Volume 14,3


SECRETS OF MICROBIAL PATHOGENS
Yale, UConn Launch New Research Center for Study of
Bacteria, Viruses and Protozans

Microbial pathogens—bacteria, viruses, protozoans—can be divided into two categories, says Yale professor of microbiology Jorge Galán. The first, which includes the virus that causes rabies, we encounter by chance. This kind will hurt us, maybe kill us. That’s because we’re unimportant to them. They don’t need us to survive, they don’t seek us out, and, indifferently, they’ll cause us to die.

But the second kind of pathogen has lived and evolved with us. They may cause some self-limiting illnesses, but they don’t usually hurt us badly. They don’t ‘want’ to hurt us: that doesn’t help them. They prefer for us to be fruitful and multiply. To this kind of pathogen, we’re very important. We are their home.

And just as we control our homes—flipping switches to bring light, turning thermostats to increase warmth—these bacteria control us, to benefit themselves. Take Salmonella. The diarrhea it induces is, to us, an inconvenience. But to the pathogen, it’s an important way to move from one host to another. (Salmonella travels by a fecal-oral route.) Microbial pathogens survive, says Galán, because they have learned to manipulate the normal processes of the host cell, subverting them to achieve the pathogens’ own ends.

Salmonella: Secrets of a Trickster

Galán, who heads Yale’s newly created Section of Microbial Pathogenesis, specializes in deciphering the tricks of Salmonella. These bacteria, he explains, have evolved the ability to invade the cells of the intestinal lining. They do this by inducing a process called phagocytosis, which compels host cells to engulf (swallow) the bacteria. Normally phagocytosis occurs only in “professional phagocytes”—immune system cells that engulf pathogens in order to destroy them. “Non-phagocytic cells” says Galán, “would not normally pick up particles this size of bacteria. It just simply does not happen.”

But Salmonella, Galán has shown, produces proteins that manipulate the host cell. One forces a reorganization of the cell’s internal structure. It causes “ruffling” of the cell membrane, making it bubble and emit pseudopods. Another stabilizes the pseudopods so they last longer, and shoot out farther. That’s an obvious advantage to Salmonella, explains Galán. “Now that you have pseudopods that are more stable, that can travel outwards, they can embrace more bacteria and internalize them.”

But just producing proteins is not enough. The bacteria must also deliver them to their destination. It’s a significant problem. Merely moving the proteins out of Salmonella is tricky: they must cross two membranes, the space between the membranes, and a blanket of molecules known as the peptidoglycan layer.

Salmonella does this through an intricate piece of cell machinery known as the type III secretion system. Discovered by Galán, it consists of a hollow, needle- like structure that emerges from the bacterial cell and is anchored to its membranes by a cylindrical base. The proteins leave the pathogen by traveling up the center of the needle; it’s not yet clear how they enter the host cell. “We don’t think the needle actually pokes into the host cell,” said Galán. “There are other, more sophisticated ways that this apparatus may work.” Proteins could, for example, be delivered by a thread-like bridge of molecules that assembles on the surface of Salmonella once it touches the host cell. But there may be other possibilities, and “it’s going to take quite a bit of work to figure it out,” concedes Galán.

The secretion system, which was isolated only last year, is surprisingly widespread. It appears to have evolved from flagella—whip-like organelles that bacteria use to propel themselves. The architecture of the two, says Galán, is very similar: both, for example, attach to the cell membrane by four rings.

“In the beginning, we didn’t suspect this system was going to be as general as it is,” said Galán. “But many labs, working with many different pathogens, began to encounter these things.” The type III system, he says, is found in bacteria that attack plants as well as those that invade animals. “This strategy—not necessarily the strategy of invading cells, but the strategy of injecting proteins into the host cell—is very common. Each bug has evolved different proteins that they want to inject into the cells, and you’d expect that, because the types of diseases are different.” And if these bacteria each uses the type III system to alter host cells in their own unique way, well, even bacteria have individual needs.

So do protozoan parasites.

Trypanosomes, protozoan parasites found mostly in South and Central America, are transmitted by crawling bugs that live in the walls of mud huts. Opossums and armadillos serve as primary hosts, but trypanosomes can infect humans and when they do, they bring Chagas’ Disease, which causes heart defects, nervous system defects, esophagus and muscle enlargements, and death.

Like Salmonella, trypanosomes reproduce inside vertebrate cells. But they’ve evolved a different solution to the problem of getting in. They’re about ten times as large as Salmonella, explains Dr. Norma Andrews, a cell biologist at the Section of Microbial Pathogenesis at Yale, who studies the parasite. That means they can’t be engulfed as easily by the ruffling trick. Instead, trypanosomes make use of host cell organelles called lysosomes.

This is unexpected, because lysosomes, which contain digestive enzymes, usually destroy pathogens. But somehow, trypanosomes use lysosomes to form a vacuole—bubble—in which they enter the host cell. The process, says Andrews, works like this: the parasite attaches to the outside of the host cell, producing a signaling molecule that raises the calcium concentration in the host cell. The lysosomes, which normally cluster around the cell nucleus, respond by moving to the cell membrane. They fuse with the membrane; the parasite slides into that spot, and within a short time the parasite has moved into the cell, inside a vacuole whose outer layer consists of former lysosomal membranes.

So what just happened here? Why did the lysosomes move to the edge of the cell? Why did they fuse with the cell membrane? How did the parasite move inside?

Oddly, says Andrews, most of this process seems to be part of the cell’s normal functioning. “All the parasite does is provide the signal that triggers the calcium elevation,” she explains.

Calcium is key. It’s used to initiate many cellular activities, from contracting muscles to transmitting nerve impulses. Andrews has recently shown that one function is to send lysosomes to the cell membrane, where they “exocytise”—fuse with the cell membrane and dump their contents outside the cell. Calcium, she says, may be acting at many steps, including rearrangement of the actin cytoskeleton and regulation of microtubule “motors,” which influence the movement of lysosomes either toward the cell nucleus, or away from it.

We believe, she says, that signals from the trypanosomes start the exocytosis process, which proceeds to the point that lysosomal membranes begin to fuse with the cell membrane. But as the parasite moves into those part-melded membranes, it apparently disrupts the process, and the motor pulls the membranes back into the cell, dragging the parasite along. “Otherwise,” she says, “it’s hard to understand why these lysosomes don’t just fuse with the plasma membrane, release their contents, and the parasite stays outside.”

But why would calcium cause lysosomes to move to the cell membrane?

“This is something we are very interested in,” says Andrews, “why this pathway of lysosome exocytosis exists.” She suspects it may be a way of repairing membrane punctures. “People have known for years that intracellular vesicles migrate to the site of damage on the membrane, and they fuse, and basically patch the hole. But nobody has determined what these vesicles are.” She believes they are lysosomes.

