Same substance, different parts of the brain. There are several different pathways that involve the release of dopamine; the mesolimbic pathway is where most of the behavioral functions of dopamine occur, and the nigrostriatal pathway, which is involved in motor control. In Parkinson's, the dopamine releasing neurons of the substantia nigra (at one end of the nigrostriatal pathway) die, leading to the characteristic motor symptoms. However, many drugs that act on dopamine pathways, particularly older ones, tend to be nonspecific, and can produce side effects from working on the other pathways- like the movement disorders associated with antipsychotic drugs, for instance.
"Protein kinase C" is really at least 10 different proteins in humans- "isozymes" that have similar function, but different structures and different regulation mechanisms. All of the protein kinaseC variant belong to the larger class of serine/threonine kinases (about 100 different enzymes), and all the work that any of those enzymes do is to add a phosphate group to a serine or threonine amino acid on a protein. That role is important because protein phosphorylation is used as a molecular switch to activate or deactivate a protein. There's nothing special about this particular protein kinase-C isozyme, other than the target it phosphorylates.
Presumably, the target of this particular kinase C form is involved in the apoptosis pathway for dopamine-releasing neurons, so keeping the molecular switch from being turned on could prevent the cell death from being carried out. Since the structures of isozymes are different, you could develop a drug that knocks out this variant of PKC without turning off PKC globally.
However, preventing apoptosis of neurons, while possibly leading to an effective treatment, still does not address why brain cells would feel the need to kill themselves. For instance, in at least some Parkinson's patients, neurons suffer from a buildup of improperly folded protein called alpha-synuclein (compare amyloid and tau in Alzheimer's, prions in prion diseases). (However, overall there are many possible causes of Parkinson's and related syndromes, including unknown causes.) Cell suicide is meant as a protective measure for the remaining cells so they are not in turn poisoned by the output of misfolded proteins. What happens when you turn off apoptosis, and cells which turn "sick" are no longer able to die?
I would put the chances that probes have already sent some microscopic earthlings to Mars as highly unlikely, but not impossible. The strains of bacteria used in this experiment are able to survive many conventional sterilization procedures. The Bacillus pumilus strain used in this particular experiment was in fact Bacillus pumilus-SAFR032. That's Spacecraft Assembly Facility Resistant Isolate 32, endospores of which were originally discovered in the JPL Spacecraft Assembly Facility, after the room had been otherwise rendered sterile with UV radiation and vaporous hydrogen peroxide.
The challenge for any microbe that would want to colonize Mars is to stay at least minimally shielded from ionizing radiation. Bacterial spores can be hardy enough to tolerate days of hard radiation, but usually not months. And at some point, the bacterium will have to have to find conditions suitable for normal stage (non-spore) survival. It would of course be disconcerting to find viable bacterial spores on the long-quiet probes we sent there decades ago (and if we happen to be on Mars in person, then we have brought lots of microbes with us, no way around that), but a few freeze-dried spores is hardly an alien invasion. For bacteria to truly colonize Mars, they would eventually have to get warm, wet, and covered. That makes the end-of-life of the Mars Phoenix mission interesting: crushed by an advancing ice cap. That seems like a process that could plow little bits of probe into the Martian soil....
No, it looks like the same definition- the bacteria that survived did so by forming desiccated, nondividing endospores. The article mentions that the bacteria which didn't protect themselves with the endospore stage died within minutes. The two strains of bacteria they tested are of particular importance because they have been known to survive the Jet Propulsion Lab standard decontamination procedures, and so could take a trip to Mars. This paper describes some of the DNA repair mechanisms that B. pumilus uses to survive under adverse conditions.
Quite a bit lower. 150 million K (I'll use Kelvin here since it's basically equal to Celsius relative to temperatures of millions of either) is routine for thermonuclear bombs, which we've managed to test while avoiding complete destruction of the earth. The highest temperature of bulk matter ever recorded on earth was about 2 billion Kelvin, and took place in the Z Machine at Sandia Nat'l Labs. Elsewhere in the universe, supernova core temperatures are estimated to reach over 100 billion K; of course, sometimes this process does in fact produce a black hole, but observations suggest that whether this occurs is pretty strongly associated with the mass of the star- neutron star remants can exist at 100 billion K without further collapse. And while the statistical definition of temperature is arguably a bad fit when talking about subatomic particles, the average kinetic energies achieved by colliding particles (in terrestrial particle accelerators and moreso in cosmic rays) equate to temperatures in excess of 10^15 Kelvin or more, at least 7 orders of magnitude greater than ITER.
Now, at some temperature, we could perhaps expect the kinetic energy of particles to be so high that the particles collapse into subatomic black holes. Whether this is physically realizable, and the temperature it would occur at, depend on which physics theory you subscribe to. A key element of the "holographic universe" idea is that many of the maximum and minimum possible values for quantities like distance, entropy, and temperature have constraints imposed by the observable universe being a projection from a lower dimension event horizon. By some interpretations, this might mean that the maximum possible temperature is about 10^17K, which is about 15 orders of magnitude lower than more conventional cosmology theories would predict.
This suggests that the collisions of the highest energy cosmic rays in the universe regularly produce subatomic black holes. The Large Hadron Collider, whenever it is up and running, is also expected to produce temperatures in that range, so it might in fact make a black hole. You may have heard some news about this recently. So, a science experiment in central Europe in the near future may produce black holes, but it won't be ITER.
