31 March 2006

Energy No-Brainer: Pluggable Hybrid Automobiles

First of all, what is a pluggable hybrid? Also called a Plug-in Hybrid, a pluggable hybrid is a car that can be powered by either internal combustion engine or electric motor--but it has larger batteries than conventional hybrids, and you can plug it in overnight to use inexpensive power grid energy for your daily commute. That constitutes a major shift in energy use from petrol to grid electricity. If the grid electricity comes from renewables (or nuclear), you can commute to work all week in a pluggable hybrid, without burning fossil fuel.

Among those who follow energy trends, the pluggable hybrid has become quite popular. Which makes many people wonder, why has Toyota gone to great lengths to distance itself from the pluggable hybrid concept?

On Tuesday, a Toyota representative wrote to an individual, "we do not currently have any announced plans to introduce a plug-in hybrid Toyota vehicle in the U.S." Find an expert who could say if that's intentionally evasive. (See our chronology of all automakers comments in the past year at http://www.calcars.org/carmakers.html .)

In a story broadcast today on NPR All Things Considered, you can hear spokeswoman Cindy Knight say, "You can certainly make a vehicle that will run, but you can't necessarily make a vehicle that people will buy.... Toyota went to great lengths to address the drawbacks of battery vehicles so that people do not have to plug our hybrids in, and our customers tell us that that is one of the features they like about the vehicle, they don't have to plug it in."

If the big carmakers distance themselves from this obviously winning concept, smaller players will rush in to fill the gap. Jim at the Energy Blog keeps close track of developments in pluggable hybrids, and he has a full array of energy links. Jim's place is an excellent site for following the progress in this war of the vehicular power plants.

Check out this Al Fin post for some of the underlying energy issues involved in the transition from internal combustion engines to fuel cell/supercapacitor/battery powered electric motor vehicles. The pluggable hybrid is a very useful intermediate step in the transition. No matter what the big auto manufacturers do, they cannot stop it from happening.

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30 March 2006

Boolean Gene Expression Map of the Brain: Logic of Expression

The basic genes of the human genome are mapped, and the gene variants that contribute to human disease are being mapped. That is a good start, but the really difficult work of understanding gene expression lies ahead. I am talking about the complex interactions of gene expression, and the many "maps" that must be compiled to detail gene expression. From MIT's Richard A.Young:

Each cell is the product of a specific gene expression program. Complex processes such as development of an organism from a single cell are the product of many cells executing many precise programs of gene expression in a temporally exact manner. These programs are controlled by transcriptional regulatory networks, and these networks are fundamental to all living processes. Such networks describe the factors that control the expression of each gene in the network, permitting the consequences of genetic or disease abnormalities to be analyzed in depth. Thus the eluciation of transcriptional regulatory networks in living organisms would be a substantial advance that could greatly contribute to the development of therapeutics and human health.

This recent newsrelease discusses the development of a Brain Gene Expression Map (BGEM) of the mouse at St. Jude Children's Research Hospital.

By St. Jude Children's Research Hospital, Scientists at St. Jude Children's Research Hospital have given investigators around the world free access to a powerful tool for studying brain development. The Internet-based tool, called the mouse Brain Gene Expression Map (BGEM), is one of the largest gene expression maps of an organ ever developed, according to the St. Jude researchers. They say the map will likely help scientists discover the genetic origins of brain cancers, which could speed development of novel drugs to treat them.

The continual updating and completion of the BGEM Web site will be crucial to scientists. More than half of the approximately 25,000 genes in the mouse are thought to be involved in the development and function of the nervous system, but scientists have determined the function of only 30 percent of them. Many brain disorders, such as tumors and some psychiatric diseases, are also believed to be caused by gene mutations that arise during development of this complex organ.

A report on the development and availability of the BGEM appears in the March 28 issue of PLoS Biology. The Web site is http://www.stjudebgem.org/

Read much more here.

Gene expression is far from straightforward. Not only do different genes interact in controlling each other, but each gene itself has differenct controller molecules and nucleotide segments, that interact in a Boolean fashion. This newsrelease discusses the Boolean nature of the regulation of gene expression:

It is easy to think of a gene acting like a light bulb, switching either on or off, remaining silent, or being transcribed by the RNA-making machinery. The region of DNA that controls the gene's output is called its regulatory region, and in this simple (and too simplistic) scenario, that region would act like a simple on–off switch.

But the regulatory regions of real genes are more complex, and act more like molecular computers, combining the effects of multiple inputs and calibrating the gene's output accordingly. The inputs are the various molecules that affect gene activity by binding to sites in the regulatory region. These molecules combine their effects in complex ways. Sometimes the gene remains silent unless both are present. Sometimes they are additive, such that the output when two factors are present is twice the output when only one is present. Sometimes they cancel each other out—in the presence of either, the gene is transcribed, but in the presence of both, it is not.

Thus, the regulatory region acts as a Boolean logic function, whose simple ANDs, ORs, and NOTs combine to determine the output of the gene. In a new study, Avi Mayo, Uri Alon, and colleagues show that mutations in the regulatory region affect this logic function in a simple and well-studied genetic system, the lac operon in Escherichia coli bacteria, whose suite of genes regulate metabolism of lactose.

Read more details at the source.

At Al Fin, we often discuss the introduction of genes into cells, to change gene expression. But it should be clear that there are many alternative mechanisms of changing gene expression, and scientists are a long way from both learning about and understanding them all.


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29 March 2006

Forced Entry: The Clever Sneaks of Gene Therapy

Sneaking genes into cells without causing damage or harm requires cleverness and skill. The first story details work by Ames (Iowa) Laboratory researchers, who have developed a very clever porous silica nanosphere that can be taken up by a cell, and deliver its payload of genes or other molecules on command.

Currently, scientists have difficulty introducing chemicals or genes into cells without either damaging the cell or causing a chain-reaction of events that can’t be tracked.

“With current gene therapy, it’s possible to switch genes on and off, but you don’t really know if you are affecting other parts and processes of the cell as well,” Lin said. “You may be able to get a plant cell to produce a certain desired product, but the yield may drop significantly.”

By using externally controlled nanospheres, Lin explains that it may be possible to sequentially release genes, chemical markers and other materials within cells in order to track what happens and what specific changes take place. This phase of Lin’s research ties into a larger plant metabolomics project at Ames Laboratory.

Read the entire fascinating report here. This report fascinated me due to the exquisite level of control it promises, at the cellular level. This approach will bear watching.

The second report on gene smuggling comes from this Eurekalert newsrelease on research from the University of North Carolina, Chapel Hill, and the University of Pittsburgh. In this case, the reserchers are using a customized vector called adeno-associated virus (AAV) to introduce the dystrophin gene into muscles of boys suffering from Duschenne Muscular Dystrophy (DMD).

The trial was launched March 28, at Columbus Children's Hospital in Ohio, an affiliate of Ohio State University's School of Medicine. In the trial, six boys with DMD will receive replacement genes for an essential muscle protein.

Each of the boys will receive replacement genes via injection into a bicep of one arm and a placebo in the other arm. Neither the investigators nor the participants will know which muscle got the genes. After several weeks, an analysis of the injected muscle tissue's microscopic appearance, as well as extensive testing of the health and strength of the trial participants, will reveal whether gene therapy for DMD is likely to be safe and whether it's likely to result in persistent production of the essential protein in muscle cells.

Muscular dystrophies are genetic disorders characterized by progressive muscle wasting and weakness that begin with microscopic changes in the muscle. As muscles degenerate over time, the person's muscle strength declines.

Duchenne muscular dystrophy is a genetic disease that begins in early childhood, causes progressive loss of muscle strength and bulk, and usually leads to death in the 20s from respiratory or cardiac muscle failure. DMD occurs when a gene on the X chromosome fails to make the essential muscle protein dystrophin. One of nine types of muscular dystrophy, DMD primarily affects boys.

