A World Without Writers

 

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[Hat Tip: Canadian Cynic]

Monday's Molecule #52

 
Today's molecule is a bit more complicated than some. Most of you probably haven't encountered it in your studies and those who have may have seen it drawn a bit differently. Your task is to give it a complete biochemical name as well as the shortened common name.

There's a direct connection between this molecule and Wednesday's Nobel Laureate(s).

The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous winners are ineligible for one month from the time they first collected the prize. There are three ineligible candidates for this week's reward. The prize is a free lunch at the Faculty Club.

Send your guess to Sandwalk (sandwalk(at)bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and the Nobel Laureate(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: We have a winner! The molecule is 3-hydroxy-3-methylglutaryl-Coenzyme A, or HMG-CoA. Wait to see who the Nobel Laureate is tomorrow.

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Crystal Tells Us about the Human Genome

According to the YouTube profile ...

Crystal is graduated from Texas A&M University w/ a degree in agricultural leadership and development with an emphasis on genetics and bio-chemistry. She is currently a professional model.

Here's her website [crystalnicole.com]. There's not much on her website about DNA or genomes. On the other hand, there's a lot of Crystal. I suspect science isn't her main interest in life.

This is a video about the human genome. Crystal tells us lots of interesting things about the size of our genome, number of genes, junk DNA, whether the DNA of different races is the same etc. etc.

It makes my blood boil. A lot of the information is basically correct but there's no explanations. For example, we know why the rice genome has more genes than the human genome—it's not a mystery. Some of the information is wrong (e.g., similarities between different species). Some of it is misleading (e.g., the definition of a gene).

I assume that this is just a regurgitation of things that Crystal learned in class. Rather than detail all of the errors I'll leave it up to you. You can list them in the comments.

The question I want answered is whether this sort of video serves a useful purpose or not. Is it better to have such a thing on YouTube than nothing at all? (I think we can all agree that the ideal situation would be to have a similar video that was accurate.)

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[Hat Tip: Curious Cat and ScienceRoll]

John Wilkins Likes Sociobiology

 
Wilkins is reviewing a soon-to-be-published paper by David Sloan Wilson and Edward O. Wilson [The two Wilsons on sociobiology]. These two are on a recent tear promoting a new, acceptable, version of group selection. John Wilkins declares that, "I have recently (i.e., in the last five years) come to be an unflinching sociobiologist ..."

This may raise some eyebrows but, as usual, John threads his way through the minefield of misconceptions about sociobiology to arrive at a position that he can support. (I don't agree with him, but that debate is for another time.)

What I particularly like about John's posting is how he separates evolutionary psychology from sociobiology by pointing out the deep flaws in the discipline of evolutionary psychology.

Evolutionary psychology has two major flaws in my opinion. One is that it is almost always adaptationist even when no evidence of adaptiveness is available. Adaptation is, as G. C. Williams noted of group selection explanations, an onerous hypothesis, to be supported or not used. It is too easy to come up with "possible scenarios", let alone possible adaptations. Such explanations need to follow the evidence rather than use, as EvPsych does, a priori arguments from the self-evident truth of natural selection and the nature of evolution.

The second major flaw relates to this. On the (a priori) assumption that selection always favours modularity, EvPsychologists claim that most of the human behavioural repertoire and its underlying neurology is modular. Each module is, as the literature has it, "informationally encapsulated and domain specific", which roughly means that it does one thing well and only that thing, without hints from the rest of our cognitive and sensorimotor system.

I agree with John 100%, although I might add one or two other flaws. I'm not sure the Wilsons would agree, however. I wonder if John knows whether E.O. Wilson is as opposed to evolutionary psychology as he (John) is?

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Where Was Anderson Cooper?

 
The latest death toll from Bangladesh is 2200 and this number will almost certainly rise. Chris Mooney knew this was coming last Wednesday and he warned everyone to expect a disaster [Still No Weakening for Cyclone Sidr].

Why didn't CNN dispatch its crack team of hurricane reporters to the scene? And why, even now, is the news media treating this so lightly?