Actually, most forms of gene therapy don't require growing cells to work. If you use a virus to carry the genes of interest into the cell, your cell will read the inserted DNA just as if it were your own. There are two routes you can go with viral vectors. You can use a retrovirus, which will actually insert genes into your permanent genome, which will cause those genes to be copied and passed on if the infected cells divide. Or you can use adenoviruses or adeno-associated viruses, which can give genes to infected cells, but those genes will not be passed on. The retroviral approach carries added risks of inserting genes in the wrong places (causing some cases of leukemia in clinical trials), and having genes pass to dividing cells is of little benefit if you want to infect the neurons of an adult brain.
Of course, adeno-type viruses (either a weakened or non-pathogenic strain is used) are not without risk, particularly if you're planning to use them to infect your brain- meningitis seems like it'd be a real concern here. Right now, viral vector gene therapy is at the level of being an early experimental treatment for conditions like cancers and inherited immunodeficiencies- making your thoughts produce light would be a very off-label use.
I would guess that the development of this sort of fractal packing was a watershed moment in the development of eukaryotic life, but the process itself can be logically seen as an extension of existing processes. Most bacteria, which lack a nucleus, arrange their DNA in a simple circle.
This has advantages: the entire genome is always accessible for transcription and replication, there aren't telomeres to deal with, and it requires less maintenance. There are disadvantages: if every gene is accessible to the cytoplasm, you have actively keep the 99% you aren't currently using shut off, which is why bacteria use the operon system, and a big circular strand floating around is liable to tie itself in an awful knot. Bacteria have the equipment to fix small topologically issues in their genome, but overall, bacterial genomes are limited in their potential size. Some more complex bacteria have found a partial solution: they draw folds of their circular genome around proteins, to make a single circle more manageable as a
group of pinched off loops. So you can see that there's an intermediate stage between "circle" and "our DNA has Hausdorff dimension 3."
Of course, if you're going to head down the road of DNA folding, you would really benefit from a plan. The beauty of fractals, and a reason they are found so often in the natural world, is that very complex behavior can come from the repeated iteration of very simple rules. Your cells don't need to understand Hilbert curves; all they need is a protein complex that grabs a strand of DNA, then puts a short, specific sequence of folds in it. As that happens along the entire strand, you make a space filling curve that would impress a mathematician.
The researchers originally wanted to use Half-Life instead of Quake 2, but they could never get the mice to do anything in the game other than murdering the scientists.
I'm not sure what exactly they use as a marker in this case, but I know that one distinguishing feature for cancer cells is increased oxidative stress that attacks membrane lipids. Due to this, cancer cells have much larger concentrations of small-chain alkanes than you would expect in a healthy cell. Using alkanes as your biomarker has the further advantage of their structural simplicity; you can just dial in on the mass of something like pentane or hexane molecular ions without having to do detective work on a bunch of fragments.
Since the shorter alkanes are highly volatile, there have already been experiments to show that lung cancers can be detected by GC-MS of collected breath, and even some experiments that dogs have a sense of smell acute enough to pick up on these markers.
I think the point of building the big superconducting wire triangle is that they couldn't feasibly place the three AC/DC and DC/AC converter setups physically any closer. Looking at the proposed site, there is a pretty limited corridor where setting up a three-grid link would be possible. If they wanted to accomplish this from a single facility (say, where the center of the proposed triangle sits), they would have to extend existing high voltage AC lines to that point, which would have increased resistive losses. Plus, they would still be building power lines- towers, cables, maintenance. American Superconductor, who in addition to being a supplier of materials, is also an equity partner in this project, wants to demonstrate that they can make high voltage superconducting DC lines cost-competitive with high voltage AC transmission lines.
The second table and the ideas surrounding it are really restatements of the theoretical basis for the rules of electron configuration (the Aufbau principle). As a consquence of following Fermi-Dirac statistics, a lot of properties for electrons fall naturally out of associated symmetry groups, including quantum numbers and the Pauli exclusion principle. So in Kibler's group theory representation, elements are really just sorted by arrangment of quantum number, which is really just an alternative positioning of what we'd consider the s-, p-, d-, and f- "blocks" of elements in the current table. The group theory table is interesting in that it makes the group theory underpinnings of the periodic table more clear, but those foundations have been known since about 1930.
There really isn't a way to integrate the lanthanoids and the actinoids into their expected circles; due to poor effective nuclear shielding from the f orbital electrons, they have smaller atomic radii than would be expected, and so their insertion would break the trends of the rest of the table. Overall, basing a periodic table on periodicity of atomic radii has some serious problems- there are trends, but not rules. There aren't precise values for atomic radii anyway- the measured values have big error bars, and only have reasonable agreement with calculated values (which vary by which set of quantum mechanical approximations were used). The standard periodic table arranges by atomic number and electron configuration, both of which are unique to each element, and both of which carry substantial predictive attributes in their periodicity.
So a black hole's entropy = "we don't know by looking what's inside"? How exactly does that contribute to the heat death of the universe? If there was a million times more entropy in black holes, how would it effect existance outside of black holes? Is there a background process constantly checking the total amount of entropy, ready to reboot the universe when it reaches an arbitrary level?
