Just remember that these are not genes (or, more correctly - alleles) that determine, in an absolute manner, whether you'll get the cancer or not (unlike, say in the case of the mutant gene for Cystic Fibrosis). They are variants that, when present alone or in combination increase the risk. It's a bit like with insurance - when you're a twenty-something, living in a large city, and want to insure a sports car, you'll pay a greater premium than a middle aged small-town father insuring a minivan, because the risk that you'll have an accident is several times higher. But that doesn't mean that all urban twenty-somethings in sports car will crash (in fact, most of them won't), and it doesn't mean that the minivan driving fathers never crash. It't the same with the association of genetic variants with cancer - there is no causative relationship - there is only an increase in risk. Which means that the test can be informative (to a varying degree), but is never definitive (unless it's a simple Mendelian trait, like CF, which the common cancers are not).
Read this informative post on The Evolution & Medicine Review for a sobering view on genetic association in complex traits.
Also, if you follow the link to the company page you'll see (in the News section) that the main paper (in NEJM) reporting the association was a study done on the Swedish population, and it's by no means certain, that it'll hold for other population backgrounds.
All this doesn't mean that it's worthless, just an advice to take it with a grain of salt.
Still, not much of a publication record for someone so long in the business. Seems he is just very good at getting government money and jumped on the bioterrorism bandwagon.
And as others have said - he'll identify mostly amino acid sequences that do not form stable folds. Actually, most proteins are built using a relatively small set of blocks or folds (think Lego) - cf. the CATH database http://www.cathdb.info/, so finding sequences that do not occur naturally would not surprise me.
Etomite (http://www.etomite.org/) may work for you. It's quite lean, and is very well suited for managing pages with static info, not a community portal or a blog site.
This one is actually a "stupid criminal" not a "stupid user" story. It was back in the days when to most people a computer meant something like a Commodore 64, Atari XL or A Spectrum. PCs were rare outside professional environments. One lab at our University had a few new, shiny PC XTs. One night someone broke into the lab. They stole all the keyboards, but left the actual computers. I'd like to see them try to hook up those keyboards to a TV.
All those who read Solaris in English lost a lot of the original's literary quality. While most English translations of Lem are good, and those by Michael Kandel are brilliant, Solaris is a sad exception. It was translated into English not from the original, but from a French translation, that was poor to begin with. It's more like a Cliff's Notes, than an original. Kandel wanted to do another translation, but was denied because the copyright is somehow legally tied to the distribution rights to the movie.
It seems that Pentax is going the same way - they just made a deal with Samsung and showed a dSLR, which is essentially *iSTDL2 with the Samsung logo replacing Pentax. Same thing will happen to Konica - there will be new cameras for the system, but with the Sony logo. Sony already own the Zeiss brand for lenses, so it could be interesting...
In what way the Minolta dSLRS are unusable compared to similarly priced offerings from Canon or Nikon? They offer the same basic set of funtcions and comparable picture quality (standard 6MP CCD sensor), but the design and ergonomics are much better. Minolta dSLRS have way better optical viewfinders than amateur Canons and Nikons, only Pentax is slightly better. The control layout is very logical to anyone with any SLR experience - main functions are controllable by dials and buttons, you don't need do go through levels of screen menus to change basic settings. The handling and feel of those cameras is way superior to entry-level Canon or Nikon models. Not to mention the excellent built-in antishake function.
SLR systems are like computer operating systems, they have their dedicated following and rabid fans. You choose what feels best for your needs and tastes, but calling Minolta dSLRs and SLRs "almost unusable" is just trolling without any factual support.
And don't forget the creative fun you can have with the RAW files better digital cameras (including all dSLRs) produce. You can simulate different processing methods (push/pull processing for example), color filters etc. and control the way your images are "developed". With film you'd have to do your own processing for that kind of flexibility, and doing own color (C41 or E6) processing isn't a viable option for amateurs. The results may still not be comparable to what a good pro lab could do with film, but you get more freedom and results that can surpass a cheap supermarket lab (or a consumer Kodak Express shop or equivalent) easily. Starting from RAW you could even get some nice BW images, simulating various types of film and filter combinations. Digital camera RAWs are a great way to learn about photography.
All this freedom is lost when you shoot JPEGs only.
