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Research Roundup

Law Students Draft a Criminal Code for Maldives

Some Penn Law School students will have a unique opportunity to help the Maldives rewrite its criminal code. The Maldives, a nation of 1,200 islands in the Indian Ocean, is in the process of reforming its criminal laws. The country's citizens are Muslim, and its current criminal code is based on the Islamic law Shari'a.  

Students in Dr. Paul Robinson's course, Seminar in Islamic Criminal Law: Drafting a Criminal Code For The Maldives, will study existing Maldivian criminal-law statutes and criminal-law principles under Shari'a. Some students will have the opportunity to travel to the Maldives with Dr. Robinson, Colin Diver Distinguished Professor of Law.  The United Nations is sponsoring the project to draft a criminal code in a modern format for the Maldivian government. "The thought occurred to me that, if I were a student, I would like to work on such a project, and that's how the idea for the seminar was born," Dr. Robinson said.  

"The Maldives does not allow the classic barbaric punishments of Shari'a, such as cutting off the hands of thieves or stoning adulterers to death. The country abolished the death penalty more than a half-century ago," Dr. Robinson said. "My goal is to help make their criminal code just. Since they are seeking advice on reforms, this is their goal as well. This will give them an alternative perspective and give them options that other parts of the world think are more palatable," Dr. Robinson said.

The criminal code draft is scheduled to be presented to the Maldivian government in early 2005.

Artificial Pores May Lead to a Future Full of Holes

In the August 12 issue of the journal Nature, Penn researchers detailed the creation of a library of small protein-like molecules that can self-assemble to form hollow corkscrew-like pores that could mimic pores seen in living systems. These molecules, formed from short chains of amino acids called peptides attached to tree-like fragments called dendrons, represent the first successful attempt at creating man-made pores that can form in solution and in bulk.

In nature, proteins that form hollow pores are ubiquitous to life, performing many essential tasks such as forming channels to cross cell membranes, generating chemical energy, guiding the shape of newly-made proteins and even puncturing holes in the cell walls of bacteria.

"The application of the technology could, for example, lead to better means of filtering drinking water from seawater or to an entirely new class of antibiotics by creating pores that poke holes in harmful bacteria," Dr. Virgil Percec, Roy & Diana Vagelos Professor of Chemistry, said.

Each peptide subunit has arm-like projections that allow it to bind to similar peptides in a spiraling fashion.  Held together by hydrogen bonds, the stable helix created by these peptides forms in such a way as to create a tube or channel, the width of which can be modified by using different combinations of amino acids.

The self-assembling peptides can form in and on the surface of microbial cell membranes, a breakthrough with enormous therapeutic potential. The ability to mimic the function of natural pores has long been a goal made very difficult by the complex chemistry of proteins. Life as we know it would not exist if it were not for the membranes that separate cells from the outside world. Likewise, cells would not exist without the protein pores to cross these membranes, importing substances necessary to sustain the cell and exporting wastes or products needed by other cells.

"It has come to our attention that, if we cannot precisely recreate the structure of proteins found in nature, then perhaps we can mimic their function and create new biologically inspired systems that achieve the same result," Dr. Percec said. Funding for the research was provided by the NSF and the Office of Naval Research.

Decoupling the Control of Brain Cancer Cells

When he's not in the operating room performing surgery, Dr. Donald M. O'Rourke,  associate professor of neurosurgery at the School of Medicine, is fighting brain tumors from the research laboratory bench. He and his colleagues are making inroads to understanding the basic molecular biology that makes brain tumors so hard to treat.

Most recently, Dr. O'Rourke and Dr. Gurpreet S. Kapoor, research associate in Dr. O'Rourke's laboratory, have discovered that two proteins sitting on the surface of cells are the interconnected switches for turning uncontrolled cell growth on or off in the brain and other tissues. These coupled proteins are the Epidermal Growth Factor Receptor (EGFR) and the Signal Regulatory Protein a 1 (SIRP a 1). They reported their findings in the September 15 issue of Cancer Research.

In past work, Dr. O'Rourke and colleagues found that if EGFR was activated, cancer cells tended to survive longer and migrate to unaffected parts of the brain to spread the cancer. In over 50% of glioblastomas—one type of brain cancer that is the leading cause of cancer-related deaths in males aged 20-39—too much EGFR is produced. In other glioblastomas, too much of a variant called EGFRvIII is also produced, which is linked to poor survival and resistance to treatment in some brain-cancer patients.