When a cell membrane ruptures, she says, the first thing that happens is that calcium pours into the cell, elevating calcium levels and causing lysosome exocytosis. “Putting these things together, we think that lysosomes are really the most important organelles in this process of lesion repair.” The cell, she suggests, responds to increased calcium by sending lysosomes to seal a hole.

The parasites take advantage of this response. By triggering a calcium flow, says Andrews, they trick the cell. “They could be making the cell think that this is a lesion on the plasma membrane and to mobilize lysosomes to fix it. This is just speculation,” she adds, “But it’s one of my favorites.”

Legionella: “A New Family of General Secretion Apparatuses”

But lysosomes are not usually helpful to invading pathogens: as mentioned earlier, they normally destroy them. The process works like this: immune system phagocytes engulf pathogens, trapping them in vacuoles called phagosomes. Lysosomes fuse with the phagosomes, releasing digestive enzymes which destroy the pathogens inside.

Some pathogens, though, live within phagosomes, which at least are easy to enter. The task for these pathogens is keeping lysosomes at bay. Legionella pneumophila, the bacteria responsible for Legionnaires’ Disease, succeeds in this: somehow, the bacteria blocks phagosome-lysosome fusion. Dr. Craig Roy, also of Yale’s Section of Microbial Pathogenesis, hopes to learn why.

Like Salmonella, Legionella seems to create a secretion system that delivers molecules that affect the host cell. “It appears to belong to a new family of general secretion apparatuses,” says Roy—one somehow related to the conjugal (cell-to-cell) transfer of DNA. The prototype, he explains, is found in the plant pathogen Agrobacterium tumefaciens. Known as the VirB system, it moves extrachromosomal DNA molecules from the bacteria into plant cells, where they produce enzymes that lead to unregulated growth of the infected plant cells, resulting in a tumor. The Legionella system contains proteins similar to those found in the VirB system, and this, he says, indicates that the transfer apparatus is related.

In fact, Roy and his colleagues have found that under some laboratory conditions, the Legionella system transfers plasmid DNA to other bacteria. There’s no evidence, though, that this happens in the real world. “We think that this system originally developed from a DNA conjugation system,” he explains. “However, the DNA substrates may have been stably incorporated into the bacterial genome, and the secretion system has been modified in such a way that the principle substrates are now protein molecules.”

Roy and his colleagues are investigating exactly how the system prevents phagosome-lysosome fusion. They know that when a bacterium comes into contact with the host cell, it produces a pore on the host’s surface membrane. They know that this pore stays in the membrane when it pinches off the surface of the host to become the membrane of the phagosome in which the bacterium will reside. They believe there must be a protein that blocks lysosome fusion, and consider it likely that the pore facilitates delivery of that protein into the host cell cytoplasm.

Though they have not yet identified the protein, they have some idea of its effect. It could, says Roy, neutralize a critical cellular protein required for fusion. “If Legionella can send into the host cell some sort of enzyme, or molecule, that can inhibit the function of normal cellular proteins, it could block the delivery of the phagosome to the lysosome.”

Or it might disguise the phagosome. In order for the lysosome and phagosome to fuse, Roy explains, there must be a receptor on the phagosome membrane that accepts only lysosomes. “What Legionella could potentially do is put something on the surface of the phagosome that would be a receptor for some other organelle.” By promoting the fusion of the phagosome with another organelle, Roy explains, Legionella could prevent the phagosome’s fusion with lysosomes.

Tell-Tale Sign of an Invader

Pathogens manipulate cells. But they don’t have it all their own way. They carry with them a tell-tale sign showing that they are intruders. In Borrelia burgdorferi, the spirochetal bacterium that causes Lyme Disease, that sign is a family of molecules called lipoproteins, which are found in the pathogen’s cell membrane. One lipoprotein, Outer Surface Protein-A (OspA), serves as target for the recently-released Lyme Disease vaccine: the vaccine “teaches” the immune system that anything presenting OspA should be destroyed.

But it’s not enough for pathogens to simply carry a sign. Somehow, the immune system must notice it. Dr. Justin Radolf, who heads the recently formed Center for Microbial Pathogenesis at the University of Connecticut Health Center (UCHC), and his colleagues, have been analyzing the way this happens.

Once again, it’s a question of signaling across membranes. The immune system macrophages—a type of phagocyte—possess a molecule on their outer surface cell membrane known as CD14. It’s a receptor, able to bind all sorts of bacterial products, including lipoproteins, explains Radolf. Researchers, he says, have known for a while that CD14 was important in starting an immune response, “because if you get rid of CD14, say, in a [genetically-mutated] mouse, you don’t get the response, or it’s much diminished.” But, he adds, they knew that CD14 couldn’t work alone, because, while it’s attached to the outside of the membrane, it doesn’t go through.

He and other investigators showed that after lipoproteins get picked up by CD14, they get passed to a protein known as Toll-like receptor 2 (TLR2). It is TLR2 that transmits information about the lipoproteins through the membrane. The lipoproteins themselves stay outside. But when one attaches to TLR2, TLR2 reconfigures itself—changes its shape—in a way that allows it to interact with a particular type of molecule inside the cell. That molecule interacts with other molecules, and so on—a cascade of reaction ultimately resulting in the activation of the immune system.

Interestingly, Toll-like molecules are also found in fruit flies. In Drosophila, explains Dr. Timothy Sellati, a cellular immunologist at the University of Connecticut Health Center, they serve as “a very primitive form of our own innate immune system.” It’s probable, he says, that ticks have Toll receptors also: like Drosophila, they are arthropods. But, for some reason, he says, the immune system of the unfed tick does not seem to attack Borrelia.

“We’re very interested,” says Radolf, “in understanding how the spirochetes adapt to their different [tick and mammalian] environments.” It’s important, he says, for two reasons: to understand the disease, and to find new vaccine targets. For example, OspA—the vaccine target—is only produced by Borrelia when it is inside the tick. This means that the antibodies developed by the vaccine only destroy the spirochete while it’s within the bug, as it is feeding on its victim. Once the spirochete enters its human host, it stops producing OspA, and begins instead to generate other molecules, for example, OspC. “By understanding this host adaptation process,” says Radolf, “we hope we’ll identify new targets on the surface of the spirochete.”

He believes it may even be possible to develop a vaccine against the tick itself. “When ticks feed,” he says, “they secrete saliva into the feeding site, and the saliva is loaded with proteins—enzymes that do all kinds of things, and are needed for the feeding process.” So, he says, “if we can figure out what those enzymes are, and how to neutralize them, we could interfere with feeding.” Such a vaccine would be important because ticks carry more than one illness. In addition to Lyme disease, they harbor babeosis and ehrlichiosis. An anti-tick vaccine could eliminate transmission of all three diseases at one stroke.

Even without the diseases, tick feeding causes significant problems; when animals are seriously bitten by ticks, the blood drain can be damaging. “In Africa,” says Radolf, “there are countries where they can’t even raise large animals for protein sources, because the tick problems are so severe.”

