how long it takes for researchers to focus in this direction, how long it takes (from there) to come up with viable results
Researchers in the pharmaceutical industry have been working on small molecule design for quite some time. The biggest hurdle is specificity.
Lately we've been hearing about monoclonal antibodies which are more specific due to their larger size and custom design. These are performing a little better in clinical trial.
The production and testing of a even a small enzyme, however, is a monolithic task. Protein crystallographers can tell you all about it. Any protein of even small size (50-100 residues) starts to take on different tertiary and quaternary configurations depending not only on pH, but the composition of the surrounding molecules and the identity of any ions present. A protein which has a desirable configuration at physiological pH in the buffer which they use to obtain the crystal from which they determine the configuration may have a completely different configuration at the same pH in the cellular environment.
Not to say that we're not working on it but, as with anything, it's much easier said than done.
Here, they show that brain homogenate from 9949 mice hit with seeded protein can induce disease in normal (FVB) mice
I missed that. Thanks for pointing it out. I believed that even the second group were still transgenic.
Where is the homogenate + CD1 mouse? The FVB + vehicle mouse?
I'd like to see the transgenic mouse + (E. coli sans MoPrP) extract. Unless it's covered in the references it's possible that the ill effects are due to an extract from E. coli, regardless of the particular E. coli strain engineered to produce MoPrP(89-230).
The positive side is that they seem to have confirmed the role of beta-rich regions in prion disease
As you pointed out to start the majority of the scientific community really doesn't argue that beta-amyloid deposits lead to CNS dysfunction which is the diagnostic symptom of Parkinson's, Alzheimer's, and prion diseases. There are different mechanisms: the beta-amyloid deposits themselves inhibit neurological activity and/or the immune system, recruited to remove the deposits, begins to misidentify neurons producing normal PrPa as producers of misfolded PrPb. As with everything it's probably a partial contribution from both pathways that leads to the downward spiral.
There are technical hurdles to using mouse models to study prion diseases. Ideally a researcher would take a completely healthy mouse and induce a prion disease with the administration of a misfolded protein. Unfortunately for researchers most healthy mice don't have a lifespan long enough to develop a prion disease from scratch. The best that the researchers are able to do is take a transgenic strain of mice (Tg196), which are known to have a DNA defect which leads to prion related disease, and administer additional amounts of the prion in order to antagonize the disease state.
The researchers in this case leave too many questions unanswered that could have been easily addressed.
1> The Tg196 transgenic mice express a low level of MoPrP(P101L) which is said to cause the CNS dysfunction. The researchers brew E. coli to produce a large amount of MoPrP(89-230) which they will use to spike the mice. To ensure that the additional disease effects are really attributable to the E. coli produced MoPrP(89-230), why do they not use a control group of mice which receive an extract from an E. coli broth which does _not_ produce MoPrP(89-230)?
2> I keep pointing this out and apparently there aren't enough scientists on/. who can answer it. The authors of the article note that Tg196 mice exhibit spontaneous disease in 30% of their population at ~550 d. The status of the control group is fairly glossed with only a single line which meantions that, as of 670 d, the control mice were still healthy. If that means _all_ the control mice why is there a deviation from the known standard? If that means _some_ of the control mice why did the peer reviewers not ask about it?
3> The bottom line worry is that a prion disease in your cow or sheep will end up in your supermarket and cause a mass plague in humans. The researchers in this study did administer Sc237 (sheep scrapie prion) to some of their mice and saw no ill effects. Paranoid people and others with a political agenda need to give up on the hype.
4> The results are statistically fuzzy. While the authors note that 30% of a population of Tg196 mice are known to be dysfunctional at ~550 days they don't have any expected dysfunctional population % for 670 days. Their own experimental groups have a range of 380-600 and 500-670 d for unseeded and seeded groups, respectively. Additionally, at the 550 d point, both experimental groups were exhibiting about 60% CNS dysfunction in the population. The researchers have shown that administering a prion, for which the mice are known to be susceptible, will hasten their illness. It may be a good bit of lab work but it's not a surprise.
5> The immunoblots are pretty but don't say much. The control group lacks many of the spots that the test groups have, but even the experimental group which received nothing more than the extraction/folding broth (PBS? PBH? I left the PDF on my desk) shows some of the additional bands present in the animals which received actual prions. Additionally there's the RML group. I couldn't find the definition for RML in the paper but noticed that the RML group exhibited 100% population CNS dysfunction by about 180 days. Is this really a prion effect if "RML" is more effective than the prions? Finally, where are the immunoblots for the Sc237 subjects? Ideally they would look like the control group immunoblots since the Sc237 subjects did not exhibit CNS dysfunction. My better sense tells me that the immunoblots for the Sc237 subjects would look more like the mice that received the blank extraction/folding buffer or even closer to the 9949. This would raise some obvious questions about the specificity of the immunoblot for active, MoPrP and inactive PrP from another species. This ties in with <3>.
