I'm sure the fact that Apple will finally have to reveal how much the iPhone will cost unlocked / sans contract has nothing to do with the fact that France is getting it last...
I agree with the basic assumption that in terms of "just working," Mythdora is pretty good. My problem with it is a sudo-enabled user with identical login and password. On a fire-walled home setup, I suppose this is less of an issue, but as I had no idea if changing the default password would break functionally, I had to ditch it.
I would think any filesystem supported by MacFUSE would be the best place to start. Their is a NTFS-3G module for MacFUSE, and it works under linux, too.
Or, you know, you could look at a depiction of the Human Genome that contains real, usable data. Heaven forbid. This is like the folks who make "music" by assigning 4 notes to the 4 different DNA bases and playing them in one long string.
I can't find mention of it anywhere, but has NPR acknowledged that they have a stake in the XM vs Sirius race? The national NPR feed is only available on Sirius.
I'm sorry, but you are wrong on the "direct interaction" front. Almost all HIV drugs interact directly with some protein belonging to the virus. I believe the cocktails attack multiple pathways at once; the protease, the integrase, etc.
The drugs that got the most press initially (and started the reversal of fortune) were protease inhibitors. They directly interact with HIV protease that cleaves the polyprotein of the virus into it's many components. If the HIV virus can't do this, it can't assemble. The protease inhibitors bind in the cleavage pocket of the protease, and shut down its function.
There is no reason why HIV couldn't randomly mutate to become resistant to this drug. However, these cocktails ensure that if one pathway of the virus assembly/infection "breaks through," it gets shut down at a different stage.
J&R is offering $100 off any iPod if you sign up for audible.com's monthy service. The monthly fee is $14.95, and entitles you to one book and one program (Car Talk, etc.) a month. So, if you are a big fan of spoken word, audio books, etc., it's a pretty good deal. Best I've found, anyway. And their price is about $10 lower than MSRP as well.
Mr. Gates does realize that these magical firewalls he speaks of do run code as well? Or is it since most firewalls are not written by Microsoft, they are therefore much more secure...
Heh. Why I thought anyone on apple/. would actually have a useful comment about this is beyond me.
As someone who uses stereo hardware for crystallography and may have to set up a structural biology lab in the (hopefully) near future, it is nice to see another major hurdle overcome. The other major hurdle is of course getting the authors of the programs to incorporate stereo support for their applications. Luckily most of the "bread and butter" apps have already been ported over. In the x-ray crystallography lab I am in we have an equal number of SGI Octanes and Macs, in the future this duality will hopefully be unnecesary, freeing up funds so that everyone can have their own (Mac OS X) workstation.
Someone mod the original post up, Newegg has been modded up in three different threads, Mwave hasn't. I also second Mwave. For a system, Mwave is hard to beat, especially because for a whopping $9 they will test the motherboard/CPU/memory for you. After having my system be dead in the water for two months while I sent parts back and forth to different vendors, I'm never buying from another place that doesn't test the bare bones for you.
I've checked out the national access pages for AOL, netzero, freewwweb. They all have downloadable software for connecting
I'll second someone else's suggestion of freewwweb. Just say you have Windows. It isn't actually software they have you download, it's just a *.ins file that sets up the networking for you in Windows. You can ferret out everything you need from that file, it's just a text file. I've been using it for the last month with kppp with no problems. Hope this helps.
Have you even looked at their web-site recently?? Their drivers have been released under the XFree license
Yes, I have, and I run them. I have a TNT2 Ultra. I disagree that they run *really* well, though. Compared to NT, they run poor at best. Yes, you can play Quake3, but for the applications I want to run, mainly molecular modelling applications, they are not up to the task. Hopefully that will change with Xfree4.0 We'll see.
Also, the drivers they have released are based on Mesa, which this press release makes no mention of, just that it is a "fully compliant OpenGL 1.2 solution." I bought a TNT2 Ultra based on their releasing the source code. I am disappointed lately in the progress of those drivers, caused mainly by Nvidia's ambivalence. Look at the G200/G400 progress for comparison, by all accounts they are leaps and bounds better than the Nvidia products for Mesa in Linux. Jerm Oh, you're not a real doctor, are you?
Not only that, but you'll also notice nowhere is it stated that it will be free, either. I was excited until I realized this may be just another accelerated X server product ala MetroX, etc. Lovely... Jerm Oh, you're not a real doctor, are you?
Saying that a viral protein could quickly evolve into one that works in an entirely different way is analogous to saying that filling rooms full of people and shooting them will select for bullet-resistant humans.
Who said anything about quickly? From the viewpoint of the virus, it has eternity to try and evolve a defense. And as far as the bullet analogy, it would select for the fastest, most nimble humans. Now, if those humans could reproduce from infant to adult in an hour (as viruses' can), they might keep ahead of the gunman.
