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Global quantitative phosphoprotein analysis using Multiplexed Proteomics technology.

Systematic parallel analysis of the phosphorylation status of networks of interacting proteins involved in the regulatory circuitry of cells and tissues is certain to drive research in the post-genomics era for many years to come. Reversible protein phosphorylation plays a critical regulatory role in a multitude of cellular processes, including alterations in signal transduction pathways related to oncogene and tumor suppressor gene products in cancer. While fluorescence detection methods are likely to offer the best solution to global protein quantitation in proteomics, to date, there has been no satisfactory method for the specific and reversible fluorescent detection of gel-separated phosphoproteins from complex samples. The newly developed Pro-Q Diamond phosphoprotein dye technology is suitable for the fluorescent detection of phosphoserine-, phosphothreonine-, and phosphotyrosine-containing proteins directly in sodium dodecyl sulfate (SDS)-polyacrylamide gels and two-dimensional (2-D) gels. Additionally, the technology is appropriate for the determination of protein kinase and phosphatase substrate preference. Other macromolecules, such as DNA, RNA, and sulfated glycans, fail to be detected with Pro-Q Diamond dye. The staining procedure is rapid, simple to perform, readily reversible and fully compatible with modern microchemical analysis procedures, such as matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Pro-Q Diamond dye technology can detect as little as 1-2 ng of beta-casein, a pentaphosphorylated protein, and 8 ng of pepsin, a monophosphorylated protein. Fluorescence signal intensity correlates with the number of phosphorylated residues on the protein. Through combination of Pro-Q Diamond phosphoprotein stain with SYPRO(R) Ruby protein gel stain, Multiplexed Proteomics technology permits quantitative, dichromatic fluorescence detection of proteins in 2-D gels. This evolving discovery platform allows the parallel determination of protein expression level changes and altered post-translational modification patterns within a single 2-D gel experiment. The linear responses of the fluorescence dyes utilized, allow rigorous quantitation of changes over an unprecedented 500-1000-fold concentration range.

Animals↗

Examining time trends in the Oldowan technology at Beds I and II, Olduvai Gorge.

The lithic analysis of the Bed I and II assemblages from Olduvai Gorge reveals both static and dynamic time trends in early hominids' technology from 1.8 to 1.2 m.y.a. The Bed I Oldowan (1.87-1.75 m.y.a.) is characterized by the least effort strategy in terms of raw material exploitation and tool production. The inclusion of new raw material, chert, for toolmaking in the following Developed Oldowan A (DOA, 1.65-1.53 m.y.a.) facilitated more distinctive and variable flaking strategies depending on the kind of raw materials. The unique characters of DOA are explainable by this raw material factor, rather than technological development of hominids. The disappearance of chert in the subsequent Developed Oldowan B and Acheulian (1.53-1.2 m.y.a.) necessitated a shift in tool production strategy more similar to that of Bed I Oldowan than DOA. However, the evidence suggests that Bed II hominids might have been more skillful toolmakers, intensive tool-users, and engaged in more active transport of stone tools than the Bed I predecessors. Koobi Fora hominids maintained a more static tool-using behavior than their Olduvai counterparts due mainly to a stable supply of raw materials. They differed from Olduvai hominids in terms of less battering of cores, consistent transport behavior, and few productions of side-struck flakes, indicating a regional variation of toolmaking and using practice. However, they shared with Olduvai hominids a temporal trend toward the production of larger flakes from larger cores after 1.6 m.y.a. Increased intake of animal resources and the expansion of ranging area of Homo ergaster would have led to the development of technological organization. Technological changes in the Oldowan industry are attested at Olduvai Gorge, Koobi Fora, and Sterkfontein, suggesting that it was a pan-African synchronous phenomenon, beginning at 1.5 m.y.a.

Animals↗

Computer Technology Training in the Workplace: A Longitudinal Investigation of the Effect of Mood.