Yesterday I watched while the CNN anchors reported on the dead and injured and the millions of people who lost their homes. They then switched immediately to light-heated banter about elderly women playing basketball. We didn't see that kind of insensitivity during Katrina, did we?

Should there be a difference just because one hurricane is killing Americans while another is killing people in Bangledesh?


UPDATE: Death Toll Might Reach 10,000.

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[Photo Credits: AFP: Bangladesh cyclone dead number 2,200, millions destitute]

Adaptationist Award #2

 
Jonathan Eisen at The Tree of Life has just given out his second adaptationist award. This "award" goes to those who exemplify the famous Dr. Pangloss referred to in Gould and Lewontin (1979).

This award goes to David Brown for his article in the Washington Post. An article that begins with ...

It used to be a rule -- actually, more of an assumption -- that the genetic machinery of living organisms was never intentionally wasteful or inaccurate. It turns out this isn't always true, either.

I think you can already see why this award is so richely deserved but if you're still in doubt check out the posting [Adaptationomics Award #2 - Washington Post and David Brown].

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Gould, S.J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme. Proc. Roy. Soc. (London) Series B, 205:581-598. [OnLine Version]

John Dennehy's Citation Classic

 
John Dennehy's citation classic for this week is a paper by Volkin and Astrachan published in 1956. That's Elliot "Ken" Volkin on the left.

I was not aware of this paper but John makes a good case for its importance in the history of molecular biology. Volkin and Astrachan deserve more recognition for discovering messenger RNA (mRNA). Get on over to The Evilutionary Biologist and read about the private meeting between Francis Crick, Sidney Brenner, and François Jabob in Brenner's room at King's College in 1960 [This Week's Citation Classic].

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[Photo Credit: Oak Ridge National Laboratory]

Bruce Alberts in Toronto

 
My Ph.D. supervisor, Bruce Alberts, was in Toronto yesterday to receive an honourary Doctor of Science degree from the University of Toronto. We had a nice luncheon in the Upper Library at Massey College. That's Bruce Alberts on the right and my former Ph.D. student and co-author Marc Perry on the left. Three "generations" of Ph.D.'s.

I'm sure three-generation pictures are quite common but four- and five-generation photographs are more unusual. Does anyone have one?

Following the luncheon we were off to the Chancellor's Office to get "gowned" for the graduation ceremony. Yesterday was graduation day for Ph.D. and Masters degree students.

The students were lined up to enter Convocation Hall. There were 391 of them and later on we waited while each one was called to the stage to receive their degree.

The procession of faculty was quite impressive with all the gowns, finery, pomp, and circumstance. Here we are (below) all dressed up on the stage of Convocation Hall. From left to right, Katherine Whiteside, Dean of Medicine; Bruce Alberts, convocation speaker and honourary degree recipient; Jack Petch, Chair Governing Council; David Peterson, Chancellor; David Naylor, President; Susan Pfeiffer, Dean School of Graduate Studies; and half of me on the end. On the right I'm delivering the citation for Bruce Alberts.


Here's part of what I said,

Bruce was very successful at Princeton where he made major advances in working out the mechanism of DNA replication, laying the groundwork for future recognition as an outstanding scientist. He has also contributed greatly to our understanding of chromosomes. In 1995 he came to Toronto to receive a Gairdner Award for his scientific achievements. He has published over 150 scientific papers.

Bruce moved to the University of California at San Francisco in 1976. He served as Chair of the Department of Biochemistry & Biophysics during the time that it rose to become one of the leading biochemistry departments in the world. Bruce’s guidance and mentorship during that time contributed in no small part to the success of the department.

Among the many honours and awards he has received I’d like to single out a few others that relate to his scientific achievements. He holds an American Cancer Society Lifetime Research Professorship. He was elected to the American National Academy of Sciences in 1981. He is a Foreign Member of the Royal Society (London) and many other international societies.