That's for bacteria, not viruses.
Viruses and bacteria evolve by almost identical mechanisms. Natural selection relies on random changes to the genome that impart advantages to the host, which are then passed on to the progeny. Bacteria and viruses just display these changes faster because in the matter of 24 hours, they can go through 24 generations. So it is also for viruses, not just bacteria. Hell, it's for every organism on this earth.
If the drug is intelligently designed and binds to a part of the protein that is critical for its proper function, for example, resistance mutations will give rise to defective viruses
Assuming the virus chooses to continue to function in the way we think it will. As soon as you introduce a drug which interferes with a function, you have placed selective pressure on that protein to evolve a new mechanism. Any which result in a non-viable virus won't propogate, obviously, that's what selective pressure is all about. Any that do, however, have an advantage over the other strains of the virus.
That's how we have Vancomycin resistant strains now. Vancomycin is a drug of "last resort," yet there are strains showing up which are resistant. If I recall correctly, the bug "changed" the chemistry it was using to synthesize its cell wall. Vancomycin blocked a protease needed in the synthesis, and the new resistant strain "decided" to use an ester bond instead of an amide bond to get around the drug. The talk I saw boiled it down to one hydrogen bond. That's almost impossible to design against. Fascinating and scary, all at the same time.
Jerm Oh I get it, you're not a real doctor, are you? No, no I'm not. Jerm Oh, you're not a real doctor, are you?
I should clarify. I don't know of anything that has come straight off the computer screen and worked. They all need tweaking. Many drugs are based on computer predictions. However, our knowledge of structure based drug design just isn't good enough. Yet. I could be wrong, though, I don't know the history of acyclovir. Jerm Oh, you're not a real doctor, are you?
Just FYI, you have in essence defined an antibiotic (though this isn't an antibiotic, it's an antiviral). Most antibiotics work by "gumming up" the bacteria's reproductive ability. Actually, ALL the ones I can think of work this way.
On a slight tangent, next time anyone wonders why we should keep our "basic science" research budget, I saw a talk on this very subject by Dr. Michael Rossman of Purdue University. In 1992. I specifically remember the "comfort index" slide, where they measured grams of snot blown out of patient's noses with and without the drug. Yum.
Which leads to my next even more off subject rant, the fact that they "designed this from scratch." The truth is, no drugs have yet to enter the market that way, even this one. Don't get me wrong, this is an extremely powerful technique, and being an x-ray crystallographer, I'm very glad the drug companies are interested in protein structure and dynamics.
That being said the way it really works is this:
- Solve the structure of the virus or protein of interest which you hypothesize is causing the disease or symptoms of the disease. - Using the structure of the protein, try to figure out the mechanism of "how it works," and localize it to a particular area of the protein. - Try to find "pockets" in the protein near this area where you could design a drug to bind which would then disrupt the function of the protein - Ask your theoreticians (computer geeks with doctorates in physics or chemistry who look like the "pulsing head" aliens in the old Star Trek) to design a drug to fit in the pocket. - If you are CNN, you have a drug, viola! If you are in the real world, here is where the real work begins. - Through an iterative process, design the drug, find out it doesn't bind quite the way you thought it should, or with a viable affinity, and turn it back over to the chemists, who then stick every chemical group known to humankind on it to try to get it to bind tighter. You then reassay it's activity, solve the structure again, but this time bound to the new drug, and see how the changes you made affected how well it binds to the protein, and try to correlate these changes to the difference in affinity you observe. - If you are lucky, you find one that binds with a suitable affinity and specificity (doesn't help if it binds the viral protein but also binds proteins in the body needed to reproduce). - Years later, your drug passes clinical trials (actually, in most cases it doesn't, because your designs don't take things like toxicity into account, only how well it binds the protein of interest) and you are now the proud parent of an antiviral, or in most cases making the news lately, an HIV protease inhibitor.
Also keep in mind when I say "you," I mean a large team of scientists with an incredible array of backgrounds. Jerm Oh, you're not a real doctor, are you?
Actually, for the next few years anyway, considering numbers instead of digits increases the rarity. Counting only digits means that 1/1/2000 is a prime day, and 1/3/2000, and 1/5/2000... and... unless 0 isn't a prime number. Hmmmm.....
It's worse, Compaq is calling their machine the "iPaq." Oy. Check out http://www.compaq.com/produ cts/internetdevices/index.html for details. I love the part about "Machines configured with Windows 2000 will ship when the operating system is available."
Slashdot Mirror
I'm sure the fact that Apple will finally have to reveal how much the iPhone will cost unlocked / sans contract has nothing to do with the fact that France is getting it last...
