Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata), in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C) residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues). Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

Adventures in the pharmacological analysis of P2 receptors

The pharmacological classification of P2 receptors owes its origin to the pioneering efforts of Geoff Burnstock and those who followed him, research that was conducted primarily in physiological experimental systems. Over recent years, the techniques of molecular biology have been increasingly applied in the study of P2 receptors while, at the same time, advances in their pharmacological analysis have been limited by a lack of potent and selective agonist or antagonist ligands. This has resulted in a classification scheme which is largely structural in nature, with relatively little contribution from pharmacology. Our endeavours in this area have been directed towards the discovery of ligands with which the pharmacological analysis and definition of P2 receptors could be advanced, the ultimate goal being the design of therapeutic agents. This article will describe some of our experiences in this challenging but rewarding Nea. (C) 2000 Elsevier Science B.V. All rights reserved.

Fabrication of cerium oxide nanoparticles: Characterization and optical properties

Ceria (CeO2) is a technologically important rare earth material because of its unique properties and various engineering and biological applications. A facile and rapid method has been developed to prepare ceria nanoparticles using microwave with the average size 7 nm in the presence of a set of ionic liquids based on the bis (trifluoromethylsulfonyl) imide anion and different cations of 1-alkyl-3-methyl-imidazolium. The structural features and optical properties of the nanoparticles were determined in depth with X-ray powder diffraction, transmission electron microscope, N-2 adsorption-desorption technique, dynamic light scattering (DLS) analysis, FTIR spectroscopy, Raman spectroscopy, UV-vis absorption spectroscopy, and Diffuse reflectance spectroscopy. The energy band gap measurements of nanoparticles of ceria have been carried out by UV-visible absorption spectroscopy and diffuse reflectance spectroscopy. The surface charge properties of colloidal ceria dispersions in ethylene glycol have been also studied. To the best of our knowledge, this is the first report on using this type of ionic liquids in ceria nanoparticle synthesis. (C) 2011 Elsevier Inc. All rights reserved.

Hybrid methods for witnessing entanglement in a microscopic-macroscopic system

We propose a hybrid approach to the experimental assessment of the genuine quantum features of a general system consisting of microscopic and macroscopic parts. We infer entanglement by combining dichotomic measurements on a bidimensional system and phase-space inference through the Wigner distribution associated with the macroscopic component of the state. As a benchmark, we investigate the feasibility of our proposal in a bipartite-entangled state composed of a single-photon and a multiphoton field. Our analysis shows that, under ideal conditions, maximal violation of a Clauser-Horne-Shimony-Holt-based inequality is achievable regardless of the number of photons in the macroscopic part of the state. The difficulty in observing entanglement when losses and detection inefficiency are included can be overcome by using a hybrid entanglement witness that allows efficient correction for losses in the few-photon regime.

Singly, doubly and triply resonant multiphoton processes involving autoionizing states in magnesium

Using the R-matrix Floquet theory we have carried out non-perturbative, ab initio one- and two-colour calculations of the multiphoton ionization of magnesium with the laser frequencies chosen such that the initial state of the atom is resonantly coupled with autoionizing resonances of the atom. Good agreement is obtained with previous calculations in the low-intensity regimes. The single-photon ionization from the 3s3p P excited state of magnesium has been studied in the vicinity of the 3p S autoionizing resonance at non-perturbative laser intensities. Laser-induced degenerate states (LIDS) are observed for modest laser intensities. By adding a second laser which resonantly couples the 3p S = and 3p3d P autoionizing levels, we show that, due to the small width of the 3p3d P state, LIDS occur between this state and the 3s3p P state at intensities of the first laser below 10 W cm . We next investigate the case in which the first laser induces a resonant two-photon coupling between the ground state and the 3p S autoionizing state, while the second laser again resonantly couples the respective 3p S and 3p3d P autoionizing states. At weak intensities, our calculations compare favourably with recent experimental data and calculations. We show that when the intensity of the first laser is increased, the effect of an additional autoionizing state, the 4s5s S state, becomes significant. This state is coupled to the 3p3d P autoionizing level by one photon, inducing a triply resonant processes. We show that LIDS occur among the three autoionizing levels and we discuss their effect on the decay rate of the ground state. We consider dressed two- and three-level atoms which can be used to model the results of our calculations.

