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T R 10 0 B I O + M E D I C I N E The convergence of biology with computing and nanotechnology is yielding safer and more effective medicines. IN THE WORLD of biomedical research, basic science is usually held in the highest regard, while applied research is often looked down upon as mere "tool building." But don't tell that to this year's TR100 honorees in biotech- nology and medicine, a group intent on turning recent biomedical advances into practical technologies with an immediate impact. ■ These researchers and entrepreneurs work in wildly divergent fields, from nano- engineering to "programming"living cells. Not surprisingly, they hold a range of opinions on which approaches and developments in biology are the most important a research basis to a practical reality for each and every one of us," and on how new technologies will affect our lives.Yet Chan says. To usher in that reality, Chan quit medical school and they share a desire to find real-life applications for their founded Woburn, MA-based U.S. Genomics. He hired biologists, physicists, nanotechnologists, and informaticists, each of whom technologies as soon as possible. They also share an awareness that plays a role in realizing his vision: a machine capable of reading the convergence of biology and medicine with fields such as an entire human genome in 10 minutes. physics, engineering, computer science, materials science, and That ambition to improve lives characterizes many of the nanotechnology is yielding powerful new ways to help them TR100. Rice University bioengineer Jennifer West says that mak- achieve their ambitions. ing a difference to patients is "one of the nicest things to see." West Take Eugene Chan. Even as an undergraduate at Harvard Uni- is developing new materials for both treating cancer and engi- versity, Chan was intrigued by the Human Genome Project, the neering replacement tissues in the body. West and her colleagues international effort to determine our genetic blueprint. But at Rice found that by attaching particular proteins to tiny, hollow Chan also appreciated that the project's true promise would gold nanoparticles, called nanoshells, they could selectively target only be realized when the technology was available to obtain full and destroy tumor cells. As a cofounder of Houston-based Nano- genetic information on individuals—prohibitively expensive spectra Biosciences, West is now helping to develop the nanoshells and time consuming with the sequencing methods used in the for cancer therapy. Here's how it might work: A doctor injects the Human Genome Project."With all these wonderful [genetic] dis- materials intravenously and waits an hour for the nanoparticles to coveries in the past 50 years, it's now time to translate that from find the cancerous cells. When the doctor shines infrared light on B Y E R I K A J O N I E T Z » I L LU S T R AT I O N B Y C E L I A J O H N S O N 72 T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 w w w. t e c h n o l o g y r e v i e w. co m w w w. t e c h n o l o g y r e v i e w. co m T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 73 the patient, the nanoshells heat up and destroy only the tumor tis- a short time ago—such as Nimmi Ramanujam's optical method sue. West believes that interdisciplinary research like hers, which of cancer diagnosis. The University of Wisconsin-Madison bio- combines advances in biology, medicine, and nanotechnology, will medical engineer studies how light interacts with human tissue yield tremendous opportunities to create new treatments."That's and the characteristic changes cancers introduce to those inter- where a lot of the successes will come from," she says. actions. Her efforts have yielded a noninvasive test for cervical can- The juncture of biology and computer science is another cer that is already in human trials. She's now working on a breast promising area of convergence. Princeton University electrical cancer test that could be an aid to expensive and often inaccurate engineer Ron Weiss is undertaking the ambitious breast biopsies. The goal, she says, is to develop task of "programming" living cells, encoding methods that can identify cancer at its earliest stages instructions using genes rather than the 1s and 0s with very high accuracy and in real time—which he used when programming computers. As a post- would be a boon to thousands of cancer patients. T R 10 0 B I O + M E D I C I N E doc at MIT, Weiss was looking to biology to inspire Pioneering work like Ramanujam's is only the new methods of computer programming. "At beginning of the transformation the TR100 hon- some point I said, 'Instead of just staring at things orees believe the accelerating pace of biomedical dis- on the screen, I really want to program cells.'" He covery will yield. Such rapid increases in knowledge, hopes soon to begin programming tissue-specific coupled with the new tools resulting from advances human stem cells, instructing them on how to in areas such as nanotechnology and computer become different types of cells and, eventually, whole organs. science, have led some in the TR100 to confidently predict that a Weiss also foresees ultrarealistic computational simulations "golden age" in biological science is emerging. "As we're getting of cells or even humans that will be able to predict precisely what more and more information from things like genomics and pro- will happen as environmental conditions change or as foods or teomics, we're gaining the ability to manipulate biology and do medicines are consumed. "Once we have that predictive power, lots of new and exciting things with it," says West."Up to this point, that's the point where progress is really going to increase," he says. we just didn't know enough to understand how to make these Such dramatic dissolution of the boundaries between biology things happen." Armed with the new technologies and this new and computer science will take years. But other frontiers have knowledge, the researchers you'll meet in the next few pages are already blurred enough to yield new technologies unimaginable now intent on making their ambitious goals happen. ◊ TR100 Startups in Biotech and Medicine INNOVATOR COMPANY FOUNDED/COFOUNDED STRATEGY/ MILESTONES Alexis Borisy CombinatoRx New medicines generated by combining drugs; drugs for cancer (Boston, MA) and rheumatoid arthritis in human trials; has raised $60 million Eugene Chan U.S.Genomics (Woburn, MA) Technology to rapidly sequence genomes; has raised more than $57 million Bassil Dahiyat Xencor Computational protein drug design; human trials of anti-inflammatory drug scheduled for late (Monrovia, CA) 2004; has raised $65 million Benjamin G. Davis Glycoform (Oxford, England) Novel drug delivery systems based on carbohydrate chemistry; has raised $2 million Christophe Echeverri Cenix BioScience Drug discovery using RNA interference technology; has raised 11 million euros working (Dresden, Germany) with corporate and academic partners to identify genetic targets for new drugs Michael E. Gertner Nanomedical Technologies Drug delivery systems using nanometer-sized pores in metallic films that can release medicine (San Francisco, CA) in devices such as artery-supporting stents over longer periods than standard polymer coatings Jay Groves Synamem (formerly Proteomic Systems) (Burlingame, CA) Drug discovery using "MembraneChip"technology Andre Koltermann Direvo Biotech "Directed evolution"to make novel proteins and enzymes for more effective drugs, detergents, (Cologne, Germany) and food products; has raised more than $25 million Anthony Lowman Gelifex (Philadelphia, PA) Hydrogel implants to relieve pain and restore motion in cases of degenerative back disc disease Gavin MacBeath Merrimack Pharmaceuticals Drug discovery using systems biology approaches to understand complex pathways; (Cambridge, MA) drug for myasthenia gravis in human trials; has raised $25 million in investments Christophe Schilling Genomatica Computational models of cells that enable biologists to engineer organisms to produce valuable (San Diego, CA) chemicals;$3 million in venture funding Mijail Serruya Cyberkinetics