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At least 829 records · Page 46

Commercial researcher perspective

Protein crystallography--a research tool used to study the structure of the complex building blocks of living systems--has a lot to gain from space-based research. In order to know how a protein works in the human body, researchers must understand its molecular structure. Researchers have identified 150,000 different proteins in the body, but they now know the structure of less than a third of them. The only viable technique for analyzing the structure of these proteins is x-ray diffraction of the proteins in their crystal form. The better the quality of a protein crystal, the more useful it is to researchers who are trying to delineate its structure. The microgravity environment of space allows protein crystals to grow nearly undisturbed by convection and other gravity-driven forces that cause flaws to form in them on the ground. In space, lack of convection enables protein crystals to grow more slowly than they do on Earth, and the slower a protein crystal grows, the fewer flaws it will have. Protein crystal growth experiments have already flown on 14 Space Shuttle missions. This year's USML-1 Spacelab mission included protein crystal growth experiments conducted for commercial researchers. The results of protein crystal experiments flown thus far have been larger crystals with more uniform morphologies. The Center for Macromolecular Crystallography (A NASA-cosponsored CCDS) currently builds flight hardware to meet researchers' needs and handles sample loading and retrieval for flight experiments. Protein crystallography enables 'rational drug design': the development of drugs that bind only with the target protein and, hence, do not cause side effects. For example, pharmaceutical companies presently are interested in developing drugs that can inhibit purine nucleoside phosphorylase (PNP), a protein that plays a role in auto-immune diseases. To continue these kinds of investigations, researchers need a constant supply of protein crystals that are as free of flaws as possible. Space Station Freedom will provide the kind of research environment that will enable the production of such supplies. In addition, Freedom will provide the kind of long-duration facility required by protein crystal researchers: 40 percent of proteins require more than two weeks to crystallize.

Delucas, Larry↗

Measuring the metastatic potential of cancer cells

Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

Morrison, Dennis R.↗

Pharmacokinetics and Pharmacodynamics in Space

The Pharmacokinetics and Pharmacodynamics Panel met on 29-30 Aug. 1988 at the Lunar and Planetary Institute in Houston, Texas to discuss pharmacokinetic and pharmacodynamic implications of space flight and make recommendations for operational and research strategies. Based on the knowledge available on the physiological changes that occur during space flight, the dependence of pharmacokinetics on physiological factors, and the therapeutic requirements for future space missions, the panel made several recommendations for research. It was suggested that using medications available with a large (wide) therapeutic window will avoid unforeseen therapeutic consequences during flight. The sequence for conducting research was outlined as follows: (1) identify ground-based simulation models (e.g., antiorthostatic bed rest) for conducting pharmacokinetic and pharmacodynamic research; (2) estimate parametric changes in these models using pharmacologic agents that have different pharmacokinetic characteristics and a narrow therapeutic index; (3) verify these findings during flight; and (4) develop and identify appropriate and effective drug delivery systems, dosage forms, and regimens. The panel recommended gaining a thorough understanding of the pharmacokinetic deviations of medications that have a narrow therapeutic index (e.g. cardiovascular drugs and sedative hypnotics) in order to ensure safe and effective treatment during flight with these agents. It was also suggested that basic information on physiological factors such as organ blood flow, protein composition and binding, tissue distribution, and metabolism by hepatic enzymes must be accumulated by conducting ground-based animal and human studies using models of weightlessness. This information will be useful to construct and identify physiologically based pharmacokinetic models that can provide valuable information on the pharmacodynamic consequences of space flight and aid in identifying appropriate therapeutic regimens.

Putcha, Lakshmi↗

Continuing adventures in lysozyme crystal growth

Results obtained on the crystal nucleation and growth of lysozyme are presented. Special attention is given to the anion-protein binding, the nucleation kinetics, the mechanisms of aggregation, and the conditions that promote or inhibit lysozyme (110)-face growth rate. The emerging theory that is currently being used for data interpretation and for designing new experimental approaches is outlined.

Pusey, Marc L.↗

Severe new limits on extragalactic models of gamma-ray bursts

A new and much more restrictive limit is imposed here on the distance of gamma ray bursts (GRBs) in extragalactic models of the bursts. This limit is based on the fact that deep optical and infrared surveys do not find any host galaxies in many GRB error boxes. It is shown that 10 of the brighter GRB sources must be farther than 1 gigaparsec and that eight of these must emit more than 10 exp 13 ergs during a burst. This result is about four orders of magnitude stricter in energy than the previous limit. Five of the sources have limits in that the energy must be greater than the binding energy of a neutron star.

