Self-assembly of a heteroduplex helicate from two different ligand strands and Cu(II) cations.

Cu(II) ions have been reacted with a 1/1 mixture of two linear ligands, one containing three 2,2'- bipyridine groups and the other three 2,2':6',2"-terpyridine groups. Absorption spectroscopy and fast atom bombardment mass spectrometry indicate the formation of a trinuclear complex containing one ligand of each kind. Determination of the crystal structure of this compound has confirmed that it is indeed a linear trinuclear complex in which two different ligands are wrapped in a helical fashion around the pentacoordinated metal ions. The central coordination geometry is trigonal bipyramidal; the two lateral Cu(II) ions are in a square pyramidal environment. Thus, a heteroduplex helicate is formed by the self-assembly of two different ligand strands and three specific metal ions induced by the coordination number and geometry of the latter. The self-assembly process may be considered to result from the reading of the steric and binding information present in the two ligands by Cu(II) ions through a pentacoordination algorithm. The same ligands have been shown earlier to yield homoduplex helicates from ions of tetrahedral and octahedral coordination geometry and strands of bidentate bipyridines and tridentate terpyridines, respectively. These two types of artificial double helical species may be related on one hand to the natural homoduplex nucleic acids and on the other hand to the DNA:RNA heteroduplex.

Preferential self-association of basic fibroblast growth factor is stabilized by heparin during receptor dimerization and activation.

Central to signaling by fibroblast growth factors (FGFs) is the oligomeric interaction of the growth factor and its high-affinity cell surface receptor, which is mediated by heparin-like polysaccharides. It has been proposed that the binding of heparin-like polysaccharides to FGF induces a conformational change in FGF, resulting in the formation of FGF dimers or oligomers, and this biologically active form is 'presented' to the FGF receptor for signal transduction. In this study, we show that monomeric basic FGF (FGF-2) preferentially self-associates and forms FGF-2 dimers and higher-order oligomers. As a consequence, FGF-2 monomers are oriented for binding to heparin-like polysaccharides. We also show that heparin-like polysaccharides can readily bind to self-associated FGF-2 without causing a conformational change in FGF-2 or disrupting the FGF-2 self-association, but that the bound polysaccharides only additionally stabilize the FGF-2 self-association. The preferential self-association corresponds to FGF-2 translations along two of the unit cell axes of the FGF-2 crystal structures. These two axes represent the two possible heparin binding directions, whereas the receptor binding sites are oriented along the third axis. Thus, we propose that preferential FGF-2 self-association, further stabilized by heparin, like "beads on a string," mediates FGF-2-induced receptor dimerization and activation. The observed FGF-2 self-association, modulated by heparin, not only provides a mechanism of growth factor activation but also represents a regulatory mechanism governing FGF-2 biological activity.

Aod1, the immunoregulatory locus controlling abrogation of tolerance in neonatal thymectomy-induced autoimmune ovarian dysgenesis, maps to mouse chromosome 16.

Mice thymectomized at three days of age (D3Tx) develop during adulthood a variety of organ-specific autoimmune diseases, including autoimmune ovarian dysgenesis (AOD). The phenotypic spectrum of AOD is characterized by the development of anti-ovarian autoantibodies, oophoritis, and atrophy. The D3Tx model of AOD is unique in that disease induction depends exclusively on perturbation of the normal developing immune system, is T-cell-mediated, and is strain specific. For example, D3Tx A/J mice are highly susceptible to AOD, whereas C57BL/6J mice are resistant. After D3Tx, self ovarian antigens, expressed at physiological levels, trigger an autoimmune response capable of eliciting disease. The D3Tx model provides, therefore, the opportunity to focus on the mechanisms of self-tolerance that are relevant to disease pathogenesis. Previous studies indicate that the principal mechanisms involved in AOD susceptibility are genetically controlled and govern developmental processes associated with the induction and maintenance of peripheral tolerance. We report here the mapping of the Aod1 locus to mouse chromosome 16 within a region encoding several loci of immunologic relevance, including scid, Igl1, VpreB, Igll, Igl1r, Mtv6 (Mls-3), Ly-7, Ifnar, and Ifgt.