Brain-computer interfaces to allow paralyzed patients to communicate or control robotic aids, (Foxborough, MA) and to treat epilepsy and depression; has raised $9.3 million Micah Siegel Concept2Company Support for university researchers who wish to start commercial ventures in medical devices, (Palo Alto, CA) life sciences, and information technology without leaving their current jobs Jennifer West Nanospectra Biosciences (Houston,TX) Hollow gold nanoparticles coated with proteins for targeted cancer therapy Daphne Zohar PureTech Ventures (Boston, MA) Venture creation; helps found and fund life sciences companies 74 T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 w w w. t e c h n o l o g y r e v i e w. co m Helene Andersson, 29 Silex Microsystems Produces portable, inexpensive, microprocessor-size labs for research and industry WITH TWO degrees and three part-time jobs, Helene Andersson is bridging disciplines to build and market microprocessor-size laboratories. At Stock- holm, Sweden-based startup Silex Microsystems, she serves as business manager and designs custom "labs-on-a-chip" for commercial uses ranging from T R 10 0 B I O + M E D I C I N E bedside medical testing to detecting chemical and biological attacks. And the electrical engineer and molecular biotechnologist is exploring other applications in her work at Sweden's Royal Institute of Technology and at Mesa+, a research institute in the Netherlands. As a doc- toral student, Andersson developed production techniques for efficiently manufacturing the microlabs, and designed ever smaller pumps, valves, and other components for them. Several of her patented microstructures "boldly demonstrate to bioanalytical researchers the great advantages of microlabs," says Mesa+ professor Albert van den Berg. These advantages include portability, speed, and economy. Andersson's life is hectic, but she Guillermo Ameer, 33 plans to continue all her pursuits. "It suits me very well," she says, "to explore new things Northwestern University and learn how to do business with them at the same time." Synthesized "biorubbers" that could replace damaged heart and lung tissue and rebuild blood vessels Sangeeta Bhatia, 35 University of California, San Diego GUILLERMO AMEER is creating a set of high- Uses microchip-manufacturing tools to build artificial livers tech tools to manage diverse medical condi- tions. "Most people in science tend to focus IN THE United States alone, 17,000 people await liver transplants. on one specific problem," says the biomedi- Sangeeta Bhatia's solution? Engineer a liver from scratch, using cal engineer, a native of Panama. His aim is photopatterning techniques borrowed from the microchip industry. A broader: "I want to build things useful to completely functional artificial liver requires different types of cells arranged in complex people's health." His top tool to date is called patterns. The University of California, San Diego, associate professor of bioengineering biorubber: a rubber-band-like material that and associate adjunct professor of medicine starts by mixing one type of liver cell with a he helped invent during a postdoctoral fel- liquid polymer and covering the mixture with a template. When ultraviolet light shines lowship. Stretchy, cheap, and biodegradable, through the template, illuminated cells get trapped in the polymer; shaded cells can be biorubber could eventually be used to washed away. By applying different templates and cell mixtures, Bhatia builds up layers replace damaged heart or lung tissues. that simulate the liver's natural structure. Human trials remain years away, but meanwhile Ameer's lab at Northwestern University is biotech firm Surface Logix is adapting her liver-cell work for drug research. currently developing second-generation biorubbers with varying degrees of elasticity and degradation rates to act as scaffolds for Alexis Borisy, 31 engineered blood vessels or ligaments.While CombinatoRx the assistant professor of biomedical engi- Believes that combining different drugs could yield better ways to fight disease neering has two patents pending on that work, he has already received a patent for FOR DECADES, "drug discovery" has meant screening millions of compounds to find one another innovation: a cartridge that uses that will block a disease process. But Alexis Borisy says that approach is too simplistic. genetically engineered antibodies to filter a Since "the body always uses mixtures of molecules to regulate itself," he says, it makes protein called beta-2-microglobulin from the sense to do the same when treating disease. In 2000 Borisy founded CombinatoRx in blood of kidney disease patients. Over time, Boston to search for molecules already proven safe for humans but that combat disease this protein—which the traditional filters in only when used in combination. Along the way, he had to reinvent drug screening. While dialysis machines don't catch—can leave pharmaceutical companies typically ask only one question about each compound—does painful deposits in bones, joints, and ten- it have an effect?—CombinatoRx examines compounds two at a time, dons. Partly funded by the National Kidney in different doses, answering that question 36 separate times. Borisy Foundation and Baxter Healthcare, Ameer's says the company had to create new lab processes and write software lab is refining the biofilter so clinical trials to analyze its masses of data. CombinatoRx has raised $60 million may be conducted—which means people and has launched human trials of three drug combinations designed could soon find out just how useful Ameer's to treat cancer and rheumatoid arthritis. "Fifty years from now," tools are. Borisy says, "a majority of drugs will be combination by design." 76 T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 w w w. t e c h n o l o g y r e v i e w. co m Eugene Chan, 29 U.S. Genomics Aims to speed genome sequencing with a machine that reads DNA letter by letter MOST BIOTECH firms have their origins in labs,but Eugene Chan dreamed up U.S.Genomics in the medical-school dorms and libraries of Harvard University. His goal: to find a quicker, cheaper, more precise way to analyze DNA so all patients might benefit from the discoveries of the Human Genome Project. Chan patented his idea for a device that would read a DNA sequence straight from a single molecule—and left medical school in his second year to found U.S. Genomics in Woburn, MA, to develop the technology. The company's latest prototypes catch fluorescence-tagged DNA on nanoscopic posts, unfurl- ing the coiled molecules.The molecules then flow one by one into a narrow channel where lasers and optical detectors "read" the bar-code-like patterns created by the tags. The T R 10 0 B I O + M E D I C I N E device can now identify certain sequences within long stretches of DNA; Chan hopes it will Benjamin G. Davis, 33 produce letter-by-letter sequences by 2006. He has raised some $57 million and recruited Glycoform such sequencing gurus as Celera Genomics founder J. Craig Venter to the firm's board."The Manipulates biological machines he's built probably have hundreds of different applications,"Venter says. sugars for more precise drug delivery RESEARCHERS HAVE long Bassil Dahiyat, 32 known that proteins— Xencor pivotal players in every- Designs proteins from scratch to create new medicines thing from embryonic development to Alz- AS AN undergraduate studying biomedical engineering, Bassil Dahiyat planned a career heimer's disease—often building medical devices. Pursuing a PhD at Caltech, however, he found himself work- have sugars attached to ing on much smaller structures: proteins. Indeed, Dahiyat designed the first completely them. But understanding precisely how artificial protein—a very simple one—by devising powerful algorithms that combine stan- those sugars influence the proteins' func- dard descriptions of the physical properties of protein molecules in novel ways. He then tions was exceedingly difficult until the constructed the protein by chemically linking its amino acid building blocks. After arrival of novel chemical reactions devised graduating in 1997, Dahiyat founded Xencor and put his technology