6> The/. headline reads "Artificial prion created". That's true. The researchers brewed a batch of MoPrP(89-230) which is a truncated form of the natu
It seems from the literature that the ability to cross-infect is taken for granted by prion researchers
Cross-infection is only taken for granted by those pitching it to politicians or who were in favor of the mass wholesale slaughter of every cow in UK and Europe several years ago.
The vast majority of sane scientists hold out that cross-infection for prions is technically possible but yet to be clinically proven. Look even at the current article in question. They did subject some of their mice to Sc237, which is the sheep scrapie prion, and saw no ill effects.
Control mice that received a brain injection without the lab-made prions did not develop prion disease after 670 days
Is that "all control mice" or just "some control mice"? The original publication doesn't say. The authors note that the transgenic mice that they use are known to develop spontaneous CNS dysfunction at about 30% of the population ~550 days. The difference between the 550 d empirical timepoint and the 670 d endpoint is 120, or about 20%. Given that the variation for the animals which were injected was about between 25-35% (380-600 d for unseeded and 500-660 d for seeded) I don't find there lack of CNS dysfunction in the control group to be statistically significant at 670 days.
To summarize:
-Control mice are historically known to be 30% dysfunctional at 550 d. -Some/few/all control mice in this study were functional at 670 d. This fact is insignificant in that it deviates from the known behavior of this strain of mice AND in that it doesn't statistically quantify the control group. -At 550 d, mice which received a purified form of a malevolent protein were about 60% dysfunctional. At best this shows that administering a toxin to a strain known to be susceptible will antagonize the toxic effect. -At 670 d, all mice which had received the malevolent protein were CNS dysfunctional. Some/none/few of the control mice were CNS dysfunctional.
Why are the statistics for the control group not in the publication? If we assume that the control mice all stayed completely healthy then why are they not exhibiting the expected 30% spontaneous illness rate?
The parent isn't an idiot. Yes, Alzheimer's and Parkinson's may be closely related to CJD.
No... No one has ever conclusively demonstrated that you can take a prion from one species and use it to induce a prion state in another species. The current article fails to show any significant effect on mice using sheep scrapie Sc237 in mice. There have been one or two other research groups who have practically saturated one species with the prion of another and then claimed to find evidence of interspecies crossing. That research is dubious at best.
Other labs should be able to duplicate the results, or not
The results will be very duplicatable. If you know someone has a bad leg then it's safe to say that kicking them in the knee will be severely debilitating. These mice are known to have bad brains and the researchers are injecting even more of the purified product of that malfunction.
More significant would be if they bothered to show the immunoblot for the Sc237 inoculated mice alongside the others.
I've been having a field day pointing this out to those of you who aren't lucky enough to have access to the full-text articles.
On page 673 of the scientific paper the others note that, for their research, they are using transgenic mice which are known to express low-levels of the mouse prion protein MoPrP(P101L). These mice, designated Tg196, are known to develop spontaneous illness at ~550 days of age for about 30% of the population. They then took this population, known to spontaneously develop illness, and injected EVEN MORE of the purified MoPrP(89-230) which is a slightly truncated form of MoPrP(P101L).
Did you read the research article? Didn't think so
I did. You obviously didn't and you're being an ass.
On page 673 they state explicitly
About 30% of Tg196 mice develop spontaneous illnessat ~550 days of age.
(emphasis mine) The researchers were using mice who were KNOWN TO GET SICK. All they did was antagonize the condition by injecting the purified product of that transgenic defect.
Note that the mice didn't just die. They developed BSE-like symptoms and their brains showed BSE-like degeneration
They all do.
About 30% of Tg196 mice develop spontaneous illness at ~550 days of age.
The transgenic mice being studied are already susceptible to this genetic defect and the researchers antagonized it by adding the purified product of the genetic defect. Is there any surprise that more mice became more sick more quickly?
And the ground up brain material was capable of passing on the disease to other mice
That's because they're using transgenic mice which already known to be susceptible.
Additionally one must look closely at the graphs on page 674. I can't locate in the article what "RML" is, but apparently administering RML caused conditions and antagonized the CNS of the mice even more than the purified MoPrP(89-231). 100% of the RML group experienced CNS dysfunction after less than 200 days. On top of that the researchers haven't proven that there's a clear prion effect. Immunoblot analysis of a brain tissue puree is hardly a characteristic identifier of MoPrP(P101L). The RML and PBS lanes are nearly identical to the lanes of mice which received the bacterial broth.
The authors acknowledge that 30% of their mice will develop spontaneous disease at ~550 days but they try to pooh-pooh that fact when they begin to discuss their findings
In earlier studies, uninoculated Tg9949 mice lived for more than 500 days without any signs of neurologic dysfunction... In the study reported here, Tg9949 mice were healthy at ~670 days of age and failed to show any signs of disease at 620 days after inoculation or 525 days with SHa Sc237 prions.
Then, on page 675
When the healthy Tg9949 mice inoculated with the Sc237 prions were killed at 525 days after inoculation, five of the seven Tg9949 mice inoculated with the seeded amyloid were already ill.
