Inaugural Article Research Articles

Computing and AI for a Sustainable Future

This inaugural article of the AI and Sustainability department sets the stage for articles in the area over the coming months and years. AI and sustainability is a nascent area, and elaborating it's brief history with pointers to recent and notable activities is this article's primary goal, as well as contextualizing AI and sustainability within the larger computing and sustainability movement.

MRS Communications publishes inaugural article

MRS Communications publishes inaugural article

QnAs with Peter H. Gleick

National Academy of Sciences member Peter Gleick is cofounder and president of the Pacific Institute for Studies in Development, Environment, and Security in Oakland, California, where he explores new ways of thinking about water issues. His creative insights have resulted in the biennial book series The World’s Water , a MacArthur Fellowship award in 2003, multiple appearances as an expert witness before Congress and the courts, and the 2010 book Bottled and Sold: The Story Behind Our Obsession with Bottled Water . Peak water, the concept introduced in his PNAS Inaugural Article (1), became one of the New York Times ’ “Words of the Year” in 2010. The following year, Gleick and the Pacific Institute were awarded the 2011 US Water Prize. Recently, Gleick spoke with PNAS about peak water, the soft water path, and how climate change will affect our global water supply in predictable and unpredictable ways. Peter H. Gleick. > PNAS:Why did you become interested in water issues? > Gleick:My interest in water grew out of a broader interest in environmental issues. I grew up, perhaps ironically, in New York City, a place with …

Profile of Stephen E. Plog

Within the confines of remote Chaco Canyon, large Pueblo great houses stand sentry among smaller dwellings, the palatial behemoths unoccupied and the nature of their growth and decline 1,000 years ago in this region of the American Southwest still under debate. In his Inaugural Article, archaeologist Stephen Plog, elected to the National Academy of Sciences in 2007, uses evidence from burials within one of these great houses to assert that these societies were not as egalitarian as their more modern Pueblo counterparts are, but that they supported a social hierarchy (1). The dead can, and do, tell tales, yet with few archaeological excavations allowed in the Chaco Canyon in the past 20 years and for the foreseeable future, it is only with data from previous excavations that researchers can tease apart its history. Thanks to Plog, over 100 years’ worth of Chaco Canyon data, much of it previously unpublished, is now meticulously archived in a relational database and publicly available (www.chacoarchive.org), the result of a 7-year labor of love to ensure that Chaco Canyon remains an active virtual excavation. Stephen E. Plog (photograph courtesy of Tom Cogill). Plog, currently the David A. Harrison Professor of Archeology at the University of Virginia, spent the first 6 years of his life in Roswell, New Mexico, before moving to El Paso, Texas, with his family in 1955. Growing up amid the rich cultural history of the American Southwest, Plog could not escape talk of archeology. But it was his older brother, Fred, who wanted to be the archaeologist. “He started on the track earlier than I did,” says Plog, who entered Grinnell College (Grinnell, IA) with the intention of majoring in economics. Plog left Grinnell in 1968, midway through his first year, and enrolled at the University of Texas at El Paso to …

New Review Articles

I am pleased to present in this issue the first of a series of specially invited review articles that seek to present the state of the art of their chosen biomechanical topic. The inaugural article is entitled “The specific growth rates of tissues: A review and a reevaluation” by Dr. Stephen C. Cowin of the Department of Biomedical Engineering, CUNY. In this article, Dr. Cowin presents a brief history of efforts to mathematically model the growth of tissues. He then continues to present a case for the reevaluation of current approaches and several novel ideas. It is one of the most thought-provoking, expansive articles I have read in recent years on the very exciting topic of tissue growth and remodeling. I hope you all enjoy it as much as I have.We are currently planning several more of these articles for this coming year. These articles receive absolute top priority for publication, are of extended length (equivalent to two to three standard manuscripts), are rapidly reviewed, with the review process handled personally by the editor, with all page charges waived, and are to be published in the next available issue. If you are interested in contributing a review article, please contact me directly with a title, abstract, and estimated completion date.Yours sincerely,Michael S. Sacks, Ph.D.EditorJohn A. Swanson ChairDepartment of Bioengineering, University of Pittsburghe-mail: msacks@pitt.edu

