Interview with Donald Knuth

Interview with Donald Knuth by Andrew Binstock, April 2008:

I currently use Ubuntu Linux, on a standalone laptop—it has no Internet connection. I occasionally carry flash memory drives between this machine and the Macs that I use for network surfing and graphics; but I trust my family jewels only to Linux. Incidentally, with Linux I much prefer the keyboard focus that I can get with classic FVWM to the GNOME and KDE environments that other people seem to like better. To each his own.
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I’m basically advising young people to listen to themselves rather than to others, and I’m one of the others. Almost every biography of every person whom you would like to emulate will say that he or she did many things against the “conventional wisdom” of the day.

Still, I hate to duck your questions even though I also hate to offend other people’s sensibilities – given that software methodology has always been akin to religion. With the caveat that there’s no reason anybody should care about the opinions of a computer scientist/mathematician like me regarding software development, let me just say that almost everything I’ve ever heard associated with the term “extreme programming” sounds like exactly the wrong way to go…with one exception. The exception is the idea of working in teams and reading each other’s code. That idea is crucial, and it might even mask out all the terrible aspects of extreme programming that alarm me.

I also must confess to a strong bias against the fashion for reusable code. To me, “re-editable code” is much, much better than an untouchable black box or toolkit. I could go on and on about this. If you’re totally convinced that reusable code is wonderful, I probably won’t be able to sway you anyway, but you’ll never convince me that reusable code isn’t mostly a menace.

Gecko-inspired Bandage

MIT creates gecko-inspired bandage

Drawing on some of the principles that make gecko feet unique, the surface of the bandage has the same kind of nanoscale hills and valleys that allow the lizards to cling to walls and ceilings. Layered over this landscape is a thin coating of glue that helps the bandage stick in wet environments, such as to heart, bladder or lung tissue. And because the bandage is biodegradable, it dissolves over time and does not have to be removed.
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Gecko-like dry adhesives have been around since about 2001 but there have been significant challenges to adapt this technology for medical applications given the strict design criteria required. For use in the body, they must be adapted to stick in a wet environment and be constructed from materials customized for medical applications. Such materials must be biocompatible, meaning they do not cause inflammation; biodegradable, meaning they dissolve over time without producing toxins; and elastic, so that they can conform to and stretch with the body’s tissues.
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When tested against the intestinal tissue samples from pigs, the nanopatterned adhesive bonds were twice as strong as unpatterned adhesives. In tests of the new adhesive in living rats, the glue-coated nanopatterned adhesive showed over a 100 percent increase in adhesive strength compared to the same material without the glue. Moreover, the rats showed only a mild inflammatory response to the adhesive, a minor reaction that does not need to be overcome for clinical use.

Among other advantages, the adhesive could be infused with drugs designed to release as the biorubber degrades. Further, the elasticity and degradation rate of the biorubber are tunable, as is the pillared landscape. This means that the new adhesives can be customized to have the right elasticity, resilience and grip for different medical applications.

Walking Without Shoes

You Walk Wrong

Last year, researchers at the University of the Witwatersrand in Johannesburg, South Africa, published a study titled “Shod Versus Unshod: The Emergence of Forefoot Pathology in Modern Humans?” in the podiatry journal The Foot. The study examined 180 modern humans from three different population groups (Sotho, Zulu, and European), comparing their feet to one another’s, as well as to the feet of 2,000-year-old skeletons. The researchers concluded that, prior to the invention of shoes, people had healthier feet. Among the modern subjects, the Zulu population, which often goes barefoot, had the healthiest feet while the Europeans – i.e., the habitual shoe-wearers – had the unhealthiest
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My new Vivo Barefoots aren’t perfect – they’re more or less useless in rain or snow, and they make me look like I’m off to dance in The Nutcracker. But when I don’t wear them now, I kind of miss them. Not because they’re supposedly making my feet healthier, but because they truly make walking more fun. It’s like driving a stick shift after years at the wheel of an automatic – you suddenly feel in control of an intricate machine, rather than coasting on cruise control. Now I better understand what Walt Whitman meant when he wrote (and I hate to quote another Transcendentalist, but they were serious walking enthusiasts): “The press of my foot to the earth springs a hundred affections.”