That's probably because Sc237 is the prion protein for sheep scrapie. While Europe was busy killing ever cow in sight, sane scientists were trying to tell them that the chance of a prion crossing the interspecies barrier is minimal. Conveniently, there is no immunoblot of the Sc237 inoculated mice. I wouldn't be surprised if it looks the same as the 9949 and RML lanes.
Here's my analysis of the key shortcomings of the scientific article.
About 30% of Tg196 mice develop spontaneous illness at ~550 days of age.
The transgenic mice being studied are already susceptible to this genetic defect and the researchers antagonized it by adding the purified product of the genetic defect. Is there any surprise that more mice became more sick more quickly?
Additionally one must look closely at the graphs on page 674. I can't locate in the article what "RML" is, but apparently administering RML caused conditions and antagonized the CNS of the mice even more than the purified MoPrP(89-231). 100% of the RML group experienced CNS dysfunction after less than 200 days. On top of that the researchers haven't proven that there's a clear prion effect. Immunoblot analysis of a brain tissue puree is hardly a characteristic identifier of MoPrP(P101L). The RML and PBS lanes are nearly identical to the lanes of mice which received the bacterial broth.
The authors acknowledge that 30% of their mice will develop spontaneous disease at ~550 days but they try to pooh-pooh that fact when they begin to discuss their findings
In earlier studies, uninoculated Tg9949 mice lived for more than 500 days without any signs of neurologic dysfunction... In the study reported here, Tg9949 mice were healthy at ~670 days of age and failed to show any signs of disease at 620 days after inoculation or 525 days with SHa Sc237 prions.
Then, on page 675
When the healthy Tg9949 mice inoculated with the Sc237 prions were killed at 525 days after inoculation, five of the seven Tg9949 mice inoculated with the seeded amyloid were already ill.
That's probably because Sc237 is the prion protein for sheep scrapie. While Europe was busy killing ever cow in sight, sane scientists were trying to tell them that the chance of a prion crossing the interspecies barrier is minimal. Conveniently, there is no immunoblot of the Sc237 inoculated mice. I wouldn't be surprised if it looks the same as the 9949 and RML lanes.
This is huge because it was still not very clear that Prions even existed
This isn't _that_ huge.
About 30% of Tg196 mice develop spontaneous illness at ~550 days of age.
The transgenic mice being studied are already susceptible to this genetic defect and the researchers antagonized it by adding the purified product of the genetic defect. Is there any surprise that more mice became more sick more quickly?
Additionally one must look closely at the graphs on page 674. I can't locate in the article what "RML" is, but apparently administering RML caused conditions and antagonized the CNS of the mice even more than the purified MoPrP(89-231). 100% of the RML group experienced CNS dysfunction after less than 200 days. On top of that the researchers haven't proven that there's a clear prion effect. Immunoblot analysis of a brain tissue puree is hardly a characteristic identifier of MoPrP(P101L). The RML and PBS lanes are nearly identical to the lanes of mice which received the bacterial broth.
The authors acknowledge that 30% of their mice will develop spontaneous disease at ~550 days but they try to pooh-pooh that fact when they begin to discuss their findings
In earlier studies, uninoculated Tg9949 mice lived for more than 500 days without any signs of neurologic dysfunction... In the study reported here, Tg9949 mice were healthy at ~670 days of age and failed to show any signs of disease at 620 days after inoculation or 525 days with SHa Sc237 prions.
Then, on page 675
When the healthy Tg9949 mice inoculated with the Sc237 prions were killed at 525 days after inoculation, five of the seven Tg9949 mice inoculated with the seeded amyloid were already ill.
That's probably because Sc237 is the prion protein for sheep scrapie. While Europe was busy killing ever cow in sight, sane scientists were trying to tell them that the chance of a prion crossing the interspecies barrier is minimal. Conveniently, there is no immunoblot of the Sc237 inoculated mice. I wouldn't be surprised if it looks the same as the 9949 and RML lanes.
a pure libertarian society would be more ruled by FUD than the one we're living in now
s/more/just as much/
At least, in a Libertarian society, you wouldn't have any illusions about government protected rights.
because there's alot of people out there that are more twisted, and more connected to the means of production than you are
Which is exactly what happens in today's society except that, in today's society, everyone has this false sense of goodness and honesty which emanates from the pretty speeches that they hear on television every day.
That's not rational. An open hole in your computer is more akin to leaving your purse on the hood of your car in a busy parking lot while you shop. Anyone can just walk by and take it. It's still stealing, and illegal, but it's hard to have any sympathy for the "victim".
Preposterous. You're completely ignoring the level of education that the criminal must have. Except for quadrapalegics, anyone in the world is physically capable of picking up an object. I would guess that less than 1% of the population is capable of writing a computer virus, and less than 50% of those have the resourcefulness to find commonly available security holes.
That still leaves us with, mathematically, 30 million black hats and 30 million script kiddies whose ratio is subject to change. That's a far cry from the 6 billion people who could steal a purse.