A Revolution in Microbe Research

Both Galán and Radolf cite increased occurance of infectious diseases as the reason UConn and Yale have established groups focusing on microbial pathogens.

Back in the 1970s or so, explains Galán, many regarded infectious diseases as a thing of the past. Antibiotics seemed to be taking care of emerging bacterial problems, and scientists turned their attention to a major push to fight cancer. But since then, the number—and seriousness—of infectious diseases has soared. Antibiotics selected for the growth of resistant organisms; improvements in medical technology created newly vulnerable populations; lifestyle changes brought people into contact with pathogens never encountered before.

But our tools for battling pathogens have kept pace. We are, says Galán, in the midst of a revolution in the acquisition of knowledge about microbes. “For example, within the next couple of years, we’ll probably know the DNA sequence of the genomes of most of the important microbial pathogens.”

It’s an exciting time, he says, in the field of microbial pathogenesis. Not least because, as he notes, talking about his Salmonella: “The biology is beautiful.”—Karen Miller, science writer.


From Transplants to Implants, UConn Reports Advances in Biomaterials Technology amd Tissue Engineering

Transplants of functional insulin-producing tissue, liver tissue, or heart muscle; scaffolds for the regrowth of damaged tissues; replacements for damaged eyes, ears, or noses -- many of these will someday be available to treat various diseases or disorders. Tissue engineering, the development of biological substitutes that restore, maintain or improve tissue function, is a field that combines aspects of cell biology, polymer chemistry, and chemical engineering, with the potential to provide new therapies for many and varied medical conditions. Tissue-engineered medical products and biomaterials comprise almost any medical implant one could imagine, including skin replacements, vascular grafts, bone and cartilage grafts, dental applications, implants to replace or enhance the function of the liver or pancreas, and cell therapies for the treatment of neurodegenerative diseases.

The University of Connecticut Health Center (UCHC), recognizing the potential for this field, has developed a strong research group within the Center for Biomaterials. In 1994, in response to a strategic planning effort at UCHC, Dr. Jon Goldberg, professor and director of the Center for Biomaterials, proposed that the university expand its research in biomaterials and tissue engineering. As a result, three new faculty positions were created and have been filled over the last three years. These new faculty members have initiated their own programs, and have begun to collaborate with other researchers at both the Farmington and Storrs campuses. Two additional faculty slots have recently been established, for which the Center is seeking individuals who can integrate the biological, engineering, and clinical aspects of these complex problems.

Biomaterials: Solutions for Diabetes

Insulin-dependent diabetes is a serious disease—when the pancreas fails to produce enough insulin, levels of sugar in the blood increase. People with diabetes can develop serious complications, such as blindness, kidney damage, and loss of fingers or toes because of poor circulation.

The development of a glucose-responsive insulin pump has been the goal of researchers for many years. One problem with insulin pumps is how to determine when the person needs another injection of insulin—a glucose sensor works in conjunction with the pump, telling the pump when the person’s glucose levels are too high and insulin is needed. Dr. Francis Moussy, assistant professor in the Center for Biomaterials, is working on a totally implantable sensor for glucose. This work is supported in part by grants from the Juvenile Diabetes Foundation.

An implantable glucose sensor would continuously monitor the glucose levels in the person’s body. “The device will be implanted under the patient’s skin,” says Moussy. “It will measure the glucose levels in the subcutaneous tissue, not directly in the blood. We have found that subcutaneous glucose levels parallel blood levels, with about a three-minute lag. One benefit of putting the sensor under the skin rather than in the bloodstream is that it will not promote clot formation, which is a big problem with anything implanted directly in the blood.”

The idea of an implantable glucose sensor is not new. According to Moussy, researchers have been working on this for about 30 years. “The sensor portion and the electronics are pretty well worked out,” he says. “The problem has always been with biocompatibility -- the tissue reaction to the implant. Whenever you put a foreign material in the body the cells around it form a scar, which can impair the ability of the sensor to function.” Moussy has a $1-million grant from the National Institutes of Health (NIH) to try to improve the biocompatibility of the glucose sensor he has been developing. Working with colleagues in the University of Connecticut’s Institute of Materials Science, the university’s school of pharmacy at Storrs, and the department of pathology at the UCHC, he is trying to increase the lifetime of the sensor by using materials that will control the tissue reaction to the implanted sensor.

“We have good results in in vitro tests,” says Moussy. “Our first prototype responds in about 30 seconds to changes in glucose levels. We are working to make the device smaller. We also have to test the biocompatibility of the new coatings in animals, and then we will test the glucose responsiveness. It will be a while before this type of device is used commonly … but we hope that soon we will have solved the problem of biocompatibility …”

Bacteria and Infections

Creating a normal healing tissue response to an implanted material is not the only goal of biomaterials research. “Both indwelling and subcutaneous biomedical implants and devices are potential sites for microbial infections,” says Dr. James D. Bryers, professor at the Center for Biomaterials. “It is very important to be able to control inflammation, the immune response, and infection in indwelling devices. Also, a number of biomedical systems (blood oxygenators, tracheal lavage, dental water units, and dialyzers) and engineered tissues are all susceptible to bacterial contamination.”

Bacterial colonization and subsequent infections can develop with a variety devices including catheters, peritoneal dialysis shunts, urinary catheters, hip replacements, vascular grafts, heart valves, contact lenses, and dental implants. Once the bacteria, which can colonize the device either before or after implantation, adhere to a surface, they genetically “up-regulate” a number of unique genes that alter their phenotype from their non-adhering cousins. This allows them to synthesize and secrete a number of very small signal molecules, which in turn prompt the bacteria colony to secrete insoluble polysaccharidic polymers. These polymers combine with the bacteria cells to create a three-dimensional matrix known as a biofilm.

Biofilm-bound bacteria have many ways to avoid the host immune system, according to Bryers: they can be “hidden” from antibody and complement factor recognition and subsequent white blood cell phagocytosis; they can modulate cytokine synthesis; and they can interrupt production of antibodies via synthesis of superantigens. The biofilm matrix, he notes, also serves to diffuse antimicrobial agents such as disinfectants and antibiotics; consequently, it requires a significantly higher concentration of chemical toxin to kill bacteria in the biofilm than to kill free-floating bacteria. “We are also discovering that mass transfer resistances are not the only reason that antibiotics are so ineffective against biofilm-bound microbes. Biofilm-bound microorganisms are physiologically less susceptible to such chemical treatments,” explains Bryers.

Up until now, efforts to prevent or reduce the likelihood of bacterial colonization and subsequent infection have involved either altering the surface chemistry of the basic biomaterial (by using different base materials or by coating a base material with a second chemical possessing the desired properties), or by allowing the biomaterial from which the device is made to release a chemical agent (an antibiotic or disinfectant) designed to kill the incoming bacteria. None of these efforts has been very effective at preventing microbial infection of devices, according to Bryers.

