Diffusion Barriers in Pulsed-Gradient Spin-Echo NMR Microscopy

Diffusion barrier effects on diffusion and flow mapping by NMR microscopy were simulated for the general case of an interface between two compartments with different relaxation properties and diffusion coefficients. The extreme case of a completely impermeable barrier (i.e. a glass wall) shows substantial changes in signal intensity and phase at distances of a few micrometers from the surface. Permeable boundaries show varying degrees of intensity and phase changes that can be used for deducing permeability properties of barriers that would otherwise be below the true spatial resolution of the image. The simulations were done for the case of a solid, water-imbibing polymer immersed in water and for water diffusion between intra- and extracellular compartments across a biological membrane. These specific boundary effects have substantial implications for the determination of image resolution and for the separation and measurement of coherent flow and random diffusion.     

Resource allocation planning helper (ralph): Lessons learned

The Jet Propulsion Laboratory's (JPL) Resource Allocation Process incorporated the decision-making software system RALPH into the planning process four years ago. The principal task of the Resource Allocation Process includes the planning and apportionment of JPL's Ground Data System composed of the Deep Space Network and Mission Control and Computing Center facilities. The addition of the data-driven, rule-based planning system, RALPH, has expanded the planning horizon from eight weeks to 10 years and has resulted in significant labor savings. Use of the system has also resulted in important improvements in science return through enhanced resource utilization. In addition, RALPH has been instrumental in supporting rapid turn around for an increased volume of special “what if” studies.

This paper reviews the status of RALPH and focuses on important lessons learned from the creation of a highly functional design team, through an evolutionary design and implementation period, and through the fundamental changes to the process that spawned the tool kit. Principal topics include proper integration of software tools within the planning environment, transition from prototype to delivered software, changes in the planning methodology as a result of evolving software capabilities, and creation of the ability to develop and process generic requirements to allow planning flexibility.     

Redetermination of the carbon-rich phase boundary of uranium monocarbide

The phase boundary between UC_1+x and β UC₂ in the temperature range of 1900–2100°C and for C/U ranging from the stoichiometric up to the congruently vaporizing composition (1.00–1.08) was redetermined. Samples containing originally 4.75–4.80 wt % C were heated at constant temperatures under vacuum in a high-temperature thermobalance. Due to preferential vaporization of U the C/U ratio continuously increased under these conditions until precipitation of the second phase took place which could be deduced from the continuously recorded weight-change curves. The respective equilibrium phase boundary thus derived is markedly different from that obtained by earlier investigators on the basis of quenching experiments. Precipitation of β UC₂ occurs at much lower C/U ratios than assumed up to now.     

Protection from lymphoma cell metastasis in ICAM-1 mutant mice: a posthoming event

It has been hypothesized that the intercellular adhesion receptors used by normal cells could also be operative in the spreading of circulating malignant cells to target organs. In the present work, we show that genetic ablation of the ICAM-1 gene confers resistance to T cell lymphoma metastasis. Following i.v. inoculation of LFA-1-expressing malignant T lymphoma cells, we found that ICAM-1-deficient mice were almost completely resistant to the development of lymphoid malignancy compared with wild-type control mice that developed lymphoid tumors in the kidneys, spleen, and liver. Histologic examinations confirmed that ICAM-1-deficient mice, in contrast to wild-type mice, had no evidence of lymphoid infiltration in these organs. The effect of ICAM-1 on T cell lymphoma metastasis was observed in two distinct strains of ICAM-1-deficient animals. Nonetheless, lymphoma cells migrated with the same efficiency to target organs in both normal and ICAM-1-deficient mice, indicating not only that ICAM-1 expression by the host is essential in lymphoma metastasis, but also that this is so at stages subsequent to homing and extravasation into target organs. These results point to posthoming events as a focus of future investigation on the control of metastasis mediated by ICAM-1.     

Multivalent ligand-receptor binding interactions in the fibroblast growth factor system produce a cooperative growth factor and heparin mechanism for receptor dimerization

The binding interactions for the three primary reactants of the fibroblast growth factor (FGF) system, basic FGF (bFGF), an FGF receptor, FGFR1, and the cofactor heparin/heparan sulfate (HS), were explored by isothermal titrating calorimetry, ultracentrifugation, and molecular modeling. The binding reactions were first dissected into three binary reactions: (1) FGFR1 + bFGF<==>FGFR1/bFGF, K1 = 41 (+/- 12) nM; (2) FGFR1 + HS<==>FGFR1/HS, K2 = 104 (+/- 17) microM; and (3) bFGF + HS<==>bFGF/HS, K3 = 470 (+/- 20) nM, where HS = low MW heparin, approximately 3 kDa. The first, binding of bFGF to FGFR1 in the absence of HS, was found to be a simple binary binding reaction that is enthalpy dominated and characterized by a single equilibrium constant, K1. The conditional reactions of bFGF and FGFR1 in the presence of heparin were then examined under conditions that saturate only the bFGF heparin site (1.5 equiv of HS/bFGF) or saturate the HS binding sites of both bFGF and FGFR1 (1.0 mM HS). Both 3-and 5-kDa low MW heparins increased the affinity for FGFR1 binding to bFGF by approximately 10-fold (Kd = 4.9 +/- 2.0 nM), relative to the reaction with no HS. In addition, HS, at a minimum of 1.5 equiv/bFGF, induced a second FGFR1 molecule to bind to another lower affinity secondary site on bFGF (K4 = 1.9 +/- 0.7 microM) in an entropy-dominated reaction to yield a quaternary complex containing two FGFR1, one bFGF, and at least one HS. Molecular weight estimates by analytical ultracentrifugation of such fully bound complexes were consistent with this proposed composition. To understand these binding reactions in terms of structural components of FGFR1, a three-dimensional model of FGFR1 was constructed using segment match modeling. Electrostatic potential calculations confirmed that an elongated cluster, approximately 15 x 35 A, of nine cationic residues focused positive potential (+2kBT) to the solvent-exposed beta-sheet A, B, E, C' surface of the D(II) domain model, strongly implicating this locus as the HS binding region of FGFR1. Structural models for HS binding to FGFR1, and HS binding to bFGF, were built individually and then assembled to juxtapose adjacent binding sites for receptor and HS on bFGF, against matching proposed growth factor and HS binding sites on FGFR1. The calorimetric binding results and the molecular modeling exercises suggest that bFGF and HS participate in a concerted bridge mechanism for the dimerization of FGFR1 in vitro and presumably for mitogenic signal transduction in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)     

State-dependent models of ECS-induced amnesia in rats.

Conducted 3 experiments with a total of 220 male albino Sprague-Dawley rats, to investigate 2 state-dependent hypotheses which state that ECS-induced amnesia occurs when (a) the physiological state during testing is dissimilar from that during training (regardless of when consolidation occurs), or (b) the state at testing differs from that during consolidation (consolidation is assumed to occur after ECS). Data were gathered in a 1-trial passive-avoidance apparatus, and amnesia as a function of states during acquisition, consolidation, and testing was examined. Exp. I failed to support the train-test, state-dependent position. Exp. II produced data consistent with the consolidate-test, state-dependent position, but Exp. III found that the consolidate-test, state-dependent data were confounded by an induced recovery effect independent of S's physiological state at the time of testing. Although inconsistent with either of the state-dependent hypotheses, data support a retrieval-failure view of experimental amnesia. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)