by University of Toronto postdoc Benjamin to work creating protein drugs. The Monrovia, CA, company has raised Davis. The reactions enabled Davis to add or $65 million and plans next year to begin human trials of its first drug, substitute sugars on proteins with Lego-like an anti-inflammatory for treatment of rheumatoid arthritis, psoria- ease—solving a problem that had stymied sis, and Crohn's disease. Today Xencor designs its drug candidates by researchers for decades. Manipulating sugars "tweaking natural proteins," says CEO Dahiyat, but he looks forward could make it easier not only to systemati- to computer models robust enough that he can design complex mole- cally study the basic biology of proteins, but cules from scratch, fulfilling his vision of completely artificial protein therapies. "The also to engineer them as drugs. Indeed, Davis dream is to mimic how nature uses proteins—to essentially do any task you can is exploiting his techniques to create a drug imagine," he says. "There's this palette that we haven't even started to paint with." delivery system in which different sugars direct protein-based drugs to target cells or organs. In November 2002, Davis, who is now Christophe Echeverri, 34 a lecturer at the University of Oxford, Cenix BioScience cofounded Glycoform in England to com- Develops fast, automated processes for figuring out genes' functions mercialize this and other work; within a week he obtained $2 million in venture funding. WHEN SCIENTISTS discovered that short pieces of RNA can shut down specific genes—a phe- The company is now conducting trials of the nomenon called "RNA interference"—they hailed the finding as "revolutionary." As a postdoc in drug delivery system and developing new 1998, Christophe Echeverri co-led the first group to successfully test the use of RNA interference sugar attachment techniques. to shut down genes selectively across an entire genome. Such an approach could prove crucial to determining what the tens of thousands of genes in animal and human genomes actually do. Scientists had devised a few RNA-based methods for determining gene function, but they were too time-consuming to stride through a full genome, sometimes taking months to analyze a single gene. Echeverri helped lead a team that developed micromachinery, chemical reac- tions, and algorithms to automate the process and record its outcome. Echev- erri says his team uncovered the roles of four to six genes per day.The triumph prompted Canadian-born Echeverri to cofound Dresden, Germany-based Cenix BioScience in 1999; the 35-employee company has raised 11 million JOHN SOARES (CHAN) euros. In partnership with Austin,TX, biotech firm Ambion, Cenix is developing the first commercially available human-genome-wide libraries of interfering RNA molecules, which clients could use to find new drug targets. 78 T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 Michael E. Gertner, 33 Jay Groves, 32 University of California, San Francisco University of California, Berkeley Set out to improve the tiny devices Patented a lab-on-a-chip to investigate cell proteins that cause disease that keep once blocked arteries open FOR JAY Groves, inspiration began with tweezers. As a graduate student, WHEN MICHAEL Gertner is convinced he's Groves was studying cell membranes—the fatty wrappers that enclose liv- right, it's damn the torpedoes, full speed ing cells—and the proteins that stud them. Though 80 percent of drugs work by binding to ahead! A resident in general surgery at these proteins, they are poorly understood and hard to study. While trying to measure the the University of California, San Fran- motion of cell membrane proteins, Groves scratched the silica surface supporting them with cisco, Medical Center, Gertner pondered his tweezers to help focus his microscope. He noticed that the molecules couldn't move across how to improve coatings for stents—tiny the scratch—and a new idea was born. Could researchers create patterns on wafers that would, T R 10 0 B I O + M E D I C I N E expandable structures like the scratch, corral proteins? Sure enough, Groves developed and patented the Membrane- that doctors implant Chip, a silica surface etched with tiny squares that partition cell membrane proteins so they can to help hold coronary be studied. In 2000 he launched a five-person biotech company, Proteomic Systems, now called arteries open once they Synamem, in Burlingame, CA, which licensed the MembraneChip to seek new drugs that sup- have been unblocked press immune response or fight infection. Groves, who is now an assistant professor of chem- by angioplasty. Each istry at the University of California, Berkeley, says the technology could affect the study of y e a r, m o r e t h a n autoimmune diseases, among other disorders."Membranes are the definitive structural feature 900,000 coronary stents are deployed in the of life," Groves says—and he is determined to master their ways. U.S., and over time they can become cov- ered with scar tissue that can once again impede blood flow. New stents are coated Justin Hanes, 34 with polymers that, for a week or two, Johns Hopkins University release a drug that inhibits scarring, but the Creates systems for delivering drugs polymers can degrade the drugs or even to where they're needed in the body harm blood vessels. Gertner reasoned that a metal coating could work better. Ignor- AFTER LOSING his grandmother to cancer ing some experts who doubted his when he was 10, Justin Hanes vowed to approach's commercial viability, he and a combat disease. Now a chemical engi- colleague developed a process for coating neer, he has already won his first battle, stents with metallic films. The metal forms designing polymer aerosols that deliver a fine lattice that carries drug molecules it drugs to the lungs. Inhaling medications can release for up to six months. Although spares patients from injections, and cer- surgery keeps Gertner busy, he has tain drugs are more effective when cofounded Nanomedical Technologies in breathed in. Hanes and his coworkers San Francisco to develop the system. A devised a way to make coated polymer stent manufacturer has already acquired particles porous; the particles serve as parts of the technology. Time will tell if drug-carrying vessels that are large those doubting experts were wrong. enough to lower the odds of attack by the immune system, but light enough to stay aloft and reach deep into the lungs. There Andre Koltermann, 34 the polymer degrades, releasing insulin, Direvo Biotech growth hormones, or asthma medica- Speeds protein evolution to improve detergents, medicines, and foods tion over hours, days, or weeks. Hanes and his colleagues' pioneering work pro- AN ADMIRER of Charles Darwin, Andre Koltermann is bent on speeding up natural evolution. vided the core technology for Advanced Bacteria, for example, produce enzymes with useful stain-fighting properties, but nature Inhalation Research, founded in Cam- has yet to make an enzyme that performs optimally alongside the harsh chemicals in laun- bridge, MA, in 1997 and sold two years dry detergents. Andre Koltermann says his company, Direvo Biotech, has. Koltermann and later for $114 million. Although Hanes his colleagues have altered an enzyme used in commercial detergents,making it a hundred received stock from the sale, he chose an times more effective at eliminating stains. They did so by adapting "directed evolution," a academic career. Now an assistant pro- technique for inducing the genes that encode the enzymes to mutate or recombine. fessor at Johns Hopkins University, he is Researchers use fluorescence spectroscopy to screen for promising building a new polymer for transporting variations. The process enabled Koltermann to find the best enzymes cancer drugs. Enzymes secreted by grow- more quickly than is possible with conventional techniques. Founded ing tumors destroy the new polymer, in Cologne, Germany, in 2000 by Koltermann and two partners, Direvo thus discharging drugs where they're WILL KIRK (HANES) has secured more than $25 million in financing. Koltermann will use needed most. "Why spread poison over the funds to expand the firm's work in directed