How does a person's mood during technology training influence motivation, intentions, and, ultimately, usage of the new technology? Do these mood effects dissipate or are they sustainable over time? A repeated-measures field study (n = 316) investigated the effect of mood on employee motivation and intentions toward using a specific computer technology at two points in time: immediately after training and 6 weeks after training. Actual usage behavior was assessed for 12 weeks after training. Each individual was assigned to one of three mood treatments: positive, negative, or control. Results indicated that there were only short-term boosts in intrinsic motivation and intention to use the technology among individuals in the positive mood intervention. However, a long-term lowering of intrinsic motivation and intention was observed among those in the negative mood condition. Copyright 1999 Academic Press.

Journal Article↗

The way ahead--the new technology in an old society.

Biotechnology is one of the most important scientific and technological revolutions of the last century and has greatly benefited various aspects of human life. The potentials are enormous and many breakthroughs have already been achieved in the area of healthcare, food, agricultural products and environmental production. The developments in this important area provide immediate benefits to mankind and offer environmentally friendly technologies for sustainable development. The Department of Biotechnology, Government of India, set up in 1986, has played an important catalytic role in promoting this revolutionary field. Research and development, technology validation and demonstration, technology transfer, human resource development, setting up of Centers of Excellence and promoting industry-academia interactions have been some of the major achievements during the last 15 years. A unique feature of this Department is the strong interaction with scientists and institutes across the country to promote biotechnology research and development efforts for commercialization and also to benefit the rural population for socio-economic development. A large number of research institutes/universities and organizations across the country have been supported in the areas of agriculture, healthcare, environment and industry. In addition, basic research has also been an important thrust area. In order to ensure that the benefits of biotechnology reach the masses at large, a very stringent biosafety mechanism has been adopted. India is a country rich in biodiversity with two hot spots and has a strong base of expertise available in nearly all fields--thus biotechnology could flourish leading to a Bioindustrial Revolution. We are today poised to be the leaders in this field in the 21st Century.

Agriculture↗

Advances in enzyme technology--UK contributions.

Enzyme technology has been a recognised part of bioprocess engineering since its inception in the 1950s and 1960s. In this article the early history of enzyme technology is discussed and the subsequent developments in enzyme isolation, enzyme modification and process technology are described. These creative developments have put enzyme technology in a position of huge potential to contribute to environmentally compatible and cost effective means of industrial chemical synthesis. Recent developments in protein modification to produce designer enzymes are leading a new wave of enzyme application.

Animals↗

Public health implications of emerging vaccine technologies.

The field of public health and medicine stands to benefit immensely from the emerging vaccine technologies and improved application of existing technologies. Technological advances may promote: (1) greater flexibility and simplicity in the design and operation of immunization campaigns or ongoing prevention programs, including reduction in number of vaccine doses, cold chain elimination, slow-release/prolonged antigenic stimulation, reduced cost and hazard and increased ease of administration through noninvasive, oral delivery systems, greater population levels of immunization and health; (2) the development of documents by FDA, WHO, and other regulatory authorities and groups, to assist the manufacturer in the appropriate manufacturing, preclinical, and clinical development of these new vaccines; (3) a greater array of vaccines to protect the civilian and military populations; (4) increased vaccine potency; (5) vaccines eliciting mucosal immunity, cytotoxic T cells, and/or neutralizing antibody. At the end of the 20th century there remain many unconquered pathogens and noninfectious indications for which medical science suggests that vaccines could be effective. New technologies may provide the best hope to address this wide array of public health needs.

Humans↗

Ethics in health care and medical technologies.