Schaefer, Bradley E.↗

The missing mass in clusters of galaxies and elliptical galaxies

We review the available data for the existence of dark matter in clusters of galaxies and elliptical galaxies. While the amount of dark matter in clusters is not well determined, both the X-ray and optical data show that more than 50 percent of the total mass must be dark. There is in general fair agreement in the binding mass estimates between the X-ray and optical techniques, but there is not detailed agreement on the form of the potential or the distribution of dark matter. The X-ray spectral and spatial observations of elliptical galaxies demonstrate that dark matter is also required in these objects and that it must be considerably more extended than the stellar distribution.

Mushotzky, Richard F.↗

The possibility of life on Mars during a water-rich past

Geomorphological evidence for past liquid water on Mars implies an early, warmer, epoch. In this review we compare this early warm environment to the first Gyr of Earth's history, the time within which we know life originated. We consider the key question about early Mars from the biological standpoint. How long was liquid water present? The range of answers encompasses the time interval for the origin of life on Earth. We use studies of early life on Earth as a guide, albeit a limited one, to the possible forms of evidence for past life on Mars. Presumptive evidence for microbial life on early Earth are stromatolites, layered deposits produced by microorganisms binding and trapping sediment. A search for fossils might be fruitful at sites on Mars that contained standing bodies of water over long periods of time. The ice-covered lakes of the dry valleys of Antarctica may provide analogs to the ultimate lakes on Mars as the surface pressure fell with a concomitant decrease in surface temperatures.

Mckay, C. P.↗

Structure and energetics of Cr(CO)6 and Cr(CO)5

The geometric structures and energetics of Cr(CO)6 and Cr(CO)5 are determined at the modified coupled-pair functional, single and double excitation coupled-cluster (CCSD), and CCSD(T) levels of theory. For Cr(CO)6, the structure and force constants for the totally symmetric representation are in good agreement with experimental data once basis set constants are taken into account. In the largest basis set at the CCSD(T) level of theory, the total binding energy of CR(CO)6 is estimated at around 140 kcal/mol, or about 86 percent of the experimental value. In contrast, the first bond energy of Cr(CO)6 is very well described at the CCSD(T) level of theory, with the best estimated value of 38 kcal/mol being within the experimental uncertainty.

Barnes, Leslie A.↗

Atomic structure and chemistry of human serum albumin

The three-dimensional structure of human serum albumin has been determined crystallographically to a resolution of 2.8 A. It comprises three homologous domains that assemble to form a heart-shaped molecule. Each domain is a product of two subdomains that possess common structural motifs. The principal regions of ligand binding to human serum albumin are located in hydrophobic cavities in subdomains IIA and ILIA, which exhibit similar chemistry. The structure explains numerous physical phenomena and should provide insight into future pharmacokinetic and genetically engineered therapeutic applications of serum albumin.

He, Xiao M.↗

Theoretical study of the bonding of the first- and second-row transition-metal positive ions to methylene

The geometries of the molecules formed by the interaction of the first- and second-row transition-metal cations with methylene are optimized at the modified coupled-pair functional (MCPF) level of theory using large Gaussian basis sets, and their dissociation energies are computed employing both the MCPF and internally contracted averaged coupled-pair functional (ICACPF) methods. The computed binding energies are generally in good agreement with the available experimental results, although the calculations indicate that the experimental values for ScCH2(+), TiCH2(+), and NbCH2(+) are probably too large. The nature of the bonding in each case and trends in the bonding patterns across the transition-metal rows are discussed.

Bauschlicher, Charles W., Jr.↗

Dust coagulation

The microphysics of coagulation between two, colliding, smooth, spherical grains in the elastic limit is investigated, and the criteria for sticking as a function of particle sizes, collision velocities, elastic properties, and binding energy are calculated. Critical relative velocities for coagulation were evaluated as a function of grain sizes for solicate, icy, and carbonaceous grains. It is concluded that efficient coagulation requires coverage of grain cores by an icy grain mantle. In this case, coagulation leads to only a doubling of the mass of a large grain within a dense core lifetime. It is concluded that coagulation can have a dramatic effect on the visible and, particularly, the UV portion of the extinction curve in dense clouds and on their IR spectrum.