evolution, with the aim the whole yard to eliminate one weed?" of improving the enzymes in medicines, foods, and animal feeds. Hanes asks. 80 T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 w w w. t e c h n o l o g y r e v i e w. co m Xiangjun Liu, 35 Tsinghua University Maps gene variations that could warn of future disease MOLECULAR BIOLOGIST Xiangjun Liu wants to know whether something in your genes can predict your likelihood of contracting a debilitating disease. The human genome contains many small person-to-person variations called single-nucleotide polymorphisms (SNPs). SNPs are associated with a variety of diseases, but defining which combination of SNPs can predict the onset of a specific disease is a formidable task. As a researcher at Celera Genomics in Rockville, MD, Liu laid the groundwork for that effort by leading a team that sifted through billions of T R 10 0 B I O + M E D I C I N E genetic sequences and produced a database of 2.8 million SNPs. Researchers worldwide are using these data to learn which genetic variations are involved in diseases and how Erin Lavik, 30 those variations might affect drug efficacy and toxicity in different people. In February Yale University 2002 Liu returned to his native China to advance this work as director of Tsinghua Uni- Helped paralyzed rats walk again versity's Bioinformatics Research Lab in Beijing. The lab is trying to pinpoint the SNPs and aims to do the same for people associated with atherosclerosis and other ailments. Liu also heads a Chinese government project to analyze SNP findings worldwide. Ultimately, Liu hopes to identify people likely A PLAYWRIGHT who has written a one-act to develop a given disease, so doctors can work proactively to prescribe treatments that farce, Erin Lavik has a day job that is no laugh- will prevent or minimize symptoms. ing matter. She uses polymers and neural stem cells to promote recovery from spinal- cord injuries, which 10,000 people suffer each Gavin MacBeath, 33 year in the United States alone. A Yale Univer- Harvard University sity assistant professor of biomedical engi- Unravels complex biological systems in his search for new drugs neering, Lavik designed polymer scaffolds that mimic the architecture of a healthy spinal BIOLOGISTS TRADITIONALLY study organisms one gene or one protein at cord, seeded the scaffolds with neural stem a time. But because organisms are collections of interwoven systems cells, and implanted them in paralyzed rats. that involve interactions of many molecules, more and more Much to everyone's surprise, the rats were researchers believe a systems-level approach to biology is critical for understanding dis- able to move their limbs, bear weight, and eases and developing cures. Gavin MacBeath is working on technology to facilitate that even walk. Although spinal-cord-injury re- approach. An assistant professor in Harvard University's chemistry and chemical search is a big field, Lavik's method is the first biology department, MacBeath has found a way to attach thousands of functional pro- to demonstrate such dramatic success.Repair- tein samples to small glass chips. Using these chips, he can study more than 25,000 inter- ing spinal-cord injuries in humans will be a actions between pairs of proteins in a single afternoon. He also plans to look for small bigger challenge, but then, Lavik didn't expect molecules that can selectively disrupt interactions—both to learn more about basic biology her injured rats to walk so soon. If she has her and to identify potential drugs. In 2000, MacBeath cofounded Merrimack Pharmaceu- way, people with spinal-cord injuries could be ticals in Cambridge, MA, to use systems biology to improve research on afflictions such walking sooner than expected, too. as cancer. "This kind of work is going to change the way we discover drugs," he says. Anthony Lowman, 33 Drexel University Packs insulin into gel pills that could replace injections for diabetes patients AS A graduate student, Anthony Lowman faced a dilemma: pursue polymers or medicine. He chose both. Now a chemical engineering professor at Drexel University, Lowman specializes in hydrogels—versatile blends of gelatinous particles and water. Certain medications, such as insulin, cannot be taken orally because enzymes in the stomach break them down before they can be absorbed into the bloodstream. Lowman created a novel way of shielding insulin inside polymer-based hydrogels. The hydrogels have pores that can hold insulin and open only in response to the high pH of the upper small intestine; there, the insulin diffuses into sur- rounding tissue.The technology, now in animal testing, could enable patients with type 1 dia- betes (more than a million in the United States) to take insulin-filled gel pills in lieu of injec- tions. Lowman is researching a similar approach to delivering drugs for cancer, osteoporosis, and other conditions. In his part-time job as chief technical officer for Gelifex, a Philadelphia- based company he cofounded in 2002, Lowman is designing injectable hydrogels for repair- ing degenerative discs, the cause of back pain in five million Americans. He recently prepared a gel that could restore disc pressure and function. Clinical trials may begin in late 2004. w w w. t e c h n o l o g y r e v i e w. co m T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 81 Nimmi Ramanujam, 35 University of Wisconsin-Madison Uses light to help make diagnosing breast and cervical cancer faster, more accurate, and less invasive have cancer? Is my unborn child in trouble? University of Wisconsin-Madison biomedical engineer Nimmi Ramanujam DO I believes that the millions of women who face these questions each year deserve more accurate answers than those afforded by today's diagnostic technologies. Consider breast biopsies. Doctors sometimes miss the tumor cells they're trying to sample, so Ramanujam has developed a device that can help guide a biopsy needle to just the right spot. An optical fiber threaded through the needle shines light of different wavelengths on cells at the needle's tip; molecules in cancer cells respond by fluorescing in characteristic ways, and sensors register the fluorescence. Ramanujam and her colleagues are already testing the technology in patients undergoing breast cancer surgery and plan to test it in patients undergoing breast biopsy within the next year. A cervical-cancer detector she began developing as a gradu- T R 10 0 B I O + M E D I C I N E ate student uses a similar approach; it is now in large-scale human trials. Ramanujam is also harnessing light to noninvasively monitor how well oxygen is getting to fetuses, an important—and currently unmeasurable—indicator of when emergency cesarean sections are needed. With Ramanujam's help, those babies will be born into a world where medical questions get better answers. Shuvo Roy, 33 Ram Samudrala, 31 Cleveland Clinic Foundation University of Washington Builds tiny machines that can warn Wrote algorithms that can of impending heart attack and monitor predict the functions of proteins healing after surgery from the sequence of a genome AS A graduate student, Shuvo Roy devel- SINCE BEFORE University of Wash- oped microelectromechanical systems ington assistant professor Ram (MEMS)—tiny machines like sensors and Samudrala was born, scientists have actuators—for airplane and rocket en- been striving to predict from an gines. He had an aerospace job lined up, organism's DNA sequence the iden- but inspired by his father, a public-health tities and workings of its many pro- physician, he wanted to "impact people's teins. Such an understanding could lives more directly."The Bangladesh native lead to improved treatments for switched career paths in 1998, cofounding diseases, which are often caused by malfunctioning proteins. Samudrala has advanced a laboratory at Ohio's Cleveland Clinic that effort by producing algorithms that can predict the structure and function of every Foundation devoted to clinical applica- protein encoded by an organism's genome. By modeling changes to specific genes or pro- tions of MEMS. Roy's efforts have yielded teins, researchers can try to determine what causes