Profile of Donald E. Canfield

An ecologist might say that the answer to nearly every question about the origin and evolution of life on Earth can be found in the ocean, where reactions fueled by ancient microbes have changed our planet's chemistry over the eons. Donald Canfield, Professor of Ecology and Director of the Nordic Center for Earth Evolution at the University of South Denmark, has spent his career studying oceans and lakes to understand the progressive oxygenation of the atmosphere through time, ultimately permitting the development of large motile animals. Donald E. Canfield. Canfield, 53, was elected to the National Academy of Sciences in 2007. His Inaugural Article, published in PNAS in November 2010, demonstrates that Escherichia coli , a well-known lover of oxygen, or “aerobe,” can grow in oxygen concentrations 100,000 times less than those found in regular air, suggesting that aerobic organisms evolved much earlier than believed (1). A native of Cincinnati, OH, Canfield spent his childhood in a handful of other midwestern cities where his father, an engineer, was transferred. Canfield was an inquisitive child with a strong interest in how things worked. “I was famous for asking question after question, and not every adult was so patient. But my dad, he just answered them all,” Canfield remembers. “Whenever he was working on something, he always let me come and see what was going on, and I would ask more questions. I never would have developed my interest in science if my father wasn't extremely patient.” Canfield also credits his grandfather for cultivating his fascination with the ocean. “My grandfather was always crazy about the water, and I was his fishing buddy,” Canfield recalls. “He had a little cottage in the Florida Keys, and my family would go there frequently. By the time I was 13 or 14 years old, …

Engineers or Scientists?

Michael Rabinovich, IEEE Internet Computing's new editor in chief, launches his term as EIC with his inaugural article. He writes about the Internet computing field from a performance and infrastructure standpoint.

Introduction: The Medium and the Message

In this issue, the Journal of Gay & Lesbian Mental Health (JGLMH) introduces a new, ongoing series on the subject of media. Our inaugural article by Svensson, Cura, and Burr (2011) explores how a t...

Profile of Charles F. Manski

Charles Manski has a history of questioning dogma. Manski, who was elected to the National Academy of Sciences in 2009 and is currently a professor of economics at Northwestern University (Evanston, IL), has developed new methods in theoretical and empirical econometrics over the course of his career. In his Inaugural Article (1), he builds on his recent work on planning under ambiguity, a common problem for many policymakers. Policymakers are in the business of making tough decisions with a paucity of data. No one can possibly know how all taxation schedules, criminal justice laws, or vaccination programs will influence labor supplies, crime rates, and spread of disease, respectively. Therefore, what is a policymaker to do under this common condition of partial knowledge? Traditional economic approaches to this problem use subjective probabilities that are often based on convenient nonrefutable assumptions. Throw those assumptions out, says Manski, “Economists usually want to find the optimal solution to something…That's not the way I operate…I'm satisfied to throw out things that are demonstrably bad.” Rather than create a solution based on so-called “assumptions of convenience,” Manski has championed an approach in which weaker but more credible assumptions can reveal informative conclusions (2). Throwing away traditional assumptions means that a single optimal solution may have to give way to a range of good solutions. However, Manski, unlike some other scientists and many politicians, is, he says, “not uncomfortable with ambiguity.” Charles Manski was born in 1948, the child of what he calls a “classic American immigrant” family, and grew up in Boston, MA. His father fled from Poland during World War II and put himself through night school to earn a Bachelor of Arts degree. His mother's education ended at high school. However, Manski and his two brothers managed to earn advanced degrees. “It's not like …

Hypoxia Increases the Expression of Stem-Cell Markers and Promotes Clonogenicity in Glioblastoma Neurospheres

Hypoxia promotes the expansion of non-neoplastic stem and precursor cell populations in the normal brain, and is common in malignant brain tumors. We examined the effects of hypoxia on stem-like cells in glioblastoma (GBM). When GBM-derived neurosphere cultures are grown in 1% oxygen, hypoxia-inducible factor 1alpha (HIF1alpha) protein levels increase dramatically, and mRNA encoding other hypoxic response genes, such as those encoding hypoxia-inducible gene-2, lysyl oxidase, and vascular endothelial growth factor, are induced over 10-fold. Hypoxia increases the stem-like side population over fivefold, and the percentage of cells expressing CD133 threefold or more. Notch pathway ligands and targets are also induced. The rise in the stem-like fraction in GBM following hypoxia is paralleled by a twofold increase in clonogenicity. We believe HIF1alpha plays a causal role in these changes, as when oxygen-stable HIF1alpha is expressed in normoxic glioma cells CD133 is induced. We used digoxin, which has been shown to lower HIF protein levels in vitro and in vivo, to inhibit the hypoxic response. Digoxin suppressed HIF1alpha protein expression, HIF1alpha downstream targets, and slowed tumor growth in vivo. In addition, pretreatment with digoxin reduced GBM flank xenograft engraftment of hypoxic GBM cells, and daily intraperitoneal injections of digoxin were able to significantly inhibit the growth of established subcutaneous glioblastoma xenografts, and suppressed expression of vascular endothelial growth factor.