Bruce’s interest in science education was apparent from the beginning. In 1983 he and his colleagues published the very first edition of his famous textbook Alberts et al. The Molecular Biology of the Cell. The book has become familiar to students all around the world. The fifth edition is due to be published in just a few weeks. The Molecular Biology of the Cell set a standard for textbook writing that few other books have matched. I dare say many of the students here have taken at least one course that used his book.

In 1993, Bruce left San Francisco and moved to Washington to become President of the National Academy of Sciences—a post he held for twelve years. During that time he was “First Scientist” in the USA and, arguably, the most influential scientist in the world.

Bruce soon became known as the “Education President” for his efforts to improve science education beginning in kindergarten and the primary grades. He is highly respected for his tireless efforts in bettering science education and research policies in the USA and around the world. This effort has continued since he left Washington. He has received numerous awards for his achievements in education including Outstanding Volunteer Coordinator in California schools, the Leadership in Education Award from Keystone Center, the Distinguished Service Award from the National Association of Biology Teachers, and the Victor Hamburger Outstanding Educator Prize from the American Association for Developmental Biology.

There are even more awards and honours, for example Bruce Alberts is a Commander of the Order of the British Empire.

Outstanding scientist, caring mentor, renowned author, and distinguished educator.

Mr, Chancellor, on behalf of the Governing Council, I ask you to confer the degree of Doctor Of Science, honoris causa, upon Bruce Alberts.

After the graduation ceremony we came back to the Biochemistry Department for a reception in Bruce's honour. Many of the graduate and undergraduate students showed up with copies of their textbooks and Bruce was delighted to sign them.

We had a wonderful, but short, visit. I hope he comes back again real soon.

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Are You as Smart as a Second Year University Student? Q2

 
Here's another question from my test.

In Icons of Evolution Jonathan Wells defines evolution as,

Biological evolution is the theory that all living things are modified descendants of a common ancestor that lived in the distant past.

Does this definition differ from the one you learned in biology class? Does it differ from the definitions of evolution commonly found in textbooks? Why does Wells choose this definition over any others?

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Are You as Smart as a Second Year University Student? Q1

 
Here's a question from last month's test in our class on the evolution/creationism debate. How would you have done?

Philip Johnson is one of the leading advocates of intelligent design creationism, He argues that science is unnecessarily atheistic because it requires methodological naturalism.

Creationists are disqualified from making a positive case, because science by definition is based on naturalism. The rules of science also disqualify any purely negative argumentation designed to dilute the persuasiveness of the theory of evolution. Creationism is thus out of court—and out of the classroom—before any consideration of evidence. Put yourself in the place of a creationist who has been silenced by that logic, and you may feel like a criminal defendant who has just been told that the law does not recognize so absurd a concept as "innocence."

Is this a good argument for intelligent design creationism? Explain your answer.

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The Johnson quotation is from Johnson, P.E. (1990) "Evolution as Dogma: The Establishment of Naturalism" first published in First Things 6:15-22. reprinted in Intelligent Design Creationism and Its Critics Robert T. Pennock ed.

Judgment Day

 
I just saw the show last night. I had to tape it on Tuesday night because the only way I could see it was on WCTS Seattle and that was too late for me to stay up [Judgment Day Is Coming].

The show was very good. I was impressed with the way it was edited and with the lack of unnecessary hype. The courtroom scenes were a bit silly but I can't think of any way to improve them short of making them look too theatrical. At least this way you weren't under any illusions that it was anything but a simulation.

I liked the emphasis on the divisions within the community. What it shows us is that no courtroom victory is going to make this issue go away. The creationists simply don't accept the results of the trial as having any relevance to their religion. Americans are going to have to go through this trauma several more times in the next few years.

I'm still a bit sad that programs like this have to go out of their way to show that evolutionists can be religious. There were obligatory scenes of Ken Miller in church and of one of the Dover evolutionist supporters teaching Bible class. This is a debate about science and religion. The whole point was to show that Intelligent Design Creationism is religion and not science. Evolution is science. So why is it necessary to focus on the religious beliefs of evolution supporters? Shouldn't their personal beliefs be irrelevant?

