The Sixty-Fourth William Lowell Putnam Mathematical Competition

Contributors

THE U.S. National Research Council has appointed a group of leading chemists, physicists and mineralogists to act as provisional executive committee of the American Section of the International Union of Crystallography, which will hold its first general assembly and congress at Harvard University during July 28–August 3. The Committee consists of Prof. L. O. Brockway, University of Michigan ; Prof. M. J. Buerger, Massachusetts Institute of Technology ; Prof. J. D. H. Donnay, Johns Hopkins University ; Prof. I. Fankuchen, Polytechnic Institute of Brooklyn ; Prof. C. Frondel, Harvard University ; Dr. D. Harker, General Electric Co. ; Dr. M. L. Huggins, Eastman Kodak Co. ; Prof. A. L. Patterson (chairman), Bryn Mawr College ; Prof. L. Pauling, California Institute of Technology ; Prof. F. Seitz, Carnegie Institute of Technology ; Prof. A. N. Winchell, American Cyanamid Co. ; and Dr. R. W. G. Wyckoff, National Institute of Health. The Committee will recommend to the National Research Council a permanent constitution for the American Section of the Union, and will also advise the Council with regard to any matters which are of general concern to crystallographers in the United States. The British National Committee for Crystallography was announced in Nature of March 13, p. 390.

