Polypyridyl-Based Copper Phenanthrene Complexes: Combining Stability with Enhanced DNA Recognition

We report a series of copper(II) artificial metallo-nucleases (AMNs) and demonstrate their DNA damaging properties and in-vitro cytotoxicity against human-derived pancreatic cancer cells. The compounds combine a tris-chelating polypyridyl ligand, di-(2-pycolyl)amine (DPA), and a DNA intercalating phenanthrene unit. Their general formula is Cu-DPA-N,N' (where N,N'=1,10-phenanthroline (Phen), dipyridoquinoxaline (DPQ) or dipyridophenazine (DPPZ)). Characterisation was achieved by X-ray crystallography and continuous-wave EPR (cw-EPR), hyperfine sublevel correlation (HYSCORE) and Davies electron-nuclear double resonance (ENDOR) spectroscopies. The presence of the DPA ligand enhances solution stability and facilitates enhanced DNA recognition with apparent binding constants (K_app) rising from 10⁵ to 10⁷ m ⁻¹ with increasing extent of planar phenanthrene. Cu-DPA-DPPZ, the complex with greatest DNA binding and intercalation effects, recognises the minor groove of guanine–cytosine (G-C) rich sequences. Oxidative DNA damage also occurs in the minor groove and can be inhibited by superoxide and hydroxyl radical trapping agents. The complexes, particularly Cu-DPA-DPPZ, display promising anticancer activity against human pancreatic tumour cells with in-vitro results surpassing the clinical platinum(II) drug oxaliplatin.     

PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αvβ3 Receptors

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin α_vβ₃ receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin α_vβ₃ receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. They act as receptors for several extracellular matrix proteins exposing the tripeptide sequence arginine-glycine-aspartic (RGD). Cyclic RDG peptidic ligands c(RGD) have been developed for integrin α_vβ₃ tumor-targeting positron emission tomography (PET) diagnosis. Several c(RGD) pharmacophores, connected with the linker and conjugated to a chelator or precursor for radiolabeling with different PET radionuclides (¹⁸F, ⁶⁴Cu, and ⁶⁸Ga), have resulted in multimeric ligands superior to c(RGD) monomers. The binding avidity, pharmacodynamic, and PET imaging properties of these multimeric c(RGD) radioligands, in relation to their structural characteristics are analyzed and discussed. Furthermore, specific examples from preclinical studies and clinical investigations are included.     

Water suppression without signal loss in HR-MAS 1H NMR of cells and tissues

In cell and tissue samples, water is normally three orders of magnitude more abundant than other metabolites. Thus, water suppression is required in the acquisition of NMR spectra to overcome the dynamic range problem and to recover metabolites that overlap with the broad baseline of the strong water resonance. However, the heterogeneous cellular environment often complicates water suppression and the strong coupling of water to membrane lipids interferes with the NMR detection of membrane associated lipid components. The widely used water suppression techniques including presaturation and double pulsed field gradient selective echo result in more than a 70% reduction in membrane associated lipid components in proton spectra of cells and tissues compared to proton spectra acquired in the absence of water suppression. A water suppression technique based on the combination of selective excitation pulses and pulsed field gradients is proposed to use in the acquisition of high resolution MAS NMR spectra of tissue specimens and cell samples. This pulse sequence methodology enables efficient water suppression for intact cells and tissue samples and eliminates signal loss from cellular metabolites.     

Directive line source model: a new model for sound diffraction by half planes and wedges

A new method termed Directive Line Source Model (DLSM) is presented for predicting the diffracted field produced by a sound wave incident on a rigid or pressure release half plane. In the new method the edge of the half plane is modeled as an infinite set of directive point sources continuously distributed along the edge. Because DLSM is fast, simple and intuitive, it is a promising tool for the study of diffraction. It can be applied for several types of incident radiation: omnidirectional cylindrical and spherical waves, plane waves, as well as waves from directional sources. Wedges may also be treated. Finally, DLSM can handle diffraction by an arbitrarily shaped edge profile, for example, a half plane having an edge that is jagged instead of straight. Results for plane, cylindrical and spherical incident waves, as well as for arrays of line and point sources, are presented and their agreement with known analytical solutions is demonstrated. Predictions based on DLSM compare favorably with experimental data.     

Edge wave on axis behind an aperture or disk having a ragged edge

Diffraction by a circular aperture or disk having a ragged edge is investigated. Theory and measurements are reported. The ragged edge is modeled as N arcs, of differing radii a(i), each of which contributes a scattered signal to the edge wave on axis behind the aperture or disk. The amplitude of each scattered signal is proportional to the angle of the arc, and the corresponding time delay is square root of [(ai)2 + (s0)2/c0], where s0 is the axial distance from the aperture plane and c0 is the sound speed. Kirchhoff theory is used to make the calculation. A formula is derived for the rms pressure of the edge wave in terms of the rms pressure and autocorrelation function of the incident wave. The formula can be evaluated for incident waves that are sinusoidal, random (e.g., noise), or transient. Predictions agree reasonably well with underwater measurements made with a spark-generated pulse incident on various apertures. The main result is that making the edge ragged reduces the rms pressure of the edge wave. Indeed, an edge profile is presented that, for a given frequency and axial observation point, eliminates the edge wave completely.     

EQUITY ISSUES AFFECTING MATHEMATICS LEARNING USING ICT

Our concern is the inequities that arise from differential access and use of educational technology in mathematics for groups characterised by gender, ethnicity, income level and ability. As access to information and communications technology (ICT) increases both in homes and schools, our paper asks whether previous inequities are being ironed out or exacerbated. Equity is considered from the three perspectives proposed by Fennema (1990), namely in terms of: (a) opportunities to learn (physical access); (b) educational treatment (how technology is used, by whom), and the social and psychological factors influencing its use; (c) educational outcomes (impacts on achievement, attitudes and motivation). Suggested policies and pedagogies for removing the boundaries between technology ‘haves’ and ‘have-nots’ are presented.     

The magnetic structure of HoCo2Si2

We have carried out neutron diffraction on a HoCo₂Si₂ powder sample at 4.2 K. The magnetic structure of this compound is collinear antiferromagnetic with the holmium magnetic moments parallel to the c-axis of the crystal. The magnetic moment value of holmium is 9.85 μ_B. The magnetic space group is I4/mm'm' (Sh⁴¹⁰₁₂₈) k = 000 The ordering temperature is t_n = 12(1) K.