proteins to go awry. One set of algo- several innovative devices and one patent— rithms Samudrala devised, with $4 million from federal and private agencies, is called with seven others pending. Among his Bioverse. Samudrala has used Bioverse to model the functions and interactions of the inventions is a wireless proteins of more than 30 organisms; other researchers are using Bioverse to find which strain and pressure proteins in pathogens would be good targets for new drugs. Posted on the Web, Bioverse microsensor that can receives 1,000 hits daily. Samudrala made the algorithms free because he is opposed to be inserted into verte- intellectual-property restrictions, as explained in his "Free Music Philosophy" statement, brae during spinal- which he published on the Web in 1994—long before the rise of Napster. fusion surgery (a main surgical option for back patients) to monitor bone fusion. Addi- Christophe Schilling, 29 tionally, Roy shrunk ultrasound imaging Genomatica technology into a high-resolution trans- Transforms microbes into fine-tuned manufacturing machines ducer small enough to glide through arter- ies on a catheter; the device can spot arte- WHEN HE was just 26, bioengineer Christophe Schilling won a small-business grant from the rial defects called vulnerable plaques, con- National Science Foundation.His plan was to reengineer the genomes of microorganisms such as sidered the leading cause of heart attacks. bacteria and yeast,which are used as living chemical factories,to produce new or better products. Roy also developed durable silicon mem- With his university mentor, Bernhard Palsson, Schilling raised $3 million to launch Genomatica in branes that could replace short-lived poly- San Diego in 2000.Today, the company is attracting partners such as Dow Chemical that want to mers as blood filters in dialysis machines— engineer microbes to churn out chemicals used to make everything from a step toward creating implantable artifi- drugs to soaps. Although that goal is not unique, Genomatica's tool is: soft- cial kidneys. "Shuvo doesn't care about ware dubbed SimPheny that decodes a microorganism's genome data into recognition," says lab codirector Aaron a "parts list"of molecular components and enables the construction of com- Fleischman. "He just wants to get tech- puter models of the microbe's metabolism. Corporate clients can then tap nology that can help people into the the models to predict a particular organism's industrial potential. Geno- hands of doctors." matica also plans to release the software to select university labs by 2004. 84 T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 w w w. t e c h n o l o g y r e v i e w. co m Mark Schnitzer, 33 Stanford University Sheds light on the functioning of individual brain cells BY COMBINING physics, neuroscience, and optics, Mark Schnitzer intends to directly observe single neurons deep below the surface of the living mammalian brain; it would be a scientific first. While working at Lucent Technologies' Bell Labs, Schnitzer crafted an incredibly small endoscope—a fiber-optic viewing device with lenses as small as 350 micrometers across. The scope illuminates brain cells that have been labeled with a fluorescent dye; detectors in the device pick up the fluorescence and software con- structs images of the cells.The device could allow neuroscientists to see how brain cells T R 10 0 B I O + M E D I C I N E function, grow, and communicate across tiny synaptic gaps. Already, researchers are preparing to use Schnitzer's tool to study how animals store long-term memories. Because it is so small, the endoscope could also be fed deep into the brain, inflicting minimal harm on surrounding neurons. Human trials are years away, but Schnitzer says eventually his tool may help doctors detect brain cancers and blood clots without biopsy. Now an assistant professor in Stanford University's departments of applied physics and biological sciences,Schnitzer continues to apply his tools to brain research. Micah Siegel, 33 Mijail Serruya, 29 Concept2Company Cyberkinetics Transforms research from universities Connects brains directly to computers in the hope of helping and national labs into successful startups paralyzed people communicate and control robotic aids THOMAS EDISON and Eli Whitney are Micah IT TAKES incredible patience to interview people so severely paralyzed they Siegel's idols—not just because they were can communicate only with the blink of an eye or the twitch of a brow. But great inventors, but because they turned it was partly impatience that inspired Mijail Serruya to do just that.The Brown University medical their inventions into revolutionary prod- student and PhD was helping to develop a "brain-machine interface," and he was eager to put it ucts. "Ninety percent of the rewards go to to work helping profoundly disabled people.Talking to them about their needs was an important the guy who figures out how to scale up step.Brain-machine interfaces could potentially allow paralyzed people to communicate through what he is doing," says Siegel. He earned computers and to control robotic wheelchairs and aids. Serruya started by fine-tuning algorithms PhDs in electrical engi- that allow signals recorded by electrode arrays implanted in the brain to change the position of neering and molecular a cursor on a computer screen. He says his colleagues were planning to explore human applica- biology at Caltech, where tions "one day,"but to him the question was,What are they waiting for? Aiming to move the inter- he codeveloped genetically face into human trials, Serruya, Brown neuroscientist John Donoghue, and two others founded engineered sensors that Foxborough, MA-based Cyberkinetics in 2001. They have hurdles to clear before they can begin change colors whenever a human tests, Serruya says, but one gets the sense that all they need is a little patience. neuron's functions are excited or inhibited. Twenty pharmaceu- tical labs are now using the sensors to test Giovanni Traverso, 27 drugs. Business success excited Siegel's Johns Hopkins University own neurons, so in 2000 he cofounded Came up with a noninvasive alternative to colonoscopy Concept2Company in Palo Alto, CA, to help other scientists commercialize A COLONOSCOPY is the best way to diagnose colon cancer, but it's so inconve- research. Since then, he has evaluated nient and unpleasant that less than 25 percent of the at-risk population ever more than 350 business proposals have one. The main alternative, a test for traces of blood in a stool sample, from university and national labs and generates a high percentage of false positives. So Giovanni Traverso, a staff has raised millions of dollars of invest- researcher at Johns Hopkins University's Kimmel Cancer Center, set out to ments in several startups. In some deals, develop a convenient gene-based stool test that would reliably detect colon C2C steps in and handles the "busi- cancer at its earliest stages—when it's still curable.Traverso had to develop A. ATEMASOV (SIEGEL); JOHN ABROMOWSKI (SERRUYA) ness functions" many scientists sophisticated methods for isolating minute amounts of relevant hate—attracting manage- DNA from feces samples patients collect at home, as well as a ment teams, licensing novel means of finding cancer-causing mutations in the DNA. In patents, schmoozing cus- an early study, the test generated no false positives, but it didn't tomers, raising capital— detect all cancers. Traverso and colleagues are working to auto- improving researchers' mate the test and boost its sensitivity; he's also about to resume chances of becoming Edis- medical school in England.With luck, as a doctor, he'll be able to ons or Whitneys. get patients to take a colon cancer test that could save their lives. w w w. t e c h n o l o g y r e v i e w. co m T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 85 Rita Vanbever, 33 Ron Weiss, 33 Catholic University of Louvain Princeton University Wants to make treating diabetes Programs living cells to sense as easy as breathing toxins or create replacement tissues DRUG FIRMS are vying to create the first inhaled RON WEISS likes to give orders. In his lab at version of