Chokshi, Arati↗

Observation of a two-vibron bound-to-unbound transition in solid deuterium at high pressure

We have observed a two-vibron bound-to-unbound transition in solid D2 by Raman scattering at a pressure of 34(2) GPa. We investigated the transition by increasing the vibron bandwidth, through the application of pressure, until it dominated the intramolecular anharmonicity. We present an analysis of a simple Hamiltonian that gives the experimental bivibron binding energy and the critical bandwidth-to-anharmonicity ratio. Our results indicate that while the vibron bandwidth increases markedly with pressure, the anharmonicity remains constant.

Eggert, Jon H.↗

Hydrogen bonding in the benzene-ammonia dimer

High-resolution optical and microwave spectra of the gas-phase benzene-ammonia dimer were obtained, showing that the ammonia molecule resides above the benzene plane and undergoes free, or nearly free, internal rotation. To estimate the binding energy (De) and other global properties of the intermolecular potential, theoretical calculations were performed for the benzene-ammonia dimer, using the Gaussian 92 (Fritsch, 1992) program at the MP2/6-31G** level. The predicted De was found to be at the lowest end of the range commonly accepted for hydrogen bonding and considerably below that of C6H6-H2O, consistent with the gas-phase acidities of ammonia and water. The observed geometry greatly resembles the amino-aromatic interaction found naturally in proteins.

Rodham, David A.↗

Condensed-matter energetics from diatomic molecular spectra

Analyses of molecular spectra and compression data from crystals show that a single function successfully describes the dependence on interatomic separation of both the potential energy of diatomic molecules and the cohesive binding energy of condensed matter. The empirical finding that one function describes interatomic energies for such diverse forms of matter and over a wide range of conditions can be used to extend condensed-matter equations of state but warrants further theoretical study.

Kim, In H.↗

Effect of disorder on the optical properties of short period superlattices

The optical properties of disordered short period superlattices are studied using a one-dimensional tight-binding model. A difference vector and disorder structure factor are proposed to characterize the disordered superlattice. The density of states, participation number, and optical absorption coefficients for both ordered and disordered superlattices are calculated as a function of energy. The results show that introduction of disorder into an indirect band gap material enhances the optical transition near the indirect band edge.

Strozier, J. A.↗

Rotational structure in the near-infrared absorption spectrum of ozone

The lowest energy members of the near-IR absorption bands of ozone possess fine structure which is probably due to the rotation of the molecule in the upper vibronic state, suggesting that this state is metastable. A preliminary analysis of the structures as rotational subbands supports a recent theoretical assignment of the near-IR vibronic features to the 3A2 - 1A1 electronic transition. A binding energy of about 0.1 eV is inferred from the breakoff in the observed structure.

Anderson, Stuart M.↗

Collisions and close encounters between massive main-sequence stars

Smooth-particle hydrodynamics is used to investigate collisions and close encounters between two massive main-sequence stars. Approximate scaling relations and fitting formulas are given for the amount of mass loss and for the critical impact parameters for capture or merging. The more massive stars, which have smaller ratios of specific binding energy to the square of escape velocity, are more easily disrupted in collisions. As the relative velocity increases, the orbital energy of the colliding stars can only be dissipated by shock heating, and the critical capture radius decreases much faster than predicted by linear theory. The average fractional mass loss per collision in a cluster is found not to depend sensitively on the stellar velocity dispersion.

Lai, Dong↗

Effect of radiation forces on disk accretion by weakly magnetic neutron stars

Radiation forces are shown to be more important than general relativistic corrections to Newtonian gravitational forces in determining the motion of particles accreting onto a slowly rotating neutron star if the luminosity of the star is greater than about 1 percent of the Eddington critical luminosity (ECL). This is so even if the radius of the star is less than the radius of the innermost stable orbit. In particular, radiation drag causes matter accreting from a disk to lose angular momentum and spiral inward. At luminosities greater than about 0.2 ECL, a substantial fraction of the accreting matter can transfer most of its angular momentum and gravitational binding energy to the radiation field before reaching the stellar surface. These results have important implications for the X-ray spectra, time variability, and spin evolution of neutron stars with very weak magnetic fields and the prospects for detecting general relativistic effects near such stars.

Miller, M. C.↗