Currently, the best medical therapy can only slow the progressive muscle weakness of DMD.

The gene for dystrophin is one of the largest genes in the human body, and miniaturizing it, while retaining the crucial elements of its set of DNA instructions, has been among the greatest challenges to the gene therapy field.

The new Biostrophin therapy uses a novel combination of advanced technologies, including a miniaturized replacement dystrophin gene and nano delivery technology called biological nanoparticles. Developed from a virus known as adeno-associated virus (AAV), the nanoparticles are engineered specifically to target and carry the "minidystrophin" gene to muscle cells.

Read more at the source. This approach uses a virus-derived vector particle that should be safer than the virus itself as a vector. Expect to see more of this type of custom vectors, derived from a number of different viruses.

The final report on forced entry of therapeutic genes comes from this eurekalert newsrelease detailing research on Alzheimer's Disease from UT Southwestern Medical Center. The "vector" in this case was gold nano-particles.

By pressure-injecting the gene responsible for producing the specific protein – called amyloid-beta 42 – the researchers caused the mice to make antibodies and greatly reduce the protein's build-up in the brain. Accumulation of amyloid-beta 42 in humans is a hallmark of Alzheimer's disease.

"The whole point of the study is to determine whether the antibody is therapeutically effective as a means to inhibit the formation of amyloid-beta storage in the brain, and it is," said Dr. Roger Rosenberg, the study's senior author and director of the Alzheimer's Disease Center at UT Southwestern.

The gene injection avoids a serious side-effect that caused the cancellation of a previous multi-center human trial with amyloid-beta 42, researchers said. UT Southwestern did not participate in that trial. In that earlier study, people received injections of the protein itself and some developed dangerous brain inflammation.

The new study is available online and appears in an upcoming issue of the Journal of the Neurological Sciences.

Here is the full report. This report interested me due to the fact that it was the gene for the errant protein, rather than the protein itself, that elicited the antibodies against the protein. In this case, the gene was not injected into the cells, but rather elicited an immune response from the extracellular space--the gene was utilised as a vaccine.

There you have it. Three different methods of introducing genes and therapeutic molecules. The clever cat burglars and drug smugglers of molecular and cell biology. We can only urge them on.
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28 March 2006

Brave Feminists Rage against the Testicle

Recent news stories about finding stem cells in the testicles of mice and humans has prompted a backlash from courageous feminist professors of Women's Studies at Balwynne College. Dr. Letisha Snotsberry and Dr. Nadine Bulsnort have graciously agreed to be interviewed by Al Fin, on this important issue.

AF: Thank you for speaking with me today. I wonder if you can each summarize your objections to the latest stem cell news, starting with Dr. Snotsberry.

LS: The issue is very simple, Al. Feminism in the western world is based upon the fact that all bad things in the world come from the human testicle. Testosterone is the maker of war, the source of domestic abuse, and the reason for the subjugation of women everywhere . . .

NB: . . . Not only that, but the testicle produces sperm, and sperm causes pregnancy which stops many women from achieving their potential. You have no idea how many women drop out of school, or even careers, just to have a sniveling little baby. It's uncivilized.

AF: But surely you can see the necessity of propagating the species, after all if there were no babies, the entire human race would . . . .

NB: . . . Don't give me that nonsense, Al. If women stopped allowing men to use them as babymakers, men would have to invent another way to have babies. Women are just too convenient . . .

LS: . . . Getting back to the topic of the human testicle, I think it's pretty clear that it already had two strikes against it. Now with the news of stem cells being derived from the human testicle--well it's simply too much! The testicle simply contains too many things--it could lead us all back to the patriarchy again.

AF: Excuse me, you are saying that because the human testicle is turning out to be the Swiss Army Knife of human organs, it should be downgraded somehow?

LS: Well, obviously, Al. For one thing, why do all men have two testicles?

NB: Exactly, Tish! It's total overkill. One testicle is plenty--maybe even too much. We've had discussions in national committee about a "Testicles-Optional Policy", or TOP for short. All newborn males would come under the policy, all overseen by a Bioethics Committee staffed by professors of Women's Studies from the local college or university.

AF: Wait a minute, Doctor. Are you suggesting neutering baby boys when they are born?

LS: Let me answer that. No, Al, you are making it sound worse than it is. The informed consent would clearly give the option of retaining one testicle or none. The parents are given a vote in the matter, along with each member of the Bioethics Committee. It is all quite democratic.

AF: But what would be done with the testicles that are removed?

The two professors exchange a quick glance, then check their watches for the time.

LS: Oh dear, Al, it seems to be getting quite late. We have another appointment--if you'll please excuse us . . .

NB: . . . Yes, we're in a big hurry Al, sorry.

AF: But surely you have some plans for the little boys' testicles?

NB: You're making too much of a big deal out of this, Al. We already told you that testicles are the source of everything bad in the world. What would we want with testicles? You seem to be insinuating . . .

AF: . . . No, not at all. I am simply curious . . .

LS: Thank you so much, Al. We have both really enjoyed this.

The professors walk away whispering furiously to each other.

AF: Well, ladies and gentlemen, I certainly appreciate the professors' sharing their thoughts. Apparently the human testicle is more controversial than I had thought previously. Please stay tuned for further developments.

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27 March 2006

Human Heart, Brain, Bone and Cartilage Cells from Stem Cells Found in Adult Male Testes

First a German team found pluripotent stem cells in mouse testes, and now a California Lab has found pluripotent stem cells in human testes.

In a breakthrough for stem cell research and cellular replacement therapies, PrimeGen Biotech LLC (www.primegenbiotech.com) today announced that its researchers have successfully developed the first human adult therapeutic germ stem cell. Derived from adult stem cells but with the advantageous genetic characteristics of embryonic stem cells, PrimeCells have successfully been transformed into human heart, brain, bone and cartilage cells -- cardio, neuro, osteo and chondrocytes.

Therapeutically reprogrammed from germ line stem cells found in the testes of adult human males, PrimeCell(TM) is the first non-embryonic stem cell showing the potential to become any type of cell from any organ, something previously thought possible only for embryonic stem cells -- the definition of true pluripotency.

This week, the company's researchers are scheduled to present a summary of their complete data and manuscript in a poster presentation at the Serono Symposia International's Therapeutic Potential of Stem Cells In Reproductive Medicine conference in Valencia, Spain. PrimeGen first presented its preliminary human experimental data at the 1st International Symposium on Germ Cells, Epigenetics, Reprogramming and Embryonic Stem Cells, held in November 2005 in Kyoto, Japan.

"We have demonstrated that there's a novel source of adult stem cells which, aside from having a role in reproduction, can be reprogrammed and used therapeutically," said Thomas C.K. Yuen, PrimeGen chairman and CEO. "We have taken the most well-preserved, highest-quality stem cell and made it pluripotent -- representing one of the most significant breakthroughs in regenerative medicine. These cells advance the potential for cellular replacement therapy for everyone."

To form PrimeCell(TM), PrimeGen extracts cells from the most protected adult stem cell source in the body -- the "germ," or reproductive, cell line, which intrinsically only can form sperm and eggs. Then, PrimeGen uses a proprietary process to reprogram the cells to become pluripotent, giving them the ability to transform into virtually any other cell type.

Because it started as a germ-line stem cell, PrimeCell retains the most conserved, highest-quality DNA generated by an organism. It suffers no damage from aging, chronic disease or injury. It is also shielded from free radical, ribosomal and mitochondrial damage -- all inherent limitations of adult stem cells, until now.