Now, however, researchers are pursuing several promising new approaches. In one development, UConn’s Bryers, working with colleagues from the University of Washington (UW), has been able to modify the standard polymer Biospan™ (poly ether urethane) -- a material used in large quantities in the biomaterials industry -- to release over a sustained period of time an antibiotic that would be lethal only to bacteria within a near region (2-5µm) around the device. Most polymers release any antibiotic chemical very rapidly; since the drug is of such low molecular weight; the technology developed by Bryers and the UW team represents the first sustained-release of such a small molecule. In vitro studies of the materials show that they are very effective at preventing bacterial adhesion for time periods up to two months.

In the course of the poly ether urethane project, Bryers and his colleagues also discovered a polymer coating technology that by itself altered the surface chemistry of the base polyurethane and prevented bacterial adhesion, without any need for the release of the toxic antibiotic. The coating process is currently being optimized, and long-term efficacy against bacterial colonization is being evaluated.

Finally, in an attempt to avoid the use of toxic chemicals altogether, Bryers’ team is exploring the use of biological means to interfere or interrupt the process of adhesion and biofilm formation. “There are a number of ways bacteria and yeast bind to and form biofilms at surfaces. A number of these processes are moderated by very specific receptor:ligand molecule binding events. An example is the binding of the bacterium Staphylococcus epidermidis, a major infective agent of cardiovascular devices, by way of specific membrane bound receptor molecules to the blood-plasma protein fibronectin, which absorbs rapidly to implanted materials. What we are investigating are a number of ways to interfere or block these specific receptor:ligand bonding events. Thus, we intend to prevent adhesion without necessarily killing the infective agent,” says Bryers. “These anti-adhesion molecules can be either released directly from the biomaterial or we are also investigating a gene therapy approach that would release from the biomedical implant surface not the anti-adhesion molecule itself but rather the genetic material required for incoming mammalian cells to synthesize this molecule. In this way, we avoid any limitations in the amount of therapy placed in the biomaterial.”

“We are talking with several companies about developing these approaches for use with their products,” says Bryers. “The approaches we have been working on are all specific for one type of bacterium or one material. Companies would love a more general approach -- something they can use with all devices, but right now all we have are the specific ones.”

Scaffolds for Tissue Regrowth

The basement membrane is a supporting structure between epithelial cells and the underlying connective tissue. It is composed of proteins such as collagen and elastin, glycoproteins such as laminin, and proteoglycans such as heparan sulfate. The primary function of the basement membrane is to support the epithelial cell layer -- collagen gives it considerable tensile strength. At the same time, it is flexible enough to permit stretching and recoil in epithelial cell layers lining organs. The basement membrane also provides cell-binding sites for specialized epithelia and acts as a sieve, filtering out molecules based on their size, shape, and electrostatic charge.

According to Dr. Steven L. Goodman, assistant professor at the Center for Biomaterials and the department of physiology, the basement membrane differs considerably between tissues, and it is important to understand these differences if one is going to build a scaffold to which cells will attach. “The texture of the matrix varies depending on the physical load normally applied to the cells,” he explains. “Skin cells experience much more of a load than do the epithelial cells of the cornea. As a result, the basement membrane underlying the skin is more densely packed than that underlying cells of the cornea.”

“Epithelial cells don’t just lie on top of the basement membrane,” continues Goodman. “They interdigitate into the structure -- that is, they send small projections right into the basement membrane. The degree of interdigitation also varies depending on where in the body the tissue is. Skin cell interdigitations are on the order of several microns in size, while those in the cornea are about 100 nanometers in size -- a difference of up to 1000 times.”

How does Goodman know this? He uses direct scanning electron microscopy to image the structure and then a technique similar to lost wax casting to replicate the topography of the basement membrane. “This is a technique that has been around for thousands of years,” he explains. “We have modified this ancient technique so that we can pick up very small structures in living tissues. We use a resin to cast a mold of the basement membrane from different tissues. We then use that mold to produce a precise replica of the structure -- we can get resolution on the order of 100 nm.”

Goodman’s group is using this technique to characterize the morphology of the basement membrane and the underlying extracellular matrix. “We need to understand the biological structures to provide a rational basis for making scaffolds to interface with biological systems,” he says. His group is making scaffolds for various tissue-engineering applications using these replicas. “We are currently doing in vitro cell biology experiments with corneal cells and have very promising results,” he says.

The molding technique provides excellent resolution, but has some limitations in terms of scale up for manufacturing and control of the chemistry, according to Goodman. “We are currently working out the details of a free-form fabrication technique,” he says. “We can build the scaffolds layer by layer using a confocal microscope with multiphoton optics. We can also deposit biological molecules into the structure as it is being built.” Using this technique, Goodman hopes to be able to build scaffolds that have enzymes or attachment factors incorporated into the matrix, or to provide controlled release of factors that can influence the cell biology. Goodman’s research is funded by the National Heart, Lung, and Blood Institute and the National Eye Institute.

Engineering of Bone Tissue

Bone may look like a hard, inert substance, but in reality it is a tissue composed of living cells, fibers, and ground substance. What makes it different from other tissues is that the extracellular substance is calcified, making bone hard and strong. As with soft tissues, the cells in bone interact with implant materials in ways that can make the medical device implant either a success or a failure.

According to Dr. Gloria Gronowicz, director of orthopedic research and associate professor in the department of orthopedic surgery, the attachment of cells to the implant material is an important indicator of the biocompatibility of the material. “We know that cells are exquisitely sensitive to the implant material,” she says. “What we don’t know is what it is about the material that determines the reaction of the cells. Is it the topography, the composition, a combination of both? We are trying to figure out which factors are important.”

Gronowicz has designed a model system to examine the response of bone cells to implant materials. “In one study, we are looking at the effects of aging on the response of bone cells to materials,” she says. “If an orthopedic implant is going to be successful, it is important that the cells attach to the material -- more than just attach, they have to proliferate and produce matrix proteins that subsequently mineralize at the implant surface, a process called osseointegration. Many orthopedic implants are placed in older adults -- the body goes through many changes with aging, and we are interested in finding out if cells from older adults respond differently to materials than do cells from young adults.” Her group has taken cells from young, middle-aged, and elderly patients and have cultured these cells in vitro with commonly used orthopedic materials, to see if the cells would make normal bone tissue. “We found that cells from older people make less bone, which might affect the success of the implant,” Gronowicz says. “Now we are studying the mechanisms and trying to augment the response of the bone cells to the material.”

In another project, Gronowicz is collaborating with a group headed by David Kaplan at Tufts University, looking at new materials for orthopedic implant applications. “We are working with spider silk -- it’s strong, flexible, and can be compressed without failure, perfect for use in small, moving parts of the body, such as hands.” Kaplan’s group has sequenced the protein that comprises spider silk and transfected the bacterium Escherichia coli with the gene to obtain recombinant spider silk protein. Gronowicz’s group is now looking at the response of bone cells to the protein. “We have found that cells attach to the silk and make bone,” says Gronowicz. “We are now characterizing the bone that is made.”

