material in this book.
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Solitaire Chess
Winning Chess Openings
Golden Treasury of Chess
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