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PubMed1998

The Himar1 mariner transposase cloned in a recombinant adenovirus vector is functional in mammalian cells.

Mariner transposons belong to the mariner /Tc1 superfamily of class II, DNA-mediated elements. One of these transposons, Himar1 , isolated from the horn fly, is independent of host-specific factors that would limit transfer between different species, making it an ideal candidate for gene transfer technology development. To determine the activity of Himar1 transposase in mammalian cells, we introduced the Himar1 transposase gene into an adenovirus (Ad) vector under control of the phage T7 RNA polymerase promoter. Mammalian cells infected with the Ad vector carrying the Himar1 gene efficiently expressed the Himar1 transposase in the presence of T7 polymerase. In in vitro inter-plasmid transposition reactions, Himar1 transposase expressed by the Ad vector mediated precise cut-and-paste transposition and resulted in a characteristic duplication of TA at the integration site of the target plasmid. Further studies showed that this transposase was capable of catalyzing transposition between twoplasmids co-transfected into 293T7pol cells, which express T7 RNA polymerase. Combining the integration capability of mariner transposons with the transduction efficiency of Ad vectors is expected to provide a powerful tool for introducing transgenes into the host chromosome.

Adenoviridae↗
PubMed2001

A homogeneous europium cryptate-based assay for the diagnosis of mutations by time-resolved fluorescence resonance energy transfer.

Oligonucleotide ligation assay (OLA) is considered to be a very useful methodology for the detection and characterization of mutations, particularly for clinical purposes. The fluorescence resonance energy transfer between a fluorescent donor and a suitable fluorophore as acceptor has been applied in the past to several scientific fields. This technique is well adapted to nucleic acid analysis such as DNA sequencing, DNA hybridization and polymerase chain reaction. We describe here a homogeneous format based on the use of a rare earth cryptate label as donor: tris-bipyridine-Eu(3+). The long-lived fluorescence of this label makes it possible to reach a high sensitivity by using a time-resolved detection mode. A non-radiative energy transfer technology, known as time-resolved amplification of cryptate emission (TRACE((R))) characterized by a temporal and spectral selectivity has been developed. The TRACE((R)) detection of characterized single nucleotide polymorphism using the OLA for allelic discrimination is proposed. We demonstrate the potentialities of this OLA-TRACE((R)) methodology through the analysis of K-ras oncogene point mutations.

DNA, Neoplasm↗
PubMed2001

The first operational dosemeter for neutrons which complies with IEC standard 1323.

Individual neutron dosimetry represents one of the current difficulties in the field of radiological protection of workers. Since March 1999, the regulatory requirements in France for active (i.e. operational) dosimetry have been those of ICRP Publication 60, applicable from May 2000, necessitating the introduction of a new generation of neutron dosemeters. Over the last few years, the Institute for Nuclear Safety and Protection has been studying an individual electronic dosemeter for neutrons based on a semiconducting detector, capable of meeting the specifications laid down by a neutron dosimetry work group, including members from all the main players in the French nuclear industry. In 1998, the IPSN began transferring technology to the Saphymo company which, by the end of 2001, will be marketing Saphydose-n, the first individual dosemeter for neutrons which complies with IEC Standard 1323. This dosemeter is of compact design and can assess the individual dose equivalent Hp(10) in mixed neutron and gamma radiation fields. It wil be usable in any nuclear facility without prior knowledge of the average neutron spectrum or of the neutron-gamma ratio. It will be possible to connect the Saphydose-n dosemeter to any of the existing gamma deserter terminals to read the dose data and recharge the batteries.

Air Pollution, Radioactive↗
PubMed1998

Mid-Atlantic Poultry Consortium: a department head's viewpoint on regionalization.

A document outlining possible areas of coordination and cooperation among university faculty to meet the research, extension, and teaching needs of the poultry industries in the Mid-Atlantic region (i.e., in the states of Pennsylvania, Delaware, Maryland, Virginia, West Virginia, North Carolina, and South Carolina) has been developed. Poultry-oriented faculty in the region's Colleges of Agriculture and Colleges of Veterinary Medicine in the 1862 and 1890 land-grant institutions participated to varying degrees in the development of the document. Poultry scientists with the ARS/USDA, Beltsville, MD, have also expressed interest in and provided input to the plan. Three university-based committees addressed potential avenues of cooperation for academic programs, teaching, research, extension, and technology transfer. Input from those committees was summarized and presented as a basic concept paper for the development of a Mid-Atlantic Poultry Consortium at the Poultry Extension Symposium at the Poultry Science Association's annual meeting in Edmonton, Alberta, Canada, in 1995. Meetings of faculty from the participating institutions have been held twice yearly at the Southeastern Poultry and Egg Association Congress in Atlanta, GA, and at the annual Poultry Science Association meetings to specifically discuss strategies for moving forward with the plan. Unfortunately, for a number of different reasons, buy-in by individual faculty at the various institutions has, at best, been very limited. Nevertheless, some progress has been made toward increasing the amount of regional cooperation underway. Most of the cooperation to date has been in interstate extension programming, with reciprocal use of specialists with different expertise between two states, and with the joint planning of regionally based educational conferences. Some joint extension publications and a few joint applied research or demonstration projects are also underway. Currently, however, no program is in place that involves all of the region's university-based poultry groups in a single program effort. The slow development of such an effort is partially due to difficulties in communication. An attempt is currently being made to get all of the poultry-oriented faculty in the region linked via an e-mail listserve, so that individuals with needs for partnering can freely communicate their needs to others in the region who might be interested in cooperating with them.