All reasonable questions. From how I understand it, the idea that the universe has a maximum possible entropy (to which black holes contribute) depends on the correctness of the holographic universe theory. The holographic universe notion is all about how the universe we observe is really a projection from a two dimensional event horizon. Central to the holographic universe is the holographic bound, which states that the total entropy of the universe is constrained by the surface area of the universe event horizon. That means that the entropy of black holes must be figured into the total entropy of the universe. What the parent is really assuming is the same thing that Stephen Hawking originally assumed with the "black hole information paradox"- that when ensembles of particles fall into a black hole, they are carrying information about their total accesible microstates- their entropy- in with them, but all a black hole ever spits out is featureless Hawking radiation. If that information disappears, it implies that black holes can reduce the entropy of the rest of the universe.
The holographic principle answers that objection by proposing that Hawking radiation isn't really featureless- it is modified by the event horizon, which contains the information. Instead of being an entropy vacuum, a black hole is an object with maximal entropy per volume. That entropy very slowly bleeds out into the rest of the universe through Hawking radiation.
If the holographic universe idea is true, this means that the entire universe is headed for a point where it reaches the maximal entropy per volume. This would be the heat death of the universe, because it would be impossible to do useful work. Finding out that black holes have the lion's share of the entropy means that there is less possible work available in the rest of the universe, since the black hole share counts towards the total. Of course, the universe couldn't reach a true thermodynamic heat death until all the black holes had evaporated (the time estimates for this process tend to be rather large), but that would be small comfort for anyone around after all the stars burn out.
There are a few different ways of doing DNA sequencing now, but most automated sequencing uses what's called the dye termination method, which is an advancement on the Sanger (aka dideoxy) method. If the sample needs to be amplified, you can use the polymerase chain reaction, which uses heat to separate strands of DNA, then uses a heat stable DNA polymerase to make copies- a process that can be cycled to exponentially increase the sample. Once again, PCR is only necessary if you need more material to work with.
The sequencing itself starts by unzipping your DNA sample to a single strand, and then making copies of this strand in an environment where a small fraction of the available deoxynucleotides used for building the copied strands are replaced with labeled dideoxynucleotides, which are added to the growing strand but then terminate further growth. This produces a series of DNA fragments of differing lengths, each with a tag on the last base added. You can use electrophoresis to separate the fragments by size, which creates a map of where your tagged dideoxy bases are located. If you have managed to tag each location at least once, then you know the entire sequence.
The original Sanger method used radioactive tags, and you had to run the reaction 4 times- with labeled A, T, C, and G separately. Modern automated sequencers usually use four fluorescent tags at different wavelengths, so all four can be run in the same pot.
Well, ten years probably excludes direct, advanced methods of age-related damage repair- gene therapy or stem-cell transplants, for instance. The main thing I think we'll have within ten years is some solid data on whether the first compounds to mimic caloric restriction diets have any effect in humans. Unfortunately, it's tough to study lifespan extension in organisms that already live for decades, but the evidence is pretty suggestive that cutting calories (while maintaining nutrients) can extend lifespan by as much as 30-40% in lab animals, while decreasing the frequency of age and metabolic related diseases like cancer, heart disease, and type II diabetes. So, you can get started on that right now if you'd like, though severely cutting caloric intake can be an unpleasant diet, and it requires caution to stay above the point where you're in fact starving, which can damage your organs, muscles, and nerves. It's been suggested that part of the reason lab animals do so well on caloric restriction diets is that they are animals that live in a laboratory setting, with few of the hazards of a natural life to threaten them.
So, several proteins that seem to be involved in the benefits of caloric restriction have been identified, and compounds that act on these proteins have been discovered, so we're starting to see drugs based on these compounds entering clinical trials. I'm not sure about the stance taken by other regulatory agencies, but the US FDA doesn't consider aging in itself to be a disease, so they are being tested for their utility as treatments for diabetes and cancer. Sirtris Pharmaceuticals (now part of GlaxoSmithKline, who essentially bet $720 million that this idea would work) has their micronized resveratrol formulation SRT501 in early Phase II trials and a pipeline of candidates along the same theme: activating a family of proteins called sirtuins which are proposed to modulate a number of pathways of metabolism and the cell cycle.
If that doesn't pan out, there's a lot of research into mTOR inhibitors. Sirolimus, also known as rapamycin (mTOR is the mammalian Target Of Rapamycin), has been shown to increase maximum lifespan in mice by about 10% even when administered late in life. Sirolimus itself is not suitable for use in human life extension, as it is a powerful immunosuppressant (approved to prevent organ rejection, in fact), but there are a number of related compounds under investigation. Temsirolimus is FDA/EMEA approved to treat renal cell carcinoma; by inhibiting mTOR in cancer cells, it stops the cell cycle of growth and division. Conceivably, a drug along that line could be developed that slowed the cell cycle for normal human cells, which would slow their aging, and reduce the chance of replication errors that would lead to either cell death or cancer. Of course, I'm not sure that any of this research will lead to a pill that slows aging and/or lengthens lifespan, especially in the next ten years, but we may get some effective new diabetes and cancer drugs from this.