Concerning resolution - larger format prints from 35mm and digital are good enough for most purposes. Don't forget that larger images are meant to be looked at from a certain distance. Flaws you may see when you stick your nose in the print, won't matter that much when viewed from a distance.
Sorry for the typo, I meant "modern" - and you're right, PCR with current enzymes (or any enzymes I could think of) would not happen in less than 30 minutes. Melting curve peaks will give you roughly the same information as elecrophoresis - how many products and what are their relative sizes. Hardly enough for genotyping, although will work just fine for pathogen/bioweapon detection.
There are methods with potential for developing very fast identification procedures - like hybridization to oligonucleotide arrays (you could even sequence this way), but they're far from being cheap and miniaturized at the time. But you still need to amplify the DNA first, and so far PCR is the ony way to go, and you can't shorten it below some 30 minutes.
Current machines on the market can do it in about 1 hour (depending on the size of the fragment you amplify), you can't make it much shorter by just speeding up the heating/cooling steps, you need time for the enzyme to do the work.
And you can buy a basic thermocycler for a few thousand $, add a few hundred $ for the equipment to do post-PCR electrophoresis, and some $ for the reagents. Hardly "millions of dollars", there are high schools that can afford to do it in the classrooom. And I doubt the new thing will be significantly cheaper than the current crop of thermocyclers.
Moder capillary based PCRs can run the amplification procedure within 20-30 minutes. If they use a system similar to the one in real-time PCR devices and do melting curve analysis instead of electrophoresis they might get the whole procedure done within about 40 minutes. Actual temperature ramping time is an insignificant fraction there, most of the time is what is needed for the enzyme to complete the elongation step. Unless you make a faster polymerase you won't speed PCR up significantly. The article is not very specific, seems like the actual improvement may lie in the size and portability of their device, they don't say however, how many samples in paralell it can run and if any disposable reaction vessels are used (and if not, then how they deal with cross-contamination issues). I guess you could make a single-tube size PCR block of a similar size using current peltier technology.
Most cases of cervical cancer are related to HPV infections. HPV uses a very clever mechanism to overcome cellular defenses. One of the main proteins that protect cells and keep them from becoming cancerous is the p53 protein. In most cancers something must happen to p53 for the cancerogenesis to proceed. HPV makes a protein (called E6) that binds p53 and by doing that marks it for degradation by the ubiquitn pathway. Understanding how that pathway works is therefore essential for treating HPV dependent cancers.
Not exactly like in programming. As far as I know (I'm not a programmer) the OO languages use object disposal to free up resources. Degradadtion of macromolecules like proteins (through ubiquitine pathway discovered by the Nobel laureates) or RNAs is, however, primarily a way to control different cellular processes. The cell adjusts to different needs by altering the set of proteins that it contains (called the proteome). If proteins were infinitely stable there would be no way of up- or downregulating their levels - once made they would stay there forever. So proteins (and mRNAs that encode them) have a built-in end-of-life mechanism that, together with varying the synthesis rate, makes regulation possible. There is more to it - protein degradation is also used to remove damaged or incorrectly made proteins. So, to sum it up: protein degradation is essential for both regulation and quality control of cell's proteins.
Even though there are no direct practical applications so far, the significance of the discovery is great - we do know that if something goes wrong with the cell's regulatory mechanisms we get cancer, understanding ubiqutination brings us closer to understanding how cancer happens.
The process that inacivates one copy of X in females is, however, random, so in some cells one copy is inactive, while in other cells it's the other that gets inactivated. So, in females some cells express the maternal X chromosme, while the others express the paternal one. If they are different with respect to a hereditary trait you get interesting results. That's how you get Calico cats (always female), or how you can detect muscle enzyme variation in some asymptomatic female carriers of Duchenne Muscular Dystrophy.
Only a portion of the Y chromosome is male-specific and indeed it encodes only a few proteins (and is full of repeats and junk DNA). A substantial portion of Y is homologous to X and contains many genes that behave like genes on any other chromosome - this is called pseudo-autosomal region (PAR), Obviously, the sex-linked portion of X (of which males have one copy and females two) contains numerous genes, most of them essential, so a YY karyotype would be inviable. There are XYY male karyotypes, however, and these are quite normal.
