Among the most important and complex molecules in the human body, sugars control not just metabolism but also how cells communicate with one another. Graduating senior Jeffery Martin has put his basic knowledge of sugars to exceptional use by creating a lab-on-a-chip device that builds complex, highly specialized sugar molecules, mimicking one of the most important cellular structures in the human body — the Golgi Apparatus.

“Almost completely independently he has been able to come closer than researchers with decades more experience to creating an artificial Golgi,” said Robert Linhardt, the Ann and John H. Broadbent Jr. ‘59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer and Martin’s adviser. “He saw a problem in the drug discovery process and almost instantly devised a way to solve it.”

Cells build sugars in a cellular organelle known as the Golgi Apparatus. Under a microscope, the Golgi looks similar to a stack of pancakes. The strange-looking organelle finishes the process of protein synthesis by decorating the proteins with highly specialized arrangements of sugars. The final sugar-coated molecule is then sent out into the cell to aid in cell communication and to help determine the cell’s function in the body.

Martin’s artificial Golgi functions in a surprisingly similar way to the natural Golgi, but he gives the ancient organelle a very high-tech makeover. His chip looks similar to a miniature checker board where sugars, enzymes, and other basic cell materials are suspended in water and can be transported and mixed by applying electric currents to the destination squares on the checker board. Through this process sugars can be built in an automated fashion where they are exposed to a variety of enzymes found in the natural Golgi. The resulting sugars can then be tested on living cells either on the chip or in the lab to determine their effects. With the chip’s ability to process many combinations of sugars and enzymes, it could help researchers quickly uncover new sugar-based drugs, according to Martin.

Scientists have known for years that certain sugars can serve as extremely beneficial therapeutics for humans. One well-known example is heparin, which is among the most widely used drugs in the world. Heparin is formed naturally in the Golgi organelle in cells of the human body as well as in other animals like pigs. Heparin acts as an anticoagulant preventing blood clots, which makes it a good therapeutic for heart, stroke, and dialysis patients.

The main source of heparin is currently the intestines of foreign livestock and, as recent news reports highlight, the risk of contamination from such sources is high. So researchers are working around the clock to develop a safer, man-made alternative to the drug that will prevent outside contamination. A synthetic alternative would build the sugar from scratch, helping eliminate the possibility of contamination he explained.

“I am very grateful to have the privilege of working with Dr. Linhardt who has discovered the recipe to make fully synthetic heparin,” Martin said. “Because we know the recipe, I am going to use it as a model to test the device. If our artificial Golgi can build fully functional heparin, we can then use the artificial organelle to produce many different sugar variants by altering the combination of enzymes used to synthesize them. Another great thing about these devices is that they are of microscale size, so that if needed we could fill an entire room with them to increase throughput for drug discovery.”

There are millions of possible sugar combinations that can be formed and scientists currently only know the function of very few of them like heparin. “Since it is known that these types of sugars play a part in many important biological processes such as cell growth, cell differentiation, blood coagulation, and viral defense mechanisms, we feel that that this artificial Golgi will help our team to develop a next generation of sugar-based drugs, known as glycotheraputics,” Martin said. “We are going to start making new combinations and we simply don’t know what we are going to find. We could find a sugar whose signal blocks the spread of cancer cells or initiates the differentiation of stem cells. We just don’t know.”

Martin, a Barry M. Goldwater Scholar and native of the small town of Boylston, Mass., is graduating from Rensselaer on May 17, 2008 with a nearly perfect GPA. He plans to continue on at Rensselaer as a graduate student, working with Linhardt to test and further develop his artificial Golgi.

[Gabrielle DeMarco @ Rensselaer Polytechnic Institute]

Berkeley Lab has signed a collaboration agreement with Tensilica, Inc. to explore the use of Tensilica’s Xtensa processor cores as the basic building blocks in a massively parallel system design. Tensilica’s Xtensa processor is about 400 times more efficient in floating point operations per watt than the conventional server processor chip shown here.