In this paper a case is used to demonstrate how ethical analysis enables health care professionals, patients and family members to make treatment decisions which ensure that medical technologies are used in the overall best interests of the patient. The claim is made and defended that ethical analysis can secure four beneficial outcomes when medical technologies are employed: (1) not allowing any medical technologies to be employed until the appropriate decision makers are identified and consulted; (2) insisting that medical technologies be employed not merely to promote the medical interests of the patient but rather on the basis of their ability to contribute to the overall well-being of the patient; (3) challenging caregivers to reflect on the dynamic interplay between their conscious and unconscious values and consequent determinations of what is in the patient's best interests; and (4) providing a justification for selected interventions which makes possible rational dialogue between caregivers espousing different viewpoints about treatment options.

Beneficence↗

Gene technology and the drugs of tomorrow.

The progress of pharmaceutical research depends on three factors: on the evolution of medical needs, on societal attitudes, and on scientific and technical feasibility. Among the factors which are 'internal' to science, molecular biology seems to be the most important driving force, at least for the foreseeable future. The influence of molecular biology on pharmaceutical research is occurring in several distinct phases. The first phase was characterized by the use of gene technology as a production instrument for known proteins. In the second phase, gene technology is instrumental in the identification of novel proteins and in the elucidation of their gene structure and physiological function. A great number of proteins which have therapeutic potential will eventually emerge from this phase, with the more important ones like the hematopoietic factors yet to come. During the third phase, gene technology will provide proteins that can serve as pharmacological tools: receptors, ligands, enzymes, cytokines and other proteins provided by gene technology will enable us to open up new fields of pharmacology from which novel drugs, often low molecular weight chemical entities, will emerge. Finally the fourth phase will be characterized by a knowledge of gene structure and regulation extensive enough to develop a pharmacology of gene regulation and to establish somatic gene therapy. New drugs that can be expected to emerge from the interaction of molecular biology and pharmaceutical research within the next ten to twelve years are discussed. It is expected that pharmaceutical research will in the end be transformed into a discipline in which molecular biology and structural chemistry play dominating roles while synthetic chemistry will be reduced to the role of an important tool.

Genetic Engineering↗

Medical specialists prefer to withdraw familiar technologies when discontinuing life support.

OBJECTIVE: To assess how members of different specialties vary in their decisions about which form of life support to withdraw. The hypothesis was that each specialty would be more comfortable withdrawing its "own" form of life support relative to other forms and other specialties. DESIGN: Mail survey. SETTING: 24 medical centers. PARTICIPANTS: 225 specialists in six specialties and 225 comparison physicians randomly matched according to percentage of time devoted to clinical practice. MEASUREMENTS: The six specialties were linked with six life-sustaining technologies related to their special expertise: 1) pulmonologists with mechanical ventilation, 2) nephrologists with hemodialysis, 3) gastroenterologists with tube feedings, 4) hematologists with blood products, 5) cardiologists with intravenous vasopressors, and 6) infectious disease specialists with antibiotics. The subjects ranked different forms of life support in the order in which they would prefer to withdraw them. They also expressed their preferences in response to hypothetical clinical vignettes. RESULTS: In five of the six specialties, the specialists had a relative preference for withdrawing their "own" form of life support, compared with the preferences of the comparison physicians. Overall, the physicians tended to prefer withdrawing a form of life support closely linked with their own specialty. CONCLUSIONS: Just as some specialist physicians tend to reach for different technologies first in treating patients, they also tend to reach for different technologies first when ceasing treatment. Specialists' preferences for different ways to withdraw life support not only may reflect a special understanding of the limits of certain technologies, but also may reveal how ingrained are physicians' patterns of practice.

Anti-Bacterial Agents↗

Hyperbaric oxygen: a novel technology for modulating myocardial schemia-reperfusion via a single drug.

