Unambiguous Intracellular Localization and Quantification of a Potent Iridium Anticancer Compound by Correlative 3D Cryo X‐Ray Imaging

The iridium half‐sandwich complex [Ir(η⁵:κ¹‐C₅Me₄CH₂py)(2‐phenylpyridine)]PF₆ is highly cytotoxic: 15–250× more potent than clinically used cisplatin in several cancer cell lines. We have developed a correlative 3D cryo X‐ray imaging approach to specifically localize and quantify iridium within the whole hydrated cell at nanometer resolution. By means of cryo soft X‐ray tomography (cryo‐SXT), which provides the cellular ultrastructure at 50 nm resolution, and cryo hard X‐ray fluorescence tomography (cryo‐XRF), which provides the elemental sensitivity with a 70 nm step size, we have located the iridium anticancer agent exclusively in the mitochondria. Our methodology provides unique information on the intracellular fate of the metallodrug, without chemical fixation, labeling, or mechanical manipulation of the cells. This cryo‐3D correlative imaging method can be applied to a number of biochemical processes for specific elemental localization within the native cellular landscape.     

Solitonlike beam propagation along light-induced singularity of space charge in fast photorefractive media

We investigate light beam propagation in a fast photorefractive medium placed in an alternating electric ac field to enhance the nonlinear response. It is shown that the joint action of the optical and material nonlinearities leads to formation of a narrow singularity of the light-induced space charge at the intensity maximum and to self-trapping of the light energy near the corresponding discontinuity of the index profile. Owing to the strong saturation of the material nonlinearity, the trapped beam propagates over long distances with only a weak loss of its power.     

Superlinear photovoltaic currents in LiNbO<Subscript>3</Subscript>: analyses under the two-center model

Superlinear photovoltaic currents in LiNbO₃ are theoretically studied by using a two active center model, with Fe²⁺/Fe³⁺ as primary center and Nb_Li⁴⁺/Nb_Li⁵⁺ as secondary center. Analytical instead of numerical results are provided, including close-form expressions for most common experimental situations. Recent photovoltaic parameters obtained for -phase proton-exchanged LiNbO₃ waveguides (very similar to the substrate) are used for applying the model and comparing with published experimental results. Thoroughly studied aspects are: the redistribution of donor/acceptor states for each species as a function of the light intensity, their contribution to the photovoltaic current density, the effect of the temperature, and the role of the center concentrations and their reduction state. This provides a detailed understanding of the photovoltaic current function shapes versus light intensity, predicts new features of interest for experimentalists and suggests further experiments to better determine the material parameters. Photovoltaic measurements and modeling appear a simpler and safer way of understanding the role of the two-center photovoltaic effect in photorefractive phenomena as well as for determining important photorefractive parameters. PACS 42.70.Nq; 72.40.+w.     

Holographic phase-shift measurement during development of a fixed grating in lithium niobate crystals

We report what is believed to be the first direct measurement of the grating phase-shift evolution during white-light illumination for the development of a fixed grating in an Fe-doped lithium niobate crystal. Stabilized holographic recording is shown to be essential for such measurements. Experimental data are in good agreement with theory and allow computation of the relevant material parameters for the sample under analysis. The results are of the utmost relevance for understanding the advantageous behavior of oxidized samples in hologram fixing.     

On some properties of the Laplacian matrix revealed by the RCM algorithm

In this paper we present some theoretical results about the irreducibility of the Laplacian matrix ordered by the Reverse Cuthill-McKee (RCM) algorithm. We consider undirected graphs with no loops consisting of some connected components. RCM is a well-known scheme for numbering the nodes of a network in such a way that the corresponding adjacency matrix has a narrow bandwidth. Inspired by some properties of the eigenvectors of a Laplacian matrix, we derive some properties based on row sums of a Laplacian matrix that was reordered by the RCM algorithm. One of the theoretical results serves as a basis for writing an easy MATLAB code to detect connected components, by using the function “symrcm” of MATLAB. Some examples illustrate the theoretical results.     

Chemo‐ and Regioselective Palladium‐Catalyzed Oxycyclization Reactions of Allendiols: Preparation of Five‐, Six‐, and Eight‐Membered Cycles

Positive discrimination : Chemo‐ and regioselective palladium‐catalyzed cycloetherification of allendiols, namely β,γ‐ and γ,δ‐allendiols, may occur by judicious choice of palladium‐catalyzed conditions owing to their potential ability to discriminate between both nucleophilic sites (see scheme).

     

Label-free detection of DNA mutations by SPR: application to the early detection of inherited breast cancer

A screening analysis of DNA hybridization and the presence of DNA mutations using an surface plasmon resonance (SPR) biosensor is shown. The influence of lateral and vertical spacers, as well as several hybridization conditions, was studied to optimize the differentiation between fully complementary and mismatched DNA strands. Our results demonstrated that SPR biosensors were able to detect mismatch sequences related to inherited breast cancer, with high specificity and sensitivity. Using PCR synthetic sequences as targets, mutant sequences were clearly discriminated from fully complementary ones, and detection limits below 50 nM were achieved.     

Analysis and optimization of propagation losses in LiNbO3 optical waveguides produced by swift heavy-ion irradiation

The propagation losses (PL) of lithium niobate optical planar waveguides fabricated by swift heavy-ion irradiation (SHI), an alternative to conventional ion implantation, have been investigated and optimized. For waveguide fabrication, congruently melting LiNbO₃ substrates were irradiated with F ions at 20 MeV or 30 MeV and fluences in the range 10¹³–10¹⁴ cm⁻². The influence of the temperature and time of post-irradiation annealing treatments has been systematically studied. Optimum propagation losses lower than 0.5 dB/cm have been obtained for both TE and TM modes, after a two-stage annealing treatment at 350 and 375^∘C. Possible loss mechanisms are discussed.     

Steady holographic gratings in semiconductor multiple quantum wells

A theoretical model based on the Dember mechanism is proposed to describe the steady state photorefractive gratings generated in semiconductor multiple quantum wells (MQW). It has been applied to an GaAs/AlGaAs MQW in parallel configuration (external electric field applied parallel to the MQW layers) for which recent experimental data are available. The model predicts a dependence of the first-order diffraction efficiency on the applied field in qualitative accordance with experiments, including the occurrence of saturation at high field values. Absolute values of the efficiencies are in good agreement with the experimental ones. Finally, high second-order diffraction efficiencies, associated with the development of a perpendicular space charge field, are also predicted by the model.     

Metal-catalyzed cycloetherification reactions of β,γ- and γ,δ-allendiols: chemo-, regio-, and stereocontrol in the synthesis of oxacycles

Versatile routes that lead to a variety of functionalized enantiopure tetrahydrofurans, dihydropyrans, and tetrahydrooxepines are based on chemo-, regio-, and stereocontrolled metal-catalyzed oxycyclization reactions of β,γ- and γ,δ-allendiols, which were readily prepared from (R)-2,3-O-isopropylideneglyceraldehyde. The application of Pd(II), Pt(II), Au(III), or La(III) salts as the catalysts gives controlled access to differently sized oxacycles in enantiopure form. Usually, chemoselective cyclization reactions occurred exclusively by attack of the secondary hydroxy group (except for the oxybromination of phenyl β,γ-allenic diols 3b and 3d) to an allenic carbon atom. Regio- and stereocontrol issues are mainly influenced by the nature of the metal catalysts and substituents.