Another major problem with WordPerfect (even on Windows) for international users was with fonts. IIRC it had its own fonts collection (and even own printer drivers, although I don't know if that lasted in later versions) that lacked many characters outside the standard charset.
Linux versions of WordPerfect (and Draw&Photopaint) had their own fonts server, which was a nightmare to use. Whatever they do with the new version, it has to use the system-wide fonts directory (freetype and all) in any language available on the system. OpenOffice can do that, and so can AbiWord now (although it did take them a while!) This is IMHO far more important than creating i18n menus and help systems.
It's not sequencing, not even real DNA viewing!
on
Home DNA Sequencing
·
· Score: 5, Informative
I took a little time to read the description of the kit on Discovery's website. It's much less than the/. post suggested. There's just some chemicals and a toy centrifuge to extract DNA. Actually there are ways to extract DNA with household chemicals, precipitate with isopropanol and spool on a glass or plastic rod.
So far it's only DNA extraction, cool as a science-for-fun thing, but nothing new.
The analysis part (with electrophoresis) seems to be fake (simulated, if you wish). The kit, according to the Discovery website contains
"DNA stain (fabricated to mimic real DNA)".
So, it's just a toy, cool, but nothing that'll allow Junior to test his paternity or do any real DNA analysis. There are educational kits that provide real DNA analysis in a classroom environment (like the Biotechnology Explorer program from BioRad), but they still require teacher's supervision.
Start there
The NCBI site also has a FTP repository, where you can download the raw files. And here you can get a nice open software suite to work on it.
I tried it on a computationally intensive program I use in my work (PAML) - plain C (not C++), on my PIII 1GHz Linux it runs about 35% faster compiled with icc with all the optimizations turned on than the gcc code (-O3 -march=i686 -mcpu=i686). This is a significant gain when my typical run of the program takes ~2 days at 90% CPU usage.
Slashdot Mirror
Just remember that these are not genes (or, more correctly - alleles) that determine, in an absolute manner, whether you'll get the cancer or not (unlike, say in the case of the mutant gene for Cystic Fibrosis). They are variants that, when present alone or in combination increase the risk. It's a bit like with insurance - when you're a twenty-something, living in a large city, and want to insure a sports car, you'll pay a greater premium than a middle aged small-town father insuring a minivan, because the risk that you'll have an accident is several times higher. But that doesn't mean that all urban twenty-somethings in sports car will crash (in fact, most of them won't), and it doesn't mean that the minivan driving fathers never crash. It't the same with the association of genetic variants with cancer - there is no causative relationship - there is only an increase in risk. Which means that the test can be informative (to a varying degree), but is never definitive (unless it's a simple Mendelian trait, like CF, which the common cancers are not). Read this informative post on The Evolution & Medicine Review for a sobering view on genetic association in complex traits. Also, if you follow the link to the company page you'll see (in the News section) that the main paper (in NEJM) reporting the association was a study done on the Swedish population, and it's by no means certain, that it'll hold for other population backgrounds. All this doesn't mean that it's worthless, just an advice to take it with a grain of salt.
Still, not much of a publication record for someone so long in the business. Seems he is just very good at getting government money and jumped on the bioterrorism bandwagon. And as others have said - he'll identify mostly amino acid sequences that do not form stable folds. Actually, most proteins are built using a relatively small set of blocks or folds (think Lego) - cf. the CATH database http://www.cathdb.info/, so finding sequences that do not occur naturally would not surprise me.
But the grandparent and most other threads were attacking her. And it's M as in "mega" or million. Ever heard of the SI system?
Yep, that was the easy part. Earning those M$ starting out as an immigrant girl - that was the hard part. Try to do better, and then comment.
Etomite (http://www.etomite.org/) may work for you. It's quite lean, and is very well suited for managing pages with static info, not a community portal or a blog site.
This one is actually a "stupid criminal" not a "stupid user" story. It was back in the days when to most people a computer meant something like a Commodore 64, Atari XL or A Spectrum. PCs were rare outside professional environments. One lab at our University had a few new, shiny PC XTs. One night someone broke into the lab. They stole all the keyboards, but left the actual computers. I'd like to see them try to hook up those keyboards to a TV.
