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.     

Isolation of Volatile Compounds with Repellent Properties against Aedes albopictus (Diptera: Culicidae) Using CPC Technology

The present work describes the use of Centrifugal Partition Chromatography (CPC) for the bio-guided isolation of repellent active volatile compounds from essential oils. Five essential oils (EOs) obtained from three Pinus and two Juniperus species were initially analyzed by gas chromatography–mass spectrometry (GC/MS) and evaluated for their repellent properties against Aedes albopictus. The essential oil from needles of P. pinea (PPI) presented the higher activity, showing 82.4% repellency at a dose of 0.2 μL/cm². The above EO, together with the EO from the fruits of J. oxycedrus subsp. deltoides (JOX), were further analyzed by CPC using the biphasic system n-Heptane/ACN/BuOH in ratio 1.6/1.6/0.2 (v/v/v). The analysis of PPI essential oil resulted in the recovery of (−)-limonene, guaiol and simple mixtures of (−)-limonene/β-pheladrene, while the fractionation of JOX EO led to the recovery of β-myrcene, germacrene-D, and mixtures of α-pinene/β-pinene (ratio 70/30) and α-pinene/germacrene D (ratio 65/45). All isolated compounds and recovered mixtures were tested for their repellent activity. From them, (−)-limonene, guaiol, germacrene-D as well the mixtures of (−)-limonene/β-pheladrene presented significant repellent activity (>97% repellency) against Ae. albopictus. The present methodology could be a valuable tool in the effort to develop potent mosquito repellents which are environmentally friendly.     

Scalable bottom‐up assembly of suspended carbon nanotube and graphene devices by dielectrophoresis

Bottom‐up assembly by dielectrophoresis (DEP) has emerged in recent years as a viable alternative to conventional top–down fabrication of electronic devices from nanomaterials, particularly carbon nanotubes and graphene. Here, we demonstrate how this technique can be extended to fabricate devices containing carbon nanotubes and graphene suspended between two electrodes over a back‐gate electrode. The suspended device geometry is critical for the development of nano‐electromechanical devices and to extract maximum performance out of electronic and optoelectronic devices. This technique allows for parallel assembly of devices over large scale. (© 2015 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Selective and Wash-Resistant Fluorescent Dihydrocodeinone Derivatives Allow Single-Molecule Imaging of μ-Opioid Receptor Dimerization

μ-Opioid receptors (μ-ORs) play a critical role in the modulation of pain and mediate the effects of the most powerful analgesic drugs. Despite extensive efforts, it remains insufficiently understood how μ-ORs produce specific effects in living cells. We developed new fluorescent ligands based on the μ-OR antagonist E-p-nitrocinnamoylamino-dihydrocodeinone (CACO), that display high affinity, long residence time and pronounced selectivity. Using these ligands, we achieved single-molecule imaging of μ-ORs on the surface of living cells at physiological expression levels. Our results reveal a high heterogeneity in the diffusion of μ-ORs, with a relevant immobile fraction. Using a pair of fluorescent ligands of different color, we provide evidence that μ-ORs interact with each other to form short-lived homodimers on the plasma membrane. This approach provides a new strategy to investigate μ-OR pharmacology at single-molecule level.     

Preparation of hydroxyapatite via microemulsion route

Hydroxyapatite (HAp) was prepared using a microemulsion route in combination with the pH-shock wave method. The samples as received consisted of amorphous aggregated particles, which had remarkable mesoporosity with a narrow pore size distribution. After being heated at 650 degrees C, the A-type carbonate hydroxyapatite was crystallized at 635 degrees C in particles of similar size (40--120 nm) with no internal porosity. At a higher temperature (900 degrees C) a sintering process took place, resulting in network of a larger particles, consisting of HAp and beta-tricalcium phosphate (beta-TCP). The crystallization of HAp occurs at 635 degrees C with an activation energy of 62.7--72.2 kcalmol(-1).     

Nafion as cosurfactant: solubilization of nafion in water in the presence of Pluronics

Incorporation of Nafion to aqueous solutions of Pluronics adversely impacts micellization due to extensive Nafion/copolymer interactions. Light scattering and zeta potential measurements provide evidence for the formation of sizable and stable Nafion/copolymer complexes, in expense of the neat copolymer micelles. At high copolymer concentrations, the overall interaction diagram of Nafion/copolymer reflects the competitive action of the release of packing constraints due to micellar destabilization induced by Nafion on one hand and the gelator nature of the Nafion on the other. Measurements using a quartz crystal microbalance (QCM-D) show that aqueous solutions of Pluronics (even at very low concentration) can dissolve the Nafion coating on the crystal resonator, while typical low molecular weight ionic surfactants fail to induce similar effects. These studies demonstrate that complexation with this class of copolymers is a facile route to impart dispersibility to Nafion in aqueous environments that otherwise can be achieved through tedious and harsh treatments.     

Boundary labeling: Models and efficient algorithms for rectangular maps

We introduce boundary labeling, a new model for labeling point sites with large labels. According to the boundary-labeling model, labels are placed around an axis-parallel rectangle that contains the point sites, each label is connected to its corresponding site through a polygonal line called leader, and no two leaders intersect. Although boundary labeling is commonly used, e.g., for technical drawings and illustrations in medical atlases, this problem has not yet been studied in the literature. The problem is interesting in that it is a mixture of a label-placement and a graph-drawing problem.

In this paper we investigate several variants of the boundary-labeling problem. We consider labels of identical or different size, straight-line or rectilinear leaders, fixed or sliding ports for attaching leaders to sites and attaching labels to one, two or all four sides of the bounding rectangle. For any variant of the boundary labeling model, we aim at highly esthetical placements of labels and leaders. We present simple and efficient algorithms that minimize the total leader length or, in the case of rectilinear leaders, the total number of bends.     

Morawetz's method for the decay of the solution of the exterior initial-boundary value problem for the linearized equation of dynamic elasticity

In this paper, the behavior of the solution of the time-dependent linearized equation of dynamic elasticity is examined.For the homogeneous problem, it is proved that in the exterior of a star-shaped body on the surface of which the displacement field is zero, the solution decays at the rate t ^-1 as the time t tends to infinity.For the non-homogeneous problem with a harmonic forcing term, it is proved that for large times, the elastic material in the exterior of the body, tends to a harmonic motion, with the period of the external force.The convergence to the steady harmonic state solution is at the rate t ^-1/2 as t tends to infinity, and is uniform on bounded sets.