Microneedle-Iontophoresis Combinations for Enhanced Transdermal Drug Delivery

It has recently been proposed that the combination of skin barrier impairment using microneedles (MNs) coupled with iontophoresis (ITP) may broaden the range of drugs suitable for transdermal delivery as well as enabling the rate of delivery to be achieved with precise electronic control. However, few reports exist on the combination of ITP with in situ drug-loaded polymeric MN delivery systems. Our in vitro permeation studies revealed that MN enhances transdermal drug delivery. The combination of dissolving MN and ITP did not further enhance the extent of delivery of the low molecular weight drug ibuprofen sodium after short application periods. However, the extent of peptide/protein delivery was significantly enhanced when ITP was used in combination with hydrogel-forming MN arrays. As such, hydrogel-forming MN arrays show promise for the electrically controlled transdermal delivery of biomacromolecules in a simple, one-step approach, though further technical developments will be necessary before patient benefit is realized.

Direct Photodetachment of F‾ by mid-infrared few-cycle femtosecond laser pulses

The recent adiabatic saddle-point approach of Shearer et al. [ Phys. Rev. A 84 033409 (2011)] is extended to multiphoton detachment of negative ions with outer p-state electrons. This theory is applied to investigate the strong-field photodetachment dynamics of F- ions exposed to few-cycle femtosecond laser pulses, without taking into account the rescattering mechanism. Numerical calculations are considered for mid-infrared laser wavelengths of 1300 and 1800 nm at laser intensities of 7.7 × 1012, 1.1 × 1013, and 1.3 × 1013 W/cm2. Two-dimensional momenta saddle-point spectra exhibit a distinct distribution in the shape of a “smile” in the complex-time plane. Electron momentum distribution maps of direct electrons are investigated. These produce a distinct pattern of above-threshold detachment (ATD) concentric rings due to constructive and destructive quantum interference of electrons detached from their parent ions. Probability detachment distributions presented, capturing the influence of saturation effects that are found to become more significant with increasing laser intensity at a fixed wavelength. ATD photoangular distributions as functions of laser intensity and wavelength near channel closings are also investigated and found to be sensitive to initial-state symmetry. Nonmonotonic structures observed in the ejected photoelectron energy spectra are attributed to interference effects from coherent electronic wave packets. Additionally the profiles of all the photoelectron emission spectra show strong dependence on the carrier-envelope phase, indicating that it is a reliable parameter for characterizing the wave form of the pulse.

Automotive waste heat recovery: Working fluid selection and related boundary conditions

This paper presents the rational for the selection of fluids for use in a model based study of sub and supercritical Waste Heat Recovery (WHR) Organic Rankine Cycle (ORC). The study focuses on multiple vehicle heat sources and the potential of WHR ORC’s for its conversion into useful work. The work presented on fluid selection is generally applicable to any waste heat recovery system, either stationary or mobile and, with careful consideration, is also applicable to single heat sources. The fluid selection process presented reduces the number of potential fluids from over one hundred to a group of under twenty fluids for further refinement in a model based WHR ORC performance study. The selection process uses engineering judgement, legislation and, where applicable, health and safety as fluid selection or de-selection criteria. This paper also investigates and discusses the properties of specific ORC fluids with regard to their impact on the theoretical potential for delivering efficient WHR ORC work output. The paper concludes by looking at potential temperature and pressure WHR ORC limits with regard to fluid properties thereby assisting with the generation of WHR ORC simulation boundary conditions.