There are lots of interesting things on the Judgment Day website [NOVA: Judgment Day]. One of them is a brief talk by Ken Miller on "Science and Religion" (follow the link "Defining Science"). I wonder if most people agree with Miller's explanation of the supernatural and how it impinges on science?

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Framing Evolution

 
Clive Thompson wrote an article for Wired titled Clive Thompson on Why Science Will Triumph Only When Theory Becomes Law.

It falls into the category of "with friends like this who need enemies." Thompson is upset about the way in which creationists misuse the word theory.

This is the central argument of evolution deniers: Evolution is an unproven "theory." For science-savvy people, this is an incredibly annoying ploy. While it's true that scientists refer to evolution as a theory, in science the word theory means an explanation of how the world works that has stood up to repeated, rigorous testing. It's hardly a term of disparagement.

But for most people, theory means a haphazard guess you've pulled out of your, uh, hat. It's an insult, really, a glib way to dismiss a point of view: "Ah, well, that's just your theory." Scientists use theory in one specific way, the public another — and opponents of evolution have expertly exploited this disconnect.

We all agree that this is a problem when we're trying to explain evolutionary theory to the general public. We need to explain that a theory is not just some wide-eyed speculation but a solid explanation of facts that has stood the test of time. Theories are as good as it gets in science. The Theory of Natural Selection, for example, is not in dispute.

It's a pain to have to do this but it's our obligation as scientists to explain science correctly, right? Clive Thompson has another suggestion.

For truly solid-gold, well-established science, let's stop using the word theory entirely. Instead, let's revive much more venerable language and refer to such knowledge as "law." As with Newton's law of gravity, people intuitively understand that a law is a rule that holds true and must be obeyed. The word law conveys precisely the same sense of authority with the public as theory does with scientists, but without the linguistic baggage.

Evolution is supersolid. We even base the vaccine industry on it: When we troop into the doctor's office each winter to get a flu shot — an inoculation against the latest evolved strains of the disease — we're treating evolution as a law. So why not just say "the law of evolution"?

Best of all, it performs a neat bit of linguistic jujitsu. If someone says, "I don't believe in the theory of evolution," they may sound fairly reasonable. But if someone announces, "I don't believe in the law of evolution," they sound insane. It's tantamount to saying, "I don't believe in the law of gravity."

It's time to realize that we're simply never going to school enough of the public in the precise scientific meaning of particular words. We're never going to fully communicate what's beautiful and noble about scientific caution and rigor. Public discourse is inevitably political, so we need to talk about science in a way that wins the political battle — in no uncertain terms.

No, no, no! Theories are not laws and under no circumstances should scientists abandon science in order to score political points.

On the other hand, Mooney and Nisbet would be proud [What Is Framing?].

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[Photo Credit: Clive Thompson from University of British Columbia]

[Hat Tip: RichardDawkins.net]

Nobel Laureate: John Cornforth

 

The Nobel Prize in Chemistry 1975.

"for his work on the stereochemistry of enzyme-catalyzed reactions"




In 1975, Sir John Warcup 'Kappa' Cornforth (1917- ) won the Nobel Prize in Chemistry for elucidating the squalene biosynthesis pathway and other pathways that generate stereospecific products [Making Squalene]. The prize was shared with Vladimir Prelog for his work on the spereospecificity of chemical reactions.

Cornforth has been deaf since he was 20 years old but overcame his deafness to become an outstanding biochemist. He is a Professor at the University of Sussex (UK). He has written a brief history of the work on the cholesterol pathway (Cornforth 2002). Here's a remarkable interview with Cornforth from the Vega Science Programmes [How to be Right and Wrong].