Over the years, the anecdotal medical use of oxygen has demonstrated, in a non-evidence-based manner, that it may have wide-ranging clinical consequences. Although oxygen is a critical substrate in the alleviation of hypoxia, anoxia, and ischemia, paradoxically, it also functions as a deleterious metabolite during the reperfusion of previously ischemic tissues. In adding to this controversy, a spate of new pioneering work has identified hyperoxygenation (hyperoxia) and its metabolites as solely and purposefully demonstrating cellular and clinical benefit,particularly in the field of ischemic reperfusion injury (IRI). Furthermore, the beneficial effects of oxygen have been technologically augmented by administration at doses above atmospheric pressure and at higher concentrations. The novel technology that involves oxygen treatment at supra-atmospheric pressures in high concentrations is known as hyperbaric oxygen (HBO). Although the concept of hyperbaric oxygen has been around since the mid 20th century, it is only during the past decade or so that its therapeutic potential as a new technology-based drug has been exploited for the purposes of cellular tolerance and protection. HBO has recently been shown to be a useful adjunct in several models of IRI, including myocardial infarction. How it does this remains to be elucidated. This article attempts to bring into the spotlight some pertinent developments regarding HBO and myocardial IRI, while simultaneously stimulating intellect, thought, and discussion as to whether this novel technology--HBO--which consists of only a singular drug--oxygen--is a therapy that warrants further laboratory and clinical investigation as a therapeutic modality that may be safe and cost-effective, without producing significant adverse effects.

Animals↗

[Modern network technologies for data communication in the hospital].

Modern network technologies provide the basic infrastructure for information and communication systems in the hospital today. The goal to build up a universal network infrastructure which meets the broadly varied requirements. Analysis of data communication in the hospital and the evaluation of established network technologies, as well as new developments, leads to the switching concept as the suitable solution. Two technologies play the major role in building enterprise networks: the Ethernet family, based on frame switching, and ATM, based on cell switching. Orientation on established standards is the key to free system choice and grants interoperability between systems from different manufacturers. However, the network design must meet the application and system architecture of the information technology in order to achieve successful mapping of the involved communication profiles. This means scaling of the bandwidth as needed, suitable segmenting of the network and resilient links. In a further step, policy-based networking takes advantages of prioritizing critical applications and therefore reduces interdependencies across the network.

Computer Systems↗

Feature-size limitations of microarray technology--a critical review.

The appeal of microarray technology is the possibility of large-scale parallel determination of a variety of variables simultaneously. Hence, microarray technologies attract the interest of both the scientific and business worlds alike. High-throughput screening has been the major focus of the utilization of microarray technologies in recent years, and has provided the strong driving force for developments in this field. DNA chip and biochip technologies have been developed as a consequence of worldwide activity in genome research. This review focuses on microarray-based analysis and emphasizes some of its principal constraints, especially detection limits.

Animals↗

Impact of technology on the utilisation of positron emission tomography in lymphoma: current and future perspectives.

Positron emission tomography (PET) has now gained a place in the management of patients with cancer, including those with Hodgkin's disease and non-Hodgkin's lymphoma. Restaging studies and those addressing the monitoring of response to treatment are especially in focus. Most of the knowledge gained has been achieved with dedicated BGO-based PET technology, but there are a number of developments that will impact on the use of this metabolic imaging technique in the investigation of patients with lymphoma. The challenges ahead are determined by the need for high-quality whole-body imaging associated with increased patient throughput and the need to investigate the role of new labelled ligands. The latter are likely to yield new insights into tumour cell characterisation, tumour behaviour and tumour outcome assessment. The study of new radiolabelled ligands will impose further demands for rapid dynamic data acquisition and accurate tracer quantification. Current and future developments in PET technology range from the use of new detector materials to different detector geometries and data acquisition modes. The search for alternatives to BGO scintillation materials for PET has led to the development of PET instruments utilising new crystals such as LSO and GSO. The use of these new detectors and the increased sensitivity achieved with 3D data acquisitions represent the most significant current developments in the field. With the increasing demands imposed on the clinical utilisation of PET, issues such as study cost and patient throughput will emerge as significant future factors. As a consequence, low-cost units are being offered by the manufacturers through the utilisation of gamma camera-based SPET systems for PET coincidence imaging. Unfortunately, clinical studies in lymphoma and other cancers have already demonstrated the limitations of this technology, with 20% of lesions <15 mm in size escaping detection. On the other hand, the recent development of combined PET/CT devices attempts to address the lack of anatomical information inherent with PET images, taking advantage of further improvement in patient throughput and hence cost-effectiveness. Preliminary studies using this multimodality imaging approach have already demonstrated the potential of the technique. Although the potential exists, certain technical issues with PET/CT require refinement of the methodology. Such issues include organ movement (such as respiratory motion), which strongly influences the image fusion of a rapidly acquired CT scan with the slower acquisition of a PET dataset, and the derivation of CT-based attenuation coefficients in the presence of contrast agents or metallic implants. The application of the technology for radiotherapy planning also poses a number of associated challenges. Finally, the development of dedicated PET systems based on planar detector arrangements with new detector components has the potential to improve clinical throughput by over 100%, but clinical trials using such systems have still to be carried out in order to establish the associated whole-body image quality.