insulin, which could deliver therapy Princeton University, the assistant professor more simply and effectively than needles to mil- of electrical engineering sets the conversa- lions of diabetics. Rita Vanbever's work might tion and dictates the action. His charges, give Eli Lilly the edge. An associate professor of however, are not students but cells. Weiss pharmaceutical technology at the Catholic Uni- builds synthetic DNA circuits—strings of T R 10 0 B I O + M E D I C I N E versity of Louvain in Belgium, Vanbever provided genes that operate much like the logic cir- much of the chemical expertise that led to low- cuits of computers—and injects them into toxicity porous aerosol particles that carry insulin E. coli bacteria, where they direct cell behav- deep into the lungs. The particles do not clump, as earlier, smaller and denser particles ior. His goal? Create networks of different did, and they can be used with both fast-acting and long-acting drugs. Cambridge, MA, cells that work together to sense environ- drug firm Alkermes has licensed Vanbever's techniques and is using them in partner- mental toxins, generate new tissue, or per- ship with Eli Lilly to develop inhaled human growth hormone in addition to insulin. form other jobs. Col- Barriers remain; Vanbever discovered that human immune cells known as macrophages laborating with re- in the lung's air sacs prevent up to 50 percent of such protein therapeutics from being searchers at Princeton absorbed into the bloodstream. But she is confident that her delivery methods will ulti- and Caltech, Weiss mately shrink that percentage significantly. shares almost $6 mil- lion in grants, much of it from the U.S. Defense Jennifer West, 32 Advanced Research Projects Agency. In one Rice University of his projects, Weiss leads a multiple- Synthesizes blood vessels that could reduce laboratory effort to program groups of cells the trauma of heart surgery to act as biological sentinels. Such systems could detect and pinpoint the locations of more than 500,000 U.S. residents undergo EVERY YEAR anthrax or other biological weapons. In coronary-artery bypass surgery. Soon, thanks to Rice Uni- another project, Weiss is devising faster, versity associate professor of bioengineering Jennifer more reliable ways to direct stem cells to West, that procedure may be less painful. To create a create new tissues to replace those lost to bypass,doctors must harvest a blood vessel—usually from disease or injury—which means that one the patient's leg. West, however, is growing vessels in the day a doctor might be able to order your lab. She starts by synthesizing polymers that contain bio- own cells to heal you. logical signal- ing molecules, the same mole- Daphne Zohar, 33 cules that guide PureTech Ventures tissue growth in Spots promising biotech work and helps build new companies to commercialize it the body. She molds the synthetic polymers into a blood-vessel-shaped template that is then DAPHNE ZOHAR is a serial entrepreneur who is comfortable moving into almost any seeded with three different types of live cells; by niche. She began by launching a successful olive oil brand. Then she pitched her optimizing the polymers for different cell types patented "hoofpad"—basically, a sneaker for racehorses—to veterinarians. Today in different regions of the template, she can re- she is forging biotech startups. The daughter of a Massachusetts General Hospital create the architecture of a natural vessel. The researcher, Zohar grew up around labs and has become good at recognizing com- signaling molecules direct the cells to form new mercial potential in lab work that might be otherwise unexplored. tissue, and the polymer support degrades in She is founder and CEO of Boston-based PureTech Ventures, response. Human tests of the technology could which evaluates 15 ideas a week and chooses three each year to start in five to 10 years, West says. Meanwhile, build businesses around. "Being an entrepreneur is like solving other heart patients might benefit from another a puzzle with most of the pieces missing," she says. PureTech's sta- West innovation: a polymer that could be used ble includes companies making chips that rapidly analyze pro- to coat an artery after angioplasty to prevent teins, ultrasensitive antibody tests to screen blood banks for new blockages from forming. And West's inno- infectious agents, and nanoscale drug delivery systems targeting lymph nodes to treat vations address more than heart disease. She cancer and HIV. Zohar's team and advisors at PureTech include former Pharmacia cofounded Nanospectra Biosciences in Houston and Upjohn CEO John Zabriskie and financier Todd Dagres of Battery Ventures, to develop a cancer therapy based on gold which manages $1.8 billion in capital. "I look for vision, determination, and entre- nanoparticles that destroy tumor cells. preneurial spirit," Dagres says. "Daphne possesses all those traits." 86 T E C H N O LO G Y R E V I E W O c to b e r 2 0 0 3 w w w. t e c h n o l o g y r e v i e w. co m
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Dr. Matthew E. Karlovsky, MD
Urological Surgery
- 2730 S Val Vista Dr Ste 177
Gilbert, AZ 85295
- 2 Locations
- (480) 394-0200
Dr. Matthew E. Karlovsky graduated from the SUNY Downstate Medical Center College of Medicine in 1998. He works in Gilbert, AZ and 1 other location and specializes in Urological Surgery. Dr. Karlovsky is affiliated with Banner Desert Medical Center, Chandler Regional Medical Center and Mercy Gilbert Medical Center. He speaks English and Spanish.
Gender: Male
Languages Spoken: English, Spanish
Urological Surgery
Medical School: SUNY Downstate Medical Center College of Medicine; Graduated 1998
*This physician has multiple office locations. See Office Information for details.


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Get Your Gay Access Now!
Category Bareback
Added December 01, 2013
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Despite his masculine name and vicious looking shaved head, porn stud Riddick is a submissive cocksucker who loves to get drilled in the ass. Balding stud Thomas Bjorn kneels in front of the shaven headed stud, his dick pointing to the ceiling. After some erotic eye contact, Riddick gets down and dirty on the pole, doing his best to deepthroat. Once the shaft is well lubricated with his spit, Riddick lies on his back, with Thomas mounting him and easing into his butt hole. There's also some great doggy fucking - it's obvious that Rick has taken it in the ass many times before, because he can cope with even a big cock like this like a pro!
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Romney urges Liberty University grads to honor family commitments
Associated Press
LYNCHBURG, Va. — Mitt Romney's Mormon faith has shaped his life, but he barely mentioned it as he spoke to graduates at an evangelical Christian university Saturday.
And he barely touched on hot-button social issues like abortion and gay marriage, instead offering a broad-based defense of values like family and hard work.
"Culture — what you believe, what you value, how you live — matters," Romney told graduates gathered in the football stadium on Liberty University's campus in the Virginia mountains. "The American culture promotes personal responsibility, the dignity of work, the value of education, the merit of service, devotion to a purpose greater than self, and at the foundation, the preeminence of the family."
Instead of a red-meat conservative policy speech, Romney discussed his own family and offered a defense of Christianity, saying that "there is no greater force for good in the nation than Christian conscience in action." Still, he was inclusive: "Men and women of every faith, and good people with none at all, sincerely strive to do right and lead a purpose-driven life," Romney said.
He had one sustained applause line in a 20-minute speech delivered days after President Barack Obama historically embraced gay marriage. "Marriage is a relationship between one man and one woman," Romney said to a cheering crowd of students who have to follow a strict code of conduct that considers sex out of wedlock and homosexuality to be sins.