Phase Behavior of Reverse Poloxamers and Poloxamines in Water

The phase behavior of two types of poly(ethylene oxide)/poly(propylene oxide) (PEO/PPO) copolymers in aqueous solutions was studied by light scattering, viscometry, and infrared spectroscopy. Both the reverse poloxamer (Pluronic 10R5) and the star type poloxamine (Tetronic 90R4) have practically the same PEO/PPO ratio with their hydrophobic blocks (PPO) located in the outer part. The temperature-composition phase diagrams show that both 10R5 and 90R4 tend to form aggregates in water. Up to four different phases can be detected in the case of Tetronic 90R4 for each temperature: unimers, random networks, micellar networks, and macrophase separation. Viscometric and infrared measurements complemented the results obtained by light scattering and visual inspection.

High resolution X-ray spectroscopy in fast electron transport studies

A detailed knowledge of the physical phenomena underlying the generation and the transport of fast electrons generated in high-intensity laser-matter interactions is of fundamental importance for the fast ignition scheme for inertial confinement fusion.

Here we report on an experiment carried out with the VULCAN Petawatt beam and aimed at investigating the role of collisional return currents in the dynamics of the fast electron beam. To that scope, in the experiment counter-propagating electron beams were generated by double-sided irradiation of layered target foils containing a Ti layer. The experimental results were obtained for different time delays between the two laser beams as well as for single-sided irradiation of the target foils. The main diagnostics consisted of two bent mica crystal spectrometers placed at either side of the target foil. High-resolution X-ray spectra of the Ti emission lines in the range from the Ly alpha to the K alpha line were recorded. In addition, 2D X-ray images with spectral resolution were obtained by means of a novel diagnostic technique, the energy-encoded pin-hole camera, based on the use of a pin-hole array equipped with a CCD detector working in single-photon regime. The spectroscopic measurements suggest a higher target temperature for well-aligned laser beams and a precise timing between the two beams. The experimental results are presented and compared to simulation results.

Design and physicochemical characterisation of novel dissolving polymeric microneedle arrays for transdermal delivery of high dose, low molecular weight drugs

We describe formulation and evaluation of novel dissolving polymeric microneedle (MN) arrays for the facilitated delivery of low molecular weight, high dose drugs. Ibuprofen sodium was used as the model here and was successfully formulated at approximately 50% w/w in the dry state using the copolymer poly(methylvinylether/maleic acid). These MNs were robust and effectively penetrated skin in vitro, dissolving rapidly to deliver the incorporated drug. The delivery of 1.5mg ibuprofen sodium, the theoretical mass of ibuprofen sodium contained within the dry MN alone, was vastly exceeded, indicating extensive delivery of the drug loaded into the baseplates. Indeed in in vitro transdermal delivery studies, approximately 33mg (90%) of the drug initially loaded into the arrays was delivered over 24h. Iontophoresis produced no meaningful increase in delivery. Biocompatibility studies and in vivo rat skin tolerance experiments raised no concerns. The blood plasma ibuprofen sodium concentrations achieved in rats (263μgml(-1) at the 24h time point) were approximately 20 times greater than the human therapeutic plasma level. By simplistic extrapolation of average weights from rats to humans, a MN patch design of no greater than 10cm(2) could cautiously be estimated to deliver therapeutically-relevant concentrations of ibuprofen sodium in humans. This work, therefore, represents a significant progression in exploitation of MN for successful transdermal delivery of a much wider range of drugs.

Massive stars exploding in a He-rich circumstellar medium - IV. Transitional Type Ibn supernovae

We present ultraviolet, optical and near-infrared data of the Type Ibn supernovae (SNe) 2010al and 2011hw. SN 2010al reaches an absolute magnitude at peak of M-R = -18.86 +/- 0.21. Its early light curve shows similarities with normal SNe Ib, with a rise to maximum slower than most SNe Ibn. The spectra are dominated by a blue continuum at early stages, with narrow P-Cygni He I lines indicating the presence of a slow-moving, He-rich circumstellar medium. At later epochs, the spectra well match those of the prototypical SN Ibn 2006jc, although the broader lines suggest that a significant amount of He was still present in the stellar envelope at the time of the explosion. SN 2011hw is somewhat different. It was discovered after the first maximum, but the light curve shows a double peak. The absolute magnitude at discovery is similar to that of the second peak (M-R = -18.59 +/- 0.25), and slightly fainter than the average of SNe Ibn. Though the spectra of SN 2011hw are similar to those of SN 2006jc, coronal lines and narrow Balmer lines are clearly detected. This indicates substantial interaction of the SN ejecta with He-rich, but not H-free, circumstellar material. The spectra of SN 2011hw suggest that it is a transitional SN Ibn/IIn event similar to SN 2005la. While for SN 2010al the spectrophotometric evolution favours a H-deprived Wolf-Rayet progenitor (of WN-type), we agree with the conclusion of Smith et al. that the precursor of SN 2011hw was likely in transition from a luminous blue variable to an early Wolf-Rayet (Ofpe/WN9) stage.