Fluorodeoxyglucose F18↗

Endovascular technology and its impact on the relationships among vascular surgeons, interventional radiologists, and other specialists.

Endovascular treatment methods that are largely catheter/guidewire-based permit treatment of a variety of vascular lesions from remote access sites in a minimally invasive manner. Because these endovascular technologies have intrinsic appeal to patients and physicians, they may, if proved safe and effective, replace a substantial proportion of current vascular surgical procedures. This change will have a substantial impact on the specialties involved in their development and use, that is, vascular surgery and interventional radiology (which in this discussion includes other interventional specialists devoted to peripheral vascular disease management). The relationship between these previously distinct specialties must also be influenced greatly by the introduction of endovascular technologies, the use of which requires skills that overlap the specialties. This paper considers several possible approaches for dealing with the altered interspecialty relationships that will result if new endovascular treatment methods prove to be safe and effective. Because the development and use of these endovascular technologies require the skills and talents of vascular surgeons and interventional radiologists (or other interventionalists), a collaborative, multispecialty approach to the use of endovascular technologies is recommended as the most reasonable and optimal for patient care. Although this approach may not be applicable for every environment, it is the one most likely to minimize costs and turf battles, particularly if interspecialty conflict can be minimized by collaboration and compromises developed by a conjoint executive committee representing the leadership of the involved specialty societies.

Angioplasty, Balloon↗

Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression.

Tissue microarray technology enables the analysis of hundreds of specimens by arranging numerous 0.6-mm tissue core biopsy specimens into a single paraffin block. Validation studies are necessary to evaluate the representativeness of small disks taken from the original tissue. We validated the tissue microarray technology in colorectal carcinoma by analyzing the immunohistochemical expression of proteins involved in the two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors, hMLH1 and hMSH2 proteins for microsatellite instability (MSI) tumors. We compared in 30 colorectal carcinomas (15 MSI(-) and 15 MSI(+)), 8 microarrays disks, and the whole section of the block from which they were derived. Tumoral tissue was present in 95.7% of the microarray disks. The analysis of three disks per case was comparable to the analysis of the whole section in 99.6% (p53), 98.8% (hMLH1), and 99.2% (hMSH2) of cases. In the second part we applied the tissue microarray technology to 263 consecutive cases of colorectal carcinoma, sampled by three cores. We showed that 48.5% overexpressed p53 and 8.7% lost hMLH1 or hMSH2. Tissue microarray technology, validated in colorectal carcinoma, appears as a useful research tool for rapid analysis of the clinical interest of molecular alterations.

Adaptor Proteins, Signal Transducing↗

Ethical issues in newborn screening and the impact of new technologies.

