The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

Simple low molecular weight (MW) chelates of Gd(3+) such as those currently used in clinical MRI are considered too insensitive for most molecular imaging applications. Here, we evaluated the detection limit (DL) of a molecularly targeted low MW Gd(3+)-based T(1) agent in a model where the receptor concentration was precisely known. The data demonstrate that receptors clustered together to form a microdomain of high local concentration can be imaged successfully even when the bulk concentration of the receptor is quite low. A GdDO3A-peptide identified by phage display to target the anti-FLAG antibody was synthesized, purified and characterized. T(1-)weighted MR images were compared with the agent bound to antibody in bulk solution and with the agent bound to the antibody localized on agarose beads. Fluorescence competition binding assays show that the agent has a high binding affinity (K(D)=150 nM) for the antibody, while the fully bound relaxivity of the GdDO3A-peptide/anti-FLAG antibody in solution was a relatively modest 17 mM(-1) s(-1). The agent/antibody complex was MR silent at concentrations below approximately 9 microM but was detectable down to 4 microM bulk concentrations when presented to antibody clustered together on the surface of agarose beads. These results provided an estimate of the DLs for other T(1)-based agents with higher fully bound relaxivities or multimeric structures bound to clustered receptor molecules. The results demonstrate that the sensitivity of molecularly targeted contrast agents depends on the local microdomain concentration of the target protein and the molecular relaxivity of the bound complex. A model is presented, which predicts that for a molecularly targeted agent consisting of a single Gd(3+) complex with bound relaxivity of 100 mM(-1) s(-1) or, more reasonably, four tethered Gd(3+) complexes each having a bound relaxivity of 25 mM(-1) s(-1), the DL of a protein microdomain is approximately 690 nM at 9.4 T. These experimental and extrapolated DLs are both well below current literature estimates and suggests that detection of low MW molecularly targeted T(1) agents is not an unrealistic goal.     

Synthesis of carbon nanotubes directly over TEM grids aiming the study of nucleation and growth mechanisms

A novel approach to produce electron-transparent multi-layer membranes over TEM grids for transmission electron microscopy analysis is presented. The membranes have been used to grow and analyze carbon nanostructured materials in a thermal-chemical vapor deposition process using Ni and Cu as catalysts and silicon oxide thin films as support layers, at temperatures as high as 900 °C. It is important that conditions of the synthesis using the electron-transparent multi-layer membrane system are similar to those for a conventional chemical vapor deposition process, where oxidized silicon wafers are employed. In particular, the thickness of the silicon oxide and the catalyst layers are the same, and similar carbon tubular structures were grown using both substrates. The use of membranes was crucial especially for the study of the nucleation mechanism for carbon nanotubes. These electron-transparent multi-layer membranes are relatively easy to obtain and they can be used for transmission electron microscopy studies of high-temperature synthesis of different nanostructured materials.     

Chaotic behavior in nonlinear Hamiltonian systems and equilibrium statistical mechanics

The relation between chaotic dynamics of nonlinear Hamiltonian systems and equilibrium statistical mechanics in its canonical ensemble formulation has been investigated for two different nonlinear Hamiltonian systems. We have compared time averages obtained by means of numerical simulations of molecular dynamics type with analytically computed ensemble averages. The numerical simulation of the dynamic counterpart of the canonical ensemble is obtained by considering the behavior of a small part of a given system, described by a microcanonical ensemble, in order to have fluctuations of the energy of the subsystem. The results for the Fermi-Pasta-Ulam model (i.e., a one-dimensional anharmonic solid) show a substantial agreement between time and ensemble averages independent of the degree of stochasticity of the dynamics. On the other hand, a very different behavior is observed for a chain of weakly coupled rotators, where linear exchange effects are absent. In the high-temperature limit (weak coupling) we have a strong disagreement between time and ensemble averages for the specific heat even if the dynamics is chaotic. This behavior is related to the presence of spatially localized chaos, which prevents the complete filling of the accessible phase space of the system. Localized chaos is detected by the distribution of all the characteristic Liapunov exponents.     