Self-standing curved crystals for X and Gamma rays focusing

The efficiency of a Laue lens for X and Gamma ray focusing in the energy range 60 ÷ 600 keV is closely linked to the diffraction efficiency of the single crystals composing the lens. A powerful focusing system is crucial for applications like medical imaging and X ray astronomy where wide beams must be focused. Mosaic crystals with a high density, such as Cu or Au, and bent crystals with curved diffracting planes (CDP) are considered for the realization of a focusing system for X rays, owing to their high diffraction efficiency. In this work, a comparison of the efficiency of CDP crystals and mosaic crystals was performed on the basis of the theory of X-ray diffraction. Si, GaAs and Ge CDP crystals with optimized thicknesses and moderate radii of curvature of several tens of metres demonstrate comparable or superior performance with respect to the higher atomic number mosaic crystals generally used. A simplified approach for calculating the integrated reflectivity of the crystals is applied. A bending technique used during this work to realize CDP crystals consists in a controlled surface damaging induced by a mechanical lapping process. A compressive strained layer of few micrometres in thickness is generated and causes the convex curvature of the damaged side of the crystal. Another new bending technique is developed and the main results are shown. The process consists on a film deposition of a selected bi-component epoxy resin on one side of crystal, made uniform in thickness by mean of a spin-coater. Choosing the speed of spin-coating, so changing the thickness of the film, a control of radius of curvature can be obtained. Moreover the possibility to combine the two bending technique to obtain CDP crystal with a stronger curvature in rather thick crystals was demonstrated. Detailed characterization of Si, and GaAs CDP crystals at low and high x-ray energies are performed on flat and bent crystals obtained with the damaging and the resin deposition technique. As expected an increase of diffraction efficiency in asymmetrical diffraction geometry in CDP crystals with respect to the flat ones is observed. On the other hand an unexpected increase of the integrated intensity in symmetrical geometry, not predicted by the theory, is observed in all the measurements performed with different set up. The experimental trend of the integrated reflectivity as a function of the radius of curvature is in a good agreement with that predicted by the theory of bent perfect crystals, so it is possible to conclude that the surface damage has a limited effect on the crystal reflectivity. A study of the integrated reflectivity in the energy range of interest (100÷350 keV) in CDP crystals realized with damaging and resin deposition technique at symmetrical and asymmetrical geometries was performed at ILL Institute. Also at these energies the diffraction efficiency of bent crystals was much larger (a 12 time increase is observed for bent crystals in asymmetrical 111 geometry) than that measured in flat crystals. The diffraction efficiency of CDP crystals realized with both techniques tends to coincide with that of flat crystals at very high energies (> 200 keV). This suggesting that also real flat perfect crystals can be considered as strongly bent or mosaic crystals at very high X ray energies.

Self-association of calcium-binding protein S100A4 and metastasis

Elevated levels of the calcium-binding protein S100A4 promote metastasis and in carcinoma cells are associated with reduced survival of cancer patients. S100A4 interacts with target proteins that affect a number of activities associated with metastatic cells. However, it is not known how many of these interactions are required for S100A4-promoted metastasis, thus hampering the design of specific inhibitors of S100A4-induced metastasis. Intracellular S100A4 exists as a homodimer through previously identified, well conserved, predominantly hydrophobic key contacts between the subunits. Here it is shown that mutating just one key residue, phenylalanine 72, to alanine is sufficient to reduce the metastasis-promoting activity of S100A4 to 50% that of the wild type protein, and just 2 or 3 specific mutations reduces the metastasis-promoting activity of S100A4 to less than 20% that of the wild type protein. These mutations inhibit the self-association of S100A4 in vivo and reduce markedly the affinity of S100A4 for at least two of its protein targets, a recombinant fragment of non-muscle myosin heavy chain isoform A, and p53. Inhibition of the self-association of S100 proteins might be a novel means of inhibiting their metastasis-promoting activities.