The crux of the issue is, as has been pointed out before, why should intelligent users be required to take on the burden of those who are lazy? Next thing you know your "Automated computer maintenance" will be a standard charge tacked on to your ISP bill to cover their investment in bandwidth and staffing resources. If things go the way they usually do we won't even see any additional charge. They'll simply hike the rates.
It'd be a perfect way for MS to shift blame for a swiss-cheese OS.
Your computer is your responsibility
While I agree I also feel that you're being too harsh. Some people really just want to play Pac-Man but find $1000 for a home PC to be far cheaper than a $15k standup. The source of the problem is an industry that found itself awash with taxpayer subsidies and no responsibility for a proper product.
Speaking of standup video games... Would game arcades EVER have made any money if the video games froze or choked during scenes of heavy pixmapping and rasterizing? _THAT_ was an era that wrote proper software. I think I saw a standup coin-op on an error screen twice in my life.
I don't understand why this is any more of a problem and any more corruptible than the current "credit rating" system
I suppose we're all satisfied with the fair and unbiased nature of the financial system here in the Corporate Conglomerate (United States) of America. Sorry I brought it up.
Just because other people are too dumb... mean my connection should get bogged with worms
It does when those people make up the voting majority. The United States is bursting with laws which have been created to protect those people while saddling you with the cost.
Imagine standing in line at the supermarket and the fellow behind you in line reaches into your back pocket. You're startled and turn around to confront him.
"Sorry", he says,"I was checking to ensure that you have properly secured your wallet."
You sense no harm done so you go back to your business. Three seconds later you feel a hand reaching for your wallet. Startled, you turn around to face the same fellow.
"Sorry", he says,"I was checking to ensure that you have properly secured your wallet."
You sense no harm done so you go back to your business. Three seconds later............
Unless it has an EULA. If it has an EULA then its your own fault for being stupid enough to carry a wallet or even be in the supermarket because you have no Constitutional right to be in the supermarket and you have no Constitutional right to carry a wallet. You have a right to be secure in your person but it says nothing about wallets. You clicked the EULA.
If the hypothetical "white knight" comes with a proper EULA for the user to click on then it's fine, even if it creates ten security holes for every one that it fixes.
If it doesn't have an EULA then the legal industry will have a field day hanging the author from a tree and subjecting him to all sorts of cruel and unusual punishment which doesn't fit the crime.
I favor a "internet rating" system in the same way you get a "credit rating"
Nifty idea. Which billionaire,who holds controlling market shares in major technology and communications companies, would you like your politicians to put in charge of this inherently incorruptible system?
Fine, then how do you suggest the problem be solved by individuals or partnerships or other small entities?
There is no problem. It's a straw man used by corporations.
and because you give away your rights
I didn't give away my rights. I had no choice in the matter. If you come up with a great idea and, a year later, a large corporation markets a million-dollar product based on the same idea, what recourse do you have? Unless you're independently wealthy, or you have a corporation of your own, you have no recourse. Your "rights" are mitigated by your available funding and resources. Corporate policy-makers know this and exploit it ruthlessly.
Seriously, though, back to reality, what do you propose would work?
I'm simply advocating the levelling of the playing field by ending the taxpayer subsidies for legal enforcement of corporate policy. In a world not sullied by laws purchased by corporate lobbying, Adam would have asked the creators of the show,"Mind if I show these?" The creators would look at the cost:profit ratio of his advertising:DVD sales and said "sure". In today's world Adam is hedged out of the game entirely by the prerequisite of dealing with corporate marketing departments and paranoid VPs who default to "no" unless they see an immediate benefit to themselves. The only time they will consider a general benefit to the company is when the idea is internal and they can use it to bolster their own performance review.
When the janitors, taxi drivers, and lower-rank actors start making significantly better salaries as a result of the MPAA/RIAA legal stomping then I will believe that these measures are in the interest of the people whose representatives enacted the laws. Until then I see them as nothing more than corporate political graft.
In a Libertarian society the community wouldn't stop you from shooting me and taking my possessions. However, after you have committed such a heinous crime, a Libertarian community will slash your truck tires, burn all of your possessions (including those which were formerly mine), and probably run out of town with tar and feathers.
You're too stupid to even comprehend the difference between a sale of goods and copyright licensing
I don't see the difference between licensing and renting aside from some legal jargon which allows the breaking of the terms of a rental agreement to become a felony. That's clearly way out of line and just reeks of ulterior motives, lobbyists, and corporate government graft.
If you buy a book, do you believe you can make infinite copies of that book and sell them? If so, you should be in prison
That's your opinion. What if I buy an educational book, rewrite the contents, and give it away, nonprofit, to all of my friends so that they can share the knowledge? Does Cliff's Notes pay a royalty to the people who publish Shakespeare's work? If so, which publisher does Cliff's Notes legitimately have to pay fees to?
It is _YOU_ who does not understand the implications of your own policies. What you really want is,"Everybody do what I say when I say it and I'm the only one allowed to change my mind at any time."
