MRI-guided neutron capture therapy by use of a dual gadolinium/boron agent targeted at tumour cells through upregulated low-density lipoprotein transporters

The upregulation of low-density lipoprotein (LDL) transporters in tumour cells has been exploited to deliver a sufficient amount of gadolinium/boron/ligand (Gd/B/L) probes for neutron capture therapy, a binary chemio-radiotherapy for cancer treatment. The Gd/B/L probe consists of a carborane unit (ten B atoms) bearing an aliphatic chain on one side (to bind LDL particles), and a Gd(III)/1,4,7,10-tetraazacyclododecane monoamide complex on the other (for detection by magnetic resonance imaging (MRI)). Up to 190 Gd/B/L probes were loaded per LDL particle. The uptake from tumour cells was initially assessed on cell cultures of human hepatoma (HepG2), murine melanoma (B16), and human glioblastoma (U87). The MRI assessment of the amount of Gd/B/L taken up by tumour cells was validated by inductively coupled plasma-mass-spectrometric measurements of the Gd and B content. Measurements were undertaken in vivo on mice bearing tumours in which B16 tumour cells were inoculated at the base of the neck. From the acquisition of magnetic resonance images, it was established that after 4-6 hours from the administration of the Gd/B/L-LDL particles (0.1 and 1 mmol kg(-1) of Gd and (10)B, respectively) the amount of boron taken up in the tumour region is above the threshold required for successful NCT treatment. After neutron irradiation, tumour growth was followed for 20 days by MRI. The group of treated mice showed markedly lower tumour growth with respect to the control group.     

Molecular Complexes of Simple Anions with Electron‐Deficient Arenes: Spectroscopic Evidence for Two Types of Structural Motifs for Anion–Arene Interactions

Anion–π interactions between a π‐acidic aromatic system and an anion are gaining increasing recognition in chemistry and biology. Herein, the binding features of an electron‐deficient aromatic system (1,3,5‐trinitrobenzene (TNB)) and selected anions (OH^?, Br^?, and I^?) are examined in the gas phase by using the combined information derived from collision‐induced dissociation experiments at variable energy, infrared multiple‐photon dissociation spectroscopy, and quantum chemical calculations. We provide spectroscopic evidence for two different structural motifs of anion–arene complexes depending on the nature of the anion. The TNB–OR^? complexes (R=H, or alkyl groups which were studied earlier) adopt an anionic σ‐complex structure whereby RO^? attacks the aromatic ring with covalent bond formation, and develops a tetrahedral ring carbon bound to H and OR. The halide complexes rather conform to a structure in which the TNB moiety is hardly altered, and the halogen is placed on an unsubstituted carbon atom over the periphery of the ring at a C–X distance that is appreciably longer than a typical covalent bond length. The ensuing structural motif, previously characterized in the solid state and named weak σ interaction, is now confirmed by an IR spectroscopic assay in the gas phase, in which the sampled species are unperturbed by crystal packing or solvation effects.     

Exact state-to-state quantum dynamics of the F + HD --> HF(v' = 2) + D reaction on model potential energy surfaces

In this paper, we present the results of a theoretical investigation on the dynamics of the title reaction at collision energies below 1.2 kcal/mol using rigorous quantum reactive scattering calculations. Vibrationally resolved integral and differential cross sections, as well as product rotational distributions, have been calculated using two electronically adiabatic potential energy surfaces, developed by us on the basis of semiempirical modifications of the entrance channel. In particular, we focus our attention on the role of the exothermicity and of the exit channel region of the interaction on the experimental observables. From the comparison between the theoretical results, insight about the main mechanisms governing the reaction is extracted, especially regarding the bimodal structure of the HF(v = 2) nascent rotational state distributions. A good overall agreement with molecular beam scattering experiments has been obtained.     

