Philip Rea
University of Pennsylvania, Biology, Faculty Member
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Research Interests: Biochemistry, Chemistry, Biology, Calcium, Enzyme Inhibitors, and 15 moreBiological Chemistry, Biological Sciences, Saccharomyces cerevisiae, Animals, Biological, CHEMICAL SCIENCES, SIGNAL PEPTIDE, Protozoan Proteins, Amino Acid Sequence, Ion Transport, Protons, Pyrophosphatase, Molecular Sequence Data, pyrophosphatases, and Medical and Health Sciences
Research Interests: Chemistry and Xenobiotic
Publisher Summary This chapter describes the noninvasive monitoring of cerebral metabolism. The main techniques currently employed or being developed to examine cerebral metabolism and brain morphology in the diagnosis of brain damage in... more
Publisher Summary This chapter describes the noninvasive monitoring of cerebral metabolism. The main techniques currently employed or being developed to examine cerebral metabolism and brain morphology in the diagnosis of brain damage in neonates includes ultrasound scanning, X-ray computed tomography, and positron emission tomography. An instrument for optically monitoring the redox state of cytochrome aa3 must, like any spectrophotometer, contain a light source with means of wavelength selection, together with a detector and processing facilities. These are then linked together through the sample cell, which in this application is the head. At present, most instruments use an incandescent source with monochromators or narrow pass band filters for wavelength selection, and a photomultiplier tube for detection. The use of solid state components such as laser diodes, and silicon photodiodes is likely to become more widespread in the future. Laser diodes can deliver peak powers of over 50 W and are pulsed at about 1 kHz with typical pulse durations of around 200 ns. They are compact and rugged but are only generally available within a limited wavelength range, and their cost is highly dependent on both the center wavelength tolerance and quantity required.
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A characteristic feature of plants is the existence of parallel metabolic pathн ways which use either nucleotides or pyrophosphate (diphosphate, PPi) as alternative energy sources. Possibly related to the greater metabolic versatility of... more
A characteristic feature of plants is the existence of parallel metabolic pathн ways which use either nucleotides or pyrophosphate (diphosphate, PPi) as alternative energy sources. Possibly related to the greater metabolic versatility of plants versus mammals (103), this ...
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ABSTRACT Two of the major causes of death and disability in the preterm newborn of the developed nations are cerebral ischaemia and intraventricular haemorrhage. It is estimated that intraventricular haemorrhage develops in 40-50% of... more
ABSTRACT Two of the major causes of death and disability in the preterm newborn of the developed nations are cerebral ischaemia and intraventricular haemorrhage. It is estimated that intraventricular haemorrhage develops in 40-50% of infants with a birthweight of 1500 g or less but precisely how many individuals are affected by haemorrhage, or how many cases of disability are antedated by cerebral ischaemia, is not known because of the lack of effective low-cost instruments for the continuous, or at least frequent, assessment of cerebral metabolic status in the high-risk individual. In the future, however, fibre-optic-based spectrophotometric techniques for the measurement of cerebral redox state may provide low-cost, portable instruments for the noninvasive assessment of cerebral metabolism during the intensive care of the neonate.
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Research Interests: Bureaucracy and Incentive
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We have a good idea of what is happening with the discovery process in the biomedical sciences in the second decade of the twenty-first century. There is a flow of new products – drugs, devices, and agricultural innovations – which... more
We have a good idea of what is happening with the discovery process in the biomedical sciences in the second decade of the twenty-first century. There is a flow of new products – drugs, devices, and agricultural innovations – which appears to be at a pace similar to or at worst only slightly below the pace of the last 40 years: 20–30 new drugs, some new devices, and an assortment of genetically modified crops. When patent protected, as they usually are, the prices of these products seem “high” by comparison with the prices of their traditional forerunners or even older patent-protected innovations. They are definitely higher than they would be if patent law did not prohibit competing producers from making the same product. While the share of newly approved drugs that promise major improvement has been increasing modestly over time, there are nevertheless many new products of relatively small marginal benefit over current offerings. The rate of failure in R&D efforts is high and growing, and both regulatory and market barriers to highly priced innovations are said to be increasing, but without much evidence of prices coming down until a drug becomes generic or the restrictions on a device's patent are relaxed. The average R&D cost per new product that makes it to market is increasing at a rapid rate, somewhat faster than the high growth in revenues, but has slowed slightly in the last few years. Biotech firms as an aggregate have had more success in R&D productivity than their big pharma counterparts, but their costs are high and also increasing. Consumers would of course like more and better new products at lower prices, but there is no mechanism in place or on the horizon that promises this. The overarching question of public policy that these trends raise is deceptively simple: In terms of current regulations, laws, taxes, and subsidies, are there any things that government could or should do (or stop doing) at any level that on balance would make present and future generations of consumers better off? Can government make things better? Simple as this question is, the answer is both complex and less than satisfactory because we lack so many of the key facts or measures needed to come up with a persuasive answer.