PrimeGen's mouse model Proof of Concept is similar to that referenced in an article published by German researchers in this month's issue of the journal Nature, and described in a March 24 Reuters article. But PrimeGen is further along -- company researchers have already begun creating therapeutically viable cell lines from human tissue. In a paper currently submitted for peer-review, PrimeGen describes the first evidence of isolation and therapeutic reprogramming of adult human germ line stem cells into heart, brain, cartilage and bone cells.

PrimeGen obtains its human tissue samples from consenting adult males between the ages of 26 and 50. For women, PrimeGen currently is reviewing the work of Jonathon Tilly, who has shown that female germ cells exist after birth, contrary to popular belief. The company is developing a female model to attempt to reproduce the results achieved using male germ line stem cells.

"We are very pleased to see that the laboratory in Germany has independently confirmed our results -- which we first described and presented in Singapore in 2005 -- on the therapeutic reprogramming of post-natal germ cells," said Francisco Silva, PrimeGen's executive vice president of research and development, and the lead researcher for the PrimeCell initiative. "Our initial research is extremely promising and we have every reason to believe that our human PrimeCells will show true pluripotentiality, as we have observed in our mouse model."

"We've already been able to reproducibly differentiate heart, brain, bone and cartilage cells, and we are excited to begin testing how these cells incorporate into tissues," Silva said. "Our goal is to create the most potent cell lines to enable the most effective treatments and therapies for as many diseases as possible. Our human PrimeCells represent a significant step in that direction."

As you can see from reading the entire report, the California lab actually preceded the German lab in terms of actual results and reporting of the results.

Thanks to Anne Leonard, whose excellent Stem Cell Research Blog has done a fine job of following this story.

As I discussed in this post, there are many sources of stem cells. Eventually, it is quite likely that virtually any cell type will have the potential to turn into just about any other cell type, given the proper sequence of inducements.

The many new sources of stem cells should stimulate new research in the area of organ regeneration in situ, and organ regrowth for transplantation. Replacing old, tired organs should get easier as the number of replacement methods multiplies.

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DNA Surprises: Gene Research Goes into High Gear

Thanks to Snowcrash for pointing to this CIT newsrelease that details new discoveries in "gene interaction."

The difficulty lies in the fact that two genes can pair up in a gigantic number of ways. If an organism has a genome of 20,000 genes, for example, the total number of pairwise combinations is a staggering total of 200 million possible interactions.

Researchers can indeed perform experiments to see what happens when the two genes interact, but 200 million is an enormous number of experiments, says Weiwei Zhong, a postdoctoral scholar at the California Institute of Technology. "The question is whether we can prioritize which experiments we should do in order to save a lot of time."

....a genetic-interaction network provides a faster and better way at determining how certain genes interact. Such a network also provides information about whether anyone has ever done an experiment to determine the interaction of two particular genes in one of several species.

"This process works like a matchmaking service for the genes," says Zhong. "It provides you with candidate matches that most likely will be interacting genes, based upon a number of specified features."

The benefit, she adds, is that biologists do not need to do a huge number of random experiments to verify if two genes indeed interact. Therefore, instead of the experimenter having to run 20,000 experiments to see if two genes randomly chosen from the genome of a 20,000-gene organism interact, they might get by with 10 to 50 experiments.

"The beneft is that you can be through in a month instead of years," says Sternberg
Read the entire report here. Hat tip Biosingularity Blog.

The next story deals with advances in developing transgenic plants--getting plants to make proteins from other species--in this instance getting tobacco plants to make human albumin. This is from a Bio.com newsrelease:

Agricultural engineer, Alicia Fernández San Millán, has developed a novel technique in Spain - plastidial transformation, in order to produce, in a recombinant form, human albumin from tobacco plants. According to her PhD thesis, plastidial transformation is an economically viable alternative, as it enables increasing the levels of HSA by between 10 and a 100 times, compared to levels obtained by nuclear transformation. Read the entire newfeature for more information.

The following story deals with "junk DNA", the 98% of all human DNA that does not code for protein. Buried within the junk DNA is hidden treasure--epigenetic control sequences that influence the gene expression of the 2% of coding DNA.

The notion that mutations in enhancers play a role in human disease progression has been difficult to confirm because usually enhancers are located in the 98 percent of the human genome that does not code for protein, termed non-coding DNA. Unlike DNA sequences that code for protein, non-coding DNA, sometimes referred to as "junk" DNA, follows few rules for organization and sequence patterns and therefore is more difficult to study.

"The difficulty with human genetic approaches to common disease is that we lack the power to precisely localize DNA sequences that are associated with disease, often leaving us immense stretches of DNA to look at," says one of the study's corresponding authors, Andy McCallion, Ph.D., an assistant professor in the McKusick-Nathans Institute. Most often one is limited to looking in the most obvious places, which may not yield the best results. "Until now," he says, "we've only been able to look under the lamplights for the car keys."

....The system is a significant advance over current methods in this model species, allowing researchers to study more sequences in a shorter period of time.
Read the entire news report here.

This report discusses a discovery of a gene variant--always think "hapmap" when hearing the term "gene variant"--that affects the onset of cancer.

Normally our genes have to be divided into two perfectly identical copies when a cell divides. The unfortunate variant causes a defect in the division of the genetic material (mitosis), which means that a daughter cell may get too few or too many genes.

If a daughter cell does not receive a gene that prevents cancer, a so-called tumour suppressor gene, then a cancer can grow. One defence mechanism against cancer is for a cell that gets faulty genes to commit suicide (apoptosis).

The defect caused by the unfortunate variant when it divides the genes is so tiny that the suicide mechanism does not detect the fault, which allows the cell to continue its growth into a cancer.
Read the rest here.

Finally, here is a glimpse into the distant past, toward the possible origin of life on earth. This Eurekalert newsrelease discusses experiments attempting to delve into possible origins of the DNA-RNA encoding system that supports all known life.

This "evolutionary conversion" provides a modern-day snapshot of how life as we understand it may have first evolved out of the earliest primordial mix of RNA-like molecules-sometimes referred to as the "pre-RNA world"-into a more complex form of RNA-based life (or the "RNA world") and eventually to cellular life based on DNA and proteins. Nucleic acids are large complex molecules that store and convey genetic information, but can also function as enzymes.

While the transfer of sequence information between two different classes of nucleic acid-like molecules-between RNA and DNA, for example-is straightforward because it relies on the one-to-one correspondence of the double helix pairing, transferring catalytic function is significantly more difficult because function cannot be conveyed sequentially. The present study demonstrates that the "evolutionary conversion" of an RNA enzyme to a DNA enzyme with the same function is possible, however, through the acquisition of a few critical mutations.

The study was released in an advance online version of the journal Chemistry & Biology.
Read more here.

This posting covers only a small cross section of ongoing genetic research. Al Fin has covered several of these topics previously. All of those past postings are available via the archives on the sidebar. Most people would feel overwhelmed if they had attempted to look deeply into any of these reports. No one is expected to know everything about everything, after all.


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26 March 2006

Gender Difference: The Gap that Will Not Close

At the elite levels of sports and athletics, the gender gap is prominent and resists closure. There is an approximate 15 minutes difference in the best times of elite male marathoners, and elite female marathoners. Other sports show similar differences at the elite level.

Remember when it was predicted that intensive training for women in athletics would close the gender gap in performance? Some years ago, when the marathon was first becoming a competitive event for women, the rapid improvement in female times led some to predict that female performances would soon equal those of men in the marathon. This has not happened, and it won't. The current world record for women is 2:21, compared to 2:06:50 for the men, a difference in speed of about 10%. This same 10% gap is present across the distance running performance spectrum The reason for the performance gap is not that women don't train as hard as men. There are some important physiological differences between the sexes that can't be overlooked or overcome.