I have no problems with intellectual property. What I do have a problem with is kicking the door down and damaging the personal possessions of a private citizen who is no more a member of an international conspiracy than our own multi-national coporations are.
what do you propose would be a suitable method to stop infringement?
Why should I pity the large corporations who have a habit of thumbing their nose at both the law and the consumers?
Infringe all you want, I say. I already publish all my material in the GPL public domain. I'm not starving or homeless. Can we drop the whining about corporate profits? 90% of those guys are fat and could use a diet anyways.
Until they can demonstrate that they're actually passing the extra profit on to the janitors, lower-paid actors, and taxi drivers... Screw 'em.
Slashdot Mirror
how long it takes for researchers to focus in this direction, how long it takes (from there) to come up with viable results
Researchers in the pharmaceutical industry have been working on small molecule design for quite some time. The biggest hurdle is specificity.
Lately we've been hearing about monoclonal antibodies which are more specific due to their larger size and custom design. These are performing a little better in clinical trial.
The production and testing of a even a small enzyme, however, is a monolithic task. Protein crystallographers can tell you all about it. Any protein of even small size (50-100 residues) starts to take on different tertiary and quaternary configurations depending not only on pH, but the composition of the surrounding molecules and the identity of any ions present. A protein which has a desirable configuration at physiological pH in the buffer which they use to obtain the crystal from which they determine the configuration may have a completely different configuration at the same pH in the cellular environment.
Not to say that we're not working on it but, as with anything, it's much easier said than done.
Here, they show that brain homogenate from 9949 mice hit with seeded protein can induce disease in normal (FVB) mice
I missed that. Thanks for pointing it out. I believed that even the second group were still transgenic.
Where is the homogenate + CD1 mouse? The FVB + vehicle mouse?
I'd like to see the transgenic mouse + (E. coli sans MoPrP) extract. Unless it's covered in the references it's possible that the ill effects are due to an extract from E. coli, regardless of the particular E. coli strain engineered to produce MoPrP(89-230).
The positive side is that they seem to have confirmed the role of beta-rich regions in prion disease
As you pointed out to start the majority of the scientific community really doesn't argue that beta-amyloid deposits lead to CNS dysfunction which is the diagnostic symptom of Parkinson's, Alzheimer's, and prion diseases. There are different mechanisms: the beta-amyloid deposits themselves inhibit neurological activity and/or the immune system, recruited to remove the deposits, begins to misidentify neurons producing normal PrPa as producers of misfolded PrPb. As with everything it's probably a partial contribution from both pathways that leads to the downward spiral.
There are technical hurdles to using mouse models to study prion diseases. Ideally a researcher would take a completely healthy mouse and induce a prion disease with the administration of a misfolded protein. Unfortunately for researchers most healthy mice don't have a lifespan long enough to develop a prion disease from scratch. The best that the researchers are able to do is take a transgenic strain of mice (Tg196), which are known to have a DNA defect which leads to prion related disease, and administer additional amounts of the prion in order to antagonize the disease state.
/. who can answer it. The authors of the article note that Tg196 mice exhibit spontaneous disease in 30% of their population at ~550 d. The status of the control group is fairly glossed with only a single line which meantions that, as of 670 d, the control mice were still healthy. If that means _all_ the control mice why is there a deviation from the known standard? If that means _some_ of the control mice why did the peer reviewers not ask about it?
/. headline reads "Artificial prion created". That's true. The researchers brewed a batch of MoPrP(89-230) which is a truncated form of the natu
The researchers in this case leave too many questions unanswered that could have been easily addressed.
1>
The Tg196 transgenic mice express a low level of MoPrP(P101L) which is said to cause the CNS dysfunction. The researchers brew E. coli to produce a large amount of MoPrP(89-230) which they will use to spike the mice. To ensure that the additional disease effects are really attributable to the E. coli produced MoPrP(89-230), why do they not use a control group of mice which receive an extract from an E. coli broth which does _not_ produce MoPrP(89-230)?
2>
I keep pointing this out and apparently there aren't enough scientists on
3>
The bottom line worry is that a prion disease in your cow or sheep will end up in your supermarket and cause a mass plague in humans. The researchers in this study did administer Sc237 (sheep scrapie prion) to some of their mice and saw no ill effects. Paranoid people and others with a political agenda need to give up on the hype.
4>
The results are statistically fuzzy. While the authors note that 30% of a population of Tg196 mice are known to be dysfunctional at ~550 days they don't have any expected dysfunctional population % for 670 days. Their own experimental groups have a range of 380-600 and 500-670 d for unseeded and seeded groups, respectively. Additionally, at the 550 d point, both experimental groups were exhibiting about 60% CNS dysfunction in the population. The researchers have shown that administering a prion, for which the mice are known to be susceptible, will hasten their illness. It may be a good bit of lab work but it's not a surprise.