Agriculture↗
PubMed2002

Knowledge diffusion in social work: a new approach to bridging the gap.

The continuing gap between research and practice has long been a problem in social work. A great deal of the empirical practice literature has emphasized practice evaluation (usually in the form of single-case methodologies) at the expense of research dissemination and utilization. An alternative focus for social work researchers can be found in the extensive theoretical and research literature on knowledge diffusion, technology transfer, and social marketing. Knowledge diffusion and social marketing theory is explored in terms of its relevance to social work education and practice, including a consideration of issues of culture and power. The authors present an integrated dissemination model for social work and use a case example to illustrate the practical application of the model. The OPTIONS (OutPatient Treatment In ONtario Services) project is an example of the effective dissemination of two research-based addiction treatment modalities to nearly 1,000 direct practice clinicians in Ontario, Canada.

Diffusion of Innovation↗
PubMed1990

Prospects for gene therapy.

Experiments in animal models and human cells in vitro suggest that gene transfer using retroviral vectors may be useful to treat genetic diseases and to gain information that may improve treatment of other common diseases such as cancer. The approach to treatment of genetic diseases by inserting genes into bone marrow cells and experimental models, and a novel application of gene transfer technology to cancer research are discussed herein.

Animals↗
PubMed2004

Turning on stem cell cardiogenesis with extremely low frequency magnetic fields.

Modulation of stem cell differentiation is an important assignment for cellular engineering. Embryonic stem (ES) cells can differentiate into cardiomyocytes, but the efficiency is typically low. Here, we show that exposure of mouse ES cells to extremely low frequency magnetic fields triggered the expression of GATA-4 and Nkx-2.5, acting as cardiac lineage-promoting genes in different animal species, including humans. Magnetic fields also enhanced prodynorphin gene expression, and the synthesis and secretion of dynorphin B, an endorphin playing a major role in cardiogenesis. These effects occurred at the transcriptional level and ultimately ensued into a remarkable increase in the yield of ES-derived cardiomyocytes. These results demonstrate the potential use of magnetic fields for modifying the gene program of cardiac differentiation in ES cells without the aid of gene transfer technologies and may pave the way for novel approaches in tissue engineering and cell therapy.

Cell Differentiation↗
PubMed1999

Targets for gene therapy of vein grafts.

Poor long-term patency and a lack of suitable systemic pharmacologic therapy for the prevention of vein graft failure have prompted the search for effective local gene therapy. Vein grafts are particularly well suited for gene transfer in the clinic because direct access to vein is available during surgical preparation for grafting. In this review, the available animal models are discussed and a new mouse model is highlighted. Recent advances in gene transfer technology are reviewed, including the use of adeno-associated virus and modified adenoviruses that can prolong in vivo transgene expression for months. Gene therapy is intended to reduce early thrombosis, reduce neointima formation, and prevent atherosclerosis in vein grafts. Promising antithrombotic targets include tissue plasminogen activator and thrombomodulin. Nitric oxide synthase, prostacyclin synthase, and tissue inhibitors of metalloproteinases have been used to reduce neointima formation, and vein graft atheroma remains a challenge for the future.

Anastomosis, Surgical↗
PubMed1990

China's quest for management of academic medicine.

The China Medical Board organized a management conference for the presidents of China's national medical universities. A three-person consulting team arranged by the Association of American Medical Colleges led the conference. Designed as a preliminary examination of the management problems faced by the national medical universities, the conference covered content similar to that of the AAMC Executive Development Seminars, including governance, financial management, faculty practice plans, technology transfer, information management, and organizational diagnosis. China's national medical universities are strategically managed by the Ministry of Public Health in Beijing, and for several years the ministry has increasingly decentralized the management and operational planning and control of these universities. The universities do not have enough properly trained personnel to absorb the additional management responsibilities, and the university presidents feel that they and their senior staffs need extensive training in adapting western-style management principles and practice to the Chinese setting.