....The "typical" young untrained male will have an absolute VO2 max of 3.5 liters/min, while the typical same-age female will be about 2 liters/min. This is a 43% difference! Where does it come from? Well first, much of the difference is due to the fact that males are bigger, on average, than females. Us humans are all (sort of) geometrically similar, so heart size scales in proportion to lean body size . If we divide VO2 by bodyweight, the difference is diminished (45 ml/min/kg vs 38 ml/min/kg) to 15 to 20%, but not eliminated.

....It is important to make note of the fact that these differences are "on average". In reality, there are many women with significantly higher VO2max values than average men. However, if we look at the "best of the best", the differences persist. Using XC skiing as an example from here in Norway, the highest reliable values for VO2 max recorded in national team XC skiers are about 90 ml/min/kg. The very best Norwegian woman has been measured at 77 ml/min/kg, a 17% difference. So, while this woman will outperform 99.9% of all men, she will not out-perform the national team level males.

Read more here.

A number of studies have demonstrated that boys inherit a performance advantage in athletics, for both pre-puberty, and even more so in post-puberty.
The stopwatch does not lie, and whether in swimming, running, weightlifting, shot put, bicycling etc. the superior VO2 max and muscle mass of males prevents the gender gap in athletics from closing. The only way to narrow the gap is to train the elite athlete girls and confine the elite athlete boys in restraints to encourage muscle atrophy and loss of VO2 max.

In the cognitive realm, you see a similar phenomenon in the measures of spatial ability and mathematical ability at the elite levels. Although hope springs eternal that training will narrow the gap, as in athletics, sometimes it seems that the only way to narrow the gap is to train the elite girls and prevent the elite boys from training somehow.

One can be excused for wondering why all the excitement about male superiority in a small area of elite cognitive performance? The number of jobs involved is minimal. Certainly an intelligent businesswoman, female physician, or female lawyer, can make much more money than an elite mathematician, physicist, or engineer. What is all the near-hysteria about?

Average intelligence levels of men and women test virtually identical. A 1995 study examined the performance of more than 100,000 American adolescents on various mental tests. The study found that on average, females performed slightly better than males on tests of reading comprehension, writing, perceptual speed, and certain memory tasks. Males tended to perform slightly better than girls on tests of mathematics, science, and social studies. In almost all cases, the average sex differences were small.

And here is how developmental psychologist David C. Geary puts it:

There was no sex difference on the IQ test, but males showed significantly higher mean scores on the arithmetical computations, arithmetical reasoning, and spatial cognition measures. A series of structural equation models indicated that individual differences in arithmetical reasoning were related to individual differences in IQ, spatial abilities, and computational fluency. Moreover, the results suggested that the male advantage in arithmetical reasoning is mediated by the male advantages in both computational fluency and spatial cognition.

Women are graduating from schools of higher education at a rate of 6 to 4 vs. men. Women have achieved virtual parity in schools of medicine and law, and make up about 70% of graduate psychologists. Women are achieving phenomenally in the modern world, and if any gender should be worried about current trends, it is the males. A few men are holding on under siege, to a small sliver of cognitive excellence, and all that many psychologists can think of doing is to try to eliminate the small gap within that tiny sliver of cognitive performance.

It is a fascinating study in academic frustration--the data will simply not behave in a politically correct fashion. Many more research studies and outreach programs will be mandated, however, to erase that gap. But I can tell the gender psy-sers exactly how to erase the gap, and I will not charge for the valuable information. Simply prescribe pro-androgenic drugs that cross the placental barrier, to pregnant women in their second trimester, who are carrying female fetuses. Some additional androgenic supplementation may be necessary at different time periods after birth--and there will be potentially unpleasant side effects. Hirsutism, deep voice, skin blemishes, a certain manly aggressiveness, etc. But all of that would be a small price to pay to erase the gender gap in this one small remaining area of academics, no?

Just as there are elite women athletes who can defeat 99% of males in their sport, there are women mathematicians and physicists who are better at their trade than 99% of males. But they are not competing against those 99%. They are competing against the elite males, a very small number, but a significantly greater number than the number of elite females in those vocations. That is the hump that the gender Procrusteans are incapable of leveling. The relatively tiny number of male elites in a relatively tiny number of fields who will simply not go away.

Lawrence Summers paidwith his job, for making a very timid suggestion about possible biological gender or sex differences in that very small, elite sliver of academic professorship in a few top rank schools. The politics of this subject are absolutely deadly to anyone in a public position who lets down his guard for even a moment.

But why? I will deal with the real reasons for the excitement in a later posting.

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Not Just Hot Air: Wind Energy Getting Bigger, Cheaper

As we convert from a dependency on fossil fuels to using renewable energy to power our societies, it is good to take stock of our progress from time to time. Jim from The Energy Blog has provided this report that wind energy now costs less than conventional power sources.

....Xcel’s 33,000 Windsource customers, who until late 2005 were paying $6 more each month for their electricity, are now paying slightly less than those using conventional electricity, which comes mostly from natural gas and coal. To meet fast-growing demand, Xcel is currently soliciting proposals from wind developers for up to 775 megawatts of new wind power generation, enough to supply 232,000 Colorado homes with electricity.

Wind energy is also proving a boon to small ranchers, who will earn royalties from the energy generated by wind turbines placed on their property.

.... When Xcel announced it would develop several hundred megawatts of additional wind-generating capacity, it got the attention of ranching communities throughout wind-rich eastern Colorado. In tiny ranch-country towns like Grover, near the Wyoming border, ranchers welcomed a proposed 300-megawatt wind farm that would span some 30 ranches.

With a large, advanced-design wind turbine generating easily $100,000 worth of electricity per year, even a 3-percent royalty would earn ranchers $3,000 a year from leasing a quarter-acre of ranchland. And they can still run cattle on the land. If the proposed project is approved as expected, these 30 or so ranchers will have an average of seven turbines each, yielding roughly $21,000 a year in additional income. A decade from now, there may be thousands of ranchers who will be earning more selling electricity than they do selling cattle.

....Wind energy is emerging as a centerpiece of the new energy economy, because it is abundant, inexpensive, inexhaustible, widely distributed, clean, and climate-benign. Three of the 50 states—North Dakota, Kansas, and Texas—have enough harnessable wind energy to satisfy national electricity needs. The cost of wind-generated electricity has fallen from 38¢ per kilowatt-hour in the early 1980s to 4¢ to 6¢ today, offering an almost endless supply of cheap energy.

Read much more from this report from the Earth Policy Institute.

Renewable energy such as wind, solar, hydroelectric, geothermal, wave, tidal, OTEC, and others, are developing solidly in the background, while the rest of the world continues to talk peak oil, and a war of the titans over oil.


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25 March 2006

Extreme Gene Expression: Taking Proteomics to the Next Level

Researchers are moving beyond mere genomics into proteomics--where most of the work of the cell is actually done. This newsrelease from the University of Toronto reports on the newest discoveries in protein-protein interactions.

The findings, which will be released in the March 30 issue of Nature, reveal how researchers used sophisticated proteomic techniques to identify close to 4,000 proteins and 550 protein complexes involved in 7,123 protein-protein interactions in yeast cells, about half of which are novel. Many of the same complexes and protein interactions that go awry in human disease are also found in yeast. While living yeast cells have only 6,000 genes compared to a human’s 25,000, the structures of their encoded proteins and interactions among the proteins are virtually identical to ours.

“Human proteins involved in disease and protein interactions gone awry found in humans are often found in yeast,” says Professor Andrew Emili of U of T’s Banting and Best Department of Medical Research, the study’s co-author. “By studying and mapping out sets of protein interactions within this basic organism, we are providing the foundation to move into a more complex organism such as a mouse and then a human.”