Gamma-hydroxybutyrate does not maintain self-administration but induces conditioned place preference when injected in the ventral tegmental area

Gamma-hydroxybutyric acid (GHB) is an endogenous brain substance that has diverse neuropharmacological actions, including rewarding properties in different animal species and in humans. As other drugs of abuse, GHB affects the firing of ventral tegmental neurons (VTA) in anaesthetized animals and hyperpolarizes dopaminergic neurons in VTA slices. However, no direct behavioural data on the effects of GHB applied in the VTA or in the target regions of its dopaminergic neurons, e.g. the nucleus accumbens (NAc), are available. Here, we investigated the effects of various doses of intravenous GHB in maintaining self-administration (from 0.001 to 10 mg/kg per infusion), and its ability to induce conditioned place preference (CPP) in rats when given orally (175-350 mg/kg) or injected directly either in the VTA or NAc (from 10 to 300 microg/0.5 microl per side). Our results indicate that while only 0.01 mg/kg per infusion GHB maintained self-administration, although not on every test day, 350 mg/kg GHB given orally induced CPP. CPP was also observed when GHB was injected in the VTA (30-100 microg/0.5 microl per side) but not in the NAc. Together with recent in-vitro findings, these results suggest that the rewarding properties of GHB mainly occur via disinhibition of VTA dopaminergic neurons.

Dissipative nonlinear structures in optical fiber systems II : self-similar parabolic pulses in active fibers

In this second talk on dissipative structures in fiber applications, we overview theoretical aspects of the generation, evolution and characterization of self-similar parabolic-shaped pulses in fiber amplifier media. In particular, we present a perturbation analysis that describes the structural changes induced by third-order fiber dispersion on the parabolic pulse solution of the nonlinear Schrödinger equation with gain. Promising applications of parabolic pulses in optical signal post-processing and regeneration in communication systems are also discussed.

Upconversion assisted self-pulsing in a high-concentration erbium doped fiber laser

We report results on experimental and theoretical characterisation of self-pulsing in high concentration erbium doped fibre laser which is free from erbium clusters. Unlike previous models of self-pulsing accounting for pair-induced quenching (PIQ) on the clustered erbium ions, new model has been developed with accounting for statistical nature of the excitation migration and upconversion and resonance-like pumpto-signal intensity noise transfer. The obtained results are in a good agreement with the experimental data.

Dissipative nonlinear structures in optical fiber systems II:self-similar parabolic pulses in active fibers

In this second talk on dissipative structures in fiber applications, we overview theoretical aspects of the generation, evolution and characterization of self-similar parabolic-shaped pulses in fiber amplifier media. In particular, we present a perturbation analysis that describes the structural changes induced by third-order fiber dispersion on the parabolic pulse solution of the nonlinear Schrödinger equation with gain. Promising applications of parabolic pulses in optical signal post-processing and regeneration in communication systems are also discussed.

Grading of corneal transparency

Aim: To examine the academic literature on the grading of corneal transparency and to assess the potential use of objective image analysis. Method: Reference databases of academic literature were searched and relevant manuscripts reviewed. Annunziato, Efron (Millennium Edition) and Vistakon-Synoptik corneal oedema grading scale images were analysed objectively for relative intensity, edges detected, variation in intensity and maximum intensity. In addition, corneal oedema was induced in one subject using a low oxygen transmissibility (Dk/t) hydrogel contact lens worn for 3 hours under a light eye patch. Recovery from oedema was monitored over time using ultrasound pachymetry, high and low contrast visual acuity measures, bulbar hyperaemia grading and transparency image analysis of the test and control eyes. Results: Several methods for assessing corneal transparency are described in the academic literature, but none have gained widespread in clinical practice. The change in objective image analysis with printed scale grade was best described by quadratic parametric or sigmoid 3-parameter functions. ‘Pupil image scales’ (Annunziato and Vistakon-Synoptik) were best correlated to average intensity; however, the corneal section scale (Efron) was strongly correlated to variations in intensity. As expected, patching an eye wearing a low Dk/t hydrogel contact lens caused a significant (F=119.2, P<0.001) 14.3% increase in corneal thickness, which gradually recovered under open eye conditions. Corneal section image analysis was the most affected parameter and intensity variation across the slit width, in isolation, was the strongest correlate, accounting for 85.8% of the variance with time following patching, and 88.7% of the variance with corneal thickness. Conclusion: Corneal oedema is best determined objectively by the intensity variation across the width of a corneal section. This can be easily measured using a slit-lamp camera connected to a computer. Oedema due to soft contact lens wear is not easily determined over the pupil area by sclerotic scatter illumination techniques.