Academic Medical Centers↗
PubMed1992

Beyond the college walls.

The author outlines historical and current reasons that the National Institutes of Health (NIH) and academic medicine are inherently political and are now facing expanding political exposure. She emphasizes especially the power of modern discoveries in biology; this power stems from the many practical benefits that these discoveries can bring and their economic implications, and the growing public awareness of these benefits and implications. She then discusses the political realities of the biomedical enterprise, illustrating them by describing the nature of issues surrounding (1) the NIH budget and (2) technology transfer. Discussion of the latter topic includes a detailed description of controversies about patents (which revolve around the issue of who owns and controls the distribution and use of scientific information) and several important policy issues that are raised by these controversies (e.g., should there be uniform international policies regarding intellectual property rights associated with discoveries of novel biologically expressed genes of uncertain in-vivo function, and if so, how is that achieved?). The author concludes by stating that these examples of the politics of knowledge and of the NIH are among many vital biomedical issues of American life (which she lists) that require the academic medicine community to look beyond its own walls and participate in the complex world of politics and public policy.

Economics, Medical↗
PubMed1993

Conflicts of interest and commercialization of research.

The author introduces questions about the commercialization of science, focusing on fairness and conflicts of interest, and suggests the bases for policy initiatives. First, is it fair for government-supported research to enrich research universities and individual scientists? The belief that it is unfair seems limited to biomedicine and is not shared by other fields and government research agencies. The main concerns, however, are conflicts of interest and of commitment (loss of objectivity, reordering of priorities, degradation of science as an open and collegial enterprise, conflicts of commitment, and exploitation of graduate students and postdoctoral fellows). The author outlines 11 principles that can be used in setting policies about conflict of interest and commitment, including the principles that these conflicts are inevitable, that technology transfer should be supported rather than hindered, that the type and amount of financial reward received by the faculty are not as important as the strings attached by the commercial sponsor, and that trainees must be protected from working in settings where they cannot discuss or promptly publish their work.

Academic Medical Centers↗
PubMed1996

Ethics issues in academic-industry relationships in the life sciences: the continuing debate.

The author reviews in detail the status of academic-industry relationships (AIRs) in the life sciences from both ethical and empirical perspectives, and identifies ethical issues that have been resolved and those that must still be debated. He summarizes by stating that ethical reasoning militates against the involvement of scientists and universities in those AIRs in which a financial conflict of interest on the part of life science investigators may affect the welfare of human subjects and trainees. Even in other types of AIRs, conflicts of interest have effects on professional decision making that could damage the integrity and productivity of life sciences research, especially scientists' withholding of data and their redirecting of research in more commercial directions. These effects could also help undermine public trust in and support of university researchers. Balanced against these worrisome effects are the benefits of AIRs in increasing some investigators' creativity and productivity, in encouraging technology transfer, and thus in promoting economic growth and public health. He concludes that more research is needed on the harms and benefits of AIRs, especially the development of better data on the effects of withholding data, and also on the economic and health benefits of AIRs and public attitudes toward issues of scientific research that involve possible conflicts of interest. More information on these questions would allow policymakers to make more realistic estimates of the gains and losses associated with AIRs. In the meantime, current information suggests that in general the conflicts of interest created by AIRs are real, consequential, but tolerable if managed carefully. Until more is known about the effects of AIRs, it is prudent for universities and faculty to participate at modest levels in such relationships and to monitor them carefully. This article is one of three in this issue of Academic Medicine that deal with issues of conflict of interest in university-industry research relationships. These articles are discussed in an overview that precedes them.

Biological Science Disciplines↗
PubMed2005

Research centers and institutes in U.S. medical schools: a descriptive analysis.

Research centers and institutes are a common mechanism to organize and facilitate biomedical research at medical schools and universities. The authors report the results of a study on the size, scope, and range of activities of 604 research centers and institutes at research-intensive U.S. medical schools and their parent universities. Centers and institutes with primary missions of patient care, education, or outreach were not included. The findings indicate that, in addition to research, centers and institutes are involved in a range of activities, including education, service, and technology transfer. The centers and institutes the authors studied were more interdisciplinary than those included in previous studies on this topic. Most research centers and institutes did not have authority comparable to academic departments. Only 22% of centers directly appointed faculty members, and most center directors reported to a medical school dean or a department chair. A small group of centers and institutes ("power centers"), however, reported to a university president or provost, and may have considerable power and influence in academic decision making and resource allocation. Two main types of centers and institutes emerge from this research. The first type, which includes the vast of majority of centers, is modest in its scope and marginal in its influence. The second type--with greater amounts of funding, larger staffs, and direct access to institutional decisionmakers--may have a more significant role in the organization and governance of the medical school and university and in the ways that researchers interact within and across academic divisions.