In a third project, Gronowicz and a graduate student have studied the response of bone cells to commercially pure titanium (cp titanium), a commonly used dental implant material, in the presence of glucocorticoids. “There is a lot of controversy in the literature over the use of glucocorticoids in people who have implants,” she explains. “We are looking at the long-term mineralization of bone in the presence of these types of hormones and other drugs. We have found that bone cells attach to cp titanium if glucocorticoids are present in the tissue culture medium, and maintain their receptors for extracellular matrix proteins. These receptors are usually inhibited by glucocorticoids, but it seems that cp titanium prevents their downregulation. We would like to determine the biological importance of that finding.”

Finally, Gronowicz’s group is working on ways to augment bone formation around implants using growth factors. “We are trying growth factors administered exogenously, bound to carriers, and tethered to the implant material,” she says. “All of our projects are aimed at prolonging the effective life of orthopedic implants. Wear is a big problem with these implants -- the life of the average implant is about 15 years. That is fine for most older adults, but for younger patients -- and we are going to be seeing more of these -- 15 years just is not long enough.”

Tissue-engineering techniques and biomaterials hold great promise for increasing the lifespan of existing medical implants devices, such as those used in dentistry, orthopedics, and vascular surgery. These techniques also may provide the key to problems that have challenged researchers for decades, such as developing a responsive and reliable way to deliver insulin to insulin-dependent diabetics. Researchers at the Center for Biomaterials at UCHC are working to help make the promise of tissue-engineered medical products a reality.—Lisa Christenson, science writer.


EMERGENCY UPGRADE. Connecticut plans to replace its obsolete analog 911 emergency system with a far faster statewide digital network. Expected to be available this fall, the SNET-installed system will reduce the time it takes operators to contact emergency personnel from an average of 10 seconds to less than 2 seconds, according to state officials. The enhanced system will also let police obtain a call-back number from cellular phones, and allow them to determine the location of cellular phone calls. It includes a telecommunications device for the deaf, and it will retrieve information about previous calls from a given address. The $8.6 million upgrade will be financed by a surcharge to residential and business customers; the 1998-99 surcharge amounts to 39 cents a month.

COMPLETE COVERAGE. A contract signed last spring between the Connecticut State Police and Motorola, Inc. guarantees state troopers a radio communication system that covers 98% of the state. The 59-year-old system it replaces is hampered by “dead zones” where troopers cannot send or receive radio transmissions, and must call 911 if they need help. The new $36 million system, which is expected to be installed in every police barracks within 18 months, will rely on added frequencies to provide the necessary coverage.

ON CALL.
Physicians at Yale took advantage of live interactive video and Internet teleconference calls to help doctors on Mount Everest track the way human bodies function under extreme conditions. The researchers, including doctors both at Yale and on the expedition, studied a team of climbers from Boston and Sweden, comparing baseline physiology taken in New Haven to data gathered as the hikers ascended from a base camp 17,500 feet above sea level toward the mountain’s 29,028-foot summit. Tiny, portable devices such as vital sign monitors and locators sent data on climber performance, endurance, and general health to physicians at the base camp and at Yale, while Doppler sonography devices mapped the climbers’ blood circulation. The $500,000-plus expedition was sponsored by Yale, NASA, the National Institutes of Health, The Explorer’s Club, and Millennium Healthcare Solutions, Inc.


AUTISM CENTER. The Connecticut Center for Child Development, in Milford, offers programs that teach autistic children and train autism researchers and care-givers. Originally organized by Suzanne Letso, of Newtown, in order to provide treatment for her own autistic child, the nonprofit school will serve up to 25 children. It will also offer a master’s program in behavior analysis through the University of North Texas. Behavior analysts record behavior change and teach through positive reinforcement, a method which has shown success with autistic youngsters. There is a need for this special degree, says Letso, because other master’s programs don’t focus on assisting autistic youngsters. The center also hopes to start an early intervention program for children aged 3 or younger.

WINNING FLUSH.
A video on handling bodily functions in space won two Coventry fifth graders first prize in a nationwide NASA-sponsored competition. “Flush Away,” produced and written by Melissa Lang and Hillary Haye, covered a range of elimination technologies, from diapers to the sophisticated apparatus found aboard space shuttles. Judged the best news report in the grades 5-8 category, it was chosen from more than 3,200 entries. The children used a Macintosh computer and two graphics software programs to put the video together. They each won a weeklong all-expenses paid trip to a NASA Space Camp.

ALZHEIMER’S ID.
Through a simple flashcard test, doctors at the Memory Assessment Program at the University of Connecticut Health Center in Farmington can often determine whether a patient is suffering from Alzheimer’s disease, or from some other kind of memory loss. When asked to name the pictures in flashcards, explains Sandra Bellantonio, Alzheimer’s sufferers tend to forget the names of objects, but recall their function. When asked to identify a mask, for example, an Alzheimer’s victim might say, “It’s that thing you use on Halloween.” While there is no cure for Alzheimer’s, the Food and Drug Administration has approved two drugs, tacrine and donepezil, that can temporarily improve memory in some cases.

DAY CARE STUDY.
A long-term study, conducted in part by Yale, showed that quality daycare can significantly improve a student’s social and academic performance at least through the early elementary grades. By tracking over 800 students at 400 childcare centers from preschool years to second grade, the study found that about 60% of those who attended high quality daycare centers had good language development and math skills, compared to 40% of those who attended poor-quality programs. The link was even greater for children whose mothers had lower levels of education. In the study, the scientists rated schools according to such criteria as the quality of the child-teacher relationship, the content of the curriculum, the extent of teacher training, and child-teacher ratio.

HOPEFUL ENCOUNTER.
Students at Talcott Mountain Academy in Avon have joined a worldwide effort to detect life in outer space. Through the SETI@home program, run by the University of California at Berkeley, the youngsters have downloaded a software program that analyzes a section of the signals collected by a 1,000 foot radio telescope in Arecibo, Puerto Rico. After the computer examines each 300-kilobyte signal unit, the results are uploaded and returned to Berkeley for interpretation. The program provides the university with some of the computer power needed to analyze the signals. Over 370,00 people in over 350 countries are participating in SETI@home.

HORMONAL IMBALANCE.
Estrogen treatments can reproduce “young” thinking patterns in post-menopausal women, according to a recently released Yale study. Younger people show high activity in the left frontal lobe and reduced activity in the right frontal lobe when memorizing, and when they remember, the pattern is reversed. But elderly people do not display these asymmetrical encoding and retrieval patterns. In the study, postmenopausal women receiving estrogen returned to a youthful activity pattern. Experiments are now underway to see if the asymmetric pattern produced by estrogen is associated with higher mental functioning, said Sally E. Shaywitz of the Yale School of Medicine, the study’s principal investigator.