Contributors

Click to increase image sizeClick to decrease image size Additional informationNotes on contributorsCharles W. BagnalCharles W. Bagnal Jr. (BS, nuclear engineering, Georgia Institute of Technology, 1980) is a consulting engineer at GRP Consulting, Inc., currently engaged in reactor physics methods development and nuclear engineering support services. He has been involved in nuclear reactor design analysis and software development for six years. His experience includes advanced light water reactor (LWR) and heavy water reactor designs, including extended burnup fuel cycles using gadolinia burnable poison.Gerard P. CavanaughGerard P. Cavanaugh (BS, physics, Massachusetts Institute of Technology, 1969; MS, 1970, and PhD, 1976, nuclear engineering, University of Illinois, Urbana-Champaign) worked from 1973 to 1975 in the Neutronics Physics Division at Oak Ridge National Laboratory. He is currently supervisor of radiation physics and criticality analysis at Combustion Engineering, Inc. (C-E). His primary technical interests are in the areas of radiation transport, stochastic sampling methodologies, and computer applications ranging from mainframes to personal computers.Robert P. HarrisRobert P. Harris (BS, 1974, and MS, 1975, nuclear engineering, and MS, 1984, metallurgy, Rensselaer Polytechnic Institute) has worked in the core design, safety analysis, and licensing of C-E pressurized water reactors since 1973. He is currently involved in the neutronic design of advanced burnable poisons and fuel assemblies. He consults in the areas of core fuel management, safety analysis, and startup physics testing.Regis A. MatzieRegis A. Matzie (BS, physics, U.S. Naval Academy, 1965; MS, 1971, and PhD, 1976, nuclear engineering, Stanford University) is currently the manager of analog plants in the nuclear engineering department at C-E. His current technical interests include advanced LWR designs, methods of improving fuel utilization and fuel cycle costs in current design LWRs, and alternate fuel cycles for advanced converter reactors.Laszlo B. TarkoLaszlo B. Tarko (BS, physics, University of Connecticut, 1980) is currently the lead engineer in the radiation physics group at C-E. His current technical interests include radiation transport, ex-core radiation physics, dose rates, energy deposition, and associated computer techniques.Howard OckenHoward Ocken (D. Eng., metallurgy, Yale University, 1966) is a project manager in the Nuclear Power Division of the Electric Power Research Institute. He has managed projects that addressed materials performance in nuclear core components. His current interests include materials aspects associated with reducing radiation fields, especially replacing cobalt sources and decontamination and preconditioning technology.Per Hedemann JensenPer Hedemann Jensen (BSc, electronic engineering, Technical University, Aarhus, Denmark, 1970) is a senior health physicist at Ris0 National Laboratory, where he is head of the Section for Applied Health Physics. He has been involved in studies of radiological consequences from hypothetical core-melt accidents at nuclear power plants. His current technical interest is experimental work on internal dosimetry problems.Ian J. HastingsIan J. Hastings (PhD, metallurgical science, University of Queensland, 1968) is head of the Fuel Properties and Behaviour Group in the Fuel Materials Branch at the Chalk River Nuclear Laboratories (CRNL) of Atomic Energy of Canada Limited. His current interests are in oxide fuel behavior under irradiation, particularly release of short-lived fission products under normal and accident conditions, and in fusion ceramics.Elio MizzanElio Mizzan (BA Sc, chemical engineering, University of Toronto, 1949) is a supervisor at the Fuel Materials Branch Hot Cell Facility at CRNL. His interests have been in the areas of postirradiation examination of reactor fuels and materials, particularly postdefect handling of spent U02 fuel.Alan M. RossAlan M. Ross (BSc, general, University of London, 1953) is a supervisor at the Recycle Fuel Fabrication Laboratories of the Fuel Materials Branch of CRNL. His interests include the fabrication, nondestructive assay, properties, irradiation behavior, and neutron radiography of current and advanced thermal reactor fuels.John R. KelmJohn