January 4, 2011 at the American Association for the Advancement of Science (AAAS) Auditorium
Moderated by Dr. Alan Leshner, AAAS Chief Executive Officer and Executive Publisher, Science.
Panel I - The Promise of Convergence.
Panelists: Dr. Phillip Sharp, Dr. Tyler Jacks, Dr. Paula Hammond and Dr. Robert Langer.
Panel II - The Future of Biomedical Research and Medicine in the Age of Convergence
Dr. Margaret Hamburg, Dr. Alan Guttmacher, Mr. Tom Kalil, Dr. Keith Yamamoto
This is the first in a planned series of three textbooks in algebraic topology having the goal of covering all the basics while remaining readable by newcomers seeing the subject for the first time. The first book contains the basic core material along with a number of optional topics of a relatively elementary nature.
Scientists look at alternatives to the mass of platinum used as international standard measure, which has lost 50 micrograms
The ‘international prototype’ kilogram, above, has lost about 50 micrograms since it was cast in 1879 – about the weight of a grain of sand. Photograph: AFP/Getty
For more than a century, all measurements of weight have been defined in relation to a lump of metal sitting in Paris. The "international prototype" kilogram has been at the heart of trade and scientific experiment since 1889, but now experts want to get rid of it.
Today, scientists will meet at the Royal Society in London to discuss how to bring the kilogram into the 21st century, by defining this basic unit of measurement in terms of the fundamental constants of nature, rather than a physical object.
"The kilogram is still defined as the mass of a piece of platinum which, when I was director of the International Bureau of Weights and Measures, I had in a safe in my lab," said Terry Quinn, an organiser of today's meeting. "It's a cylinder of platinum-iridium about 39mm high, 39mm in diameter, cast by Johnson Matthey in Hatton Garden in 1879, delivered to the International Committee on Weights and Measures in Sevres shortly afterwards, polished and adjusted to be made equal in mass to the mass of the old French kilogram of the archives which dates from the time of the French Revolution. Then, in 1889, it was adopted by the first general conference for weights and measures as the international prototype of the kilogram."Many of the other units of scientific measurement rely on the standard definition of the kilogram. A newton of force, for example, is the amount required to accelerate one kilogram at one metre per second squared. The unit of pressure, the pascal, is defined as one newton per unit metre squared.
One problem with using a lump of metal to define such a basic quantity as the kilogram is that it is liable to change over time. Measurements over the past century have shown that the international prototype has lost around 50 micrograms, around the weight of a grain of sand.
"Why should it [the current standard] be stable? It's a piece of platinum cast in London 130 years ago, full of holes, full of hydrogen," said Quinn. "What's on the surface, it's impossible to know. There are all sorts of surface layers of hydrocarbons."
Instead, experts want to link the kilogram to a fundamental unit of measurement in quantum physics, the Planck constant. Using a device called a watt balance, scientists can relate the mass of an object to the electrical energy needed to move it, using the Planck constant.
This redefinition would bring the kilogram into line with the six other base units that make up the International System of Units (SI) – the metre, the second, the ampere, the kelvin, the mole and the candela. None of these are now based on a physical reference object – the metre is defined in terms of the speed of light, for example, while the second is based on atomic clocks.
Any proposals to change the definition of the kilogram would have to be agreed at the General Conference on Weights and Measures, due to meet in Paris later this year.
Multiplexed assays that can measure protein biomarkers and internal standards are highly desirable given the potential to reduce false positives and negatives. We report here the use of a chip-based platform that achieves multiplexed immunosensing of the ovarian cancer biomarker CA-125 without the need for covalent labeling or sandwich complexes. The sensor chips allow the straightforward comparison of detectors of different sizes, and we used this feature to scan the microscale size regime for the best sensor size and optimize the limit of detection exhibited down to 0.1 U/mL. The assay has a straightforward design, with readout being performed in a single step involving the introduction of a noncovalently attached redox reporter group. The detection system reported exhibits excellent specificity, with analysis of a specific cancer biomarker, CA-125, performed in human serum and whole blood. The multiplexing of the system allows the analysis of the biomarker to be performed in parallel with an abundant serum protein for internal calibration.