Academies and Institutes↗
PubMedDate not supplied

The role of technology in rising healthcare costs.

Historically, science and technology have been considered a means to improve the quality of life and to foster economic growth. Technology applied to healthcare has unquestionably improved the quality of life; however, the economic implications of the use of technology in medicine have created considerable controversy. How much technology is responsible for the total cost of healthcare is not clear because its role in rising costs follows the biases of who is doing the analysis. Only addressing the appropriate use of technology in medicine will result in improved health outcomes and long-term healthcare savings.

Economic Competition↗
PubMed2001

The museum's mummies: an inside view.

We applied medical and scientific methodology in a study of the mummies in the Metropolitan Museum of Art in New York, New York, by computed tomographic scanning and other radiographic methods. These noninvasive procedures allow us to "unwrap" these mummies without unwrapping them. This is, in effect, technology transfer of routine diagnostic techniques used in medicine to Egyptology. After this noninvasive information-gathering procedure, the mummies are preserved intact for possible future investigations that may be more sophisticated and more informative. The data are presented and put into perspective by a review of pertinent literature.

Adult↗
PubMed2003

Foundations for offshore wind turbines.

An important engineering challenge of today, and a vital one for the future, is to develop and harvest alternative sources of energy. This is a firm priority in the UK, with the government setting a target of 10% of electricity from renewable sources by 2010. A component central to this commitment will be to harvest electrical power from the vast energy reserves offshore, through wind turbines or current or wave power generators. The most mature of these technologies is that of wind, as much technology transfer can be gained from onshore experience. Onshore wind farms, although supplying 'green energy', tend to provoke some objections on aesthetic grounds. These objections can be countered by locating the turbines offshore, where it will also be possible to install larger capacity turbines, thus maximizing the potential of each wind farm location. This paper explores some civil-engineering problems encountered for offshore wind turbines. A critical component is the connection of the structure to the ground, and in particular how the load applied to the structure is transferred safely to the surrounding soil. We review previous work on the design of offshore foundations, and then present some simple design calculations for sizing foundations and structures appropriate to the wind-turbine problem. We examine the deficiencies in the current design approaches, and the research currently under way to overcome these deficiencies. Designs must be improved so that these alternative energy sources can compete economically with traditional energy suppliers.

Journal Article↗
PubMed2000

Transgenic tobacco and Arabidopsis plants expressing the two multifunctional sorghum cytochrome P450 enzymes, CYP79A1 and CYP71E1, are cyanogenic and accumulate metabolites derived from intermediates in Dhurrin biosynthesis.

Novel cyanogenic plants have been generated by the simultaneous expression of the two multifunctional sorghum (Sorghum bicolor [L.] Moench) cytochrome P450 enzymes CYP79A1 and CYP71E1 in tobacco (Nicotiana tabacum cv Xanthi) and Arabidopsis under the regulation of the constitutive 35S promoter. CYP79A1 and CYP71E1 catalyze the conversion of the parent amino acid tyrosine to p-hydroxymandelonitrile, the aglycone of the cyanogenic glucoside dhurrin. CYP79A1 catalyzes the conversion of tyrosine to p-hydroxyphenylacetaldoxime and CYP71E1, the subsequent conversion to p-hydroxymandelonitrile. p-Hydroxymandelonitrile is labile and dissociates into p-hydroxybenzaldehyde and hydrogen cyanide, the same products released from dhurrin upon cell disruption as a result of pest or herbivore attack. In transgenic plants expressing CYP79A1 as well as CYP71E1, the activity of CYP79A1 is higher than that of CYP71E1, resulting in the accumulation of several p-hydroxyphenylacetaldoxime-derived products in the addition to those derived from p-hydroxymandelonitrile. Transgenic tobacco and Arabidopsis plants expressing only CYP79A1 accumulate the same p-hydroxyphenylacetaldoxime-derived products as transgenic plants expressing both sorghum cytochrome P450 enzymes. In addition, the transgenic CYP79A1 Arabidopsis plants accumulate large amounts of p-hydroxybenzylglucosinolate. In transgenic Arabidopsis expressing CYP71E1, this enzyme and the enzymes of the pre-existing glucosinolate pathway compete for the p-hydroxyphenylacetaldoxime as substrate, resulting in the formation of small amounts of p-hydroxybenzylglucosinolate. Cyanogenic glucosides are phytoanticipins, and the present study demonstrates the feasibility of expressing cyanogenic compounds in new plant species by gene transfer technology to improve pest and disease resistance.

Arabidopsis↗