Bacteriophages: The Most Common Life-Like Form on Earth

There are more bacteriophages on Earth than any other life-like form. These small viruses are not clearly a form of life, since when not attached to bacteria they are completely dormant. Bacteriophages attack and eat bacteria and have likely been doing so for over 3 billion years. Although initially discovered early last century, the tremendous abundance of phages was realized more recently when it was found that a single drop of common seawater typically contains millions of them. Extrapolating, phages are likely to be at least a billion billion times more numerous than humans. Pictured above is an electron micrograph of over a dozen bacteriophages attached to a single bacterium. Phages are very small — it would take about a million of them laid end-to-end to span even one millimeter. The ability to kill bacteria makes phages a potential ally against bacteria that cause human disease, although bacteriophages are not yet well enough understood to be in wide spread medical use.

Photo credit: Wikipedia Electron micrograph of bacteriophages attached to a bacterial cell. These viruses have the size and shape of coliphage T1.; Insert: Mike Jones

Amazon Molly Fish are All Female

No sex for all-girl fish species

A fish species, which is all female, has survived for 70,000 years without reproducing sexually, experts believe.
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The species, found in Texas and Mexico, interacts with males of other species to trigger its reproduction process. The offspring are clones of their mother and do not inherit any of the male’s DNA. Typically, when creatures reproduce asexually, harmful changes creep into their genes over many generations.
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One theory is that the fish may occasionally be taking some of the DNA from the males that trigger reproduction, in order to refresh their gene pool.

Dr Laurence Loewe, of the university’s School of Biological Sciences, said: “What we have shown now is that this fish really has something special going on and that some special tricks exist to help this fish survive. “Maybe there is still occasional sex with strangers that keeps the species alive. Future research may give us some answers.”

He added that their findings could also help them understand more about how other creatures operate. “I think one of the interesting things is that we are learning more about how other species might use these tricks as well,” he said. “It might have a more general importance.”

$60 Million for Science Teaching at Liberal Arts Colleges

HHMI Awards $60 Million to Invigorate Science Teaching at Liberal Arts Colleges

A year ago, the Howard Hughes Medical Institute issued a challenge to 224 undergraduate colleges nationwide: identify creative new ways to engage your students in the biological sciences.

Now 48 of the nation’s best undergraduate institutions will receive $60 million to help them usher in a new era of science education. This includes the largest number of new grantees in more than a decade; more than a quarter have never received an HHMI grant before.

Colleges in 21 states and Puerto Rico will receive $700,000 to $1.6 million over the next four years to revitalize their life sciences undergraduate instruction. HHMI has challenged colleges to create more engaging science classes, bring real-world research experiences to students, and increase the diversity of students who study science.
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Creating interdisciplinary science classes and incorporating more mathematics into the biology curriculum were among the major themes proposed by the schools. Many schools will also allow more students to experience research through classroom-based courses and summer laboratory programs.
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HHMI is the nation’s largest private supporter of science education. It has invested more than $1.2 billion in grants to reinvigorate life science education at both research universities and liberal arts colleges and to engage the nation’s leading scientists in teaching. In 2007, it launched the Science Education Alliance, which will serve as a national resource for the development and distribution of innovative science education materials and methods.

Potential Viral Therapy for Difficult Cancers

Potential viral therapy weapon for difficult cancers is safe and effective in study

Combining a herpes virus genetically altered to express a drug-enhancing enzyme with a chemotherapy drug effectively and safely reduced the size of highly malignant human sarcoma grafted into mice. This new finding may add to the growing arsenal of so called oncolytic viruses under development as novel cancer treatments, especially for difficult, inoperable tumors
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“Based on these findings and other preclinical studies, we expect oncolytic viral therapy will be one additional treatment modality available in the future for oncologists,” Dr. Cripe said. “The challenge over the next decade will be determining which viruses work best for which cancers, at what doses, schedules, routes of administration, and in what combinations with other treatments.”