To map the protein complexes within the cell, researchers combined purification techniques with analysis using mass spectrometry, a technique that breaks down and identifies chemical substances within molecules. Using the combined approach of purification and mass spectrometry, the researchers were able to ensure accuracy and reveal more than 250 complexes that have not yet been reported in previous public databases. The researchers have posted their current findings on a publicly available comprehensive database (http://tap.med.utoronto.ca) and hope the findings will spur further advances within the scientific community. “This database will be linked with other sites, so that results can be compared and contrasted,” says co-author Professor Jack Greenblatt, also of U of T’s Banting and Best Department of Medical Research. “The methods we used to identify protein interactions and protein complexes in yeast appear to be the best currently available, and so are likely to be used soon to identify protein interactions involved in human disease.”

....The next step, according to Emili, is to analyse these new complexes to determine their roles in living cell functions. “Now that we have the pieces of the puzzle, we have to put them together to get the overall picture,” Emili says. “It is painstaking work, but it brings us closer to answer science’s most fundamental question: how does life operate?”

Read more here.

For more on proteomics and genomics, read here and here. For more on mass spectrometry, read here.

Hat tip Biosingularity Blog.


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24 March 2006

Important Advance in Genetic Research: RNA Tools to Silence Genes

Genetics researchers have used various methods to determine the functions of different genes, in the course of determining useful therapeutic targets for gene therapy. One method is to create a "knockout" animal, where the target gene is permanently silenced. That method has been effective, but now there is a better method that is capable of temporarily silencing genes--RNAi, RNA interference. RNAi is a form of non-coding RNA, a very exciting field of research.

This Eurekalert newrelease details the new tools that have been made available to researchers by the Broad Institute of MIT and Harvard.

An international public-private research team led by scientists at the Broad Institute of MIT and Harvard announced today the construction and availability of an extensive library of molecular reagents to silence most human and mouse genes. As described in the March 24 issue of Cell, this library consists of small RNA molecules that can switch off genes individually, allowing the user to dissect the genetic underpinnings of normal biology and disease. These RNA-interference (RNAi)-based gene inhibitors are packaged in lentiviruses, enabling their use in virtually all types of human and mouse cells. This work springs from the RNAi Consortium (TRC), a unique collaboration among academic research institutions and leading life science companies with the mission to build comprehensive RNAi libraries and make them available to scientists worldwide.

"Switching off a single gene through RNAi reveals how that gene functions in a particular biological process. When RNAi's potential is applied to thousands of genes – as it has been in fruit flies and nematodes – it can provide a more complete picture of that process," said David Root, a senior author of the Cell paper and the director of TRC and the RNAi platform at the Broad Institute. "Thanks to this unique public-private effort, we now have new tools to enable the entire research community to realize the potential of RNAi in the two most important species in biomedicine."

"The RNAi library developed by TRC is a rich resource for biological discovery," said Nir Hacohen, assistant professor at Massachusetts General Hospital and Harvard Medical School, associate member of the Broad Institute and a senior author. "Ongoing studies in my own laboratory to understand how the immune system senses pathogens and appropriately targets its response will be accelerated using these tools."

RNAi gives scientists the ability to turn off an individual gene. Its workhorses are small RNA molecules, each of which is tailored to match a fragment of a gene's unique DNA. This RNA can then bind to its gene target, rendering it inactive. In order to get the small RNAs into cells, TRC scientists packaged them in lentiviruses. "Across the spectrum of biomedicine, there is a need for tools that can be applied to diverse cell types. This is particularly true in cancer research," said Bill Hahn, assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, associate member of the Broad Institute and a senior author of the study. "For TRC's library, lentiviral delivery is an especially effective means to meet this need."

The parallel analysis of thousands of genes using RNAi allows researchers to more readily pinpoint the genes that control a biological process. Therefore, TRC developed the high-throughput techniques and quality-control measures required for such genome-scale studies. "It is a distinct challenge to achieve consistent and cost-effective RNAi methods and we placed a strong emphasis on this part of the process," said David Sabatini, member of Whitehead Institute for Biomedical Research, assistant professor at Massachusetts Institute of Technology, associate member of the Broad Institute and a senior author. "In the quest to develop comprehensive tools for gene discovery in mice and humans, this technology will be a key piece in the puzzle."

Read more here.

This is an important advance, made available now to biolabs all over the world. For more background information on RNAi, check out this website, or this resource. For an animation of RNAi, go here.

As the tools of discovery become more sophisticated and more available, eventually the point is reached where the new tools make possible newer and better tools, and so on. This is the exponential process of discovery that Kurzweil talks about.


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Glycation in Diabetes and Aging: Routes to Life Extension and Longevity

High blood sugar levels, as are seen in diabetes, insulin resistance, and other forms of hyperglycemia, leads to a process called glycation. Glycation changes the shape and properties of proteins. Crosslinking reduces the flexibility, elasticity, and functionality of the proteins. Furthermore, the chemical modifications of glycation and crosslinking can initiate harmful inflammatory and autoimmune responses. "AGE and nonenzymatic crosslinks are demonstrated to signal inflammatory cytokines, extracellular matrix expansion, angiogenesis, and growth factors." [deGroof] Glycation has been found in connective tissue collagen, arterial collagen, kidney glomerular basement membrane, eye lens crystallins, nerve myelin proteins and in the circulating low-density lipoprotein (LDL) of the blood.

Prolonged glycation leads to creation of advanced glycation end products, AGE. The end result of AGE is all the deadly complications that lead to excessive morbidity and mortality in diabetic patients. Blindness, renal failure, arteriosclerotic heart disease, neuropathies, loss of limbs, etc.

What is not generally known, is that the same process of glycation and AGE formation occurs in normal people, at a much slower rate. You may think that that giant soda, or huge piece of pie is not doing anything bad to your body, but you would probably be wrong. Your connective tissues are being cross-linked beneath your level of awareness. You are ageing prematurely.

This article in Scientific American discussed this issue a few years ago. This brief background article gives more information, with links to more sources.

Various drugs and nutriceuticals have been used to treat glycation and AGE. This article discusses the use of ginger in preventing diabetic kidney damage.
An estimated 19 million people are affected by diabetes in the EU, equal to four per cent of the total population. This figure is projected to increase to 26 million by 2030.

The rhizome of the ginger plant (Zingiber officinale) is a rich source of antioxidants, including gingerols, shogaols, zingerones and other ketone derivatives. It has long been used as a remedy for nausea, especially associated with morning sickness.

The new study, published on-line in Food Chemistry (doi: 10.1016/j.foodchem.2006.01.013), assessed the effects of ginger on the blood antioxidant levels and kidney health of diabetic rat models.

Twenty-four male rats were divided into three groups of eight. The first group (control 1) were healthy rats, the second group (control 2) were diabetic and non-supplemented, and the third group (test) was diabetic and had the diet supplemented with ginger powder as five per cent of the daily food intake.

After eight weeks of supplementation the researchers, led by Dr Ali Taghizadeh Afshari from the Emam Khomeini Hospital, reported: “Antioxidant capacity in the ginger supplemented rats was higher when compared to the other groups.”

The primary drug used to treat glycation and AGE is aminoguanidine. Over the counter nutraceuticals used to treat AGE include carnosine, pyridoxamine, and various forms of thiamine. Ginger may also provide some benefit in preventing diabetic complications, but that research is ongoing.

Glycation end products also accumulate in the brain in Alzheimer's Disease. Scientists are still trying to define any relationship between AGE accumulation in the CNS and neuronal apoptosis. The recent discovery that lower brain insulin may predispose to Alzheimer's Disease probably has something to do with accumulation of AGE.

I will be writing much more on this topic in the future, since it is of great importance in the overall strategy of retarding the ageing process.