In a paper published in the May issue of the International Journal of High Performance Computing Applications, Michael Wehner and Lenny Oliker of Berkeley Lab’s Computational Research Division, and John Shalf of the National Energy Research Scientific Computing Center (NERSC) lay out the benefit of a new class of supercomputers for modeling climate conditions and understanding climate change. Using the embedded microprocessor technology used in cell phones, iPods, toaster ovens and most other modern day electronic conveniences, they propose designing a cost-effective machine for running these models and improving climate predictions.

In April, Berkeley Lab signed a collaboration agreement with Tensilica, Inc. to explore such new design concepts for energy-efficient high-performance scientific computer systems. The joint effort is focused on novel processor and systems architectures using large numbers of small processor cores, connected together with optimized links, and tuned to the requirements of highly-parallel applications such as climate modeling.

Understanding how human activity is changing global climate is one of the great scientific challenges of our time. Scientists have tackled this issue by developing climate models that use the historical data of factors that shape the earth’s climate, such as rainfall, hurricanes, sea surface temperatures and carbon dioxide in the atmosphere. One of the greatest challenges in creating these models, however, is to develop accurate cloud simulations.

Although cloud systems have been included in climate models in the past, they lack the details that could improve the accuracy of climate predictions. Wehner, Oliker and Shalf set out to establish a practical estimate for building a supercomputer capable of creating climate models at 1-kilometer (km) scale. A cloud system model at the 1-km scale would provide rich details that are not available from existing models.

To develop a 1-km cloud model, scientists would need a supercomputer that is 1,000 times more powerful than what is available today, the researchers say. But building a supercomputer powerful enough to tackle this problem is a huge challenge.

Historically, supercomputer makers build larger and more powerful systems by increasing the number of conventional microprocessors — usually the same kinds of microprocessors used to build personal computers. Although feasible for building computers large enough to solve many scientific problems, using this approach to build a system capable of modeling clouds at a 1-km scale would cost about $1 billion. The system also would require 200 megawatts of electricity to operate, enough energy to power a small city of 100,000 residents.

In their paper, Towards Ultra-High Resolution models of Climate and Weather, the researchers present a radical alternative that would cost less to build and require less electricity to operate. They conclude that a supercomputer using about 20 million embedded microprocessors would deliver the results and cost $75 million to construct. This “climate computer” would consume less than 4 megawatts of power and achieve a peak performance of 200 petaflops.

“Without such a paradigm shift, power will ultimately limit the scale and performance of future supercomputing systems, and therefore fail to meet the demanding computational needs of important scientific challenges like the climate modeling,” Shalf said.

The researchers arrive at their findings by extrapolating performance data from the Community Atmospheric Model (CAM). CAM, developed at the National Center for Atmospheric Research in Boulder, Colorado, is a series of global atmosphere models commonly used by weather and climate researchers.

The “climate computer” is not merely a concept. Wehner, Oliker and Shalf, along with researchers from UC Berkeley, are working with scientists from Colorado State University to build a prototype system in order to run a new global atmospheric model developed at Colorado State.

“What we have demonstrated is that in the exascale computing regime, it makes more sense to target machine design for specific applications,” Wehner said. “It will be impractical from a cost and power perspective to build general-purpose machines like today’s supercomputers.”

Under the agreement with Tensilica, the team will use Tensilica’s Xtensa LX extensible processor cores as the basic building blocks in a massively parallel system design. Each processor will dissipate a few hundred milliwatts of power, yet deliver billions of floating point operations per second and be programmable using standard programming languages and tools. This equates to an order-of-magnitude improvement in floating point operations per watt, compared to conventional desktop and server processor chips. The small size and low power of these processors allows tight integration at the chip, board and rack level and scaling to millions of processors within a power budget of a few megawatts.

Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our Website at www.lbl.gov.

[Ucilia Wang @ DOE/Lawrence Berkeley National Laboratory]

But it’s not just weight gain that poses a risk. People who are underweight also have an elevated risk of dementia, unlike people who are normal weight or overweight.

US researchers carried out a detailed review of 10 international studies published since 1995, covering just over 37,000 people, including 2,534 with various forms of dementia. Subjects were aged between 40 and 80 years when the studies started, with follow-up periods ranging from three to 36 years.