E. Coli Individuality

Expressing Our Individuality, the Way E. Coli Do by Carl Zimmer

A good counterexample is E. coli, a species of bacteria that lives harmlessly in every person’s gut by the billions. A typical E. coli contains about 4,000 genes (we have about 20,000). Feeding on sugar, the microbe grows till it is ready to split in two. It makes two copies of its genome, almost always managing to produce perfect copies of the original. The single microbe splits in two, and each new E. coli receives one of the identical genomes. These two bacteria are, in other words, clones.
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A colony of genetically identical E. coli is, in fact, a mob of individuals. Under identical conditions, they will behave in different ways. They have fingerprints of their own.
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E. coli appears to follow a universal rule. Other microbes exploit noise, as do flies, worms and humans. Some of the light-sensitive cells in our eyes are tuned to green light, and others to red. The choice is a matter of chance. One protein may randomly switch on the green gene or the red gene, but not both.

In our noses, nerve cells can choose among hundreds of different kinds of odor receptors. Each cell picks only one, and evidence suggests that the choice is controlled by the unpredictable bursts of proteins within each neuron. It’s far more economical to let noise make the decision than to make proteins that can control hundreds of individual odor receptor genes.

Identical genes can also behave differently in our cells because some of our DNA is capped by carbon and hydrogen atoms called methyl groups. Methyl groups can control whether genes make proteins or remain silent. In humans (as well as in other organisms like E. coli), methyl groups sometimes fall off of DNA or become attached to new spots. Pure chance may be responsible for changing some methyl groups; nutrients and toxins may change others.

Viruses Eating Bacteria

All the World’s a Phage by John Travis:

“Believe it or not, nobody had looked before,” says Suttle. “On average, there are 50 million viruses per milliliter in seawater. The question is, What the heck they’re doing there?” Microbiologists then documented similar, and even higher, concentrations of phages in soil samples. This led to estimates of 10³¹ bacteriophages worldwide, a staggeringly large number that many scientists initially dismissed. “We can’t wrap our brains around it,” says Pedulla. “If phages were the size of a beetle, they would cover the Earth and be many miles deep.”
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According to estimates put forth by Suttle, phages destroy up to 40 percent of the bacteria in Earth’s oceans each day.
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The students collected soil from barnyards, gardens, and even the monkey pit at the Bronx Zoo. The scientists then taught the students how to isolate a bacteriophage from the soil by growing the viruses in Mycobacterium smegmatis, a harmless bacterial relative of the microbe that causes tuberculosis. “We guarantee them that the bacteriophage they find will never have been discovered before. We know that because the diversity is so high, and we’ve never isolated the same bacteriophage twice,” says Hatfull.

In the April 18 Cell, Hatfull and his professional and teenage collaborators describe the genomes of 10 soil-dwelling bacteriophages that they had isolated. Of the more than 1,600 genes that the team identified, about half are novel, that is, they don’t match any previously described genes in any other organism.

Science is full of amazing new frontiers. Some other amazing stuff: Thinking Slime Moulds – Tracking the Ecosystem Within Us – Retroviruses – Energy Efficiency of Digestion – One Species’ DNA Discovered Inside Another’s

Sudden Oak Death

Sudden Oak Death pathogen is evolving, says new study that reconstructs the epidemic

The pathogen responsible for Sudden Oak Death first got its grip in California’s forests outside a nursery in Santa Cruz and at Mt. Tamalpais in Marin County before spreading out to eventually kill millions of oaks and tanoaks along the Pacific Coast, according to a new study led by researchers at the University of California, Berkeley. It provides, for the first time, evidence of how the epidemic unfolded in this state.
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The study, scheduled to appear later this month in the online early edition of the journal Molecular Ecology, also shows that the pathogen is currently evolving in California, with mutant genotypes appearing as new areas are infested.
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The most likely scenario, said Garbelotto, is that the pathogen arrived in California through the nursery trade, and that it then spread from the nursery in Santa Cruz to trees bordering the facility. While the site at Mt. Tamalpais is not adjacent to a nursery, there is anecdotal evidence of frequent use of ornamental plants from nurseries in landscaping projects in the area, said Garbelotto.