5>
The immunoblots are pretty but don't say much. The control group lacks many of the spots that the test groups have, but even the experimental group which received nothing more than the extraction/folding broth (PBS? PBH? I left the PDF on my desk) shows some of the additional bands present in the animals which received actual prions. Additionally there's the RML group. I couldn't find the definition for RML in the paper but noticed that the RML group exhibited 100% population CNS dysfunction by about 180 days. Is this really a prion effect if "RML" is more effective than the prions? Finally, where are the immunoblots for the Sc237 subjects? Ideally they would look like the control group immunoblots since the Sc237 subjects did not exhibit CNS dysfunction. My better sense tells me that the immunoblots for the Sc237 subjects would look more like the mice that received the blank extraction/folding buffer or even closer to the 9949. This would raise some obvious questions about the specificity of the immunoblot for active, MoPrP and inactive PrP from another species. This ties in with <3>.
6>
The
It seems from the literature that the ability to cross-infect is taken for granted by prion researchers
Cross-infection is only taken for granted by those pitching it to politicians or who were in favor of the mass wholesale slaughter of every cow in UK and Europe several years ago.
The vast majority of sane scientists hold out that cross-infection for prions is technically possible but yet to be clinically proven. Look even at the current article in question. They did subject some of their mice to Sc237, which is the sheep scrapie prion, and saw no ill effects.
Control mice that received a brain injection without the lab-made prions did not develop prion disease after 670 days
Is that "all control mice" or just "some control mice"? The original publication doesn't say. The authors note that the transgenic mice that they use are known to develop spontaneous CNS dysfunction at about 30% of the population ~550 days. The difference between the 550 d empirical timepoint and the 670 d endpoint is 120, or about 20%. Given that the variation for the animals which were injected was about between 25-35% (380-600 d for unseeded and 500-660 d for seeded) I don't find there lack of CNS dysfunction in the control group to be statistically significant at 670 days.
To summarize:
-Control mice are historically known to be 30% dysfunctional at 550 d.
-Some/few/all control mice in this study were functional at 670 d. This fact is insignificant in that it deviates from the known behavior of this strain of mice AND in that it doesn't statistically quantify the control group.
-At 550 d, mice which received a purified form of a malevolent protein were about 60% dysfunctional. At best this shows that administering a toxin to a strain known to be susceptible will antagonize the toxic effect.
-At 670 d, all mice which had received the malevolent protein were CNS dysfunctional. Some/none/few of the control mice were CNS dysfunctional.
Why are the statistics for the control group not in the publication? If we assume that the control mice all stayed completely healthy then why are they not exhibiting the expected 30% spontaneous illness rate?
The parent isn't an idiot. Yes, Alzheimer's and Parkinson's may be closely related to CJD.
No... No one has ever conclusively demonstrated that you can take a prion from one species and use it to induce a prion state in another species. The current article fails to show any significant effect on mice using sheep scrapie Sc237 in mice. There have been one or two other research groups who have practically saturated one species with the prion of another and then claimed to find evidence of interspecies crossing. That research is dubious at best.
Other labs should be able to duplicate the results, or not
The results will be very duplicatable. If you know someone has a bad leg then it's safe to say that kicking them in the knee will be severely debilitating. These mice are known to have bad brains and the researchers are injecting even more of the purified product of that malfunction.
More significant would be if they bothered to show the immunoblot for the Sc237 inoculated mice alongside the others.
What's the natural lifespan of mice?
I've been having a field day pointing this out to those of you who aren't lucky enough to have access to the full-text articles.
On page 673 of the scientific paper the others note that, for their research, they are using transgenic mice which are known to express low-levels of the mouse prion protein MoPrP(P101L). These mice, designated Tg196, are known to develop spontaneous illness at ~550 days of age for about 30% of the population. They then took this population, known to spontaneously develop illness, and injected EVEN MORE of the purified MoPrP(89-230) which is a slightly truncated form of MoPrP(P101L).
So what's the surprise?
I did. You obviously didn't and you're being an ass.
On page 673 they state explicitly
(emphasis mine)
The researchers were using mice who were KNOWN TO GET SICK. All they did was antagonize the condition by injecting the purified product of that transgenic defect.
They all do.
The transgenic mice being studied are already susceptible to this genetic defect and the researchers antagonized it by adding the purified product of the genetic defect. Is there any surprise that more mice became more sick more quickly?
And the ground up brain material was capable of passing on the disease to other mice
That's because they're using transgenic mice which already known to be susceptible.
Additionally one must look closely at the graphs on page 674. I can't locate in the article what "RML" is, but apparently administering RML caused conditions and antagonized the CNS of the mice even more than the purified MoPrP(89-231). 100% of the RML group experienced CNS dysfunction after less than 200 days. On top of that the researchers haven't proven that there's a clear prion effect. Immunoblot analysis of a brain tissue puree is hardly a characteristic identifier of MoPrP(P101L). The RML and PBS lanes are nearly identical to the lanes of mice which received the bacterial broth.