Silica promoted self-assembled mesoporous aluminas. Impact of the silica precursor on the structural, textural and acidic properties

This paper investigates the effect of silica addition on the structural, textural and acidic properties of an evaporation induced self-assembled (EISA) mesoporous alumina. Two silica addition protocols were applied while maintaining the EISA synthesis route. The first route is based on the addition of a Na-free colloidal silica suspension (Ludox®), and the second method consists of the co-hydrolysis of tetraethyl orthosilicate (TEOS) with aluminium tri-sec-butoxide, to favour a more intimate mixing of the Al- and Si-hydrolysed species. The properties of the so derived materials were compared to the SiO2-free counterpart. The SiO2 addition was always beneficial from a structural and textural standpoint. TEOS appears to have a truly promoting effect; the ordering, surface area and pore volume are all improved. For Ludox®, the enhancement comes from the formation of smaller pores by a densification of the structure. The crystallization of γ-alumina depends on the interaction between the Al- and Si-species in the mesophase. Ludox®-based materials achieved crystallization at 750 °C but the intimate mixing in the TEOS-based mesophases shows a suppression of the phase transformation by 50-100 °C, with respect to the SiO2-free counterpart. This reduces the textural features substantially. For all SiO2-modified materials, the enhancement in the surface area is not accompanied by a concomitant improvement of total acidity, and the formation of weak Lewis acid sites was promoted. These effects were ascribed to SiO2 migration to the surface that blocks part of the acidity.

Condensation-enhanced self-assembly as a route to high surface area α-aluminas

High surface area nanosized α-alumina has been obtained by thermally treating a sol-gel-derived mesophase at 1200 C; the mesophase was synthesized by a sol-gel route involving evaporation induced self-assembly (EISA) of a hydrolyzed gel from Al-tri-sec-butoxide in s-BuOH in the presence of a nonionic surfactant (EO20PO70EO20), HCl as catalyst, and water (H2O/Al = 6). The activated material renders moderate surface areas of about 8.4-10 m2 g-1, associated with significant crystallite coarsening. The key aspect to produce smaller crystallites is making the mesophase more resistant to coarsening. This was achieved by enhancing the condensation step by treating the hydrolyzed gel with tetrabutyl ammonium hydroxide (TBAOH) before evaporation. The characteristics of the mesophase indicate condensation of the primary particles with less AlO5 unsaturated sites, at the expense of a lower solid yield due to small crystallites dissolution. The activated TBAOH condensed EISA material is composed of α-alumina aggregated crystallites of about 60-100 nm, and the material possesses surface areas ranging from 16 to 24 m2 g -1 due to the improved resistance to coarsening. At least two aspects are suggested to play a role in this. The worm-hole morphology of the mesophase aggregates yields high particle coordination, which favors densification rather than coarsening. Furthermore, the decrease of the AlO5 defect sites by the TBAOH condensation makes the mesophase less reactive and consequently more resistant to coarsening. © 2013 American Chemical Society.