CELL IT. GE Power Systems has finalized an agreement with Plug Power, of New York, to sell fuel cells to homes and small businesses worldwide through a joint venture, GE Fuel Cell Systems. While fuel cells, which produce only water and heat as by-products, offer many advantages over conventional methods of producing energy, until now they have not been a viable option for small-scale power generation because of their relatively high cost. However, technical and production advances will allow GE to offer residential sized systems for $7,500 to $10,000, with the cost eventually
expected to drop to about $3,500. The fuel cells are expected to be available to consumers in 2001.

POSSI-PILL-ITY.
A state panel has recommended potassium iodide trials be conducted in three towns—East Lyme, New London, and Waterford—because of their proximity to the Millstone nuclear reactor. Because of evidence showing that the drug reduced the incidence of thyroid cancer among Polish children after the 1996 Chernobyl nuclear accident, the federal government has concluded that it is “reasonable and prudent” to stockpile potassium iodide pills near nuclear reactors. The drug, which protects against thyroid cancer, will benefit primarily infants, children, and pregnant women.


SLIPPERY SLOPE. A cast aluminum fishway that allows fish to migrate upstream past Landon’s Dam in Guilford could help restore fish populations to century-old levels. The fishway, which provides a way for fish to pass the 12-foot high dam, will give blueblack herring, sea run brown trout, white perch, minnows, and alewife a place to spawn. Known as an Alaskan steppass, the structure consists of two sections, each 2 feet wide, 10 feet long and 29 inches tall. Steve Gephard, Department of Environmental Protection supervisory fish biologist, expects that several hundred fish will migrate in each of the first few years, followed by a drastic increase, after which the numbers will level off. The project, which cost $15,000, was begun in 1995.

DISEASE CARRIERS.
State officials hope to prevent summer outbreaks of eastern equine encephalitis, which is carried by mosquitoes and can be fatal, through a combination of monitoring and control. The mosquito management program includes applying larvacide to breeding sites along the shore, trapping mosquitoes at 37 state locations from June through October, and monitoring mosquito larvae around the trap sites. The mosquitoes will be tested at The Connecticut Agricultural Experiment Station (CAES), in New Haven. Results will be reported weekly to town officials and local health directors; they can also found at the CAES website at www.state.ct.us/caes/

PEST MANAGEMENT.
Middletown’s Woodrow Wilson Middle School reduced pesticide use by 98% over the past year by participating in a state Department of Environmental Protection Integrated Pest Management (IPM) demonstration program. IPM uses a combination of strategies to control pests, including monitoring of pests, sanitation, structural repair and maintenance, and physical controls such as traps; pesticides may be used if pest populations have exceeded a given threshold. “The awareness created at Woodrow Wilson will be shared with other schools as we take their experience and develop it into a statewide program,” said DEP Commissioner Arthur J. Rocque.

NESTING BIRDS.
Osprey populations may have doubled in Connecticut over the past two or three years, according to Milan G. Bull, director of the Connecticut Audubon Center. One nesting pair in Fairfield is the first to settle there since the late 19th century, he said. In 1974, Connecticut sheltered only 9 pairs of nesting ospreys, but by last year, the numbers had rebounded to 141. That osprey and cormorants, both fish eaters, have increased their numbers in Long Island Sound is noteworthy, Bull said. “Something must be right in Long Island Sound to support all this wildlife.”


BLOOMING PROJECT. A new computer-controlled, $1.39 million greenhouse will help teach students at Wallingford’s Lyman Hall High School state-of-the-art agricultural skills. The facility, which has taken three years to complete, will use a computer to track growing conditions, measure humidity and sunlight, and control temperature, ventilation, and shade. Students can monitor their crops via computer printout. The program serves approximately 200 students from Wallingford, Cheshire, Hamden, East Haven, New Haven and West Haven.

PIGS TO THE RESCUE. Using neurons from genetically altered fetal pigs, scientists at Alexion Pharmaceuticals, of New Haven, and Harvard University were able to restore some learning ability to rats with damaged brains. The experiment, which provides the best evidence so far that “replacement” neurons can restore nerve function, could eventually help lead to treatments for Alzheimer’s, Parkinson’s, spinal cord injuries, and other disorders. Like Alzheimer’s victims, the rats suffered from impaired memory caused by brain cells that could not produce the chemical messenger aceytlcholine. When fetal pig neurons were placed into the rats’ brains, the new cells grew connections to surrounding rat neurons, and aceytlcholine production increased. While the treated rats did not perform as well as normal rats, they did perform 70% better than untreated animals. In a related study, transplanted pig cells were able to restore the damaged protective sheath around the spine, allowing the regeneration of damaged nerve cells. Alexion hopes to begin human trials in one to two years.

PARASITE-FREE.
In an effort to salvage his oyster harvest from parasites that destroyed up to 90% of the oysters in Long Island Sound, oysterman Jonathan Waters is testing a method that allows him to farm his mollusks in a more protected environment. With his “upweller” system, Waters keeps fingernail-sized baby oysters in 500-gallon tubs on his dock. He reproduces the tidal flows of their natural environment by pumping sea water over them; when they grow big enough, he will return them to the Sound so that they can reach market size. Other techniques for dealing with the parasites include developing resistant species and establishing state-run hatcheries to accelerate the oysters’ natural growing cycle.

COW COUP.
For the first time, a clone has been produced using the non-reproductive cells of an adult animal. The breakthrough took place at the University of Connecticut (UConn), where researchers were able to clone a calf with skin cells from the ear of a 14-year-old cow. According to some researchers, it’s particularly significant that the cells used to create the calf were taken from such an easily accessible part of the body. That means, said Xiangshong “Jerry” Yang, head of UConn’s Transgenic Animal Facility, that the technique might be used to preserve endangered species. Clones can also be used to provide embryonic stem cells, which could provide replacements for damaged human tissues. The clone was produced by a process known as nuclear transfer, in which cultured cells are fused with an unfertilized cow egg, which is later transferred to a surrogate mother.

SECOND CHANCE. Using a complex breeding procedure which can pluck immature eggs from cow ovaries, University of Connecticut researcher Maneesh Taneja was able to salvage the genetic line of Snowflake, a champion Connecticut cow. The procedure, known as transvaginal ultrasound-guided oocyte pickup (OPU), uses ultrasonography to locate the oocytes, or immature eggs, within a cow’s ovaries. The oocytes are removed, fertilized in vitro, and transferred to another cow for gestation. While OPU is usually used to produce offspring from pre-pubertal heifers, Taneja salvaged the eggs from Snowflake’s ovaries after the cow’s death; a single calf, Sarah, was born.