Macrocyclic polyfunctional Lewis bases. XIII: Structure of the trichlorocuprate of benzo-15-crown-5 complexed potassium

The structure of the trichlorocuprate of benzo-15-crown-5 complexed potassium was determined from diffractometer data by direct and refined by least squares toR(F)=0.049. The complex of the formula [(C₁₄H₂₀O₅)₂K]₂Cu₂Cl₆ is triclinic. It consists of two sandwich-like crown-ether-complexed potassium cations and the Cu₂Cl ₆ ^2– anion lying in the corner of the unit cell. The sandwich complexes do not exhibit any elements of symmetry. The anion has a flatter structure in comparison to dimers of chlorocuprates of crown-complexed sodium and large organic cations.     

Effect of dehydration on the viscosity of sol-gel processed silica

For short times and low temperatures, the dehydration of silica gels is limited by the diffusion of water species. For long times and temperatures 600°C and higher, dehydration shows first order kinetics. That is dehydration rates decrease with increasing temperature where silica gels have less surface area and consequently fewer hydroxyls.

For comparison with samples treated isothermally, samples were heated to 600, 700, 800 and 850°C at 100°C intervals and held 4 h at each temperature starting with 500°C. Comparison of isothermal and multistep treatments shows the contributions of structural relaxation and dehydration to the viscosity. At a given temperature, two gels of different water content may show the same viscosity, because the difference in water is matched by the difference in degree of structural relaxation. More complete dehydration is accomplished by constant rate heating to a single isothermal treatment rather than heating in steps.     

Relaxation functions and time-reversal invariance in thermal and electric conduction

Summary By assuming the invariance of the entropy production under time-reversal, the authors develope a second-order theory for thermal and electric conduction in rigid materials with memory. In the limiting case of instantaneous response, the properties derived for the relaxation functions provide the well known conditions on the ? transversal effects ?.

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Sunto Assumendo la invarianza della produzione entropica per inversione temporale, si sviluppa una teoria al secondo ordine per la conduzione termica ed elettrica in materiali rigidi con memoria. Nel caso limite di risposta istantanea, le proprietà dedotte per le funzioni di rilassamento forniscono le note condizioni sugli ? effetti trasversali ?.

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Entrata in Redazione il 14 luglio 1976.

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This work was supported by the ? Gruppo Nazionale per la Fisica Matematica ? of C.N.R.

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This paper was the last one written by prof.R. Borghesani before his sudden death on 25 october 1976.     

Concave cost minimization on networks

The paper deals with the problem of finding a minimum cost multicommodity flow on an uncapacitated network with concave link costs. Problems of this type are the optimal design of a network in the presence of scale economies and the telpack problem.Two different definitions of local optimality are given and compared both from the point of view of the computational complexity and from the point of view of the goodness of the solution they may provide.A vertex following algorithm to find a local optimum is proposed. The computational complexity of each iteration of the algorithm is O(n³), where n is the number of nodes of the network, and is independent of the differentiability of the objective function.Experimental results obtained from a set of test problems of size ranging from 11 nodes and 23 arcs to 48 nodes and 174 arcs, with number of commodities up to 5, are given.     

Mass spectrometry of heterocyclic compounds—II: Electron-impact induced fragmentation of 3,5-diphenyl-1,2,4-oxadiazole

The electron-impact induced fragmentation of 3,5-diphenyl-1,2,4-oxadiazole has been investigated by labelling experiments, defocused metastable ion detections and high resolution mass measurements. The main fragmentation process suggests heterocyclic cleavage at the 1 to 5 and 3 to 4 bonds confirming our previous interpretation. The structure of the major fragment ion [C₇H₅NO]⁺· has been interpreted as being represented by the isomeric benzonitrile oxide and phenylisocyanate structures, the latter isomerising irreversibly from the former. The benzonitrile oxide structure is consistent with [C₇H₅NO]⁺· formation by cleavage of the 1 to 5 and 3 to 4 bonds.     

Sviluppo delle funzioni implicitamente definite da un sistema di equazioni nel campo reale

Sunto Per la funzione reale del punto P(x, y): F[ξ(P), η(P)], ove u=ξ(P), v=η(P) sono implicitamente definite nel campo reale dal sistema delle due equazioni u−x+ϕ(u, v)=0, v−y+φ(u, v)=0 si dà uno sviluppo che estende quello ottenuto dalLevi-Civita per la funzione F[y(x)], ove y(x) è definita dalla equazione y−x+ϕ(y)=0. Ad Antonio Signorini nel suo 70^mo compleanno.