Double ionization in R-matrix theory using a two-electron outer region

We have developed a two-electron outer region for use within R-matrix theory to describe double ionisation processes. The capability of this method is demonstrated for single-photon double ionisation of He in the photon energy region between 80 eV to 180 eV. The cross sections are in agreement with established data. The extended RMT method also provides information on higher-order processes, as demonstrated by the identification of signatures for sequential double ionisation processes involving an intermediate He⁺ state with n=2.

Multiuser relaying over mixed RF/FSO links

A multiuser dual-hop relaying system over mixed radio frequency/free-space optical (RF/FSO) links is investigated. Specifically, the system consists of m single-antenna sources, a relay node equipped with n≥ m receive antennas and a single photo-aperture transmitter, and one destination equipped with a single photo-detector. RF links are used for the simultaneous data transmission from multiple sources to the relay. The relay operates under the decode-and-forward protocol and utilizes the popular V-BLAST technique by successively decoding each user's transmitted stream. Two common norm-based orderings are adopted, i.e., the streams are decoded in an ascending or a descending order. After V-BLAST, the relay retransmits the decoded information to the destination via a point-to-point FSO link in m consecutive timeslots. Analytical expressions for the end-to-end outage probability and average symbol error probability of each user are derived, while closed-form asymptotic expressions are also presented. Capitalizing on the derived results, some engineering insights are manifested, such as the coding and diversity gain of each user, the impact of the pointing error displacement on the FSO link and the V-BLAST ordering effectiveness at the relay.

A comparison of gold nanoparticle surface co-functionalization approaches using Polyethylene Glycol (PEG) and the effect on stability, non-specific protein adsorption and internalization

To create clinically useful gold nanoparticle (AuNP) based cancer therapeutics it is necessary to co-functionalize the AuNP surface with a range of moieties; e.g. Polyethylene Glycol (PEG), peptides and drugs. AuNPs can be functionalized by creating either a mixed monolayer by attaching all the moieties directly to the surface using thiol chemistry, or by binding groups to the surface by means of a bifunctional polyethylene glycol (PEG) linker. The linker methodology has the potential to enhance bioavailability and the amount of functional agent that can be attached. While there is a large body of published work using both surface arrangements independently, the impact of attachment methodology on stability, non-specific protein adsorption and cellular uptake is not well understood, with no published studies directly comparing the two most frequently employed approaches. This paper compares the two methodologies by synthesizing and characterizing PEG and Receptor Mediated Endocytosis (RME) peptide co-functionalized AuNPs prepared using both the mixed monolayer and linker approaches. Successful attachment of both PEG and RME peptide using the two methods was confirmed using Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy and gel electrophoresis. It was observed that while the 'as synthesized' citrate capped AuNPs agglomerated under physiological salt conditions, all the mixed monolayer and PEG linker capped samples remained stable at 1M NaCl, and were stable in PBS over extended periods. While it was noted that both functionalization methods inhibited non-specific protein attachment, the mixed monolayer samples did show some changes in gel electrophoresis migration profile after incubation with fetal calf serum. PEG renders the AuNP stable in-vivo however, studies with MDA-MB-231 and MCF 10A cell lines indicated that functionalization with PEG, blocks cellular uptake. It was observed that co-functionalization with RME peptide using both the mixed monolayer and PEG linker methods greatly enhanced cellular internalization compared to PEG capped AuNPs.