R. Kelm is a research technician in the Fuel Materials Branch at CRNL. His research responsibility is the operation of a special project hot cell. His current interest is U02 oxidation and stress corrosion cracking.Real J. ChenierReal J. Chenier is a research technician in the Fuel Materials Branch at CRNL. His current research responsibility is operation of the postirradiation metallographic facilities.D. H. RoseD. H. Rose is a research technologist in the Fuel Properties and Behaviour Group of the Fuel Materials Branch at CRNL. His current responsibility is fabrication and operation of instrumented in-reactor experiments.J. NovakJ. Novak (BASc, engineering science, University of Toronto, 1974) is employed in Central Nuclear Services, Nuclear Generation Division of Ontario Hydro. Since 1976 he has been engaged in the areas of nuclear fuel production and development. His current technical interests include behavior of irradiated fuel in air, U02 powder characteristics, and fuel performance improvement.Claudio RonchiClaudio Ronchi (Dr. rer. nat. phys., State University, Milan, Italy, 1965) is a research officer at the Joint Research Centre (JRC) of the Commission of European Communities. After having worked in the research and development of advanced fuels for fast breeders, he is now engaged in reactor safety studies.Jacques van de LaarJacques van de Laar (Ingenieur Fysische Techniek, H.T.S., Heerlen, The Netherlands, 1974) works in thec mathematical modeling department of JRC-Karlsruhe. He is currently involved in the development and execution of computer programs for reactor fuel performance and safety analysis.Hubert BlankHubert Blank (PhD, metal physics, Technical University of Stuttgart, 1957), head of the Physics Division of the European Institute for Transuranium Elements, Karlsruhe, has directed the “Swelling of Advanced Fuels” project at this institute since 1973.Tetsuo FukasawaTetsuo Fukasawa (BS, 1976; MS, 1978; and Dr. Eng., 1981, nuclear engineering, Tohoku University) is a researcher in the Energy Research Laboratory (ERL), Hitachi, Ltd. He has specialized in the radiochemistry of actinide elements and is currently working in the field of low-level radioactive waste treatment and spent fuel reprocessing.Koichi ChinoKoichi Chino (BS, 1972, and MS, 1974, mechanical engineering, Tokyo Institute of Technology) is a researcher at ERL. His primary areas of interest are transport phenomena and radioactive waste management.Osamu KuriyamaOsamu Kuriyama (BS, 1973, and MS, 1975, Tohoku University) is a researcher at ERL. His current interests include the radioactive waste management and chemistry of nuclear waste.Fumio KawamuraFumio Kawamura (BS, chemical engineering, Gunma University,1970; MS, 1972, and Dr. Eng., 1976, Tohoku University) is a researcher at ERL where he is involved in radioactive waste management and reactor water chemistry.Hideo YusaHideo Yusa (BS, physics, Tohoku University, 1959; Dr. Eng., Osaka University, 1969) is a chief researcher at ERL. He is responsible for the research and development of radioactive waste management systems.Bernard L. CohenBernard L. Cohen (BS, Case Institute of Technology, 1944; MS, University of Pittsburgh, 1948; DSc, Carnegie Institute of Technology, 1950) did basic research on nuclear structure using accelerators at Oak Ridge National Laboratory from 1950 to 1958 and at the University of Pittsburgh until the mid-1970s. He then turned his research efforts to the environmental impacts of energy generation, including studies of radioactive waste, health effects of radiation, risk and risk aversion, radon problems, and reactor safety. He is a professor of physics at the University of Pittsburgh and a former director (1965 to 1978) of its Scaife Nuclear Laboratories.K. TasakaK. Tasaka (PhD, nuclear engineering, University of Tokyo, 1976) first worked in breeder reactor safety and fission product characteristics research for ten years and in light water reactor (LWR) safety research for nine years at the Japan Atomic Energy Research Institute (JAERI). He is the project leader of the Rig of Safety Assessment (ROSA) program, and his current interests include analysis of thermal-hydraulic behavior during a loss-of-coolant accident (LOCA) and an anticipated transient without scram in LWRs.M. SuzukiM. Suzuki (MS, mechanical engineering, Kyoto University, 1971) has worked for the ROSA program since 1974. His current interests include safety evaluation of an LWR.Y. AnodaY. Anoda (PhD, mechanical engineering, University of Tokyo, 1979) is a research engineer for the ROSA program. His current interests include two-phase flow during a LOCA.Y. KoizumiY. Koizumi (PhD, mechanical engineering, University of Tokyo, 1977) is a research engineer for the ROSA program. His current interests include analysis of thermal-hydraulic behavior during a LOCA with emphasis on two-phase flow characteristics and heat transfer.T. YonomotoT. Yonomoto (MS, nuclear engineering, University of Osaka, 1982) is a research engineer for the ROSA program. His current interests include analysis of thermal-hydraulic behavior during a LOCA.H. KumamaruH. Kumamaru (PhD, nuclear engineering, University of Tokyo, 1980) is a research engineer for the ROSA program. His current interests include core heat transfer under LOCA conditions.H. NakamuraH. Nakamura (MS, crystalline material engineering, Nagoya University, 1981) is a research engineer for the ROSA program. His current interests include analysis of thermal-hydraulic behavior during a LOCA.M. ShibaM. Shiba (MS, mechanical engineering, Waseda University, 1959) is the general manager of Reactor Safety Laboratory 1 at JAERI. He has worked for 22 years at JAERI in the field of reactor engineering and safety and is currently responsible for simulated LOCA experiments.Genichi MatsumotoGenichi Matsumoto (BS, physics, Tokyo University, 1946) has been an associate professor of nuclear engineering at Nagoya University from 1963 to the present, where he is responsible for research and education in nuclear reactor engineering. He worked as a member of the Scientific Research Institute of Tokyo following his graduation from Tokyo University, and from 1950 to 1963, he served on the technical staff of the Research Reactor Operation Division of the Japan Atomic Energy Research Institute. His current research field includes nuclear safety, neutron radiography (especially neutron television technology), and heat pipe technology.Soichi DoiSoichi Doi (BS, 1976, and MS, 1978, nuclear engineering, Nagoya University) has been employed by the Mitsubishi Atomic Power Industry Co. since 1978, where he is responsible for the nuclear fuel engineering of light water reactors.Kohei OhkuboKohei Ohkubo (BS, mechanical engineering, Aichi Institute of Technology, 1975) is a staff member of Nagoya University.Yasushi IkedaYasushi Ikeda (BS, physics, 1963, and PhD, nuclear engineering, 1982, Nagoya University) has been an assistant staff member of Nagoya University from 1964 to the present. He has investigated thermodynamics of nuclear materials using mass spectrometric technology; neutron radiography technology is also included in his research interests.Günther HesselGünther Hessel [BS, physics, Technical University Dresden, German Democratic Republic (GDR), 1970] is a research scientist at the Central Institute of Nuclear Research (CIN), Rossendorf. He is involved in experimental investigations and developments for technical diagnosis, especially at nuclear power plants.Hans-Erich KöppenHans-Erich Köppen (BS, computer science, Technical University Dresden, 1973) is a research scientist at the CIN. His area of expertise is microprocessor hard- and software and the construction of autonomously working monitors.Peter LiewersPeter Liewers (BS, physics, University of Halle, GDR, 1957; PhD, physics, University of Leipzig, GDR, 1962) is the scientific leader of the group for reactor diagnostics at the CIN. His interests and activities have shifted from reactor physics to technical diagnostics.Peter SchumannPeter Schumann (BS, nuclear engineering, Technical University Dresden, 1963; PhD, physics, Bergakademie Freiberg, GDR, 1970) is a staff scientist at the CIN where he is concerned with digital signal processing and computer software. Formerly he worked in the field of in-core measuring techniques and neutron spectrometryFrank-Peter WeiβFrank-Peter Weiβ (BS, physics, Technical University Dresden, 1973) is a research scientist in the group for technical diagnostics at the CIN. His current interest is the application of statistical pattern recognition to technical diagnostics.