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23 March 2006

Lipid Nano Structures Used for Gene Therapy

For a decade or more, scientists at UC Santa Barbara have been working to develop lipid DNA complexes for inserting genes into cells. Such nano structures are considered safer than viruses, although less efficient. This Eurekalert newsrelease details the latest lipid nano structure developed by the UCSB group.

For more than two decades, gene delivery has been accomplished by using engineered viruses as a vehicle to get into diseased cells and 70 percent of clinical trials worldwide continue to use this method. But, the viruses used for gene delivery occasionally evoke severe immune responses, so scientists continue to search for non-viral delivery vehicles.

Reporting in an article to appear in the March 29 print edition of the Journal of the American Chemical Society (published on-line on March 8), the authors describe the synthesis of the new lipid molecule.

Lipid DNA complexes are attracting increasing attention as non-viral DNA delivery vehicles. They have been described as one of the "hottest new technologies" for gene therapy, accounting for nearly 10 percent of ongoing clinical trials.

Lipids are molecules with two parts, a water-liking "headgroup" and oily tails that assemble together to avoid water. Lipids, along with carbohydrates and proteins, constitute the main structural material of living cells.

The novel lipid molecule created at UC Santa Barbara has a tree-shaped, nanoscale headgroup and displays unexpectedly superior DNA-delivery properties. "It generates a honeycomb phase of lipid DNA complexes," said Cyrus R. Safinya, a professor of materials; of molecular, cellular and developmental biology; and of physics at UCSB. The new molecule was synthesized in Safinya's laboratory by first author Kai K. Ewert, a synthetic chemist who is a project scientist in the research group.

"We've been trying to get a lipid-based honeycomb lattice for a long time," said Ewert. The structure of lipid DNA complexes strongly affects their ability to deliver DNA.

"Complexes containing sheets or tubes of lipids have been known since Safinya's group found these structures in 1997 and 1998, but no one had ever seen nanoscale cylinders such as the ones in our honeycomb lattice," Ewart said. The scientists proved the formation of this novel structure with X-ray scattering experiments. Ewert designed and synthesized the new lipid by manipulating the size, shape and charge of a series of molecules. He explained that the new lipid molecule has 16 positive charges in its tree-shaped headgroup, the largest number by far in the field of gene delivery.

The process of delivering a gene of interest into the cell is known as "transfection." In the paper, the authors describe transfection efficiency studies carried out in four cancer cell lines using the new molecule. Two of these are mouse cell lines and two are human cell lines. The honeycomb structure turned out to be highly effective.

Read the entire report here.

By intelligent selection and design, researchers are developing better and safer transfection methods for inserting genes into cells, for many therapeutic purposes.

This article will give more details and links to different aspects and targets of gene therapy. This is a rapidly changing field, like much of biotechnology, and promises unimaginable therapeutic advances in the foreseeable future.
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22 March 2006

A Brief Primer on Pin1, Amyloid Beta, and Alzheimer's

Pin1 is an enzyme, that can twist the joints of proteins in specific places, so that they may change shape. While it has been known that the enzyme Pin1 can prevent the formation of tangles inside neurons in Alzheimer's Disease, it now appears that Pin1 also can block formation of extracellular plaques. Pin1 is a protein of the parvulin family within the peptidyl-prolyl cis-trans isomerase (PPIase) group of proteins and was the first member of this family to be found in humans.

This newsreport from Beth Israel Deaconess Medical Center, Boston, discusses new research findings supporting the protective effect of the enzyme Pin1 against amyloid beta (abeta) plaques (via amyloid precursor protein, APP) and Alzheimer's Disease. The newsreport describes a paper published in Nature.

The researchers, in collaboration with Linda Nicholson at Cornell University, observed through NMR that when APP was phosphorylated (a process in which an extra phosphate is acquired) it became misshapen and could not be easily restored to its original condition. However, once Pin1 was introduced, APP returned to its normal shape – with dramatic speed.

“We had previously proposed that Pin1 was regulating protein function by greatly accelerating structural changes, but this activity had never actually been visualized,” explains Lu. “Now, for the first time, we were able to actually see this process as it occurred.”

Using cell models the authors next went on to examine the effects of Pin1 on Abeta production, says Lu explaining, “We were able to show that while upregulation of Pin1 reduced Abeta generation, removing the Pin1 gene dramatically increased Abeta production by shifting APP processing away from the normal pathway into the pathological pathway.”

....“Because the effects of Pin1 knockout are age-dependent, we compared Abeta levels in the brains of the mice at different ages,” explains Lu. And indeed their results showed that Pin1 knockout again switched APP processing away from the normal pathway into the pathological pathway in the mouse brains. Moreover, he adds, while Pin1 knockout did not significantly change the levels of Abeta40, it did selectively increase levels of insoluble Abeta42 by a significant 30 to 50 percent in two separate mouse models, to an extent that is similar to what would be found in the brains of Alzheimer’s patients and in mouse models of the disease.

The most common cause of dementia among the elderly, Alzheimer’s disease affects an estimated 4 million individuals in the United States, a number that is expected to increase significantly in the coming years with the aging of the baby boomer generation.

“As was earlier shown with tau proteins, it appears that Pin1 acts to restore misshapen amyloid precursor proteins to their original healthy shape, possibly preventing the onset of neurodegeneration and development of dementia,” says D. Stephen Snyder, PhD, of the Etiology of Alzheimer’s Disease program at the National Institute on Aging, which supported this study. “This finding offers important new insights into the molecular events that lead to Alzheimer’s as we work to develop therapies for the treatment of this widespread disease.”

Read the entire report here.

Here is a brief primer on Pin1 with several links to research papers on Pin1. It provides a review by Julian Thorpe of the above paper in Nature by Lu. Here are some excerpts:

"....Lu and colleagues have previously shown that available, soluble Pin1 is depleted in tangle-bearing neurons of AD brain. Very importantly, they also showed that, in vitro, Pin1 could restore the ability of tau to re-associate with, and reconstitute the integrity of, the microtubules. In this latest research, their hypothesis of a potentially neuroprotective role for Pin1 has been strengthened. Not only do they show that there are lower levels of Pin1 protein in susceptible regions of normal human brain, but also that there is an inverse correlation of neuronal Pin1 and tangle content in AD-affected brain. Finally, and most notably, they have shown that aged Pin1 knockout mice have behavioural and motor deficits, neuronal loss and an accumulation of phosphorylated proteins, including tau that forms filaments and assumes a tangle-like conformation.

Overall, this work establishes Pin1 as an important protein in AD and, implicitly, the other tauopathies. Future work should also provide insights into the effects of Pin1 levels on the course of neurodegenerative disease progression through its control of transcription, translation, endocytosis and apoptosis.”

Here is more background on Pin1 from Julian Thorpe. Here is more on Pin1 involvement in amyloid precursor protein proteolysis and plaque formation.

More pieces of the puzzle seem to be falling into place. More potential therapeutic targets. The most fascinating thing about Pin1 appears to be its association with both neurofibrillary tangles (intracellular) and amyloid plaques (extracellular),the major tissue manifestations of Alzheimer's disease.


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Can Cancer Vaccine plus Nanotechnology Stop Cancer?

Cancer scientists have been working on cancer vaccines for decades. Presently there is active development work for vaccines against prostate cancer, breast cancer, leukemia, cervical cancer, and others.

This newsrelease discusses recent work at the Karolinska Institute in Sweden, in isolating a useful tumor antigen that is more accessible to the immune system T cells than many more elusive tumor antigens.

The researchers have identified a short peptide molecule that the T cell in the study recognises. Using this peptide, the researchers can vaccinate and protect against the spread of tumours from different tissues, including melanoma, colon cancer, lymphoma, and fibrosarcoma.

"So far we've only conducted research on mice, so it's too early to get out hopes up too much," says research scientist Elisabeth Wolpert at the Microbiology and Tumour Biology Centre. "However, the study does point towards new possible ways of developing a treatment for advanced tumour diseases."