 "We believe that development of malignancy in the brain is not simply related to cell division; it's a combined process that involves cell division, cell survival, cell migration and movement, and ultimately angiogenesis—the building of new blood vessels in tumors," said Dr. O'Rourke. All four of these processes occur at the same time. Many of the conventional chemotherapies for brain tumors are directed at stopping cell division, which makes these therapies not completely successful.

Using human glioblastoma cells, they found that when another protein called SHP-2 is bound to EGFR, the cell goes into an overactive state, resulting in cancerous growth. However, when SHP-2 is bound to SIRP a 1, uncontrolled cell growth is stopped.

Dr. O'Rourke showed in earlier work that when SIRP a1 is activated in cancer cells it can inhibit cell growth and eventually kill them. In the present study, though, Dr. O'Rourke and Dr. Kapoor demonstrate that when EGFR is turned on, the genetic machinery to produce SIRP a1 is shut down, effectively bypassing the cell's natural ability to control unchecked growth. Another way a cancer cell circumvents the brakes on reproducing is to sequester SHP-2 away from SIRP a 1, so the cell keeps on dividing.

Many of the newer cancer therapies inhibit EGFR activation, which is an indirect way of treating cancer. Stimulating SIRP a1 may be a more direct way to stop cancer because that receptor is a naturally occurring way that the body inhibits cancerous growth. "We may then have a greater chance at beating brain cancer than by inhibiting EGFR in a cell that already has an abundance of EGFR in it," said Dr. O'Rourke.

This research was funded by the NIH, the Department of Veterans Affairs, and The Brain Tumor Society.

9/11 Search-and-Rescue Dogs Exhibit Few Effects

The search-and-rescue dogs deployed following the September 11, 2001, terrorist attacks have not suffered either immediate or short-term effects from exposure to the disaster sites, researchers from the School of Veterinary Medicine report. The findings, presented in the September 15 issue of the Journal of the American Veterinary Medical Association,  help relieve fears about the after-effects of working at the 9/11 sites. 

For the last three years, the researchers tracked the health of dogs and handlers from the World Trade Center, the Pentagon and the Fresh Kills Landfill site, where debris from the WTO was further searched.   

"Overall, the lack of clear adverse medical or behavioral effects among the 9/11 dogs is heartening, both for the animals and the human rescue workers," said lead researcher Dr. Cynthia M. Otto, associate professor of critical care. "Since dogs age more rapidly than humans, they can serve as sentinels for human disease. We are encouraged that we do not see significant increases in cancer and respiratory diseases."

The researchers compared the dogs to a control group of search-and-rescue dogs that were trained similarly but not deployed. Although there is no single registry of all dogs deployed to search the 9/11 sites, the researchers identified 212 deployed handlers, and 97 consented to participate.  

Despite rumors of numerous deaths of 9/11 search-and-rescue dogs, only one was confirmed to have died during the search period. In addition, the study was able to demonstrate that the injuries and ill effects of the search itself were minor. After the first year of surveillance, of the 97 deployed dogs enrolled in the study, only one died. During the past three years, 15 deployed dogs have died, of which eight had cancer. At the current time, neither the death rate nor the cancer rate is different from that of the control group. 

Initially, blood tests showed that the deployed dogs exhibited higher bilirubin concentration and alkaline phosphatase activity, which indicates that their livers were actively filtering toxins from their bloodstream. The serum globulins were also higher in the first year in deployed dogs, suggesting activation of the immune system. As the study progressed, however, these numbers came down to close to those of the dogs in the control group. 

Since there was a concern about airborne pollutants, such as asbestos, Dr. Otto and her colleagues also examined X-rays taken of the dogs. The examinations showed no apparent lung abnormalities. While it usually takes humans at least 20 years to develop mesothelioma after asbestos exposure—a major fear at all three sites—the shorter life span of dogs often means a relatively shorter latency period for developing cancer.    

To assess the psychological well-being of the dogs, their handlers were given questionnaires that focused on behavioral disorders, such as aggression or fearfulness, which may have arisen since 9/11. Here also the deployed dogs seemed similar to those of the control group.

Support for the study came from the AKC Canine Health Foundation, the American Kennel Club, Ralston Purina Co., the Veterinary Pet Insurance Co. and the Geraldine R. Dodge Foundation. The study also includes researchers at Michigan State University and the CDC in Atlanta.



  Almanac, Vol. 51, No. 4, September 21, 2004


September 21, 2004
Volume 51 Number 4


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