All those who read Solaris in English lost a lot of the original's literary quality. While most English translations of Lem are good, and those by Michael Kandel are brilliant, Solaris is a sad exception. It was translated into English not from the original, but from a French translation, that was poor to begin with. It's more like a Cliff's Notes, than an original. Kandel wanted to do another translation, but was denied because the copyright is somehow legally tied to the distribution rights to the movie.
It seems that Pentax is going the same way - they just made a deal with Samsung and showed a dSLR, which is essentially *iSTDL2 with the Samsung logo replacing Pentax. Same thing will happen to Konica - there will be new cameras for the system, but with the Sony logo. Sony already own the Zeiss brand for lenses, so it could be interesting...
In what way the Minolta dSLRS are unusable compared to similarly priced offerings from Canon or Nikon? They offer the same basic set of funtcions and comparable picture quality (standard 6MP CCD sensor), but the design and ergonomics are much better. Minolta dSLRS have way better optical viewfinders than amateur Canons and Nikons, only Pentax is slightly better. The control layout is very logical to anyone with any SLR experience - main functions are controllable by dials and buttons, you don't need do go through levels of screen menus to change basic settings. The handling and feel of those cameras is way superior to entry-level Canon or Nikon models. Not to mention the excellent built-in antishake function. SLR systems are like computer operating systems, they have their dedicated following and rabid fans. You choose what feels best for your needs and tastes, but calling Minolta dSLRs and SLRs "almost unusable" is just trolling without any factual support.
And don't forget the creative fun you can have with the RAW files better digital cameras (including all dSLRs) produce. You can simulate different processing methods (push/pull processing for example), color filters etc. and control the way your images are "developed". With film you'd have to do your own processing for that kind of flexibility, and doing own color (C41 or E6) processing isn't a viable option for amateurs. The results may still not be comparable to what a good pro lab could do with film, but you get more freedom and results that can surpass a cheap supermarket lab (or a consumer Kodak Express shop or equivalent) easily. Starting from RAW you could even get some nice BW images, simulating various types of film and filter combinations. Digital camera RAWs are a great way to learn about photography. All this freedom is lost when you shoot JPEGs only.
Concerning resolution - larger format prints from 35mm and digital are good enough for most purposes. Don't forget that larger images are meant to be looked at from a certain distance. Flaws you may see when you stick your nose in the print, won't matter that much when viewed from a distance.
Sorry for the typo, I meant "modern" - and you're right, PCR with current enzymes (or any enzymes I could think of) would not happen in less than 30 minutes. Melting curve peaks will give you roughly the same information as elecrophoresis - how many products and what are their relative sizes. Hardly enough for genotyping, although will work just fine for pathogen/bioweapon detection. There are methods with potential for developing very fast identification procedures - like hybridization to oligonucleotide arrays (you could even sequence this way), but they're far from being cheap and miniaturized at the time. But you still need to amplify the DNA first, and so far PCR is the ony way to go, and you can't shorten it below some 30 minutes.
Current machines on the market can do it in about 1 hour (depending on the size of the fragment you amplify), you can't make it much shorter by just speeding up the heating/cooling steps, you need time for the enzyme to do the work. And you can buy a basic thermocycler for a few thousand $, add a few hundred $ for the equipment to do post-PCR electrophoresis, and some $ for the reagents. Hardly "millions of dollars", there are high schools that can afford to do it in the classrooom. And I doubt the new thing will be significantly cheaper than the current crop of thermocyclers.
Moder capillary based PCRs can run the amplification procedure within 20-30 minutes. If they use a system similar to the one in real-time PCR devices and do melting curve analysis instead of electrophoresis they might get the whole procedure done within about 40 minutes. Actual temperature ramping time is an insignificant fraction there, most of the time is what is needed for the enzyme to complete the elongation step. Unless you make a faster polymerase you won't speed PCR up significantly. The article is not very specific, seems like the actual improvement may lie in the size and portability of their device, they don't say however, how many samples in paralell it can run and if any disposable reaction vessels are used (and if not, then how they deal with cross-contamination issues). I guess you could make a single-tube size PCR block of a similar size using current peltier technology.