There are a few extraordinary cases where the prize was awarded within a few years of the relevant discovery. Bednorz and Muller discovered Type II superconductivity in 1986, and were awarded the Physics prize in 1987. Rubbia and Van der Meer won the 1984 Physics prize for work towards the discovery of the W and Z bosons, which occurred in 1983. Banting and Macleod discovered and isolated insulin in 1921-22, and received the 1923 Medicine prize (Banting was 32 at the time!). Quite a few of the major figures in quantum theory and nuclear fission received either Physics or Chemistry Nobels within a few years of the work that got them the prize. So, it does happen, but it's pretty rare. In general, the science prizes are much more cautious than the Economics and Peace prizes, which have produced some regrettable prize selections in hindsight.
Viruses have very small genomes in comparison with the human genome; many viruses get by with fewer than ten genes, while we have around twenty thousand. In addition, viruses don't arrange their genes in structures anything like the chromatin we use. Packaging a replacement human genome to infect human cells would require a vector so completely re-engineered from what we would currently recognize as a virus that we'd probably want to call it something else. Getting that infection procedure to work without killing the patient is far, far beyond current technology, and I'm not sure that it would confer biological immortality anyway. Your mitochondria have their own little genome, separate from that of the nucleus, which would be difficult to replace with a virus- and mitochondrial aging may play a significant role in producing the outward effects of human aging. If you turned your mitochondria off, you would die very quickly- the effect would be as if you had been poisoned with cyanide.
It is possible to add very small numbers of genes using viral vectors- human gene therapy is something that may indeed take off in years to come. There are presently many difficulties with using viruses to insert genes- you can use a retrovirus to insert the gene permanently into the genome, but it's hard to control insertion, so it's possible to get many copies- or none- in a given cell. Genes may also insert themselves in the middle of other genes, causing all sorts of deleterious effects.
Probably not, to be honest. If they're just starting Phase I right now, figure on at best 6-8 years or more before a possible approval by regulatory agencies, which naturally assumes that this treatment would be demonstrated as both safe and efficacious. Phase I doesn't take much time, but Phases II and III can easily take years- particularly for a disorder like ALS, where patients would need to be monitored for months to determine the treatment's effects. In Stephen Hawking's particular and remarkable case, it is not merely the progression of his ALS that would be an issue; the man is 67 years old right now.
From the Interorbital Systems site, it says, "Storable, high-density white fuming nitric acid (WFNA) and Hydrocarbon-X (HX) are the rocket's primary propellants." I'd presume "Hydrocarbon-X" is some sort of kerosene-like blend of petroleum distillates.
I think they actually did both of those checks- both the reference Y chromosome and comparison to blood DNA. From the article itself:
For the filtered candidate mutations, we designed PCR primers by using Primer3 17 S. Rozen and H. Skaletsky, Primer3 on the WWW for general users and for biologist programmers, Methods Mol. Biol. 132 (2000), pp. 365-386. View Record in Scopus | Cited By in Scopus (1518)[17] (http://frodo.wi.mit.edu/) to amplify 400-700 bp fragments (primer sequences and PCR conditions are in Table S2), purified them by standard ExoSAP treatment, and sequenced them by using BigDye terminator chemistry on both forward and reverse strands [18]. Initial analyses were performed on the cell line DNAs from the two individuals. Candidate mutations confirmed in the cell-line DNAs were then sequenced in blood DNAs from the same individuals as well as five other family members (Figure 1). All the confirmed candidate mutations are supported by four or more capillary sequence reads.
As part of getting enough Y chromosomes for their experiment, they inserted their two donor genomes into two groups of cell cultures to amplify the amount of genetic material. The cell lines are made from lymphocytes which have been infected with the Epstein-Barr virus; it's more or less a culture of Hodgkin's lymphoma cancer cells. They isolated the Y chromosomes (they got around 600 nanograms of each of the two lines), and then did their sequencing.
The problem with amplifying the material in this manner is that it's bound to introduce a few more mutations, since there is cell division involved, and cancer cells in particular can be a bit sloppy in replicating genes. So, to account for the mutations caused by their amplification procedure, they double checked the twelve candidate mutations they found against the donor's DNA from blood samples (not amplified by cell culture) and against the same regions in very close male relatives of the donors (if you are male and have a biological full brother, then your Y chromosomes should be almost completely identical). They scratched eight candidate mutations off as coming from the cell culture process, leaving four.
Ultimately, yes, mutations like the ones studied here drive evolution and speciation. They are the mechanism behind generating completely new genetic information. However, in terms of following the genetics of a diverse population, genetic recombination events like crossover have a greater effect on the changes from generation to generation than mutations.
As this experiment shows, you might have accumulated a few hundred single nucleotide polymorphisms- differences at one base pair- in the lineage from your great-grandfathers to you. However, so much shuffling of the genetic deck occurs in each generation's gametes that, as may be obvious to you, two people (siblings, for example) can be closely related but display very distinct traits. The reason why you'd want to focus on the Y chromosome if you wanted to isolate the mutation rate is that it doesn't undergo all of this shuffling; you probably only have a maximum of one (there are a few XYY males)and it passes down patrilineally with only random mutations to change it. Those two men tested could well have very similar Y chromosomes, but otherwise be genetically very different.
I would argue that there is a survivorship bias in studying mutation in the Y chromosome, though. There aren't many genes on the Y chromosome, but the ones it does have tend to be critical for producing healthy, fertile males. It might be the case that mutation rates that might be tolerable on other (somatic) chromosomes produce completely inviable offspring when they occur at that rate on the Y.