I agree with the basic assumption that in terms of "just working," Mythdora is pretty good. My problem with it is a sudo-enabled user with identical login and password. On a fire-walled home setup, I suppose this is less of an issue, but as I had no idea if changing the default password would break functionally, I had to ditch it.
I would think any filesystem supported by MacFUSE would be the best place to start. Their is a NTFS-3G module for MacFUSE, and it works under linux, too.
Or, you know, you could look at a depiction of the Human Genome that contains real, usable data. Heaven forbid. This is like the folks who make "music" by assigning 4 notes to the 4 different DNA bases and playing them in one long string.
I can't find mention of it anywhere, but has NPR acknowledged that they have a stake in the XM vs Sirius race? The national NPR feed is only available on Sirius.
Right, did you want the 5 minute argument or the full half hour, then?
I'm sorry, but you are wrong on the "direct interaction" front. Almost all HIV drugs interact directly with some protein belonging to the virus. I believe the cocktails attack multiple pathways at once; the protease, the integrase, etc.
The drugs that got the most press initially (and started the reversal of fortune) were protease inhibitors. They directly interact with HIV protease that cleaves the polyprotein of the virus into it's many components. If the HIV virus can't do this, it can't assemble. The protease inhibitors bind in the cleavage pocket of the protease, and shut down its function.
There is no reason why HIV couldn't randomly mutate to become resistant to this drug. However, these cocktails ensure that if one pathway of the virus assembly/infection "breaks through," it gets shut down at a different stage.
J&R is offering $100 off any iPod if you sign up for audible.com's monthy service. The monthly fee is $14.95, and entitles you to one book and one program (Car Talk, etc.) a month. So, if you are a big fan of spoken word, audio books, etc., it's a pretty good deal. Best I've found, anyway. And their price is about $10 lower than MSRP as well.
Mr. Gates does realize that these magical firewalls he speaks of do run code as well? Or is it since most firewalls are not written by Microsoft, they are therefore much more secure...
Uhh... you mean besides these? Currently getting 0.5M/sec using the 3.1a client
Heh. Why I thought anyone on apple /. would actually have a useful comment about this is beyond me.
As someone who uses stereo hardware for crystallography and may have to set up a structural biology lab in the (hopefully) near future, it is nice to see another major hurdle overcome. The other major hurdle is of course getting the authors of the programs to incorporate stereo support for their applications. Luckily most of the "bread and butter" apps have already been ported over. In the x-ray crystallography lab I am in we have an equal number of SGI Octanes and Macs, in the future this duality will hopefully be unnecesary, freeing up funds so that everyone can have their own (Mac OS X) workstation.
Someone mod this to funny. You are well suited to run PROPOGANDA, sir. A link to the APA does not a legitimate claim make.
Someone mod the original post up, Newegg has been modded up in three different threads, Mwave hasn't. I also second Mwave. For a system, Mwave is hard to beat, especially because for a whopping $9 they will test the motherboard/CPU/memory for you. After having my system be dead in the water for two months while I sent parts back and forth to different vendors, I'm never buying from another place that doesn't test the bare bones for you.
I've checked out the national access pages for AOL, netzero, freewwweb. They all have downloadable software for connecting
I'll second someone else's suggestion of freewwweb. Just say you have Windows. It isn't actually software they have you download, it's just a *.ins file that sets up the networking for you in Windows. You can ferret out everything you need from that file, it's just a text file. I've been using it for the last month with kppp with no problems. Hope this helps.
Jerm
Oh, you're not a real doctor, are you?
Have you even looked at their web-site recently?? Their drivers have been released under the XFree license
Yes, I have, and I run them. I have a TNT2 Ultra. I disagree that they run *really* well, though. Compared to NT, they run poor at best. Yes, you can play Quake3, but for the applications I want to run, mainly molecular modelling applications, they are not up to the task. Hopefully that will change with Xfree4.0 We'll see.
Also, the drivers they have released are based on Mesa, which this press release makes no mention of, just that it is a "fully compliant OpenGL 1.2 solution." I bought a TNT2 Ultra based on their releasing the source code. I am disappointed lately in the progress of those drivers, caused mainly by Nvidia's ambivalence. Look at the G200/G400 progress for comparison, by all accounts they are leaps and bounds better than the Nvidia products for Mesa in Linux.
Jerm
Oh, you're not a real doctor, are you?
Not only that, but you'll also notice nowhere is it stated that it will be free, either. I was excited until I realized this may be just another accelerated X server product ala MetroX, etc. Lovely...
Jerm
Oh, you're not a real doctor, are you?
Saying that a viral protein could quickly evolve into one that works in an entirely different way is analogous to saying that filling rooms full of people and shooting them will select for bullet-resistant humans.