They did break the first version, it was later upgraded with an additional wheel, and that upgraded one was cracked by Turing at Bletchley. A few links: http://www.codesandciphers.org.uk/virtualbp/poles/ poles.htm, http://www.armyradio.com/publish/Articles/The_Enig ma_Code_Breach/The_Enigma_Code_Breach.htm, http://www.enigmahistory.org/enigma.html.
This and other Polish contributions to WWII were kept quiet at the end of the war to avoid annoying Stalin, and it was carried into history writing (especially in the UK) for a long time. Too many exaples to mention, the Enigma is but one...
Most cases of cervical cancer are related to HPV infections. HPV uses a very clever mechanism to overcome cellular defenses. One of the main proteins that protect cells and keep them from becoming cancerous is the p53 protein. In most cancers something must happen to p53 for the cancerogenesis to proceed. HPV makes a protein (called E6) that binds p53 and by doing that marks it for degradation by the ubiquitn pathway. Understanding how that pathway works is therefore essential for treating HPV dependent cancers.
Not exactly like in programming. As far as I know (I'm not a programmer) the OO languages use object disposal to free up resources. Degradadtion of macromolecules like proteins (through ubiquitine pathway discovered by the Nobel laureates) or RNAs is, however, primarily a way to control different cellular processes. The cell adjusts to different needs by altering the set of proteins that it contains (called the proteome). If proteins were infinitely stable there would be no way of up- or downregulating their levels - once made they would stay there forever. So proteins (and mRNAs that encode them) have a built-in end-of-life mechanism that, together with varying the synthesis rate, makes regulation possible. There is more to it - protein degradation is also used to remove damaged or incorrectly made proteins. So, to sum it up: protein degradation is essential for both regulation and quality control of cell's proteins. Even though there are no direct practical applications so far, the significance of the discovery is great - we do know that if something goes wrong with the cell's regulatory mechanisms we get cancer, understanding ubiqutination brings us closer to understanding how cancer happens.
The process that inacivates one copy of X in females is, however, random, so in some cells one copy is inactive, while in other cells it's the other that gets inactivated. So, in females some cells express the maternal X chromosme, while the others express the paternal one. If they are different with respect to a hereditary trait you get interesting results. That's how you get Calico cats (always female), or how you can detect muscle enzyme variation in some asymptomatic female carriers of Duchenne Muscular Dystrophy.
Only a portion of the Y chromosome is male-specific and indeed it encodes only a few proteins (and is full of repeats and junk DNA). A substantial portion of Y is homologous to X and contains many genes that behave like genes on any other chromosome - this is called pseudo-autosomal region (PAR), Obviously, the sex-linked portion of X (of which males have one copy and females two) contains numerous genes, most of them essential, so a YY karyotype would be inviable. There are XYY male karyotypes, however, and these are quite normal.
Linux versions of WordPerfect (and Draw&Photopaint) had their own fonts server, which was a nightmare to use. Whatever they do with the new version, it has to use the system-wide fonts directory (freetype and all) in any language available on the system. OpenOffice can do that, and so can AbiWord now (although it did take them a while!) This is IMHO far more important than creating i18n menus and help systems.
I took a little time to read the description of the kit on Discovery's website. It's much less than the /. post suggested. There's just some chemicals and a toy centrifuge to extract DNA. Actually there are ways to extract DNA with household chemicals, precipitate with isopropanol and spool on a glass or plastic rod.
So far it's only DNA extraction, cool as a science-for-fun thing, but nothing new.
The analysis part (with electrophoresis) seems to be fake (simulated, if you wish). The kit, according to the Discovery website contains
"DNA stain (fabricated to mimic real DNA)".
So, it's just a toy, cool, but nothing that'll allow Junior to test his paternity or do any real DNA analysis. There are educational kits that provide real DNA analysis in a classroom environment (like the Biotechnology Explorer program from BioRad), but they still require teacher's supervision.
Start there The NCBI site also has a FTP repository, where you can download the raw files. And here you can get a nice open software suite to work on it.
I tried it on a computationally intensive program I use in my work (PAML) - plain C (not C++), on my PIII 1GHz Linux it runs about 35% faster compiled with icc with all the optimizations turned on than the gcc code (-O3 -march=i686 -mcpu=i686). This is a significant gain when my typical run of the program takes ~2 days at 90% CPU usage.