Profile of Charles M. Newman

In Newman’s Inaugural Article published in PNAS, Camia and Newman (1) provide a representation of the magnetization field of a 2D Ising model at its critical point—in the scaling limit, in which the model, an array of discrete points, shrinks into continuity.

Profile of Ronald Levy

Over the past 2 decades, a fresh wave of cancer therapies have changed the way that the disease is treated. Some of the newest therapies are not drugs but antibodies, which provoke the body's immune system into destroying and, hopefully, eliminating its own tumors. Ronald Levy, who helped develop and test the first US Food and Drug Administration (FDA)-approved antibody against cancer for the treatment of lymphoma, was elected to the National Academy of Sciences in 2008. His Inaugural Article, published in this issue of PNAS, reveals a subpopulation of lymphoma cells whose numbers at the time of diagnosis predict the severity and lethality of these tumors (1). Ronald Levy. Levy, 68, now a professor of medicine and chief of the Division of Oncology at Stanford University School of Medicine, was born in Carmel, CA, and moved to Palo Alto, CA, during high school. He attended Harvard University (Cambridge, MA) as an undergraduate and had his first exposure to research in Konrad Bloch's laboratory shortly before Bloch won the Nobel Prize in Physiology or Medicine for his work on cholesterol and fatty acid metabolism. Levy worked on the biosynthesis of monounsaturated fatty acids by bacteria (2). After graduating from Harvard with a degree in biochemistry in 1963, Levy enrolled in medical school at Stanford University. Then, Stanford had a 5-year curriculum that gave students extra time to pursue their own interests. These free periods were important formative events for Levy, which he used to work in the laboratory of another Nobel Prize winner, Arthur Kornberg, and in the laboratories of other Stanford scientists. Two more scientists were strong role models for Levy as a budding physician-scientist. The first, Henry Kaplan, founded the field of modern radiotherapy by using a linear accelerator to treat Hodgkin's lymphoma, which is now …

Profile of Jeffery L. Dangl

If you make the mistake, as some do, of calling Jeff Dangl a botanist, his embarrassment is palpable. Trained as a mouse immunologist, he admits to a “certain lack” of botanical knowledge. The John N. Couch distinguished professor of biology and adjunct professor of microbiology and immunology at the University of North Carolina, Chapel Hill, will, however, give you an earful about the lack of respect, and with it, funding, historically given to the plant sciences compared with his former field of immunology. Jeffery L. Dangl. He studies Arabidopsis thaliana , a fast-growing, weedy plant known as thale cress, which has become the Drosophila of plant-based molecular biology. Long before it became the first plant to have its entire genome sequenced, Dangl was among a handful of researchers who pioneered its use as a model system for studying plant disease resistance, not solely as botanists but using all of the powerful tools of molecular biology, genetics, and plant pathology combined. He was at the cutting edge of what he calls a mini-revolution that not only showed that plants have an immune system, but that, at the genetic and molecular levels, the system shares basic organizational traits with mammals. For his work in deciphering how plants interact, at the molecular level, with pathogens to fight off disease, Dangl was elected into the National Academy of Sciences in 2007. In his Inaugural Article (1), Dangl, his graduate/postdoctoral student David Hubert, and colleagues build on that work using genetics techniques to show how three chaperone molecules interact to control the levels of nucleotide-binding domain and leucine-rich repeat (NB-LRR) proteins—critical intracellular receptors for proper immune function in plants. Dangl grew up in Redding, northern California, surrounded by mountains, lakes, and streams and close enough to the ocean for frequent visits. His mother, a teacher …

Has biology disproved free will and moral responsibility?

In his Inaugural Article entitled “The Lucretian swerve: The biological basis of human behavior and the criminal justice system,” Andrew Cashmore suggests that penal systems based on moral responsibility have to be reformed because science has refuted the notion of free will (1). Brain imaging and other functional neuroscience methods have indeed been used not only to map neuronal covariates to behaviors but also to detect action potentials for simple movements hundreds of milliseconds before the conscious decision to act (2). Genetic factors have been shown to explain at least one half of the interindividual differences in the liability for criminality in different types of epidemiological study designs (e.g., adoption, twins, and family) (3), whereas molecular genetic studies indicate that no single genetic mechanism accounts for more than a couple of percentages of the variance in crime-related phenotypes (i.e., that the existence of one or a few “crime genes” can be discarded) (4). These facts are very useful. We now know that the chances to refrain from criminality are unfairly distributed and partly under the influence of constitutional susceptibility factors. Some of these, such as childhood hyperactivity and lead poisoning, have been identified in population-based epidemiological or clinical studies and may guide preventive efforts. Hopefully, this is just the beginning of a scientific endeavor to establish explanatory models and evidence-based, acceptable treatment for people at increased risk of aggressive antisocial behavior. Does it, however, have a bearing on moral responsibility and penal law?