Medical ethics is an integral part of medical practice. The general principles are well known: autonomy (the right to choose), beneficence (do good), non-maleficence (do no harm), and justice (be fair and equitable). In newborn screening these principles must be especially carefully applied, as the intervention, screening, has not been sought by the patient, but is a form of preventive medicine. In proposing a screening programme questions to be asked are: should we do it? (is there enough benefit, not too much harm?); can we do it? (do we have the technology and skill to find the cases sought); can we afford it? The first question, with its ethical implications, is often ignored. New issues have arisen with new technology, but underlying ethical themes are the same. Tandem mass spectrometry can be used to detect about 30 very rare disorders in a single test. Proving the benefit of this (and other screening tests) is difficult because randomised controlled trials seem impractical, because of power considerations, long follow-up time, and because there is already a perceived benefit. Best possible evidence of a lower order must be sought. In future, DNA microarray technology is likely to become sufficiently inexpensive to apply to newborn screening. It is difficult to predict all the future possibilities of DNA technology in this fast-moving field. Major ethical problems are likely with the ability to detect adult-onset disorders or susceptibility to these in babies. Under what circumstances would this be ethical? We need to start debating these issues.

Ethics, Medical↗

Value of the SAGES Learning Center in introducing new technology.

BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Learning Center is a group of educational "classrooms" designed to tutor meeting attendees on specific technology-intensive content areas. The objectives of the Robotics Station were to familiarize participants with basic laparoscopic skills as implemented with surgical robotic assistance and to help them explore the benefits and drawbacks of using robotics in their institutions. METHODS: Sixty-six volunteer surgeon attendees of the 2003 SAGES meeting representing a diverse group of backgrounds and possessing varying levels of surgical experience were directed through a series of drills on two different surgical robots. Each participant was directed through a series of three drills that practiced surgically relevant skills. Participants were given feedback on their performance. They then completed a 12-question computer-based questionnaire that surveyed their personal demographic backgrounds, their impressions of robotic surgery, and their opinions regarding the learning center's utility in educating them about new technology. RESULTS: Sixty-eight percent of participants had never used a surgical robot, and 89% had never used a robot clinically. Eighty-eight percent of respondents found one or both robots easier to use than they had expected, and 91% found that one or both robots made simple surgical tasks easier compared to standard laparoscopy. Sixty-four percent of participants stated that they were more likely to pursue purchase of a robotic system for use in their practice as a result of their exposure to robotics in the Learning Center. After completing the Robotics Station, 80% of surgeons believed that current surgical robots are of clinical benefit. However, 71% of participants stated that surgical robotic systems priced above $500,000 would not be financially viable in their practices. CONCLUSION: The structured learning environment used in the SAGES Learning Center fostered among participants a positive attitude toward surgical robotics. The format of their exposure to this technology at the Robotics Station also enabled participants to gauge the potential financial value of surgical robots in clinical practice. The SAGES Learning Center Robotics Station succeeded in exposing surgeons to surgical robotics in a way that helped them assess the value of this technology for their individual practices and institutions.

Adult↗

Potential impact of advanced clinical information technology on cancer care in 2015.

New clinical information technologies now sporadically available will soon be in routine clinical use, bringing many changes to all phases of the cancer care continuum. For example, new technologies such as: (1) The next generation Internet; (2) Real-time clinical decision support systems; (3) Off-line, population-based systems; (4) Large, integrated, individual patient-level phenotypic and genotypic databases with intelligent data mining capabilities; (5) Wireless, invasive and non-invasive physiologic monitoring devices; (6) Natural Language Processing (NLP) systems; and (7) Mathematical models of complex biological systems all have the potential to impact significantly the provision of cancer care throughout its continuum. While new information management and communication techniques and technologies will reduce many of the inefficiencies and inaccuracies of our present systems, there will be an equal, and potentially far more dangerous, set of unintended consequences. Informatics investigators, cancer specialists, and health system administrators must focus on the study of what is working and what is not, as well as, on development and testing of the new clinical information management and communication technologies, if we are to be ready for the future.

Cancer Care Facilities↗