Nanotechnology is also being brought into the fight, to aid cancer vaccine research. The US National Cancer Institute's (NCI) Center for Cancer Research, is using nanotechnology in several ways.

CCR’s Nanobiology Program (CCRNP) promotes multidisciplinary research that leads to the development of tools for nanoscale, biologically based strategies to prevent, diagnose, and treat cancer, AIDS, and biodefense-related viral diseases. The CCRNP works to understand the structure and function of biomolecules to aid in the design of nanodevices for in vivo imaging, diagnostics, and targeted drug delivery systems.

Principle investigators who are active in the program have several areas of interest, including membrane structure and function, protein interactions, biomedical image and database analysis, structural bioinformatics, structural glycobiology, molecular information theory, and computational RNA structure.

CCRNP investigators have formed collaborative partnerships with CCR investigators in other programs, labs, and branches, including the Molecular Imaging Program, the Radiation Oncology Branch, the Laboratory of Cell Biology, and the Laboratory of Medicinal Chemistry.

Using nanoparticles to "tag" dendritic cells, cancer researchers can keep better track of those important immune system cells.

In a later posting, I will discuss oncogenes and tumor suppressor genes, and how they may relate to cancer vaccines.

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21 March 2006

Virtual Schools Win Real Victory in Court

Virtual schools won a major victory in a Wisconsin courtroom recently. The largest teachers union in Wisconsin had filed suit against Wisconsin Virtual Academy in 2004, but Judge Joseph McCormack ruled against the union.

The Wisconsin Education Association Council claimed that virtual schools rely on parents to do some teacher duties instead of using state-certified teachers.

It also said such schools misuse the state's open enrollment program.

But the judge dismissed the council's arguments, saying the School Board is within its rights to figure out how to partner teachers and parents for the best interest of students.

He also says the open enrollment program doesn't prohibit students from using the Internet to get a public education.

Virtual schools are run by several states, including Wisconsin, Texas, and Florida. South Carolina legislators are considering a bill to establish a statewide virtual school. Some universities are also running virtual schools.

This CSM article discusses some of the issues involved in virtual schooling, and how the concept relates at times to the charter school and home school movements.

For those readers who want to delve more deeply into the history, and more technical details of virtual schooling, take a look at this pdf study from one of the foremost experts on virtual schooling.

I like the idea of educational choice. Corruption in government education has become much too blatant and destructive toward students, taxpayers, and the body politic. Being able to sidestep that corruption in any way possible, is not a bad thing.

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Mmmmmmm! Cabernet! Quercetin, Resveratrol, and Cancer Apoptosis

Many plants and fruits are rich in anti-oxidant and anti-inflammatory compounds. Recently, scientists have focused on resveratrol due to its possible role in reduced cardiovascular morbidity and mortality. A closely related flavonoid, quercetin, apparently plays a strong role in the inducing of apoptosis in various cancer lines, including prostate cancer and leukemia.

This doctoral dissertation by Susanne U. Talcott is a very rich source of information on the topic of apoptosis induction by compounds contained in the cabernet and muscadine grapes. I cannot recommend it highly enough. You will find it worth your time to look through the text, tables, figures, and sources.

Here is Dr. Talcott describing this line of research, from another presentation:

The consumption of fruits and vegetables has been associated with a lowered risk for several chronic diseases including coronary heart disease and several types of cancer, which has been demonstrated in several epidemiological and intervention studies. In part, this risk reduction has been associated with the occurrence of antioxidant phytochemicals such as polyphenolics in these foods. Several of the polyphenolics have been demonstrated to have cancer-preventive and anticarcinogenic effects in in vitro and in vivo experiments. Underlying mechanisms include antioxidant effects, which prevent chemical or stress-induced damage to cells, and the induction of apoptosis in cancer cells through intracellular signal transduction. Recent research efforts include the investigation of the relationship between the antioxidant capacity of polyphenols or polyphenol-containing foods and their in vivo disease-preventive potential. Limitations of this approach arise from aspects of bioavailability and post-absorptive metabolism leading to the generation of metabolites, which have been shown to differ from their parent compound in antioxidant capacity and mechanism of action. This presentation will give an overview of recent advances and limitations in the area of anticancer effects of polyphenolics. In addition, data demonstrating the anticarcinogenic effects of red wine polyphenolics in cell culture experiments with cancer cell lines and consumption trials with human subjects will be discussed.

I discussed quercetin and resveratrol in previous postings in relation to anti-ageing properties. Finding such innocuous natural substances that both contribute to life extension AND provide protection from multiple cancer types, is like finding a four leafed clover, or winning the lottery.
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Alzheimer's, Beta Amyloid, and the Choroid Plexus

The Choroid Plexus is a complex of capillary rich cells located in the ventricles of the brain, which produce cerebral spinal fluid, and perform other functions protective of the brain. This Purdue University newsrelease discusses a recent research finding that links the choroid plexus to the function of filtering beta amyloid from brain fluid and CSF.

The researchers found that the choroid plexus acts as a sort of "fishnet" that captures the protein, called beta-amyloid, and prevents it from building up in the cerebrospinal fluid, which surrounds and bathes the brain and spinal cord. Moreover, tissue in the organ is able to soak up large amounts of the protein and may contain enzymes capable of digesting beta-amyloid, said Wei Zheng (pronounced Way Zsheng), an associate professor in the School of Health Sciences at Purdue University.

The findings represent the first time that researchers have identified the potential existence of a natural mechanism in the brain for removing beta-amyloid.

"This newly uncovered pathway may help explain how normal brains balance this protein and how an imbalance caused by aging, genetic or environmental factors may lead to or worsen Alzheimer's disease," Zheng said.

Researchers had already known that the cerebrospinal fluid in the brains of Alzheimer's patients contains abnormally high quantities of beta-amyloid fragments. Beta-amyloid deposits accumulate over a period of years, resulting in abnormal clumps, or plaque, typical of Alzheimer's disease. Scientists do not yet know whether the disease is caused by the plaque formations or beta-amyloids themselves.

The discovery suggests that a malfunctioning choroid plexus could allow too much of the protein to build up in the brain.

Read the rest here. For further study, this helpful article further details choroid plexus malfunction and breakdown in ageing and Alzheimer's disease.

In this article, I discussed some recent research evidence linking beta amyloid to memory loss and neuron death in Alzheimer's. Today's Purdue report adds more information to the overall picture.

It is important to understand the complete dynamic story of beta amyloid, from its formation to its action on neurons, to its breakdown and removal, if we are to understand all of our potential therapeutic choices in reducing the detrimental effect of this protein.


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Math: More Getting What You Need

Most of you will probably agree that government schools--and schools in general--are shortchanging our children, particularly in the areas of math, science, and in world view perspectives. For now, we will concentrate more on math. As a follow-on to my previous post, I wanted to explain that reading wikipedia-math for 15-30 minutes daily is not just for adults who want to brush up and round off their math knowledge. It might be particularly helpful for those young brains that are in the middle of the pruning process. A good parent will lead his children to such resources, and help the child to utilise them, while the children are still young enough to have faith in the parents' judgment.

Here is a good essay on "how to read mathematics." It is meant to aid in reading math journal articles and texts, but it can also be adapted to the wikipedia and mathworld approach.

A reading protocol is a set of strategies that a reader must use in order to benefit fully from reading the text. Poetry calls for a different set of strategies than fiction, and fiction a different set than non-fiction. It would be ridiculous to read fiction and ask oneself what is the author's source for the assertion that the hero is blond and tanned; it would be wrong to read non-fiction and not ask such a question. This reading protocol extends to a viewing or listening protocol in art and music. Indeed, much of the introductory course material in literature, music and art is spent teaching these protocols.