Authors: Nagasuma Chandra, Raghu Bhagavat, Eshita Sharma, P Sreekanthreddy and Kumaravel Somasundaram
Abstract (provisional)
Background
Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes nicotinamide phosphoribosyltransferase (NMPRTase), which catalyses the rate limiting step in the salvage pathway of NAD+ metabolism in mammalian cells. PBEF1 transcript and protein levels have been shown to be elevated in glioblastoma and a chemical inhibitor of NMPRTase has been shown to specifically inhibit cancer cells.
Methods
Virtual screening using docking was used to screen a library of more than 13,000 chemical compounds. A shortlisted set of compounds were tested for their inhibition activity in vitro by an NMPRTase enzyme assay. Further, the ability of the compounds to inhibit glioma cell proliferation was carried out.
Results
Virtual screening resulted in short listing of 34 possible ligands, of which six were tested experimentally, using the NMPRTase enzyme inhibition assay and further with the glioma cell viability assays. Of these, two compounds were found to be significantly efficacious in inhibiting the conversion of nicotinamide to NAD+, and out of which, one compound, 3-amino-2-benzyl-7-nitro-4-(2-quinolyl-)-1,2-dihydroisoquinolin-1-one, was found to inhibit the growth of a PBEF1 over expressing glioma derived cell line U87 as well.
Conclusions
Thus, a novel inhibitor has been identified through a structure based drug discovery approach and is further supported by experimental evidence.
1. Department of Biochemistry and Biophysics and, Hormone Research Institute, University of California at San Francisco, San Francisco, California 94143, USA
2. Whitehead Institute for Biomedical Research and, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
Reactions of nitric oxide with cysteine-ligated iron−sulfur cluster proteins typically result in disassembly of the iron−sulfur core and formation of dinitrosyl iron complexes (DNICs). Here we report the first evidence that DNICs also form in the reaction of NO with Rieske-type [2Fe-2S] clusters. Upon treatment of a Rieske protein, component C of toluene/o-xylene monooxygenase from Pseudomonas sp. OX1, with an excess of NO(g) or NO-generators S-nitroso-N-acetyl-d,l-pencillamine and diethylamine NONOate, the absorbance bands of the [2Fe-2S] cluster are extinguished and replaced by a new feature that slowly grows in at 367 nm. Analysis of the reaction products by electron paramagnetic resonance, Mssbauer, and nuclear resonance vibrational spectroscopy reveals that the primary product of the reaction is a thiolate-bridged diiron tetranitrosyl species, [Fe2(μ-SCys)2(NO)4], having a Roussin’s red ester (RRE) formula, and that mononuclear DNICs account for only a minor fraction of nitrosylated iron. Reduction of this RRE reaction product with sodium dithionite produces the one-electron-reduced RRE, having absorptions at 640 and 960 nm. These results demonstrate that NO reacts readily with a Rieske center in a protein and suggest that dinuclear RRE species, not mononuclear DNICs, may be the primary iron dinitrosyl species responsible for the pathological and physiological effects of nitric oxide in such systems in biology.
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Sau đây là link download và chi tiết về Word Formation in English:
ssbauer, and nuclear resonance vibrational spectroscopy reveals that the primary product of the reaction is a thiolate-bridged diiron tetranitrosyl species, [Fe2(μ-SCys)2(NO)4], having a Roussin’s red ester (RRE) formula, and that mononuclear DNICs account for only a minor fraction of nitrosylated iron. Reduction of this RRE reaction product with sodium dithionite produces the one-electron-reduced RRE, having absorptions at 640 and 960 nm. These results demonstrate that NO reacts readily with a Rieske center in a protein and suggest that dinuclear RRE species, not mononuclear DNICs, may be the primary iron dinitrosyl species responsible for the pathological and physiological effects of nitric oxide in such systems in biology.