A New Era

Focus on Authors

In January 1967 the Atomic Energy Commission established a Panel on High Energy Physics, for the purpose of providing advice and guidance to the commission in this area of physical science research. The panel reports to the Division of Research of the Atomic Energy Commission. It was established to consider important matters relating to this area of research and advise the commission concerning the best course of action to be taken in the interest of a vigorous and productive national high-energy-physics program. The panel is composed of 11 physical scientists; at present the membership list is as follows: Rodney L. Cool, Brookhaven National Laboratory; Earle C. Fowler, Duke University; Leon Ledermann, Columbia University; Edward J. Lofgren, Lawrence Radiation Laboratory; George E. Pake, Washington University; W. K. H. Panofsky, Stanford University; Robert Sachs, Argonne National Laboratory; Keith R. Symon, University of Wisconsin; Robert L. Walker, California Institute of Technology; C. N. Yang, State University of New York, Stony Brook; V. F. Weisskopf (chairman), Massachusetts Institute of Technology. When the following report was written, R. R. Wilson, of Cornell University, was also a member. He resigned because of the pressures of his new duties as director of the 200-Bev National Accelerator Laboratory. One of the first tasks which the panel has set itself is a review of the present status and problems of high-energy physics in the United States and, in particular, the impact of the recent budget restrictions on these activities. The panel has issued a status report on this subject, pointing out the difficulties arising from the large discrepancy between the long-range budget forecasts made in a policy statement of the AEC which was submitted to Congress by the President in 1965 and the financial support actually provided high-energy physics. The report analyzes the serious consequences for the future of this fundamental field in which the United States has invested much effort and money. The report was submitted to the Atomic Energy Commission and was subsequently transmitted to the Joint Committee for Atomic Energy of the Congress. It is presented here with minor changes for a wider audience.

Authors

Authors

In America Fledges Wings R. M. Cleveland [1] stated: Despite the importance of the role played by the Daniel Guggenheim Fund for the promotion of aeronautics as a herald, as an awakener, as a quickening spark in the manifold fields of practical aviation, its most important and probably most lasting contribution lay in its implementation and its creation of centers of research. These centers of research are the well-known great schools of aeronautical engineering at the New York University, the Stanford University, the University of Michigan, the Massachusetts Institute of Technology, the California Institute of Technology, the University of Washington, and the Georgia School of Technology. It is a fact that a great majority of practicing aeronautical engineers today are either wholly educated in one of these centers or have had contact with one of these centers. Moreover, the strong influence of the Guggenheim Fund is not limited to this phase of aeronautical engineering. These centers of research contributed to a large extent to the fundamental knowledge of aeronautical science which forms the scientific basis of aeronautical engineering. Today we see an even more broadened effect exerted by the Guggenheim schools as men originally educated in these Guggenheim research centers establish new research laboratories and new schools of aeronautics in universities all over the world.

Preliminary operation of the new synchrotron at the California Institute of Technology has been announced by R. F. Bacher, chairman of the Caltech physics division and director of the eight-man team cooperating on construction of the machine under contract with the Atomic Energy Commission. Electrons have already been accelerated to 460 Mev, and when a lead plate was put in the path of the electron beam for test purposes, x-rays of the same energy were obtained. The previous high in electron energies was between 325 and 340 Mev produced by synchrotrons at the University of California at Berkeley, Cornell University, and the Massachusetts Institute of Technology, and by the betatron at the University of Illinois.