BREATHE EASY. Widespread vaccinations could be one reason that asthma rates in this country have jumped from 6.8 million cases in 1980 to over 15 million in 1998, according to research done at Yale. The vaccinations, along with antibiotics, have nearly eliminated the childhood diseases that activate a key portion of the immune system, Th1 cells. In addition to destroying pathogens, these cells also regulate another piece of the immune system, the Th2 cells. “The lack of Th1 immunity allows Th2 activity to go unchecked,” said immunobiology professor Kim Bottomly, who discovered the two kinds of immune functions. Without the Th1 controls, Th2 cells may become oversensitive to common, normally benign air-borne substances like pollen and dust mites, producing the changes in lung tissue that result in asthma.

FOOT REST. Reconstructive surgery could save the feet of some diabetics, according to orthopaedist Raymond J. Sullivan of the University of Connecticut Health Center. The operation, which could take up to five hours, involves rebuilding the foot by breaking the bones, realigning them, inserting rods to realign the foot with the ankle, and placing plates on the sole of the foot; full recovery takes a year. The complicated procedure, said Sullivan, might be appropriate for diabetics suffering from Charcot’s Neuroarthropathy, which causes a decalcification of the bone on joint surfaces, leading to deformity and, frequently, amputation.

VIRAL DECEPTION.
Scientists at Boehringer Ingelheim Pharmaceuticals, in Ridgefield, may have found a way to prevent the common cold: they’ve devised a decoy that lures the cold-causing rhinovirus away from healthy cells. The virus, which causes about half of all colds, latches onto cells at a surface molecule called ICAM-1. The researchers developed a version of ICAM-1, tremacamra, which also attracts the virus, keeping it from causing infections. Recent tests on 177 volunteers exposed to the rhinovirus showed that less than half of those receiving tremacamra developed colds, compared two-thirds of those given a placebo.

TICK TICK TICK.
State entomologist Louis A. Magnarelli, who was among the first to investigate the clusters of juvenile arthritis cases that led to the discovery of Lyme Disease, has turned his attention to human granulocytic ehrlichiosis (HGE), another tickborne disease. Unlike Lyme Disease, HGE, which destroys white blood cells, could be fatal. However, it can effectively treated by antibiotics, and, according to Magnarelli, the disease is not likely to become as widespread as Lyme Disease because it is not as effectively transmitted by ticks. Fifty-four cases of the disease were reported last year. Magnarelli and other researchers at The Connecticut Agricultural Experiment Station in New Haven are conducting studies that could lead to an accurate test for HGE, and, eventually, to an effective vaccine.

BOOSTING IMMUNITY.
Tricking a child’s body into thinking it’s as old as an adult may be way to prevent lymphatic filariasis, says University of Connecticut Health Center pathologist T.V. Rajan, who is developing a vaccine for the disfiguring disease. Although the illness attacks adults, it occurs only if the parasites that cause it enter the victim’s body before the child reaches the age of 15. According to Rajan, this may be because the immune system does not become fully effective until adulthood, allowing the filariasis parasites to establish themselves in youngsters before the adult immune system can provide an effective defense. Rajan’s vaccine would provide children with the same powerful immune protection that mature white blood cells give adults; this might shield youngsters not only against filariasis, but against other pathogens as well.

TOOTHSOME STUDY.
Low doses of an antibiotic may help prevent tooth loss, according to the preliminary results of research being conducted in part at the University of Connecticut School of Dental Medicine. The antibiotic doxycycline, sold commercially as Periostat, may inhibit the bacteria that encourage production of collagenase, an enzyme that breaks down the protein that allows the gums and jaw bone to hold the teeth. The dose is considered too low to affect the body’s good bacteria. “The idea isn’t to replace deep cleaning or periodontal surgery with Periostat,” said researcher John W. Dean III, “but to use it as an adjunct to traditional treatments.” The study, part of a six-university investigation, is expected to last nine months.

A MATTER OF TASTE.
“Taste phantoms,” unpleasant, illusory sensations, often result from damage to the chorda tympani, a nerve that links the taste buds at the front of the tongue to the brain, according to Yale psychologist Linda Bartoshuk. The chorda tympani, one of three cranial nerves involved in sensing taste, appears to inhibit both the other taste nerves and the pain fibers in the tongue. When it is damaged, activity in the other nerves increases, which can prompt phantom tastes. In a series of experiments, Bartoshuk and Yale otological surgeon John Kveton found that anesthetizing the chorda tympani intensifies sensation in areas served by the other taste nerves. Phantom tastes were experienced by about 40% of the test subjects; sensitivity to pain also increased.


SOUND INFORMATION. As part of a national program to assess environmental health, scientists at the University of Connecticut (UConn) are using three solar-powered research buoys to monitor water conditions on Long Island Sound. One of 25 EMPACT (Environmental Monitoring for Public Access) projects around the country, UConn’s is the only study to focus on water quality. Scientists here are primarily interested in tracking levels of dissolved oxygen, because low oxygen levels, which can result from factors such as fertilizer runoff, can harm certain marine species. Information collected by the buoys, which includes data about water temperature and currents, can be found at www.mysound.uconn.edu.

KILLER APP.
The South Windsor police department has leased a $120,000 FATS III virtual reality simulator to train its officers in the use of deadly force. The simulator, which offers more than 30 scenarios that require students to respond to high stress and life-threatening situations, evaluates each officer on judgment, accuracy, and reaction time. The officers are scored on their decisions in shoot/don’t shoot situations, target identification, and on their responses to lethal threats. As in real life, they are given only seconds to decide, although the instructor can replay the exercise in both real time and slow motion.

FAR SEEING.
Police officers may soon be able to analyze crime scenes with a device based on one of NASA’s probes: a portable x-ray fluorescent scanner being developed by University of Connecticut physics professor Jeffrey Schweitzer. The device detects atoms heavier than magnesium by observing their distinctive radiation patterns, and, while NASA relies on a similar technology to identify trace elements on the surface of other planets, Schweitzer’s scanner will seek out remnants of gunpowder, which could help identify the type of ammunition used in a crime. Schweitzer’s technology, which could be in use within the year, would also measure background elements, such as the lead in paint. Schweitzer is part of a joint NASA-Justice Department project to develop remote measuring technology.

INSIDER VIEW.
The InstaTrak System, used during sinus operations at the University of Connecticut Health Center (UCHC) in Farmington, provides an added measure of safety by allowing surgeons a three-dimensional view of the inside of patient’s head. Because sinus surgery occurs so close to the brain and eyes, slips could result in blindness, loss of smell, or even death. “Millimeters can make a difference,” said UCHC otolaryngologist Gerald Leonard. The system consists of an electromagnetic “localizer,” which comprises a magnetic field generator and a magnetic field receiver linked to a computer processor; doctors use a headset, detachable probes, and a high resolution monitor. InstaTrak, which was recently acquired by the center, is used in operations to correct chronic sinus infections, remove nasal polyps, and address sinus diseases.