The presentation speech was delivered, in Swedish, by Professor Arne Fredga of the Royal Academy of Sciences.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

The laureates in chemistry of this year have both studied reaction mechanisms, especially from a stereochemical, i.e. a geometrical point of view. In a chemical experiment some compounds are mixed, then something happens, and finally one can isolate one or more other compounds. What has really happened, and why, and how? The situation is as if someone had abbreviated a classical tragedy, say Hamlet, by showing only the opening scenes of the play and the final scene of the last act. The principal characters are introduced, then the scene closes and when the curtain rises again you see a number of dead bodies on the stage and a few survivors. Of course the spectators would like to know what has happened in the meantime.

What I have said is valid not least for enzymatic reactions. Many such reactions are perpetually going on in all living organisms; one could say that they really concern all of us although we don't observe them. When a chemist tries to find out what really happens, he often comes across the problem: right or left? It is the same in common life. If you leave Stockholm by Norrtull, you soon come to a place where the main road branches: the left branch leads to Oslo, the right one to Sundsvall or, if you like, to Haparanda.

Professor Cornforth has among other things studied the biological synthesis of the hydrocarbon squalene from six molecules of mevalonic acid. This hydrocarbon is necessary for the formation of steroids, which are of vital importance in many respects. The synthesis of squalene takes place in 14 steps and at each the enzyme must find the proper way. That means that there are just 214 = 16384 different routes and only one of them leads to squalene. If the enzyme should make a mistake in the first step (which it does not), the final result could be rubber or various other things but definitely not squalene. The problem at each step concerns which of two hydrogen atoms is to be eliminated, the right one or the left one. Professor Cornforth has shown which choice the enzyme makes at each of the 14 steps. For this purpose he has, with brilliant mastership, utilized the properties of the hydrogen isotopes: the ordinary hydrogen, the heavy hydrogen and the radioactive hydrogen. The lastmentioned isotope can only be used in tracer quantities, which means that only about one part per million of the participating molecules are radioactive. In a similar way, Professor Cornforth has studied several other biologically important reactions. All problems connected with the reaction mechanisms are not solved at that point, but the results constitute a very important step on the way.

Professor Prelog has worked in many fields of stereochemistry, and often the problems have been connected with the geometrical shapes of the molecules and their influence on the course of the reactions.

An impressive series of investigations deal with the "medium rings", i.e. molecules containing rings of 8 to 11 carbon atoms. Such rings are not rigid but rather limp. Parts of the ring which may seem rather distant may come into close contact with each other leading to unexpected reactions. Professor Prelog has been able to elucidate such reactions by utilizing the carbon isotopes.

Many important investigations refer to reactions between chiral molecules. The term chiral is derived from a word in ancient Greek, meaning hand. The molecules are unsymmetrical and may exist in two forms differing in the same way as a right hand and a left hand. The molecules are so small that you can't see them, but one can gain much knowledge by studying the reactions between chiral molecules of different kind.

Professor Prelog has also made important contributions to enzyme chemistry. He has studied enzymatic reactions on small molecules and in particular oxidation or reduction processes. The experiments may be more or less successful depending on how the enzyme and the other molecule fit together geometrically. By systematic experiments with various small molecules of well-defined shapes, it was possible to construct a "map" of the active part of the enzyme molecule. The results have recently been confirmed in a special case by Swedish scientists using x-ray methods.

Professor Prelog has also with ingenuity and penetration discussed and analysed the fundamental concepts of stereochemistry, not least the conditions for chirality in large and complicated molecules.

Professor Cornforth. Enzymatic reactions have always had a certain air of magic, perhaps witchcraft. Of course this is due to our imperfect knowledge of what really happens. This air of magic is, however, gradually dispersing, and your contributions, utilizing the isotopes of hydrogen, imply most striking advances. The handling of compounds with chiral methyl groups is an achievement of the highest intellectual standard.

Let me also express our admiration for the skill and perseverance with which you have pursued your work in spite of a serious physical handicap. Perhaps it had not been possible without the never-failing help and support of Mrs. Cornforth. I think she should not be forgotten on this day. In recognition of your services to chemistry and to natural science as a whole, the Royal Academy of Sciences has decided to confer upon you the Nobel Prize. To me has been granted the privilege to convey to you the most heartly congratulations of the Academy.