Re:Interesting Background Material
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Robotic Mold
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· Score: 5, Informative
Yeah, the reason slime molds are referred to as plasmodium is because the slime mold colony lacks defined cell walls or membranes between what would normally be considered individual cells. The mold can essentially be thought of as a single cell with many nuclei, since cytoplasm is continous throughout the entire colony. As the parent notes, this type of structure (a lifecycle stage, really) has nothing to do with the protozoa which cause malaria, which just happen to be of genus Plasmodium.
Slashdot Mirror
Same substance, different parts of the brain. There are several different pathways that involve the release of dopamine; the mesolimbic pathway is where most of the behavioral functions of dopamine occur, and the nigrostriatal pathway, which is involved in motor control. In Parkinson's, the dopamine releasing neurons of the substantia nigra (at one end of the nigrostriatal pathway) die, leading to the characteristic motor symptoms. However, many drugs that act on dopamine pathways, particularly older ones, tend to be nonspecific, and can produce side effects from working on the other pathways- like the movement disorders associated with antipsychotic drugs, for instance.
"Protein kinase C" is really at least 10 different proteins in humans- "isozymes" that have similar function, but different structures and different regulation mechanisms. All of the protein kinaseC variant belong to the larger class of serine/threonine kinases (about 100 different enzymes), and all the work that any of those enzymes do is to add a phosphate group to a serine or threonine amino acid on a protein. That role is important because protein phosphorylation is used as a molecular switch to activate or deactivate a protein. There's nothing special about this particular protein kinase-C isozyme, other than the target it phosphorylates.
Presumably, the target of this particular kinase C form is involved in the apoptosis pathway for dopamine-releasing neurons, so keeping the molecular switch from being turned on could prevent the cell death from being carried out. Since the structures of isozymes are different, you could develop a drug that knocks out this variant of PKC without turning off PKC globally.
However, preventing apoptosis of neurons, while possibly leading to an effective treatment, still does not address why brain cells would feel the need to kill themselves. For instance, in at least some Parkinson's patients, neurons suffer from a buildup of improperly folded protein called alpha-synuclein (compare amyloid and tau in Alzheimer's, prions in prion diseases). (However, overall there are many possible causes of Parkinson's and related syndromes, including unknown causes.) Cell suicide is meant as a protective measure for the remaining cells so they are not in turn poisoned by the output of misfolded proteins. What happens when you turn off apoptosis, and cells which turn "sick" are no longer able to die?
I would put the chances that probes have already sent some microscopic earthlings to Mars as highly unlikely, but not impossible. The strains of bacteria used in this experiment are able to survive many conventional sterilization procedures. The Bacillus pumilus strain used in this particular experiment was in fact Bacillus pumilus-SAFR032. That's Spacecraft Assembly Facility Resistant Isolate 32, endospores of which were originally discovered in the JPL Spacecraft Assembly Facility, after the room had been otherwise rendered sterile with UV radiation and vaporous hydrogen peroxide.
The challenge for any microbe that would want to colonize Mars is to stay at least minimally shielded from ionizing radiation. Bacterial spores can be hardy enough to tolerate days of hard radiation, but usually not months. And at some point, the bacterium will have to have to find conditions suitable for normal stage (non-spore) survival. It would of course be disconcerting to find viable bacterial spores on the long-quiet probes we sent there decades ago (and if we happen to be on Mars in person, then we have brought lots of microbes with us, no way around that), but a few freeze-dried spores is hardly an alien invasion. For bacteria to truly colonize Mars, they would eventually have to get warm, wet, and covered. That makes the end-of-life of the Mars Phoenix mission interesting: crushed by an advancing ice cap. That seems like a process that could plow little bits of probe into the Martian soil....
No, it looks like the same definition- the bacteria that survived did so by forming desiccated, nondividing endospores. The article mentions that the bacteria which didn't protect themselves with the endospore stage died within minutes. The two strains of bacteria they tested are of particular importance because they have been known to survive the Jet Propulsion Lab standard decontamination procedures, and so could take a trip to Mars. This paper describes some of the DNA repair mechanisms that B. pumilus uses to survive under adverse conditions.
Quite a bit lower. 150 million K (I'll use Kelvin here since it's basically equal to Celsius relative to temperatures of millions of either) is routine for thermonuclear bombs, which we've managed to test while avoiding complete destruction of the earth. The highest temperature of bulk matter ever recorded on earth was about 2 billion Kelvin, and took place in the Z Machine at Sandia Nat'l Labs. Elsewhere in the universe, supernova core temperatures are estimated to reach over 100 billion K; of course, sometimes this process does in fact produce a black hole, but observations suggest that whether this occurs is pretty strongly associated with the mass of the star- neutron star remants can exist at 100 billion K without further collapse. And while the statistical definition of temperature is arguably a bad fit when talking about subatomic particles, the average kinetic energies achieved by colliding particles (in terrestrial particle accelerators and moreso in cosmic rays) equate to temperatures in excess of 10^15 Kelvin or more, at least 7 orders of magnitude greater than ITER.