On Saturday, Obama was not seeking to revisit the issue of gay marriage. In his weekly radio and Internet address, the president didn't mention his history-making endorsement. Instead, he repeated his call for congressional lawmakers to take up a "to-do list" of tax breaks, mortgage relief and other initiatives that he insists will create jobs and help middle-class families struggling in the sluggish economy.
Having spent part of the week on the West Coast raising money for his re-election effort, Obama appeared in the Rose Garden of the White House to honor award-winning law enforcement officers.
It was Obama's first joint appearance with Vice President Joe Biden after Biden, according to aides, apologized to the president for pushing gay marriage to the forefront of the presidential campaign and inadvertently pressuring Obama to declare his support for same-sex unions.
Obama and Biden were all smiles as they walked to the sun-splashed ceremony together. Introducing Obama, Biden credited the president's commitment to law enforcement and the two quickly embraced before Obama spoke.
The late Rev. Jerry Falwell founded Liberty University in 1971 to be for evangelical Christians "what Notre Dame is to young Catholics and Brigham Young is to young Mormons," as his son, University Chancellor Jerry Falwell Jr., said on commencement day. It's become a destination for Republican politicians looking to speak to the religious right, and Romney's campaign team — planning the speech long before gay marriage became a central issue — viewed it as an opportunity to address the kind of socially conservative audience that had been wary of him during the prolonged GOP primary fight.
For Romney, the challenge is twofold. His past policy positions, including support for abortion rights, don't sit well. But his personal faith is also an issue because many evangelicals don't consider Mormons to be fellow Christians. Evangelicals are a critical segment of the GOP base; many of those voters backed his GOP rivals in the prolonged primary.
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text:
Easy On The Eyes
Easy On The Eyes
- 26 Pins
Hair salon, 1960's
Hair Salons, Hairstyles, Vintage Hair, Makeup, 1960S, Big Hair, Hair Style, Vintage Beautiful, 60S Hair
60s Hair Salon.... Big hair to die for.
"VINTAGE HAIR AND MAKEUP" (at Mishmash Vintage Hiar: is just as the titles says) is a collection of photos Tumbler style of all vintage beauty, like hair styles, facial looks, makeup, etc. It has a unique style and collection, especially the beauty parlor and school shots included. A must check up on often type of place.
Reminds me of "Where The Wild Things Are" :)
The Queens, Invisible Crowns, Black And White, Invi Crowns, Black White, Modern Princesses, Queens Bees, Hair, Queens Of Heart
photo booth idea: queen of hearts
Modern princess
Don't call me princess, I'm the Queen Bee :)
beautiful, black and white
always were your invisible crown #princess #fashion #style #lifestyle
Thomas Beaudoin
Etcof Men, Eye Candyyyy, Handsome Men, Thomas Beaudoin, Man Candies, Eye Candies, Flower Kind, Handsome Man, Hot Guys
I honestly think this guy is the most handsome man I have ever seen in my life!
Thomas Beaudoin Canadian actor and model,
Photo: Im not a hearts and flowers kind of man. I dont do romance - CG
Thomas Beaudoin - Fireman with the kitten and margaritas :)
Sauza Tequila, Hot Fireman, Fuzzy Firemen, Firemen Hotties, Sauza Fireman, Sell Sauza, Eye Candies, Fireman Sell, Drinks Tequila
Time for me to start drinking tequila again!
Sexy Fireman Sells Sauza Tequila!!! i want a drink!!
Jill Smith
That ad made me scream with laughter when I first saw it.
Elaine Tomei Wolfson
I laughed, too. Funny AND sexy. It's about time that women have some commercials aimed at them that feature hot guys; men have had sexy women in their commercials for year.
Rottweil, Baden-Wurttemberg, Germany
Doors, Bays Windows, Balconies Gardens, Windowboxes, Windows Boxes, Beautiful, Germany, Baden Wurttemberg, Flower Boxes
beautiful windowboxes
Rottweil, Baden-Wurttemberg, Germany (by SBA73) Balcony Garden
window boxes on a bowed bay window - Rottweil - Baden-Württemberg Germany
Beautiful window boxes in Germany, but could have been anywhere in Europe
window boxes in Germany OK, it's not a door, but wow!
Flower boxes under bay windows in Rottweil - Baden-Württemberg Germany
~ r\ottweil ~ baden wurttemberg ~ germany ~
Linda Evangelista
Fashion Photographers, Fun Photography, Avec Style, De Vintage, Super Models, Super Linda, Colours Photography, Linda Evangelista, Supermodels Style
When Models were, Super. Linda Evangilista
Gorgeous, vintage, supermodel style with LInda Evangelista.
Yıllar geçse de vintage ruhu hiç bir zaman eskimeyecek.
Peacocks Inspiration, Inspiration Necklaces, Peacocks Design, Artsy Fartsy, Things Peacocks, Pretty Peacocks, Peacocks Feathers, Pictures Wall, Peacocks Brooches
Peacock inspired necklace, perfect with a long chain.
I can't tell if it's a peacock brooch or picture wall art but I can tell its sooo pretty!!!
I love Peacock designs!
pretty peacock feathers
Fall in Paris. Perfection. via thingsthatsparkle...
Parisians Sensibility, Adorable J Paris, Adventure, Dreamy Paris, Eiffel Towers, Beautiful, Places I D, Paris Interiors, Photography
Eiffel Tower
dreamy Paris
Parisian sensibility
Loving this art work series by Rosanne Olson
Red Toes, Swimming Pools, Painting Toes, Roseanne Olson, Rosanne Olson, Water Prints, Water Series
love the color of the water and her pretty painted toes
Beautiful lady in water print
Blue Swimming Pool
Women in Water series by Rosanne Olson.
roseanne olson... little red toes.
Mathilde Nivet, living in Paris - works in paper
Lights, Paris, Paper Architecture, Art Photography, Paper Art, Windows Display, Architecture Exhibitions, Mathilde Nivet, Mathildenivet
Mathilde Nivet paper-cut buildings with lighting, trees, balconies, and other decorative details. #paper #art
paper architecture exhibition in paris
Paper cut window display
paper! by #mathildenivet
delicate pink Cherry Blossoms
Cherries Blossoms, White Flower, Secret Gardens, Spring Flower, White Rose, Company Picnics, Summer Picnics, Cherries Trees, Flower Photography
Secret Garden Cherry Blossoms
Beautiful white flowers.
spring flower
Beautiful white #Rose garden #Rose flowers #Roses| http://roseflowergardens847.blogspot.com
delicate pink Cherry #summer picnic #picnic #prepare for picnic #company picnic| http://picnic184.blogspot.com
Blossom #nature #flower #Photography
Cherry tree (Sakura)
Juliet's house
House Loveforeverromeo
mixed media
Thoughts, Woman Quotes, Art Journals, Stronger, Mixed Media, Collage, Quotes Women, Inspiration Quotes, Jeanne Olive
Stronger than she thought. Mixed media. Jeanne Oliver.