Profile of Peter R. Grant

In 1940, as the Second World War escalated, 4-year-old Peter Grant was evacuated from London to a school in the English countryside on the Surrey–Hampshire border. Far from being traumatized by his sudden relocation, Grant, already a budding naturalist, remembers those years fondly. Peter Grant. “Our school was in the middle of fields with access to a little bit of forest,” he recalls. “I was just fascinated by the great big diversity of organisms that live in the outside world.” Safe from the destruction in London, Grant collected butterflies, watched birds, and identified flowers. This early experience helped shape his career in ecology and evolutionary biology, which has resulted in some remarkable accomplishments. Grant is now an emeritus professor and Class of 1877 Professor of Zoology at Princeton University (Princeton, NJ). He was elected to the National Academy of Sciences in 2007. Grant and his wife Rosemary, who was elected to the Academy in 2008, received the Kyoto Prize in Japan in December 2009. No strangers to international acclaim, the Grants are also members of the Royal Society of London, the Royal Society of Canada, and have won the Royal Society Darwin Medal, the Darwin-Wallace Medal of the Linnean Society, and the Balzan Foundation Prize. Grant’s Inaugural Article in the November 16, 2009 issue of PNAS details both the random and deterministic processes that can influence the development of a species (1). Grant and his wife observed the immigration in 1981 of a medium ground finch ( Geospiza fortis ) to Daphne Major, the small volcanic island in the Galapagos chain that has played host to much of the couple’s research. The lone bird was unusual in many respects; it sang an atypical song, was larger than similar birds, had a pointed, oversized beak, and contained alleles that marked it as a …

Profile of Arthur D. Riggs

A molecular biologist and pioneer in the field of DNA methylation epigenetics, Arthur Riggs was elected to the National Academy of Sciences in 2006. Riggs and his colleagues were the first to produce human insulin in Escherichia coli . He is also known for his work on mammalian DNA replication, protein-DNA interactions, and the production of recombinant antibodies. Arthur Riggs. Riggs has spent most of his career as a researcher, and later the director, at the Beckman Research Institute of the City of Hope National Medical Center, a National Institutes of Health sponsored cancer center in Duarte, California. His current work focuses primarily on mammalian epigenetics. Riggs’ Inaugural Article, published in the January 22, 2009 issue of PNAS (1), investigates genome-wide DNA methylation. Specifically, he and his colleagues examined at high resolution the pattern in DNA of 5-methylcytosine, an epigenetic mark formed by the enzymatic addition of a methyl group to cytosine in double-stranded DNA after replication. Among a number of possible functions, DNA methylation is thought to help pass information with high fidelity from parent cells to daughter cells, providing an information coding system in addition to that of the primary nucleotide sequence. These epigenetic marks are thought to lock genes in an inactive state and help stable maintenance of cell phenotype. In the article, the authors describe the DNA methylation pattern of the genome of a human B cell. Riggs conducted this work in collaboration with Gerd Pfeifer after stepping down from an eight-year stint as director of the Beckman Research Institute. Riggs was born in Modesto, in central California, to parents who lost their farm in the Great Depression and moved to San Bernardino in southern California. His mother, a nurse, encouraged his interest in biology and chemistry and gave him a chemistry set at age 10. …