Mathematics has a reading protocol all its own, and just as we teach students to read literature, we should teach them to read mathematics.This article categorizes some of the strategies for a mathematics reading protocol. I am sure my readers will think of many strategies that I missed. The point is that there *is* such a protocol, that we all know and use it, and that we should make an attempt to share the secret with our students.

....."Reading Mathematics is not at all a linear experience ...Understanding the text requires cross references, scanning, pausing and revisiting" (ibid page 16).

Don't assume that understanding each phrase, will enable you to understand the whole idea. This is like trying to see a painting by staring at each square inch of it from the distance of your nose. You will get the detail, texture and style but miss the picture completely. A math article has a story! Try to see what the story is before you delve into the details. You can go in for a closer look once you have a framework to fill with details, just as you might reread a novel.

....Mathematics says a lot with a little. The reader must participate! At every stage, he must decide whether or not the idea presented was clear. Why is it true? Do I really believe it? Could I convince someone else that it is true? Why didn't the author use a different argument? Do I have a better argument or method of explaining the idea? Why didn't the author explain it the way that I understand it? Is my way wrong? Do I really get the idea? Am I missing some subtlety? Did this author miss a subtlety? If I still can't understand the point, perhaps I can understand a similar but simpler idea? Which simpler idea? Is it really necessary to understand the idea? Perhaps I will just accept this point without understanding the details? Perhaps, my understanding of the whole story will not suffer from this?

Putting too little effort into this participation, is like reading a novel without concentrating. After half an hour, you wake up to realize the pages have turned, but you have been day dreaming and don't remember a thing you read.

....Reading mathematics too quickly, results in frustration. A half hour of concentration in a novel buys you 20-60 pages with full comprehension (depending on how experienced you are at reading novels). The same half hour in a math article buys you 0-3 lines (depending on how experienced you are at reading mathematics). There is no substitute for work and time. You can speed up your math reading skill by practicing, but be careful. Like any skill, trying too much too fast can set you back and kill your motivation. Imagine trying to do an hour of high energy aerobics if you have not worked out in two years. You may make it through the first class, but you are not likely to come back. The frustration from seeing the experienced class members effortlessly do twice as much as you, while you moan the whole next day from soreness, is too much to take.

And so on. Scan through the essay as you can, then apply the approach to your next 15 minute math session. Persistence plus good technique. It takes time to learn the right technique for you--the best approach--but persistence is there for everyone, for just a little willpower.

You might also want to check out something called Visual Math. Math can be very beautiful, visually and esthetically. Here are some links to visual geometry.

Finally, here is a math reference website, to add to all the others in my previous posting, and the ones on the sidebar.

Combining the information in this posting and the previous one, you may be in a better postion to compensate for any deficits in your own math education, and to prevent large gaps from forming in your children's math educations. Math is not all they will need to know, but it will be a key part.


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20 March 2006

Math: Getting What You Need

If you want to succeed in the modern world, you need to know some math. In many of the hottest research and technology fields, you have to know a lot of math. Corporate executives in North America constantly complain at the lack of well trained engineers and scientists within their applicant pool. Poor math skills among college graduates leads corporations to hire from abroad, and outsource jobs overseas.

This blog post relates the tale of a programmer who found that he needed to go back and brush up on his math skills. It provides suggestions for self teaching of math that can prove useful. Many of the comments following the posting are also helpful.

I think the best way to start learning math is to spend 15 to 30 minutes a day surfing in Wikipedia. It's filled with articles about thousands of little branches of mathematics. You start with pretty much any article that seems interesting (e.g. String theory, say, or the Fourier transform, or Tensors, anything that strikes your fancy. Start reading. If there's something you don't understand, click the link and read about it. Do this recursively until you get bored or tired.

Doing this will give you amazing perspective on mathematics, after a few months. You'll start seeing patterns — for instance, it seems that just about every branch of mathematics that involves a single variable has a more complicated multivariate version, and the multivariate version is almost always represented by matrices of linear equations. At least for applied math. So Linear Algebra will gradually bump its way up your list, until you feel compelled to learn how it actually works, and you'll download a PDF or buy a book, and you'll figure out enough to make you happy for a while.

Read the rest here.

One of the commenters suggested that Mathworld might be just as helpful as Wikipedia, but other commenters felt that Wikipedia was better for self-teaching math.

I agree with Steve that math is not taught well in school, generally. By the time students get to college, they are so disillusioned with math--due to poor preparation in K-12--that they opt out of the career paths that require a lot of math. Following Steve's suggestion not only gives you gradual familiarity with math topics, but by jumping into the topic daily, you reinforce the material and are more likely to retain it in a meaningful, subconscious way.

For further study online, after you have exhausted Wikipedia and Math World, go here, here, and here for links to quite a few free online math texts. Also feel free to follow links to math resources and tutorials in the right hand sidebar here.

Math geeks are very much in demand in the high tech world. Government schools are wasting a lot of potential tech workers by absurdly poor preparation in the early years, and by often substituting political indoctrination for basic learning. The way that present government schools fail to prepare students for the future is a recipe for societal suicide.

Fortunately, human ingenuity is constantly devising paths around the institutional obstacles and corruption that are a constant threat to any middle-aged society.
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Solar Power from Outer Space

Whatever happened to the idea of using satellites to harvest solar power 24 hours a day? Jim from the Energy Blog has an update from the Space Island Group (SIG) and their current project to place photovoltaic arrays in orbit.

The Space Island Group, Inc. (SIG) will design and finance two categories of space hardware to make these results possible. Both categories will incorporate components now used on NASA’s space shuttles and other launch vehicles, and on today’s communications satellites. This is not an R&D project. Because we will not develop new rocket engines, guidance systems or other components and because we’ll manage the program with private industry procedures, our development costs will be far below those of comparable government efforts.

The first hardware category will be very large structures up to several kilometers wide called solar power satellites and solar reflectors, which will be assembled in space.

The second will be very low-cost manned and unmanned launch vehicles, and very large, low-cost living quarters in orbit able to comfortably house several hundred occupants at a time. These occupants will, among other tasks, assemble and maintain the orbiting solar satellites and solar reflectors.

....This is not a government program. We feel that taxpayers have already funded most of the hardware we’ll use.

Now it’s our job to use that proven hardware to let a broad range of industries profitably capitalize on that investment. Along the way, we expect that we and these industries will create millions of high-paying American jobs that overseas competitors won’t be able to take away for decades. In fact we’ll make those American jobs a lease-condition for our tenants.

These jobs will start with the defense contractors. Some 90% of our development funds will go to the firms that now build shuttle components for NASA. Tens of thousands of current aerospace jobs will end when the shuttles retire in 2010. Our first launch in 2008 or 2009 will not only absorb those employees, but will increase their numbers many times over during the following decade. Many of the same firms will build our space hardware, but we’ll use simpler, commercial procedures rather than the more complex ones used for government work.

Read more at the SIG website. SIG has quite a few plans for their solar satellites, including energy production, hurricane control, reflecting sunlight to croplands to prolong the growing season, and many more . . . They have a section discussing global warming, ice age, and many other fascinating topics.

Read more about solar power satellites, and other peaceful uses of outer space, here. This might be a good time to go back and review my posting about access to space. You have to get there before you can do all these things. This post from Power From Space blog provides links to all the companies involved in the race to place solar power satellites in orbit.

The main limit to human progress is the limit of the human brain. Humans are presently intelligent enough to get into a lot of trouble. If you are a singularitarian, you are pinning your hopes on intelligent machines, nanotechnology, and the exponential increase in knowledge. Personally, I prefer the idea of enabling more intelligent humans. Either approach holds risks, but the alternative is to let things take their current course. There are also problems with that approach.

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