The authors acknowledge that 30% of their mice will develop spontaneous disease at ~550 days but they try to pooh-pooh that fact when they begin to discuss their findings
Then, on page 675
That's probably because Sc237 is the prion protein for sheep scrapie. While Europe was busy killing ever cow in sight, sane scientists were trying to tell them that the chance of a prion crossing the interspecies barrier is minimal. Conveniently, there is no immunoblot of the Sc237 inoculated mice. I wouldn't be surprised if it looks the same as the 9949 and RML lanes.
Does anyone else read these things critically?
The transgenic mice being studied are already susceptible to this genetic defect and the researchers antagonized it by adding the purified product of the genetic defect. Is there any surprise that more mice became more sick more quickly?
Additionally one must look closely at the graphs on page 674. I can't locate in the article what "RML" is, but apparently administering RML caused conditions and antagonized the CNS of the mice even more than the purified MoPrP(89-231). 100% of the RML group experienced CNS dysfunction after less than 200 days. On top of that the researchers haven't proven that there's a clear prion effect. Immunoblot analysis of a brain tissue puree is hardly a characteristic identifier of MoPrP(P101L). The RML and PBS lanes are nearly identical to the lanes of mice which received the bacterial broth.
The authors acknowledge that 30% of their mice will develop spontaneous disease at ~550 days but they try to pooh-pooh that fact when they begin to discuss their findings
Then, on page 675
That's probably because Sc237 is the prion protein for sheep scrapie. While Europe was busy killing ever cow in sight, sane scientists were trying to tell them that the chance of a prion crossing the interspecies barrier is minimal. Conveniently, there is no immunoblot of the Sc237 inoculated mice. I wouldn't be surprised if it looks the same as the 9949 and RML lanes.
Does anyone else read these things critically?
This isn't _that_ huge.
The transgenic mice being studied are already susceptible to this genetic defect and the researchers antagonized it by adding the purified product of the genetic defect. Is there any surprise that more mice became more sick more quickly?
Additionally one must look closely at the graphs on page 674. I can't locate in the article what "RML" is, but apparently administering RML caused conditions and antagonized the CNS of the mice even more than the purified MoPrP(89-231). 100% of the RML group experienced CNS dysfunction after less than 200 days. On top of that the researchers haven't proven that there's a clear prion effect. Immunoblot analysis of a brain tissue puree is hardly a characteristic identifier of MoPrP(P101L). The RML and PBS lanes are nearly identical to the lanes of mice which received the bacterial broth.
The authors acknowledge that 30% of their mice will develop spontaneous disease at ~550 days but they try to pooh-pooh that fact when they begin to discuss their findings
Then, on page 675
That's probably because Sc237 is the prion protein for sheep scrapie. While Europe was busy killing ever cow in sight, sane scientists were trying to tell them that the chance of a prion crossing the interspecies barrier is minimal. Conveniently, there is no immunoblot of the Sc237 inoculated mice. I wouldn't be surprised if it looks the same as the 9949 and RML lanes.
Does anyone else read these things critically?
a pure libertarian society would be more ruled by FUD than the one we're living in now
s/more/just as much/
At least, in a Libertarian society, you wouldn't have any illusions about government protected rights.
because there's alot of people out there that are more twisted, and more connected to the means of production than you are
Which is exactly what happens in today's society except that, in today's society, everyone has this false sense of goodness and honesty which emanates from the pretty speeches that they hear on television every day.
That's not rational. An open hole in your computer is more akin to leaving your purse on the hood of your car in a busy parking lot while you shop. Anyone can just walk by and take it. It's still stealing, and illegal, but it's hard to have any sympathy for the "victim".
Preposterous. You're completely ignoring the level of education that the criminal must have. Except for quadrapalegics, anyone in the world is physically capable of picking up an object. I would guess that less than 1% of the population is capable of writing a computer virus, and less than 50% of those have the resourcefulness to find commonly available security holes.
That still leaves us with, mathematically, 30 million black hats and 30 million script kiddies whose ratio is subject to change. That's a far cry from the 6 billion people who could steal a purse.
The crux of the issue is, as has been pointed out before, why should intelligent users be required to take on the burden of those who are lazy? Next thing you know your "Automated computer maintenance" will be a standard charge tacked on to your ISP bill to cover their investment in bandwidth and staffing resources. If things go the way they usually do we won't even see any additional charge. They'll simply hike the rates.
It'd be a perfect way for MS to shift blame for a swiss-cheese OS.
Your computer is your responsibility
While I agree I also feel that you're being too harsh. Some people really just want to play Pac-Man but find $1000 for a home PC to be far cheaper than a $15k standup. The source of the problem is an industry that found itself awash with taxpayer subsidies and no responsibility for a proper product.
Speaking of standup video games... Would game arcades EVER have made any money if the video games froze or choked during scenes of heavy pixmapping and rasterizing? _THAT_ was an era that wrote proper software. I think I saw a standup coin-op on an error screen twice in my life.
Is it just me or are the processor names getting lamer and lamer
Since the government controls >50% of the GDP all systems are, naturally, going to mimic the trends being set by the government.
This is a natural counterpart of things like "War against Terror" and "Office of Homeland Security".
Everything in life is becoming lamer and lamer...