Stabilization of self-assembled alumina mesophases

An efficient route to stabilize alumina mesophases derived from evaporation-induced self-assembly is reported after investigating various aspects in-depth: influence of the solvent (EtOH, s-BuOH, and t-BuOH) on the textural and structural properties of the mesophases based on aluminum tri-sec-butoxide (ATSB), synthesis reproducibility, role of nonvolatile acids, and the crystallization and thermal stability of the crystalline counterparts. Mesophase specific surface area and pore uniformity depend notably on the solvent; s-BuOH yields the highest surface area and pore uniformity. The optimal mesophase synthesis is reproducible with standard deviations in the textural parameters below 5%. The most pore-uniform mesophases from the three solvents were thermally activated at 1023 K to crystallize them into γ-alumina. The s-BuOH mesophase is remarkably thermally stable, retaining the mesoscopic wormhole order with 300 m2/g (0.45 cm3/g) and an increased acidic site density. These features are not obtained with EtOH or t-BuOH, where agglomerated γ-Al2O3 crystallites are formed with lower surface areas and broader pore size distributions. This was rationalized by the increase of the hydrolysis rate using EtOH and t-BuOH. t-BuOH dehydrates under the synthesis conditions or reacts with HCl, situations that increase the water concentration and rate of hydrolysis. It was found that EtOH exchanges rapidly, producing a highly reactive Al-ethoxide, thus enhancing the hydrolysis rate as well. Particle heterogeneity with random packing of fibrous and wormhole morphologies, attributed to the high hydrolysis rate, was observed for mesophases derived from both solvents. Such a low particle coordination favors coarsening with enlargement of the pore size distribution upon thermal treatment, explaining the lower thermal stability. Controlled hydrolysis and formation of low-polymerized Al species in s-BuOH are possibly responsible for the adequate assembly onto the surfactant. This was verified by the formation of a regular distribution of relatively size-uniform nanoparticles in the mesophase; high particle coordination prevents coarsening, favors densification, and maintains a relatively uniform pore size distribution upon thermal treatment. The acid removal in the evaporation is another key factor to promote network condensation in this route. © 2013 American Chemical Society.

Elemental analysis of glass and ink by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser induced breakdown spectroscopy (LIBS)

The necessity of elemental analysis techniques to solve forensic problems continues to expand as the samples collected from crime scenes grow in complexity. Laser ablation ICP-MS (LA-ICP-MS) has been shown to provide a high degree of discrimination between samples that originate from different sources. In the first part of this research, two laser ablation ICP-MS systems were compared, one using a nanosecond laser and another a femtosecond laser source for the forensic analysis of glass. The results showed that femtosecond LA-ICP-MS did not provide significant improvements in terms of accuracy, precision and discrimination, however femtosecond LA-ICP-MS did provide lower detection limits. In addition, it was determined that even for femtosecond LA-ICP-MS an internal standard should be utilized to obtain accurate analytical results for glass analyses. In the second part, a method using laser induced breakdown spectroscopy (LIBS) for the forensic analysis of glass was shown to provide excellent discrimination for a glass set consisting of 41 automotive fragments. The discrimination power was compared to two of the leading elemental analysis techniques, μXRF and LA-ICP-MS, and the results were similar; all methods generated >99% discrimination and the pairs found indistinguishable were similar. An extensive data analysis approach for LIBS glass analyses was developed to minimize Type I and II errors en route to a recommendation of 10 ratios to be used for glass comparisons. Finally, a LA-ICP-MS method for the qualitative analysis and discrimination of gel ink sources was developed and tested for a set of ink samples. In the first discrimination study, qualitative analysis was used to obtain 95.6% discrimination for a blind study consisting of 45 black gel ink samples provided by the United States Secret Service. A 0.4% false exclusion (Type I) error rate and a 3.9% false inclusion (Type II) error rate was obtained for this discrimination study. In the second discrimination study, 99% discrimination power was achieved for a black gel ink pen set consisting of 24 self collected samples. The two pairs found to be indistinguishable came from the same source of origin (the same manufacturer and type of pen purchased in different locations). It was also found that gel ink from the same pen, regardless of the age, was indistinguishable as were gel ink pens (four pens) originating from the same pack.

Myostatin dysfunction is associated with reduction in overload induced hypertrophy of soleus muscle in mice

Acknowledgements This project was also supported by Marie Curie International Reintegration Grant 249156 (A. Lionikas) and the grants VP1-3.1-SMM-01-V-02-003 (A. Kilikevicius) and MIP-067/2012 (T. Venckunas) from the Research Council of Lithuania as well as the grant from the Ministry of Higher Education of Saudi Arabia (Y. Alhind). We wish also to thank Mrs Indre Libnickiene for her excellent technical assistance provided during the project