The review, which included studies from the USA, France, Finland, Sweden and Japan, also included a sophisticated meta-analysis of seven of the studies, published between 2003 and 2007 with a follow-up period of at least five years.

All kinds of dementia were included, with specific reference to Alzheimer’s Disease and to vascular dementia — where areas of the brain stop functioning because the blood vessels that supply them are damaged by conditions such as high blood pressure or heart disease.

“Our meta-analysis showed that obesity increased the relative risk of dementia, for both sexes, by an average of 42 percent when compared with normal weight” says Dr Youfa Wang, Associate Professor of International Health and Epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore.

“And being underweight increased the risk by 36 percent.

“But when we looked specifically at Alzheimer’s Disease, the increased risk posed by obesity was 80 percent. The increased risk for people with vascular dementia was 73 percent.

“The risks were greater in studies where sufferers developed Alzheimer’s Disease or vascular dementia before the age of 60 or in studies with follow-up periods of more than 10 years.

“We also found that obesity was more likely to be a risk factor for women when it came to developing Alzheimer’s Disease and for men when it came to vascular dementia.”

The authors estimate that 12 percent of the dementia risk in the study population could be attributed to obesity, with this rising to just over 21 percent in patients with Alzheimer’s Disease.

It’s estimated that up to 10 percent of people aged 65 or more suffer from some form of dementia and two-thirds of those have Alzheimer’s Disease.

“There has been controversy about the links between obesity and dementia for a number of years, but previous findings have been mixed and inconclusive” says Dr Wang.

“The advantage of carrying out a meta-analysis is that it provides researchers with access to a large number of study subjects and it is possible to iron out the inconsistencies and come to overarching conclusions.

“Our detailed analysis clearly shows a U-shaped relationship between weight and dementia, with people who are obese or underweight facing a greater risk.

“We believe that our results show that reducing the prevalence of obesity is a promising strategy for preventing the progression of normal ageing into Alzheimer’s Disease.”

[Annette Whibley @ Wiley-Blackwell]

Professor Downing found that constructed ponds and lakes on farmland in the United States bury carbon at a much higher rate than expected; as much as 20-50 times the rate at which trees trap carbon. In addition, ponds were found to take up carbon at a higher rate than larger lakes.

“Aquatic ecosystems play a disproportionately large role in the global carbon budget,” Downing said. “Despite being overlooked in the past, it’s small bodies of water that are important because they take up carbon at a high rate and there are more of them than previously thought. The combined effect is that farm ponds could be burying as much carbon as the world’s oceans, each year.”

Ponds capture carbon in two main ways:

The research estimated there are 304 million natural lakes and ponds in the world, covering an area of 4.2 million square kilometers, twice the area previously thought. As many as 90 percent of these water bodies are one hectare (two acres) or less in area.

Downing’s research team published its most recent findings in the Feb. 15 issue of the journal Global Biogeochemical Cycles in a paper titled, “Sediment organic carbon burial in agriculturally eutrophic impoundments over the last century.” The team included members from Europe, the United States and Canada. The work was sponsored by the National Center for Ecological Analysis and Synthesis and the Iowa Department of Natural Resources.

Downing has presented invited seminars on this research to the International Society of Limnology, the American Society of Limnology and Oceanography, and at several major research institutions in North America and Europe. Most recently, he was invited to discuss his research by the Pond Conservation, a charity in the United Kingdom dedicated to creating and protecting ponds and the wildlife they support. He will spoke today at University College London. An upcoming presentation is scheduled for the annual meeting of the European Pond Conservation Network in Valencia, Spain.

Jeremy Biggs, Pond Conservation director of policy and research, said the research has exciting implications. “It may be that ponds will be the modern equivalent of the swamps that formed coal in the past. But before we all rush into making ponds to trap carbon we need to do some basic research here in the UK. If the rate of carbon uptake in ponds in Europe is the same as that found in the USA study, we may well have discovered an important new natural way of trapping carbon,” he said.

Downing’s ongoing research, partnering with the United States Geological Survey, and his contributions to the Iowa Lakes Survey will investigate the role of small Iowa lakes in the absorption of atmospheric carbon dioxide and other important gases such as methane.

[John Downing @ Iowa State University]