Annals of the New York Academy of SciencesVolume 61, Issue 4 p. 801-805 KINETICS OF THE RELEASE OF POLIOMYELITIS VIRUS FROM SINGLE CELLS A. Lwoff, A. Lwoff Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this authorR. Dulbecco, R. Dulbecco Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this authorM. Vogt, M. Vogt Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this authorM. Lwoff, M. Lwoff Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this author A. Lwoff, A. Lwoff Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this authorR. Dulbecco, R. Dulbecco Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this authorM. Vogt, M. Vogt Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this authorM. Lwoff, M. Lwoff Kerckhoff Laboratories of Biology, California Institute of Technology, Pasadena, Calif.Search for more papers by this author First published: September 1955 https://doi.org/10.1111/j.1749-6632.1955.tb42536.xCitations: 8 This work was aided in part by a grant from the National Foundation for Infantile Paralysis, Inc., New York, N. Y., and in part by a grant from Abbott Laboratories, Teterboro, N. J. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume61, Issue4Biology of PoliomyelitisSeptember 1955Pages 801-805 RelatedInformation

April 01 2009 What Makes Terrorists Tick Erica Chenoweth, Erica Chenoweth Erica Chenoweth is Assistant Professor of Government at Wesleyan University. Search for other works by this author on: This Site Google Scholar Nicholas Miller, Nicholas Miller Nicholas Miller is an undergraduate Government major at Wesleyan. Search for other works by this author on: This Site Google Scholar Elizabeth McClellan, Elizabeth McClellan Elizabeth McClellan is an undergraduate Comparative Government and Studio Art double major at Wesleyan. For a longer, more detailed version of this letter, see Erica Chenoweth's website, http://wesfiles.wesleyan.edu/home/echenoweth/web/home.htm. Search for other works by this author on: This Site Google Scholar Hillel Frisch, Hillel Frisch Hillel Frisch is Associate Professor in the Departments of Political Studies and Middle East History at BarIlan University. He thanks Stuart Cohen, Efraim Inbar, and Gordon McCormick for their helpful comments. Search for other works by this author on: This Site Google Scholar Paul Staniland, Paul Staniland Paul Staniland is a Ph.D. candidate in the Department of Political Science and member of the Security Studies Program at the Massachusetts Institute of Technology, and a Research Fellow at the Belfer Center for Science and International Affairs in the Harvard Kennedy School at Harvard University. The author would like to thank Brendan Green, Vipin Narang, Joshua Rovner, and Cyrus Samii for helpful comments. Search for other works by this author on: This Site Google Scholar Max Abrahms Max Abrahms Max Abrahms is a Social Science Predoctoral Fellow in the Center for International Security and Cooperation at Stanford University, and a Ph.D. candidate in the Department of Political Science at the University of California, Los Angeles. He would like to thank Mia Bloom, Martha Crenshaw, Matthew Gottfried, Peter Krause, Jessica Stern, Paul Stockton, and Robbie Totten for their helpful comments. He is especially grateful to Richard English for sharing his expertise over the years on the Irish Republican Army. Search for other works by this author on: This Site Google Scholar Author and Article Information Erica Chenoweth Erica Chenoweth is Assistant Professor of Government at Wesleyan University. Nicholas Miller Nicholas Miller is an undergraduate Government major at Wesleyan. Elizabeth McClellan Elizabeth McClellan is an undergraduate Comparative Government and Studio Art double major at Wesleyan. For a longer, more detailed version of this letter, see Erica Chenoweth's website, http://wesfiles.wesleyan.edu/home/echenoweth/web/home.htm. Hillel Frisch Hillel Frisch is Associate Professor in the Departments of Political Studies and Middle East History at BarIlan University. He thanks Stuart Cohen, Efraim Inbar, and Gordon McCormick for their helpful comments. Paul Staniland Paul Staniland is a Ph.D. candidate in the Department of Political Science and member of the Security Studies Program at the Massachusetts Institute of Technology, and a Research Fellow at the Belfer Center for Science and International Affairs in the Harvard Kennedy School at Harvard University. The author would like to thank Brendan Green, Vipin Narang, Joshua Rovner, and Cyrus Samii for helpful comments. Max Abrahms Max Abrahms is a Social Science Predoctoral Fellow in the Center for International Security and Cooperation at Stanford University, and a Ph.D. candidate in the Department of Political Science at the University of California, Los Angeles. He would like to thank Mia Bloom, Martha Crenshaw, Matthew Gottfried, Peter Krause, Jessica Stern, Paul Stockton, and Robbie Totten for their helpful comments. He is especially grateful to Richard English for sharing his expertise over the years on the Irish Republican Army. Online ISSN: 1531-4804 Print ISSN: 0162-2889 © 2009 by the President and Fellows of Harvard College and the Massachusetts Institute of Technology.2009 International Security (2009) 33 (4): 180–202. https://doi.org/10.1162/isec.2009.33.4.180 Cite Icon Cite Permissions Share Icon Share Facebook Twitter LinkedIn MailTo Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Search Site Citation Erica Chenoweth, Nicholas Miller, Elizabeth McClellan, Hillel Frisch, Paul Staniland, Max Abrahms; What Makes Terrorists Tick. International Security 2009; 33 (4): 180–202. doi: https://doi.org/10.1162/isec.2009.33.4.180 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsInternational Security Search Advanced Search This content is only available as a PDF. © 2009 by the President and Fellows of Harvard College and the Massachusetts Institute of Technology.2009 Article PDF first page preview Close Modal You do not currently have access to this content.