On the Newtonian limit of general relativity

We establish rigorous results about the Newtonian limit of general relativity by applying to it the theory of different time scales for non-linear partial differential equations as developed in [4, 1, 8]. Roughly speaking, we obtain a priori estimates for solutions to the Einstein's equations, an intermediate, but fundamental, step to show that given a Newtonian solution there exist continuous one-parameter families of solutions to the full Einstein's equations — the parameter being the inverse of the speed of light — which for a finite amount of time are close to the Newtonian solution. These one-parameter families are chosen via aninitialization procedure applied to the initial data for the general relativistic solutions. This procedure allows one to choose the initial data in such a way as to obtain a relativistic solution close to the Newtonian solution in any a priori given Sobolev norm. In some intuitive sense these relativistic solutions, by being close to the Newtonian one, have little extra radiation content (although, actually, this should be so only in the case of the characteristic initial data formulation along future directed light cones).Our results are local, in the sense that they do not include the treatment of asymptotic regions; global results are admittedly very important — in particular they would say how differentiable the solutions are with respect to the parameter — but their treatment would involve the handling of tools even more technical than the ones used here. On the other hand, this local theory is all that is needed for most problems of practical numerical computation.     

Self-assembling of multi-jets by pyro-electrohydrodynamic effect for high throughput liquid nanodrops transfer

Destabilization of liquid film by electro-hydro-dynamics (EHD) pressure is achieved through the pyroelectric effect on a polar dielectric crystal. We show that by destabilizing the liquid film, periodical self-assembled multi-jets are obtained. The multi-jets operate simultaneously and could be exploited to dispense liquids with nanolitre drops. Such multiple self-assembled liquid jets have significant potential applicability for high-throughput liquid transfer by this novel pyro-EHD ink-jet approach. Since the method avoids the use of nozzles and electrodes, it is especially suitable for highly viscous liquids. Here we present and discuss the new multi-jet process and the results obtained with a liquid polymer (PDMS).     

Tuning Glutamine Binding Modes in Gd‐DOTA‐Based Probes for an Improved MRI Visualization of Tumor Cells

Three new magnetic resonance imaging probes that target glutamine transporters have been synthesized. They consist of a Gd‐DOTA‐monoamide moiety (DOTA=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) linked through a six carbon atom chain to a vector represented by a glutamine residue bound through α‐carboxylic, γ‐carboxamidic, or α‐amino functionalities. Their uptake by HTC (rat hepatocarcinoma) and healthy rat hepatocytes has shown that the system containing the glutamine vector bound through the α‐carboxylic group displays a markedly higher affinity for tumor cells. The observed behavior is rationalized in terms of the exploitation of an additional glutamine transporter active in hepatic tumor cells.     

Lattice-dynamical calculations for fluorene,carbazole, dibenzofuran and dibenzothiophen

For crystalline fluorene, carbazole, dibenzofuran and dibenzothiophen several properties have been calculated using semi-empirical atom-atom potentials Calculated geometrical parameters, Raman-active lattice frequencies, enthalpies of sublimation and crystallographic temperature factors agree with observed values. However, except for dibenzothiophen, infrared-active lattice frequencies are not consistent with any potential so far tried     

An extended hückel study of adsorption of acetylene on Pt(111)

The parameterization of Extended Hückel MO Theory for the study of the interactions between hydrocarbons and Pt is analysed in detail. Single-ζ and double-ζ d functions of variable diffuseness are tested. The stability of acetylene and many molecular fragments and atoms on the surface is discussed in terms of binding energies and hydrocarbon—surface bond stretching force constants. Pt…H non-bonded repulsions are seen to be relevant, and a formula is proposed to describe these interactions. The metal is shown to offer a large catalytic effect in the reactions of rearrangement of acetylene, and, depending on the temperature and the availability of free hydrogen, H₃CC or H₃CCH are shown to be the most likely surface species. The geometries of adsorption compare rather favourably with LEED intensity studies. The use of EHT in the calculation of density of states curves and electronic spectra is discussed.     

The structure of hydrogen adsorbed on Ni(111) at low temperature by leed intensity analysis

Observed and calculated LEED intensity spectra for the p(2 × 2) pattern given by the adsorption of hydrogen on Ni(111) at 173 K are reported. Among the several model geometries tried that with the hydrogen atoms adsorbed in one of the two possible hollow sites seems to be the most probable.     

Ab initio calculations including solvent effects of the structure of pyrazine, 4-nitropyridine and dicyanobenzenes ion pairs

The potential surfaces of pyrazine, 4-nitropyridine, 1,2-, 1,3-, 1,4- dicyanobenzene radical anions have been calculated within theab initio and electrostatic molecular potential formalism, including the effect of the solvent. These potential surfaces suggest models of ion pairs with alkali cations, which are in agreement with those deduced from related ESR spectra.