Professor Prelog. Ich habe hier versucht, einen Kurzbericht über Ihre wichtigsten Leistungen in der Stereochemie zu erstatten. Das war gewiss etwas schwierig. Ihre schönen Experimentalarbeiten erstrecken sich über weite Felder der heutigen organischen Chemie. Öfters haben Sie die Fortführung Ihrer Arbeiten anderen Forschern überlassen, und viele Chemiker hohen Ranges sind zurzeit auf den Gebieten tätig, die Sie einst eröffnet haben. Sie haben auch die fundamentalen Grundlagen der Stereochemie, besonders den Chiralitätsbegriff, in tiefsinnigen Auseinandersetzungen diskutiert und klargelegt.

In Anerkennung Ihrer Verdienste um die Entwicklung der Chemie hat die Konigliche Akademie der Wissenschaften entschlossen, Ihnen den Nobelpreis zu verleihen. Mir ist die Aufgabe zugefallen, Ihnen die wärmsten Glückwünsche der Akademie zu überbringen.

Professor Cornforth. In the name of the Academy I invite you to receive your prize from the hands of His Majesty the King.

Professor Prelog, Im Namen der Akademie bitte ich Sie aus den Händen Seiner Majestät des Königs den Nobelpreis in Empfang zu nehmen.

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Cornforth, J.W. (2002) Sterol biosynthesis: the early days. Biochem. Biophys. Res. Commun. 292:1129-38. [PubMed]

Making Squalene

 
Squalene is the essential precursor for making cholesterol [How to Make Cholesterol]. The pathway for synthesis of squalene is complicated and it was only worked out in second half of the last century.

The initial substrate is a compound called mevalonate. It's a six carbon branched organic acid. In a later posting we'll wee how cells make mevalonate and learn how that pathway can be controlled by Lipitor® and other drugs that regulate cholesterol levels.

Mevalonate is first phosphorylated by mevalonate kinase in a reaction that requires ATP.


The product of this reaction is mevalonate-5-phosphate and it is immediately phosphorylated again to produce the disphospate derivative. The next step removes the carboxylate group, which is released as a bicarbonate ion (CO₂ dissolved in water produces bicarbonate). This decarboxylation reaction is associated with the formation of a double bond at the end of the product molecule, isopentenyyl diphosphate. This is an important step in the pathway to squalene since squalene has a lot of carbon-carbon double bonds.

The five-carbon isopentenyl group of isopentenyl diphosphate is known as an isoprenyl unit. This molecule (isopentenyl diphosphate) is the source of isoprenyl units for many other biosynthesis reactions in addition to squalene synthesis. &Beta:-carotene and the lipid vitamin A (retinol) are good example of compounds with these isoprene units [Vitamin A (retinol)]. Ubiquinone is an absolutely essential cofactor in many important biochemical reactions an it has an isoprenoid tail [Ubiquinone and the Proton Pump]. Vitamin K, which is required for blood clotting, has a derived isoprenoid tail [THEME: Blood Clotting].

The pathway from isopentenyl diphosphate to squalene is complicated but the basic strategy is quite simple. The idea is to join two five carbon (C₅) isoprene units to make the C₁₀ molecule geranyl diphosphate. Then another C₅ isoprenyl unit is added to make C₁₅ farnesyl diphosphate. Finally, two molecule of farnesyl diphosphate are joined head-to-head to make C₃₀ squalene.


The difficult part of this reaction was figuring out the mechanism so that all of the double bonds would be in the trans conformation. Most of the work was done by John Cornforth who received the Nobel Prize in 1975 [Nobel Laureate: John Cornforth].

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Praying for Rain

 
Here's a video from CNN of Georgia Governor Sonny Perdue praying for rain [Georgia's governor prays for rain on Capitol steps]. It's the sort of thing you might expect from a tribe of hunter-gathers about 50,000 years ago. It didn't work very well back then. I wonder if it will work today?

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