HILL OUT. University of Connecticut physics professor William Stwalley, who was among the first to use atomic properties to understand and predict molecular properties, is studying the behaviors of long-range molecules, in which the atoms are separated by large distances, yet the attractive forces are still strong enough to maintain a “molecular” nature. Stwalley works with atoms that are chilled by laser cooling techniques to ultracold temperatures. His research, financed by a $439,000 National Science Foundation grant, will help unravel the way chemical bonds attract and “congeal” atoms, and could explain how atoms assemble into more complex groupings—from atoms, to molecules, to clusters, and so on, into condensed phases.

FAT FREE.
The recent continuation of a collaboration between Neurogen Corp., of Branford, and Pfizer, Inc. may lead to the development of an anti-obesity drug that works by suppressing the desire to eat; the agreement will channel up to $3.2 million toward Neurogen’s research costs. The companies hope to find a drug that blocks a neurotransmitter that signals when the body is hungry. The molecule, neuropeptide Y, induces ravenous hunger when given to even recently fed animals. In addition to its work on neuropeptide Y, Pfizer is researching a possible diet drug based on an African plant used by tribesmen to suppress hunger pangs on long hunting trips.

WHATEVER LOLA WANTS.
An award-winning software program designed largely by Aetna employees simplifies detection of Medicare fraud by providing analysts with a fast way to analyze the Medicare claims database. LOLA Plus allows analysts to search for anomalies in any of the 80 categories of information that Medicare providers must submit, including the patient’s diagnosis, treatment, sex, zip code, and doctor. Insurance companies can use the program to find Medicare providers who bill for services they never gave, such as one clinic, detected by a LOLA Plus zip code analysis, that claimed to treat patients living a thousand miles away.

HOT STUFF.
Computers fail if they overheat, and as they have become more miniaturized and more powerful, the techniques required to cool them have become both more critical and more sophisticated. The cooling devices used in today’s most advanced processors were developed at the University of Connecticut (UConn). “At UConn we have developed and designed heat pipes to improve existing electrically cooled components exponentially,” said UConn professor and CASE member Amir Faghri. Heat pipes, which have no moving parts, transport heat via evaporation and condensation. They offer low weight, zero maintenance, and reliability, according to Faghri. In part developed at the behest of NASA to maintain spacecraft components and circuitry, heat pipe technology can be used in a variety of commercial applications.


TRAIN STOP. The state-of-the-art “quad gate” that guards the railroad crossing at School Street in Groton offers a prototype safety system that could be used by Amtrak across the nation. The quad gate/sensor system, which is the first rail crossing safety device to establish communication between the crossing gate and an oncoming locomotive, uses underground sensors to detect vehicles stuck on the tracks. If a vehicle on the track fails to move, the sensor notifies the approaching train, allowing the engineer to slow down or stop. If the engineer does not respond, the train stops automatically. The combination of quad gates, which seal off the tracks, and underground sensors is currently used in Europe.

HEALING THE SICK.
A high-tech medical evacuation helicopter recently introduced by Sikorsky Aircraft offers the Army a way to provide immediate medical attention to patients on the way to the hospital, according to one company official. Unlike existing medevac helicopters, Sikorsky’s newest offering boasts a hoist that is anchored to the roof of the aircraft. This allows the crew to raise a patient right into the helicopter. The Army surgeon general considers the Medevac units his top aircraft priority, according to Connecticut congressman James Maloney.

LOCATION, LOCATION, LOCATION.
SNET Corp. has begun to outfit its company vehicles with satellite-tracking systems that will allow officials to follow the movements of the upgraded cars and trucks. The devices, which rely on global positioning satellites (GPS), will be deployed mostly on repair and installation trucks. They are intended to improve efficiency in handling service calls. Initially the tracking equipment will only be used to review service routes at the end of each day, but eventually it could be upgraded to provide real-time, moment-to-moment information about the whereabouts of each vehicle.

GO WITH THE FLOW.
Pratt and Whitney plans to modify its popular PW4000 engines to prevent surges, which can cause a momentary loss of power. The problem occurs when, over time, a slight gap develops between the tips of some compressor blades and the wall of the inside of the engine. This gap allows the air to flow backward, a disruption that can cause the engine to lose power for a second or two. The planned modifications, which include providing new coatings for blades, changing the profile of other airfoils to stabilize the air flow, and changing the electronic controls, reduce the backfires from one in every 8,000 flights to one every 32,000 flights. About 2,000 of the affected engines are currently in use; they are found in many Boeing 747s and 767s.

- Compiled and edited by Karen Miller


FROM THE ACADEMY
On Communication Skills in Science and Engineering

This past spring, CASE President Anthony J. DeMaria addressed a conference sponsored by the New England Board of Higher Education entitled: “Communication Skills in Science and Engineering at the Millenium.” His remarks are excerpted below.

“We in the science and engineering community are indebted to the arts and humanities communities for impressing on us the highly desirable attributes of having a good education in the arts and humanities. They have impressed on us the fact that knowledge of art, religion, philosophy, languages, history, social sciences, etc., enriches our lives, and even illuminates our souls, and uplifts our spirits as well as enabling us to better communicate and understand our fellow humans, and to respect and enjoy the wide diversity of race, creed, and cultures that exists in the human race ...

Unfortunately, we in the science and engineering community have not undertaken a similar effort to impress on the liberal arts community the importance of being literate in science and technology. This is especially true for the engineering community. In most universities, the physical science departments are located within the Liberal Arts [schools] Consequently, they provide physics, chemistry, and other similar scientific introductory ... courses for students not pursuing science or engineering studies. How many colleges and universities have similar types of introductory technology type courses taught by their schools of engineering for non-engineering majors ...? The fact is that engineering schools have not traditionally provided courses for non-technically oriented students....

... engineering schools must teach such [technology] courses for the following reasons: Technology is one of the strongest forces shaping our world today.... Thanks to the contributions of scientists and engineers, all the ingredients are in place for a surge of innovation that could rival any in human history.... the impact of technology on how we play, how we work, how we travel, and how we communicate, educate, entertain, feed ourselves and treat our sickness will continue to be immense....

In spite of these immense impacts, apathy about science and technology is [widespread]... among most of my fellow Americans, an indifference toward science and technology is considered almost a badge of honor. Most non-technical people feel intimidated by technical subjects. Science and engineering achievements are increasingly taken for granted. One reason for this ... is widespread scientific and technological illiteracy among ... those who hold high-level decision-making positions. ...

I echo Norman Augustine’s two recommendations to help America survive and thrive in the technologically-driven 21st century:

First … our universities need to teach “rocket science” for beginners. We need introductory technology courses for our non-technically oriented students....

Second: Both scientists and engineers must learn to communicate far more effectively with non-technical audiences....
Until these two recommendations are enacted ... there will be plenty of work and an increasing need, on the national level, for institutions such as the National Academy of Sciences, the Institute of Medicine, and the National Academy of Engineering, and on the state level, for equivalent institutions such as the Connecticut Academy of Science and Engineering.”—Anthony J. DeMaria, President, CASE

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