Who said anything about quickly? From the viewpoint of the virus, it has eternity to try and evolve a defense. And as far as the bullet analogy, it would select for the fastest, most nimble humans. Now, if those humans could reproduce from infant to adult in an hour (as viruses' can), they might keep ahead of the gunman.
That's for bacteria, not viruses.
Viruses and bacteria evolve by almost identical mechanisms. Natural selection relies on random changes to the genome that impart advantages to the host, which are then passed on to the progeny. Bacteria and viruses just display these changes faster because in the matter of 24 hours, they can go through 24 generations. So it is also for viruses, not just bacteria. Hell, it's for every organism on this earth.
Jerm
Oh, you're not a real doctor, are you?
If the drug is intelligently designed and binds to a part of the protein that is critical for its proper function, for example, resistance mutations will give rise to defective viruses
Assuming the virus chooses to continue to function in the way we think it will. As soon as you introduce a drug which interferes with a function, you have placed selective pressure on that protein to evolve a new mechanism. Any which result in a non-viable virus won't propogate, obviously, that's what selective pressure is all about. Any that do, however, have an advantage over the other strains of the virus.
That's how we have Vancomycin resistant strains now. Vancomycin is a drug of "last resort," yet there are strains showing up which are resistant. If I recall correctly, the bug "changed" the chemistry it was using to synthesize its cell wall. Vancomycin blocked a protease needed in the synthesis, and the new resistant strain "decided" to use an ester bond instead of an amide bond to get around the drug. The talk I saw boiled it down to one hydrogen bond. That's almost impossible to design against. Fascinating and scary, all at the same time.
Jerm
Oh I get it, you're not a real doctor, are you?
No, no I'm not.
Jerm
Oh, you're not a real doctor, are you?
I should clarify. I don't know of anything that has come straight off the computer screen and worked. They all need tweaking. Many drugs are based on computer predictions. However, our knowledge of structure based drug design just isn't good enough. Yet. I could be wrong, though, I don't know the history of acyclovir.
Jerm
Oh, you're not a real doctor, are you?
Just FYI, you have in essence defined an antibiotic (though this isn't an antibiotic, it's an antiviral). Most antibiotics work by "gumming up" the bacteria's reproductive ability. Actually, ALL the ones I can think of work this way.
On a slight tangent, next time anyone wonders why we should keep our "basic science" research budget, I saw a talk on this very subject by Dr. Michael Rossman of Purdue University. In 1992. I specifically remember the "comfort index" slide, where they measured grams of snot blown out of patient's noses with and without the drug. Yum.
Which leads to my next even more off subject rant, the fact that they "designed this from scratch." The truth is, no drugs have yet to enter the market that way, even this one. Don't get me wrong, this is an extremely powerful technique, and being an x-ray crystallographer, I'm very glad the drug companies are interested in protein structure and dynamics.
That being said the way it really works is this:
- Solve the structure of the virus or protein of interest which you hypothesize is causing the disease or symptoms of the disease.
- Using the structure of the protein, try to figure out the mechanism of "how it works," and localize it to a particular area of the protein.
- Try to find "pockets" in the protein near this area where you could design a drug to bind which would then disrupt the function of the protein
- Ask your theoreticians (computer geeks with doctorates in physics or chemistry who look like the "pulsing head" aliens in the old Star Trek) to design a drug to fit in the pocket.
- If you are CNN, you have a drug, viola! If you are in the real world, here is where the real work begins.
- Through an iterative process, design the drug, find out it doesn't bind quite the way you thought it should, or with a viable affinity, and turn it back over to the chemists, who then stick every chemical group known to humankind on it to try to get it to bind tighter. You then reassay it's activity, solve the structure again, but this time bound to the new drug, and see how the changes you made affected how well it binds to the protein, and try to correlate these changes to the difference in affinity you observe.
- If you are lucky, you find one that binds with a suitable affinity and specificity (doesn't help if it binds the viral protein but also binds proteins in the body needed to reproduce).
- Years later, your drug passes clinical trials (actually, in most cases it doesn't, because your designs don't take things like toxicity into account, only how well it binds the protein of interest) and you are now the proud parent of an antiviral, or in most cases making the news lately, an HIV protease inhibitor.
Also keep in mind when I say "you," I mean a large team of scientists with an incredible array of backgrounds.
Jerm
Oh, you're not a real doctor, are you?
Actually, for the next few years anyway, considering numbers instead of digits increases the rarity. Counting only digits means that 1/1/2000 is a prime day, and 1/3/2000, and 1/5/2000... and... unless 0 isn't a prime number. Hmmmm.....
It's worse, Compaq is calling their machine the "iPaq." Oy. Check out http://www.compaq.com/produ cts/internetdevices/index.html for details. I love the part about "Machines configured with Windows 2000 will ship when the operating system is available."