"Stronger Than She Thought" by #JeanneOliver // #type #collage #mixedmedia awesome
Yes you are! Great art journal page...
Love the modern home, but the green wall outside definitely wins.
Green Home, Kitchens Interiors, Kitchens Design, Dreams Kitchens, Mim Design, Interiors Design, Greenhouses, Windows, Glasses House
Love love love the full window walls in this conservatory kitchen...reminds me of the glass house
kitchen designs 0 Mystery Misc. (35 photos)
#kitchen #interior #design #homedecor
Green home
kitchen with sunroom ... and windows / skylight ... and black / green = my dream kitchen!
Dream kitchen #dreamyrooms #lovelykitchen #greenhouse #calm #peace
greenhouse kitchen - Mim Design
Absolutely stunning- Fairytale tree tunnel - Ireland
Forests, Trees Tunnel, Nature, Treetunnel, Northern Ireland, Places, Tree Tunnel, Robert Frostings, Fairies Tales
Fairy tale like natural tree tunnel in Ireland
Tree Tunnel, Meath, Ireland from sun-surfer.com I know it's crazy, but i've seen this place in my dreams
Tree Tunnel in Ballynoe, Northern Ireland I love how nature never ceases to amaze me. This tree tunnel can be found in Ballynoe, Northern Ireland near the site of the Ballynoe Stone Circle.Absolutely beautiful. #tunnel #trees #forest #dark #ireland #ballynoe
Gormanston, County Meath. | 14 Magnificent TreeTunnels
Two roads diverged in a wood, and I— I took the one less traveled by, And that has made all the difference. -Robert Frost
Beautiful autumn picture of Ireland - hay bale and sun
Beautiful Sunset, Hay Bale
Beautiful autumn picture of Ireland. Beautiful sunsets!
Stilettos Nails, Nude Nails, Hair Colors, Nails Colors, Red Hair, Rihanna Makeup, Beautiful, Popular Music, Redhair
Rihanna makeup
How much does it cost to make a hit song? I would like to make a lesson on popular music careers based on this article. check out hip hop beats @ http://kidDyno.com
love the natural makeup and nude nail color
I <3 her hair color
Loving Rihanna's look! She's rockin' it with the stiletto nails and red hair. She's my inspiration today! #nails #rihanna #redhair #beauty #BritTip Facebook.com/britpaige.style
Vintage Engagement Ring.
Vintage Engagement Rings, Vintage Wedding, Diamonds Rings, Vintage Rings, Wedding Rings, Dreams Rings, Art Deco, Antiques Rings, Vintage Style
vintage wedding ring vintage wedding ring vintage wedding ring.... WOW... dream ring right here
Art deco diamond ring
Vintage Engagement Rings | Vintage Wedding Rings for the Happy Bride Groom › Vintage Engagement ...little too much design
vintage wedding ring. Starting to love these vintage rings
Vintage Engagement Ring. Have to have an antique ring. Have to.
Art deco vintage style
vintage wedding ring vintage wedding ring vintage wedding #Vintage Styles| http://vintage-life-styles-76.blogspot.com
tree of life
Fall Leaves, Nature, Autumn, Colors, Beautiful, Japanese Gardens, Fall Trees, Japan Gardens, Portland Oregon
Under The Canopy. photo by Roman Johnston #fall #colors #trees #autumn #nature #photography
I think that I shall never see A poem lovely as a tree. A tree whose hungry mouth is prest Against the earth's sweet flowing breast; A tree that looks at God all day And lifts her leafy arms to pray; A tree that may in Summer wear A nest of robins in her hair; Upon whose bosom snow has lain; Who intimately lives with rain. Poems are made by fools like me, But only God can make a tree. ~ Joyce Kilmer, "Trees," 1914 #tree #autumn #maple #red #fall #leaves #colors #forest
Japanese garden in Portland, Oregon Beautiful tree color to enjoy
Japan garden in portland Oregon
Beautiful Fall tree in the gardens of Portland, Oregon. #autumn
Old Trees, Autumn, Trees Of Life, Beautiful, Mothers Nature, Dark Forests, Old Wood, Fall Trees, Places
I love fall. This picture perfectly captures the beauty and eeriness of autumn.
deep dark forest
LOVE LOVE LOVE! So beautiful! Old trees.
Tree of life
beautiful tree - this would be a wonderful place to relax with a good book.
old wood
mother nature is truly amazing
fall trees.
Beautiful #tree
New Orleans, Old Trees, Trees Of Life, Weeping Willow, Beautiful, Sunris, Places, Savannah Georgia, Spanish Moss
City Park New Orleans - The tree of life
Spanish moss in various places in the state, I love it and I have seen it in CA - by Monterey bay, Georgia in Atlanta and some other quaint towns And in LA near New Orleans
Spanish Moss Sunrise, Savannah, Georgia IN ABSOLUTE LOVE w/Moss dripping weeping willows!
Old trees and Spanish moss, Savannah, Georgia
Spanish Moss Sunrise, Savannah, Georgia - One of our favorite places, beautiful, we will be back!
Rinzai-ji, 1900-1910
Gardens Ideas, Albumen Prints, Temples Gardens, Forests House, Beautiful Places, 1900 1910, Handtint Albumen, Japan Gardens, Backyards
Forest house!
Temple garden In the garden of the Rinzai-ji in Shizuoka. Handtinted albumen print made between 1900 and 1910. Unknown photographer.
. . . if my backyard looked like this, I would never leave home.
I would never leave ...


text:
The Chief Minister told the Assembly that the total cost of the 1,200 buses was Rs. 253.80 crore.
Chief Minister Jayalalithaa on Thursday unveiled a major modernization programme for the State owned transport corporations and as part of the plan her government had decided to buy 1,200 new buses in the current year to replace old ones.
The Chief Minister told the Assembly that the total cost of the 1,200 buses was Rs. 253.80 crore.
She said after the AIADMK assumed office three years ago, it had completely revamped the public transport system in the State and as many as 20,684 buses were being operated for the benefit of the people.
The government also had granted Rs. 38.91 crore towards redeeming the government buses impounded by various courts in connection with accidents and transport corporations failure to pay compensation to accident victims. The government will once again release Rs. 39.73 crore as advance towards redeeming 544 buses impounded by courts.
The Chief Minister said a total of 100 small buses were being operated in Chennai to connect areas not covered by public transport. Encouraged by the response to the small buses from the public, the government has decided to buy 100 more small buses at a cost of Rs 16.75 crore.
Ms. Jayalaithaa said as many places in the state were witnessing growth on a par with district headquarters and it had necessitated new transport offices for registration of vehicles and for obtaining driving licenses. New transport offices will be set up at Manmangalam, Usilampatti, Tiruttani and Cheyyar at a cost of Rs 2.79 crore. The existing offices at Chidambaram and Tiruchendur would be upgraded as Region Transport Offices.