Dean Ho, PhD, a professor in the division of oral biology and the division of advanced prosthodontics as well as codirector of The Jane and Jerry Weintraub Center for Reconstructive Biotechnology at the University of California at Los Angeles (UCLA) School of Dentistry, is excited about the promise nanotechnology holds in better treating and diagnosing cancer. “A major challenge in cancer therapy is drug resistance, and our group and others are finding that when drugs are modified with nanoparticles, they are less toxic and stay in the tumor longer,” he says. “You also can add targeting agents and antibodies to focus drug delivery more effectively.” Dr. Ho's work involves nanoscale, diamond-like particles called nanodiamonds. They resemble mini soccer balls and are made from a carbon material that is well tolerated in living organisms. He and his colleagues have used nanodiamonds to deliver doxorubicin, a highly toxic cancer drug. The synthesis of the 2, known as NDX, has been studied in a variety of cancers, including those of the breast, blood, liver, and brain, generating promising results. In the realm of imaging, Dr. Ho's research team also has investigated the use of nanodiamonds in helping to better locate tumors and significantly reduce the toxicity of dyes that are injected into patients for magnetic resonance imaging. Dr. Ho began his research on nanodiamonds while at Northwestern University in 2007. “Taking this sustainable biomaterial made from mining and refining operations and watching it go from just a proof of concept to showing it's safe in large animals has been a very interesting clinical journey,” he says. “Hopefully, in the next 9 to 12 months we'll have a small clinical study.” His work is just one example of the many research projects being performed across the country that are developing nanomedical approaches to combatting cancer. The first nano drugs approved by the US Food and Drug Administration (FDA) for the treatment of patients with cancer were doxorubicin in 1995 and paclitaxel in 2005. Since that time, the field has continued to evolve. The National Cancer Institute (NCI) Alliance for Nanotechnology in Cancer has been leading funding efforts in the use of nanotechnology since 2004. The Alliance will start its third funding cycle next year and at press time was about to issue its latest grants solicitation. “Round 1 was very open, and in round 2 we suggested focusing on 4 tumor types with low survival rates: ovarian, pancreatic, lung, and brain,” says Piotr Grodzinski, PhD, director of the Alliance. “We are continuously encouraging translational work and having academics involved in the program reach out for alternative funding to move the technology to the translational and even commercial phase.” Toward that end, the Alliance funds 9 centers of excellence at academic medical centers across the country charged with developing nanotechnology applications for clinical oncology. One example of a technology that is already in clinical trials was developed by Robert Langer, ScD, codirector of the MIT (Massachusetts Institute of Technology)- Harvard Center of Cancer Nanotechnology Excellence in Cambridge, Massachusetts. Dr. Langer, who began working on nanotechnologies in the 1970s, helped to lay much of the groundwork for the field. He and his Harvard Medical School colleague Omid Farokhzad, MD, founded BIND Therapeutics in 2007 to develop innovative pharmaceutical products based on nanomedicine. Their second-generation therapeutics, known as accurins, are polymeric nanoparticles designed to deliver a payload to the tumor site and have prolonged circulation in the bloodstream. Accurins are designed to target tumors at the tissue, cellular, and molecular levels. They also have been engineered for controlled and timely release. BIND Therapeutics has collaborated or is collaborating with Amgen, Pfizer, AstraZeneca, and Roche to develop these therapeutics. The company is conducting 2 phase 2 trials of 40 patients each in the second-line treatment of non-small cell lung cancer and the first-line treatment of metastatic, castrate-resistant prostate cancer. They expect to report top-line results from these studies later this year. Other investigators who have developed promising nanotechnologies for cancer include Mark Davis, PhD, of the California Institute of Technology (Caltech) in Pasadena, California, who has developed a nanoparticle for the delivery of chemotherapeutics and small interfering RNA (siRNA), which is currently being tested in clinical trials; Chad Mirkin, PhD, of Northwestern University in Chicago, Illinois, who has designed a wide range of diagnostic devices for the detection of biomarkers; and James Heath, PhD, also of Caltech, who has developed devices that monitor levels of protein in the blood and in single cells, which are being used in immunotherapy clinical trials. “We have a good mix of diagnostic and therapeutic discoveries that are becoming more practical,” Dr. Grodzinski says, noting that in therapeutics, promising new nanoparticle platforms not only appear to reduce side effects but also enable greater accumulations of drugs at the tumor site. He points to 2 other NCI Alliance nanotechnology initiatives that are helping to advance the field. The first, known as the Nanotechnology Characterization Lab (NCL), performs preclinical efficacy and toxicity testing of nanoparticles. The NCL serves as a resource for cancer researchers investigating nanoscale particles and devices and is a collaboration between the NCI, the National Institute of Standards and Technology, and the FDA. The second is a public-private industry partnership known as Translation of Nanotechnology in Cancer. The consortium brings together government entities as well as pharmaceutical, biotechnology, and other health care-related companies to expose them to and seek their input on future directions of nanotherapeutics. Dr. Grodzinski hopes to see more clinicians involved in the early development of cancer nanotechnologies well before the clinical trial stage. “We need to have a broader exposure of these technologies to practicing clinicians so they can guide the selection of the application and become more involved in the design process,” he says. Drs. Grodzinski, Langer, and Ho agree that nanotechnology faces the same challenges as other new cancer treatments and diagnostics in terms of funding, regulatory pathways, and weighing risks versus benefits. Nevertheless, they anticipate seeing FDA approvals for some of these