Now, at some temperature, we could perhaps expect the kinetic energy of particles to be so high that the particles collapse into subatomic black holes. Whether this is physically realizable, and the temperature it would occur at, depend on which physics theory you subscribe to. A key element of the "holographic universe" idea is that many of the maximum and minimum possible values for quantities like distance, entropy, and temperature have constraints imposed by the observable universe being a projection from a lower dimension event horizon. By some interpretations, this might mean that the maximum possible temperature is about 10^17K, which is about 15 orders of magnitude lower than more conventional cosmology theories would predict.
This suggests that the collisions of the highest energy cosmic rays in the universe regularly produce subatomic black holes. The Large Hadron Collider, whenever it is up and running, is also expected to produce temperatures in that range, so it might in fact make a black hole. You may have heard some news about this recently. So, a science experiment in central Europe in the near future may produce black holes, but it won't be ITER.
Actually, most forms of gene therapy don't require growing cells to work. If you use a virus to carry the genes of interest into the cell, your cell will read the inserted DNA just as if it were your own. There are two routes you can go with viral vectors. You can use a retrovirus, which will actually insert genes into your permanent genome, which will cause those genes to be copied and passed on if the infected cells divide. Or you can use adenoviruses or adeno-associated viruses, which can give genes to infected cells, but those genes will not be passed on. The retroviral approach carries added risks of inserting genes in the wrong places (causing some cases of leukemia in clinical trials), and having genes pass to dividing cells is of little benefit if you want to infect the neurons of an adult brain.
Of course, adeno-type viruses (either a weakened or non-pathogenic strain is used) are not without risk, particularly if you're planning to use them to infect your brain- meningitis seems like it'd be a real concern here. Right now, viral vector gene therapy is at the level of being an early experimental treatment for conditions like cancers and inherited immunodeficiencies- making your thoughts produce light would be a very off-label use.
I would guess that the development of this sort of fractal packing was a watershed moment in the development of eukaryotic life, but the process itself can be logically seen as an extension of existing processes. Most bacteria, which lack a nucleus, arrange their DNA in a simple circle.
This has advantages: the entire genome is always accessible for transcription and replication, there aren't telomeres to deal with, and it requires less maintenance. There are disadvantages: if every gene is accessible to the cytoplasm, you have actively keep the 99% you aren't currently using shut off, which is why bacteria use the operon system, and a big circular strand floating around is liable to tie itself in an awful knot. Bacteria have the equipment to fix small topologically issues in their genome, but overall, bacterial genomes are limited in their potential size. Some more complex bacteria have found a partial solution: they draw folds of their circular genome around proteins, to make a single circle more manageable as a group of pinched off loops. So you can see that there's an intermediate stage between "circle" and "our DNA has Hausdorff dimension 3."
Of course, if you're going to head down the road of DNA folding, you would really benefit from a plan. The beauty of fractals, and a reason they are found so often in the natural world, is that very complex behavior can come from the repeated iteration of very simple rules. Your cells don't need to understand Hilbert curves; all they need is a protein complex that grabs a strand of DNA, then puts a short, specific sequence of folds in it. As that happens along the entire strand, you make a space filling curve that would impress a mathematician.
The researchers originally wanted to use Half-Life instead of Quake 2, but they could never get the mice to do anything in the game other than murdering the scientists.
I used to bullseye womp cysts with my T-16 electroscalpel back home. They're not much bigger than two centimeters.
I'm not sure what exactly they use as a marker in this case, but I know that one distinguishing feature for cancer cells is increased oxidative stress that attacks membrane lipids. Due to this, cancer cells have much larger concentrations of small-chain alkanes than you would expect in a healthy cell. Using alkanes as your biomarker has the further advantage of their structural simplicity; you can just dial in on the mass of something like pentane or hexane molecular ions without having to do detective work on a bunch of fragments.
Since the shorter alkanes are highly volatile, there have already been experiments to show that lung cancers can be detected by GC-MS of collected breath, and even some experiments that dogs have a sense of smell acute enough to pick up on these markers.
I think the point of building the big superconducting wire triangle is that they couldn't feasibly place the three AC/DC and DC/AC converter setups physically any closer. Looking at the proposed site, there is a pretty limited corridor where setting up a three-grid link would be possible. If they wanted to accomplish this from a single facility (say, where the center of the proposed triangle sits), they would have to extend existing high voltage AC lines to that point, which would have increased resistive losses. Plus, they would still be building power lines- towers, cables, maintenance. American Superconductor, who in addition to being a supplier of materials, is also an equity partner in this project, wants to demonstrate that they can make high voltage superconducting DC lines cost-competitive with high voltage AC transmission lines.
The second table and the ideas surrounding it are really restatements of the theoretical basis for the rules of electron configuration (the Aufbau principle). As a consquence of following Fermi-Dirac statistics, a lot of properties for electrons fall naturally out of associated symmetry groups, including quantum numbers and the Pauli exclusion principle. So in Kibler's group theory representation, elements are really just sorted by arrangment of quantum number, which is really just an alternative positioning of what we'd consider the s-, p-, d-, and f- "blocks" of elements in the current table. The group theory table is interesting in that it makes the group theory underpinnings of the periodic table more clear, but those foundations have been known since about 1930.
