Distribution of gadomelitol in a human breast tumor model in mice

The study evaluates the tumor distribution of the rapid clearance blood pool agent (RCBPA) gadomelitol, in a breast tumor model. Different techniques were used : (1) tissue gadolinium concentrations measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES), (2) whole body quantitative autoradiography using radiolabeled [¹⁵³Gd] gadomelitol and (3) dynamic contrast-enhanced MRI with compartmental analysis. An accumulation of gadomelitol in tumors compared to muscle was observed 30 min and 3 h post injection (p.i.). Thirty minutes p.i., the gadomelitol tumor distribution evaluated by autoradiography showed a marked difference between the rim and the center, whereas both areas showed comparable concentrations after 3 h. Using dynamic contrast-enhanced MRI, three phases could be observed during the 1 hour observation period: (1) rapid tumor uptake within the first few minutes post-injection (2) a progressive increase in tumor signal enhancement over 10 min and (3) a steady-state phase. Average +/− SD (n=5) transendothelial permeability K^PS and the fractional blood volume fBV were 12.2±1.6 μl/min⁻¹/g and 5.4±0.2% respectively. Due to its slow extravasation and high tumor residence time, gadomelitol may potentially be useful to improve characterization between benign versus malignant tumors using dynamic MRI.     

Failure and Dilatancy Properties of Sand at Relatively Low Stresses

Analysis of geotechnical problems concerned by low confinement such as design of shallow foundations and analysis of slope stability and soil liquefaction requires modeling of the soil behavior at low stresses. This note includes a laboratory study of the behavior of Hostun RF sand at low cell pressure (20–50?kPa). Isotropic and triaxial compression drained tests were performed. Drained tests show that both failure and dilatancy angles at low stresses are stress dependent. The contractive/dilative phase transition is observed for loose sand, which may result from the overconsolidated nature of this sand for low values of cell pressure.     

Solution chemistry of HNO3/HF pickle mixtures

Fundamental aspects of nitric and hydrofluoric mixed-acid pickle solution chemistry are discussed. Results from a computer model designed to predict the behavior of the pickle acid mixture are compared with measured parameters. There is a continuous increase in the complexed fluoride-to-iron ratio as the solution HF/Fe ratio and the F (total)/Fe ratio increases. Dissolved chromium only marginally reduces the HF concentration. The complexation reactions result in the generation of nitric acid with the consumption of hydrofluoric acid, leading to higher than expected nitric acid concentration values. Although further refinements to the computer model are needed, the model gives new insight to the behavior of pickle solutions, such as the distribution of various fluoride species at different F/Fe ratios. Lancelot A. Fernando, formerly Research Specialist, Technical Center, Allegheny Ludlum Corporation, Brackenridge, PA 15014, may be contacted at P.O. Box 1763, Pittsburg, CA 94565.     

Novel and selective partial agonists of 5-HT3 receptors. 2. Synthesis and biological evaluation of piperazinopyridopyrrolopyrazines, piperazinopyrroloquinoxalines, and piperazinopyridopyrroloquinoxalines

In continuation of our previous work on piperazinopyrrolothienopyrazine derivatives, three series of piperazinopyridopyrrolopyrazines, piperazinopyrroloquinoxalines, and piperazinopyridopyrroloquinoxalines were prepared and evaluated as 5-HT3 receptor ligands. The chemical modifications performed within these new series led to structure-activity relationships regarding both high affinity and selectivity for the 5-HT3 receptors that are in agreement with those established previously for the pyrrolothienopyrazine series. The best compound (8a) obtained in these new series is in the picomolar range of affinity for 5-HT3 receptors with a selectivity higher than 10(6). Four of the high-affinity 5-HT3 ligands (8a, 15a,b, and 16d) were selected in both the pyridopyrrolopyrazine and the pyrroloquinoxaline series and were characterized in vitro and in vivo as agonists or partial agonists. Compound 8a was also evaluated in the light/dark test where it showed potential anxiolytic-like activity at very low doses per os.     

A microdialysis study investigating the mechanisms of hydroxyl radical formation in rat striatum exposed to glutamate

Considerable evidence has linked hydroxyl radicals (.OH) to excitotoxicity. Glutamate infused through a microdialysis probe into rat striatum induced a massive .OH production, which was completely blocked by PBN and attenuated by dizocilpine, 2-amino-5-phosphonopentanoic acid (AP-5), NG-nitro-L-arginine methyl ester (L-NAME) and mepacrine. Thus, we suggest that the neurotoxic effects of glutamate in vivo may derive from an increased formation of .OH resulting from excessive activation of NMDA receptors and downstream enzymes such as NOS and PLA2.     