new nanoparticles and devices within the next 5 years. Although it is not completely clear how these materials might affect patients in the long term, that should not discourage scientists and clinicians from working to bring them into the clinic, Dr. Ho says. “People should embrace [nanotechnology] and learn as much as they can about it, because the benefits are there.” Our group and others are finding that when drugs are modified with nanoparticles, they are less toxic and stay in the tumor much longer. — Dean Ho, PhD Below are 2 recent nanotechnology drug developments in the treatment of cancer. In recent years, scientists have developed nanoparticles that deliver 1 or 2 chemotherapy drugs, but they have been unable to make particles that can deliver a larger number of drugs in a precise ratio. Recently, chemists at MIT in Cambridge, Massachusetts, have accomplished that goal. Senior author Jeremiah Johnson, PhD, an assistant professor of chemistry at MIT, and colleagues published an article in the Journal of the American Chemical Society describing how they were able to load their particles with 3 drugs commonly used to treat ovarian cancer.1 Dr. Johnson says he believes their research is the first example of a nanoparticle that delivers a precise ratio of 3 drugs and can release them in response to 3 different triggering mechanisms. The particles could potentially be designed to deliver more than 3 drugs, which would enable new treatments that could more effectively kill cancer cells while avoiding the side effects of traditional chemotherapy, he says. The investigators reported that the nanoparticles were able to more effectively kill ovarian cancer cells than particles with only 1 or 2 drugs. They have begun testing in tumors in animals. The work of encapsulating small drug molecules inside of, or chemically attaching them to, the nanoparticles becomes increasingly difficult with each new drug that is added. Dr. Johnson and his colleagues created a new type of particle that would enable the loading of many different drugs. Rather than building the particle and attaching drug molecules, they created building blocks that already include the drug and can be joined together in a very specific structure. In that way, scientists can control how much of each drug is loaded into the particle. The building block includes the drug molecule, a linking unit that can connect to other blocks, and a chain of polyethylene glycol that helps protect the protein from being broken down in the body. Hundreds of these molecules can be linked using an approach the researchers developed called “brush-first polymerization.” The study involved creating particles that carried cisplatin, doxorubicin, and camptothecin, which are used alone or in combination to treat ovarian cancer. The particles contained a ratio of the maximum tolerated dose of each drug, each of which had its own release mechanism. Cisplatin and camptothecin were designed to be released quickly whereas doxorubicin was designed to be released only when ultraviolet light shines on the particle. Once the drugs are released, polyethylene glycol is easily biodegradable, they say. The team is now working on particles that carry 4 drugs as well as ways with which to tag the particles with molecules, thereby allowing them to target tumors by interacting with proteins found on cell surfaces. Dr. Johnson adds that the nanoparticles could enable large-scale testing of potential new cancer treatments. A drug delivery system using nanomedicine technologies can precisely target cancer cells in the bone and increase bone strength to prevent the disease's progression, according to a study published recently in the Proceedings of the National Academy of Sciences.2 Researchers from Brigham and Women's Hospital and the Dana-Farber Cancer Institute in Boston, Massachusetts, developed stealth nanoparticles made of a combination of clinically validated biodegradable polymers and alendronate, which is a therapeutic agent that belongs to the bisphosphonate class of drugs. Bisphosphonates bind to calcium, which is highly concentrated in bones. The surface of the nanoparticles is decorated with alendronate, which can kill the tumor cells and stimulate new bone growth. Co-lead author Michaela Reagan, PhD, of the Dana-Farber Cancer Institute Center for Hematologic Oncology, notes that few treatment options exist for patients with bone cancer. At the same time, her colleague and co-lead author, Archana Swami, PhD, of the Brigham and Women's Hospital Laboratory of Nanomedicine and Biomaterials, says that bone is a favorable microenvironment for cancer cells that migrate from tumors such as those from the breast, prostate, and blood. The team tested the nanoparticles in mice with multiple myeloma. The mice were initially pretreated with nanoparticles loaded with the anticancer drug bortezomib before being injected with myeloma cells. The treatment led to slower cancer growth and longer survival. The drug also enhanced the strength and volume of the bone. The study authors add that their work provides proof of concept that targeting the bone marrow niche can prevent or delay bone metastasis and will pave the way for future clinical trials.

Determining both the expression levels of mRNA and the regulation of its translation is important in understanding specialized cell functions. In this study, we describe both the expression profiles of cells within spatiotemporal domains of the Arabidopsis thaliana flower and the post-transcriptional regulation of these mRNAs, at nucleotide resolution. We express a tagged ribosomal protein under the promoters of three master regulators of flower development. By precipitating tagged polysomes, we isolated cell type-specific mRNAs that are probably translating, and quantified those mRNAs through deep sequencing. Cell type comparisons identified known cell-specific transcripts and uncovered many new ones, from which we inferred cell type-specific hormone responses, promoter motifs and coexpressed cognate binding factor candidates, and splicing isoforms. By comparing translating mRNAs with steady-state overall transcripts, we found evidence for widespread post-transcriptional regulation at both the intron splicing and translational stages. Sequence analyses identified structural features associated with each step. Finally, we identified a new class of noncoding RNAs associated with polysomes. Findings from our profiling lead to new hypotheses in the understanding of flower development.