There really isn't a way to integrate the lanthanoids and the actinoids into their expected circles; due to poor effective nuclear shielding from the f orbital electrons, they have smaller atomic radii than would be expected, and so their insertion would break the trends of the rest of the table. Overall, basing a periodic table on periodicity of atomic radii has some serious problems- there are trends, but not rules. There aren't precise values for atomic radii anyway- the measured values have big error bars, and only have reasonable agreement with calculated values (which vary by which set of quantum mechanical approximations were used). The standard periodic table arranges by atomic number and electron configuration, both of which are unique to each element, and both of which carry substantial predictive attributes in their periodicity.
All reasonable questions. From how I understand it, the idea that the universe has a maximum possible entropy (to which black holes contribute) depends on the correctness of the holographic universe theory. The holographic universe notion is all about how the universe we observe is really a projection from a two dimensional event horizon. Central to the holographic universe is the holographic bound, which states that the total entropy of the universe is constrained by the surface area of the universe event horizon. That means that the entropy of black holes must be figured into the total entropy of the universe. What the parent is really assuming is the same thing that Stephen Hawking originally assumed with the "black hole information paradox"- that when ensembles of particles fall into a black hole, they are carrying information about their total accesible microstates- their entropy- in with them, but all a black hole ever spits out is featureless Hawking radiation. If that information disappears, it implies that black holes can reduce the entropy of the rest of the universe.
The holographic principle answers that objection by proposing that Hawking radiation isn't really featureless- it is modified by the event horizon, which contains the information. Instead of being an entropy vacuum, a black hole is an object with maximal entropy per volume. That entropy very slowly bleeds out into the rest of the universe through Hawking radiation.
If the holographic universe idea is true, this means that the entire universe is headed for a point where it reaches the maximal entropy per volume. This would be the heat death of the universe, because it would be impossible to do useful work. Finding out that black holes have the lion's share of the entropy means that there is less possible work available in the rest of the universe, since the black hole share counts towards the total. Of course, the universe couldn't reach a true thermodynamic heat death until all the black holes had evaporated (the time estimates for this process tend to be rather large), but that would be small comfort for anyone around after all the stars burn out.
There are a few different ways of doing DNA sequencing now, but most automated sequencing uses what's called the dye termination method, which is an advancement on the Sanger (aka dideoxy) method. If the sample needs to be amplified, you can use the polymerase chain reaction, which uses heat to separate strands of DNA, then uses a heat stable DNA polymerase to make copies- a process that can be cycled to exponentially increase the sample. Once again, PCR is only necessary if you need more material to work with.
The sequencing itself starts by unzipping your DNA sample to a single strand, and then making copies of this strand in an environment where a small fraction of the available deoxynucleotides used for building the copied strands are replaced with labeled dideoxynucleotides, which are added to the growing strand but then terminate further growth. This produces a series of DNA fragments of differing lengths, each with a tag on the last base added. You can use electrophoresis to separate the fragments by size, which creates a map of where your tagged dideoxy bases are located. If you have managed to tag each location at least once, then you know the entire sequence.
The original Sanger method used radioactive tags, and you had to run the reaction 4 times- with labeled A, T, C, and G separately. Modern automated sequencers usually use four fluorescent tags at different wavelengths, so all four can be run in the same pot.
Well, ten years probably excludes direct, advanced methods of age-related damage repair- gene therapy or stem-cell transplants, for instance. The main thing I think we'll have within ten years is some solid data on whether the first compounds to mimic caloric restriction diets have any effect in humans. Unfortunately, it's tough to study lifespan extension in organisms that already live for decades, but the evidence is pretty suggestive that cutting calories (while maintaining nutrients) can extend lifespan by as much as 30-40% in lab animals, while decreasing the frequency of age and metabolic related diseases like cancer, heart disease, and type II diabetes. So, you can get started on that right now if you'd like, though severely cutting caloric intake can be an unpleasant diet, and it requires caution to stay above the point where you're in fact starving, which can damage your organs, muscles, and nerves. It's been suggested that part of the reason lab animals do so well on caloric restriction diets is that they are animals that live in a laboratory setting, with few of the hazards of a natural life to threaten them.
So, several proteins that seem to be involved in the benefits of caloric restriction have been identified, and compounds that act on these proteins have been discovered, so we're starting to see drugs based on these compounds entering clinical trials. I'm not sure about the stance taken by other regulatory agencies, but the US FDA doesn't consider aging in itself to be a disease, so they are being tested for their utility as treatments for diabetes and cancer. Sirtris Pharmaceuticals (now part of GlaxoSmithKline, who essentially bet $720 million that this idea would work) has their micronized resveratrol formulation SRT501 in early Phase II trials and a pipeline of candidates along the same theme: activating a family of proteins called sirtuins which are proposed to modulate a number of pathways of metabolism and the cell cycle.
If that doesn't pan out, there's a lot of research into mTOR inhibitors. Sirolimus, also known as rapamycin (mTOR is the mammalian Target Of Rapamycin), has been shown to increase maximum lifespan in mice by about 10% even when administered late in life. Sirolimus itself is not suitable for use in human life extension, as it is a powerful immunosuppressant (approved to prevent organ rejection, in fact), but there are a number of related compounds under investigation. Temsirolimus is FDA/EMEA approved to treat renal cell carcinoma; by inhibiting mTOR in cancer cells, it stops the cell cycle of growth and division. Conceivably, a drug along that line could be developed that slowed the cell cycle for normal human cells, which would slow their aging, and reduce the chance of replication errors that would lead to either cell death or cancer. Of course, I'm not sure that any of this research will lead to a pill that slows aging and/or lengthens lifespan, especially in the next ten years, but we may get some effective new diabetes and cancer drugs from this.