Physicochemical and consolidation properties of compacted lateritic soil treated with cement

The consolidation of a fine-grained lateritic soil, treated with compound Portland cement (CEMII/BM 32.5 N) up to 9% by weight of the dry soil and prepared at three different molding water contents (ω_DRY, OMC, and ω_WET), was investigated by means of a one-dimensional consolidation test. The physicochemical and microstructural properties of the compacted lateritic soil-cement mixture were investigated using Raman spectroscopy, polarized light microscopy (PLM), scanning electron microscopy (SEM), and pH measurement. The results show that cement admixtures resulted in the formation of tobermorite, afwillite, ettringite, portlandite, and calcite. However, tobermorite and afwilite, which are calcium silicate hydrates (CSH) whose mechanisms of formation are the pozzolanic and alkali silica reactions, appear from 6% added cement. The fixing point of the pH (12.4) is also obtained from 6% added cement. It is the threshold value at which the material begins to develop an adequate mechanical performance. In general, as the content of cement in the soil is increased, the yield stress increases from 1 to 3 times in comparison to untreated soil. For effective vertical stresses smaller than the cement-induced yield stress, the primary consolidation process for specimens treated with cement is 2–7 times faster than that for specimens not treated with cement, while for effective vertical stresses higher than the cement-induced yield stress, the primary consolidation process for specimens treated with cement is about 0.5–1.5 times faster than that for specimens not treated with cement. Permeability and secondary compression are reduced 1–9 times and 2–11 times that of the untreated samples, respectively. These changes are attributed to the creation of chemical bonds and aggregation that accompany the addition of cement. The results also show that it would be desirable for soil samples to be prepared at the dry side of optimum (ω_DRY) when the optimum moisture content (OMC) is not reached at the site. These results indicate that significant and desirable changes in soil behavior can be achieved when the soil is admixed with CEM II/BM 32.5 N cement, thus providing the possibility of using the tested lateritic soil in road construction.     

Future climates: Markov blankets and active inference in the biosphere

We formalize the Gaia hypothesis about the Earth climate system using advances in theoretical biology based on the minimization of variational free energy. This amounts to the claim that non-equilibrium steady-state dynamics—that underwrite our climate—depend on the Earth system possessing a Markov blanket. Our formalization rests on how the metabolic rates of the biosphere (understood as Markov blanket''s internal states) change with respect to solar radiation at the Earth''s surface (i.e. external states), through the changes in greenhouse and albedo effects (i.e. active states) and ocean-driven global temperature changes (i.e. sensory states). Describing the interaction between the metabolic rates and solar radiation as climatic states—in a Markov blanket—amounts to describing the dynamics of the internal states as actively inferring external states. This underwrites climatic non-equilibrium steady-state through free energy minimization and thus a form of planetary autopoiesis.     

An ordered hydrophobic P6mm mesoporous carbon with graphitic pore walls and its application in aqueous catalysis

A hydrophobic ordered mesoporous carbon with hexagonal arrays of rods was synthesized by a nanocasting process by using silica SBA-15 as a template and 2,3-dihydroxynaphthalene as a fused-aromatic carbon precursor. Impregnation of 2,3-dihydroxynaphthalene and its subsequent conversion into carbon occurred inside the mesopores of the silica template through a dehydration reaction between the surface silanols and hydroxyl groups of the carbon source and mild carbonization under inert atmosphere. After silica removal, X-ray scattering, transmission electron microscopy, pore size analysis and Raman spectroscopy showed that the resulting material was a negative replica of the silica template with a 2D-hexagonal P6mm ordered structure, possessing a large surface area (724 m² g⁻¹), a monomodal pore size distribution (3.4 nm) and a relative hydrophobic surface with graphitic pore walls. These features give the system substantial advantages to play a beneficial role in aqueous organometallic catalysis. The material appeared to be an excellent mass transfer promoter to enhance the overall reaction rate of the palladium-catalyzed cleavage reaction of water-insoluble allylundecylcarbonate (Tsuji–Trost reaction).     

Solution structure of a selectively 13C-labeled intramolecular DNA triplex

The three-dimensional structure of an intramolecular triple helix whose three strands have been linked by a hexaethylene glycol chain, and selectively 13C-enriched in position C1' on the third strand was investigated by NMR spectroscopy and constrained molecular mechanics calculations. Starting from different initial conformations, we show that the NOE constraints determined by the complete relaxation matrix calculation and iterative back-calculations allowed us to reach the same final restrained triple helix, taking into account implicitly the solvent effect. We conclude that this triplex adopted a B-type conformation rather than a A-type. The sugar pucker was found predominantly in the S-type conformation, in the range of C2'-endo geometry.     

Measurement of high gas-stream temperature using dynamic thermocouples

The dynamic probe technique using the transient response of a thermocouple is one of the methods of measuring high temperature flowing gases. In this paper, the complete dynamic response of a thermocouple has been solved consisting of convective, conductive, and radiative terms. The solution has been used to arrive at correction factors for actual experimental data. The use of dynamic thermocouples in the measurement of temperature profiles has also been illustrated by experiment. The model is verified at lower temperatures using a bunsen flame.