I don't understand why this is any more of a problem and any more corruptible than the current "credit rating" system
I suppose we're all satisfied with the fair and unbiased nature of the financial system here in the Corporate Conglomerate (United States) of America. Sorry I brought it up.
Just because other people are too dumb ... mean my connection should get bogged with worms
It does when those people make up the voting majority. The United States is bursting with laws which have been created to protect those people while saddling you with the cost.
Not doing any damage? I don't care
... ... ...
Agreed.
Imagine standing in line at the supermarket and the fellow behind you in line reaches into your back pocket. You're startled and turn around to confront him.
"Sorry", he says,"I was checking to ensure that you have properly secured your wallet."
You sense no harm done so you go back to your business. Three seconds later you feel a hand reaching for your wallet. Startled, you turn around to face the same fellow.
"Sorry", he says,"I was checking to ensure that you have properly secured your wallet."
You sense no harm done so you go back to your business. Three seconds later...
Unless it has an EULA. If it has an EULA then its your own fault for being stupid enough to carry a wallet or even be in the supermarket because you have no Constitutional right to be in the supermarket and you have no Constitutional right to carry a wallet. You have a right to be secure in your person but it says nothing about wallets. You clicked the EULA.
If the hypothetical "white knight" comes with a proper EULA for the user to click on then it's fine, even if it creates ten security holes for every one that it fixes.
If it doesn't have an EULA then the legal industry will have a field day hanging the author from a tree and subjecting him to all sorts of cruel and unusual punishment which doesn't fit the crime.
The key is the EULA.
I favor a "internet rating" system in the same way you get a "credit rating"
,who holds controlling market shares in major technology and communications companies, would you like your politicians to put in charge of this inherently incorruptible system?
Nifty idea. Which billionaire
Fine, then how do you suggest the problem be solved by individuals or partnerships or other small entities?
There is no problem. It's a straw man used by corporations.
and because you give away your rights
I didn't give away my rights. I had no choice in the matter. If you come up with a great idea and, a year later, a large corporation markets a million-dollar product based on the same idea, what recourse do you have? Unless you're independently wealthy, or you have a corporation of your own, you have no recourse. Your "rights" are mitigated by your available funding and resources. Corporate policy-makers know this and exploit it ruthlessly.
Seriously, though, back to reality, what do you propose would work?
I'm simply advocating the levelling of the playing field by ending the taxpayer subsidies for legal enforcement of corporate policy. In a world not sullied by laws purchased by corporate lobbying, Adam would have asked the creators of the show,"Mind if I show these?" The creators would look at the cost:profit ratio of his advertising:DVD sales and said "sure". In today's world Adam is hedged out of the game entirely by the prerequisite of dealing with corporate marketing departments and paranoid VPs who default to "no" unless they see an immediate benefit to themselves. The only time they will consider a general benefit to the company is when the idea is internal and they can use it to bolster their own performance review.
When the janitors, taxi drivers, and lower-rank actors start making significantly better salaries as a result of the MPAA/RIAA legal stomping then I will believe that these measures are in the interest of the people whose representatives enacted the laws. Until then I see them as nothing more than corporate political graft.
Hehehe.
In a Libertarian society the community wouldn't stop you from shooting me and taking my possessions. However, after you have committed such a heinous crime, a Libertarian community will slash your truck tires, burn all of your possessions (including those which were formerly mine), and probably run out of town with tar and feathers.
I think you mean "both major parties," not just one
At the end of the day there's no difference. Unless there's a difference between the dog and pony in a circus act.
You're an idiot
Namecalling will get you no where.
You're too stupid to even comprehend the difference between a sale of goods and copyright licensing
I don't see the difference between licensing and renting aside from some legal jargon which allows the breaking of the terms of a rental agreement to become a felony. That's clearly way out of line and just reeks of ulterior motives, lobbyists, and corporate government graft.
If you buy a book, do you believe you can make infinite copies of that book and sell them? If so, you should be in prison
That's your opinion. What if I buy an educational book, rewrite the contents, and give it away, nonprofit, to all of my friends so that they can share the knowledge? Does Cliff's Notes pay a royalty to the people who publish Shakespeare's work? If so, which publisher does Cliff's Notes legitimately have to pay fees to?
It is _YOU_ who does not understand the implications of your own policies. What you really want is,"Everybody do what I say when I say it and I'm the only one allowed to change my mind at any time."
I have no problems with intellectual property. What I do have a problem with is kicking the door down and damaging the personal possessions of a private citizen who is no more a member of an international conspiracy than our own multi-national coporations are.
what do you propose would be a suitable method to stop infringement?
Why should I pity the large corporations who have a habit of thumbing their nose at both the law and the consumers?
Infringe all you want, I say. I already publish all my material in the GPL public domain. I'm not starving or homeless. Can we drop the whining about corporate profits? 90% of those guys are fat and could use a diet anyways.
Until they can demonstrate that they're actually passing the extra profit on to the janitors, lower-paid actors, and taxi drivers... Screw 'em.