There are a few extraordinary cases where the prize was awarded within a few years of the relevant discovery. Bednorz and Muller discovered Type II superconductivity in 1986, and were awarded the Physics prize in 1987. Rubbia and Van der Meer won the 1984 Physics prize for work towards the discovery of the W and Z bosons, which occurred in 1983. Banting and Macleod discovered and isolated insulin in 1921-22, and received the 1923 Medicine prize (Banting was 32 at the time!). Quite a few of the major figures in quantum theory and nuclear fission received either Physics or Chemistry Nobels within a few years of the work that got them the prize. So, it does happen, but it's pretty rare. In general, the science prizes are much more cautious than the Economics and Peace prizes, which have produced some regrettable prize selections in hindsight.
Viruses have very small genomes in comparison with the human genome; many viruses get by with fewer than ten genes, while we have around twenty thousand. In addition, viruses don't arrange their genes in structures anything like the chromatin we use. Packaging a replacement human genome to infect human cells would require a vector so completely re-engineered from what we would currently recognize as a virus that we'd probably want to call it something else. Getting that infection procedure to work without killing the patient is far, far beyond current technology, and I'm not sure that it would confer biological immortality anyway. Your mitochondria have their own little genome, separate from that of the nucleus, which would be difficult to replace with a virus- and mitochondrial aging may play a significant role in producing the outward effects of human aging. If you turned your mitochondria off, you would die very quickly- the effect would be as if you had been poisoned with cyanide.
It is possible to add very small numbers of genes using viral vectors- human gene therapy is something that may indeed take off in years to come. There are presently many difficulties with using viruses to insert genes- you can use a retrovirus to insert the gene permanently into the genome, but it's hard to control insertion, so it's possible to get many copies- or none- in a given cell. Genes may also insert themselves in the middle of other genes, causing all sorts of deleterious effects.
Probably not, to be honest. If they're just starting Phase I right now, figure on at best 6-8 years or more before a possible approval by regulatory agencies, which naturally assumes that this treatment would be demonstrated as both safe and efficacious. Phase I doesn't take much time, but Phases II and III can easily take years- particularly for a disorder like ALS, where patients would need to be monitored for months to determine the treatment's effects. In Stephen Hawking's particular and remarkable case, it is not merely the progression of his ALS that would be an issue; the man is 67 years old right now.
From the Interorbital Systems site, it says, "Storable, high-density white fuming nitric acid (WFNA) and Hydrocarbon-X (HX) are the rocket's primary propellants." I'd presume "Hydrocarbon-X" is some sort of kerosene-like blend of petroleum distillates.
It stands for Burning Snow Of Death. An unfortunate consequence of using a hot-ice computer.
As part of getting enough Y chromosomes for their experiment, they inserted their two donor genomes into two groups of cell cultures to amplify the amount of genetic material. The cell lines are made from lymphocytes which have been infected with the Epstein-Barr virus; it's more or less a culture of Hodgkin's lymphoma cancer cells. They isolated the Y chromosomes (they got around 600 nanograms of each of the two lines), and then did their sequencing.
The problem with amplifying the material in this manner is that it's bound to introduce a few more mutations, since there is cell division involved, and cancer cells in particular can be a bit sloppy in replicating genes. So, to account for the mutations caused by their amplification procedure, they double checked the twelve candidate mutations they found against the donor's DNA from blood samples (not amplified by cell culture) and against the same regions in very close male relatives of the donors (if you are male and have a biological full brother, then your Y chromosomes should be almost completely identical). They scratched eight candidate mutations off as coming from the cell culture process, leaving four.
Ultimately, yes, mutations like the ones studied here drive evolution and speciation. They are the mechanism behind generating completely new genetic information. However, in terms of following the genetics of a diverse population, genetic recombination events like crossover have a greater effect on the changes from generation to generation than mutations.
As this experiment shows, you might have accumulated a few hundred single nucleotide polymorphisms- differences at one base pair- in the lineage from your great-grandfathers to you. However, so much shuffling of the genetic deck occurs in each generation's gametes that, as may be obvious to you, two people (siblings, for example) can be closely related but display very distinct traits. The reason why you'd want to focus on the Y chromosome if you wanted to isolate the mutation rate is that it doesn't undergo all of this shuffling; you probably only have a maximum of one (there are a few XYY males)and it passes down patrilineally with only random mutations to change it. Those two men tested could well have very similar Y chromosomes, but otherwise be genetically very different.
I would argue that there is a survivorship bias in studying mutation in the Y chromosome, though. There aren't many genes on the Y chromosome, but the ones it does have tend to be critical for producing healthy, fertile males. It might be the case that mutation rates that might be tolerable on other (somatic) chromosomes produce completely inviable offspring when they occur at that rate on the Y.
Yeah, the reason slime molds are referred to as plasmodium is because the slime mold colony lacks defined cell walls or membranes between what would normally be considered individual cells. The mold can essentially be thought of as a single cell with many nuclei, since cytoplasm is continous throughout the entire colony. As the parent notes, this type of structure (a lifecycle stage, really) has nothing to do with the protozoa which cause malaria, which just happen to be of genus Plasmodium.