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AGRIS record. Record number, US882696188. Titles, A third-category and a fourth-category H+-phosphohydrolase at the tonoplast. Personal Authors, Rea, PA,Griffith, CJ,Sanders, D. Publication Date, (1987). AGRIS Subj. Cat. Plant physiology... more
AGRIS record. Record number, US882696188. Titles, A third-category and a fourth-category H+-phosphohydrolase at the tonoplast. Personal Authors, Rea, PA,Griffith, CJ,Sanders, D. Publication Date, (1987). AGRIS Subj. Cat. Plant physiology and biochemistry. ...
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Research Interests: Biology and Arabidopsis
Two types of proton-pumping, membrane-bound inorganic pyrophosphatases (PPases), both from photosynthetic organisms, have been characterized to date and their genes cloned: the vacuolar PPase (V-PPase) of higher plants [1,2] and the PPi... more
Two types of proton-pumping, membrane-bound inorganic pyrophosphatases (PPases), both from photosynthetic organisms, have been characterized to date and their genes cloned: the vacuolar PPase (V-PPase) of higher plants [1,2] and the PPi synthase/PPase of chromatophores of the non-sulfur purple bacterium Rhodospirillum rubrum [3,4]. Despite their occurrence in phylogenetically very distant organisms, these proteins exhibit remarkable structural similarities, a property we have exploited to survey the distribution of membrane-bound PPases and their genes in different groups of photosynthetic prokaryotes, namely, non-sulfur purple bacteria, Chromatiaceae, Chlorobiaceae and cyanobacteria. Evidence obtained both at protein and DNA levels indicates that membrane-bound PPases are present in a broad range of phototrophic prokaryotes, being therefore more widely distributed than was previously thought.
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Research Interests: Biology, Metabolic Engineering, Biological Chemistry, Medicine, Protein Engineering, and 12 moreBiological Sciences, Saccharomyces cerevisiae, Heavy metals, Mutagenesis, Poisoning, Metal, Arabidopsis, Cadmium, CHEMICAL SCIENCES, Recombinant Proteins, Chelating Agents, and Medical and Health Sciences
Publisher Summary This chapter describes a method for the preparation of tonoplast vesicles. The membranes collected from the 10%–23% sucrose have two predominant enzyme activities, an ATPase and a PPase, which are qualitatively similar... more
Publisher Summary This chapter describes a method for the preparation of tonoplast vesicles. The membranes collected from the 10%–23% sucrose have two predominant enzyme activities, an ATPase and a PPase, which are qualitatively similar to those of isolated intact vacuoles. Marker enzyme activities indicate only small amounts of other identifiable membranes in the tonoplast vesicle fraction. Various applications to H + -coupled transport are discussed. For a substrate to be transported across a membrane, both a pathway and a driving force are required. Two transport systems serve to build up the proton motive force (PMF) by the direct utilization of metabolic energy (ATP or PP i ). Active transport of cations through antiport mechanisms across the tonoplast operates by coupling the flux of cations to the opposite flux of H + . The measurement of H + -coupled transport requires, then, prior loading of the vesicles with one of the exchangeable substrates (cation or H + ).
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In this book, distinguished scholars Philip A. Rea, Mark V. Pauly, and Lawton R. Burns explore the science and management behind marketable biomedical innovations. They look at how the science actually played out through the interplay of... more
In this book, distinguished scholars Philip A. Rea, Mark V. Pauly, and Lawton R. Burns explore the science and management behind marketable biomedical innovations. They look at how the science actually played out through the interplay of personalities, the cultures within and between academic and corporate entities, and the significance of serendipity not as a mysterious phenomenon but one intrinsic to the successes and failures of the experimental approach. With newly aggregated data and case studies, they consider the fundamental economic underpinnings of investor-driven discovery management, not as an obstacle or deficiency as its critics would contend or as something beyond reproach as some of its proponents might claim, but as the only means by which scientists and managers can navigate the unknowable to discover new products and decide how to sell them so as to maximize the likelihood of establishing a sustainable pipeline for still more marketable biomedical innovations.
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This review addresses the recent molecular identification of several members of the glutathione S-conjugate (GS-X) pump family, a new class of ATP-binding cassette (ABC) transporters responsible for the elimination and/or sequestration of... more
This review addresses the recent molecular identification of several members of the glutathione S-conjugate (GS-X) pump family, a new class of ATP-binding cassette (ABC) transporters responsible for the elimination and/or sequestration of pharmacologically and agronomically important compounds in mammalian, yeast and plant cells. The molecular structure and function of GS-X pumps encoded by MRP, cMOAT, YCF1, and AtMRP genes, have been conserved throughout molecular evolution. The physiologic function of GS-X pumps is closely related with cellular detoxification, oxidative stress, inflammation, and cancer drug resistance. Coordinated expression of GS-X pump genes, e.g., MRP1 and YCF1, and -y-glutamylcystaine synthetase, a rate-limiting enzyme of cellular glulathione (GSH) biosynthesis, has been frequently observed.