Profile of Carolyn Bertozzi

Glycans, also known as complex sugars, can be engineered in any number of ways. They can be designed to glow, and illuminating the small molecules is a challenge accepted by Carolyn Bertozzi. Carolyn Bertozzi. Bertozzi, who was elected to the National Academy of Sciences in 2005, has spent much of her career devising methods to visualize glycans inside living organisms. Although glycans are critical participants in cell–cell adhesion and help mediate the mammalian immune system, the biopolymers are not directly genetically encoded and are therefore difficult to label using typical biochemical methods such as lectin and antibody labeling. The search for glycans in their natural environment has proven elusive even to Bertozzi, recipient of the prestigious MacArthur Fellowship in 1999, among a litany of other honors and awards. In her Inaugural Article, published in the January 6, 2009, issue of PNAS, Bertozzi and her coauthor Scott Laughlin demonstrate a process that images glycans inside living zebrafish embryos without perturbing the natural function of the target molecule (1). By adding small, biologically inert chemical reporters that get incorporated as the sugar is built, the method provides a functional handle for subsequent attachment of fluorescent probes via a chemical reaction that takes place inside the organism. Born in 1966, Bertozzi grew up in Lexington, Massachusetts. Her father, William, was a physics professor at Massachusetts Institute of Technology (MIT, Cambridge, MA). “Science was focus of the house,” she says. “We wore MIT T-shirts and went to MIT day camp.” When teachers asked Bertozzi and her two sisters what they wanted to be, Bertozzi remembers that their answers were “nuclear physicist.” Their father often asked where they were going to get their Ph.D.’s, Bertozzi recalls. “He had this idea that all three of us would go to MIT—a mixture of pride and the …

Profile of David J. Anderson

You are at a picnic and a wasp is circling. You swat it away, but it buzzes back again and again, more persistent each time. The wasp seems angry. Or is it? Can insects be “angry”? David J. Anderson believes that what we perceive as insect anger may share a foundation with human frustration or aggression. His model is Drosophila , which “has been such a powerful system for studying so many aspects of behavior,” he said, “that it's appropriate to ask whether flies have the building blocks of emotion.” “Insect emotion” is the latest focus of Anderson's group, which has previously worked on the developing nervous and circulatory systems. He enjoys the creative freedom of the pioneer, and his group is perpetually in transition to new fields. Anderson, a professor at the California Institute of Technology in Pasadena, was named to the National Academy of Sciences in 2007. “Aggressive behavior has a lot of negative consequences in society,” Anderson said. “People are concerned about the extent to which the origins of impulsive violence are genetic or environmental.” His inaugural article, published in the April 15, 2008 issue of PNAS, considers how the environment acts on a fly's genes during its lifetime to affect its level of aggression (1). Fruit flies, like other insects, exhibit aggressive behavior, which is perhaps related to territoriality and competition for mates. Drosophila aggression has been documented for nearly a century, but research into this topic has recently been reinvigorated, thanks to new work by Edward Kravitz, who for many years studied aggression in lobsters and who also taught Anderson during a summer neurobiology course in 1979. Across the animal kingdom, research has shown that males that mature in solitude tend to be more aggressive as adults than well-socialized individuals. Anderson's graduate student Liming Wang …

Profile of Jeffrey Ravetch

In his inaugural article, Ravetch and colleagues identified a receptor for sialylated Fc that stimulates anti-inflammatory pathways (1). The receptor could potentially be a useful therapeutic for many autoimmune diseases, according to the study.

Profile of Philip Cohen

Sir Philip Cohen, a biochemist elected as a foreign associate to the National Academy of Sciences in 2008, remembers the moment in his distinguished career when his studies in cell signaling and protein phosphorylation took off. The moment arrived during a 1978 seminar given by Thomas Vanaman at the University of Dundee (Dundee, Scotland, UK). At that time, Cohen had been working on the first kinase to be studied, phosphorylase kinase, which helps to regulate the breakdown of glycogen. Cohen had purified the kinase to study how it was regulated by cAMP and calcium, but he could not untangle the mechanisms by which calcium activated it. That afternoon, Vanaman spoke about work he had done on calmodulin, a calcium-binding protein and a known intermediary in calcium-regulated processes. Vanaman's descriptions of calmodulin—its small size and heat stability—gave Cohen a better idea of the perplexing faint blue smear that he had observed at the bottom of his polyacrylamide gels. Cohen had been so focused on the massive kinase subunits controlled by cAMP that he had missed the small protein that ran off the end of the gel. Philip Cohen Rushing back to his laboratory after Vanaman's seminar, Cohen prepared a different type of gel and identified a small band ahead of the dye front—a band that appeared even after the sample had been boiled, indicating the component was heat-stable. “Then I knew what the answer was going to be,” Cohen said. “This must be the missing component.” Shortly after, Cohen's hypothesis was confirmed: calmodulin mediated the action of calcium ions on phosphorylase kinase. Cohen has remained at the University of Dundee since 1971 and has worked on many areas of signal transduction, from protein phosphorylation to ubiquitination. His inaugural article, published in a recent issue of PNAS, identifies the phosphorylation sites on Pellino that activate this signaling protein that controls ubiquitination events in the innate immune system (1).