CO2 will probably not help to save Venice from the sea

It has been proposed to rise Venice by injecting CO₂ into an aquifer lying 600–800 m below its lagoon. It is shown that because of the prevailing ambient conditions in the aquifer phase change of CO₂ cannot be avoided. The ensuing change of specific volume and compressibility will inhibit a uniform uplift pattern which is needed to avoid cracks in historical buildings. Further, both liquid and gaseous CO₂ produce capillary effects at the contact surface with water in the voids of the reservoir rock and this affects its mechanical response. Hence further non homogeneity in the uplift pattern will be produced. This prevents the use of CO₂ in the proposed conditions.     

A surface wipe sampling and LC–MS/MS method for the simultaneous detection of six antineoplastic drugs commonly handled by healthcare workers

An effective wipe sampling and LC–MS/MS method was developed to simultaneously analyze six commonly administered antineoplastic drugs in stainless steel surface. The analyzed drugs were methotrexate, paclitaxel, cyclophosphamide, 5-fluorouracil, vincristine, and oxaliplatin, a frequently prepared antineoplastic drug that has not been included among any of the published simultaneous detection methods. The established method was used to evaluate the recoveries of antineoplastic drugs on brand new and worn stainless steel surfaces by wiping the plates with a Whatman filter paper wetted with 0.5 mL of water/methanol (20:80) with 0.1 % formic acid followed by LC–MS/MS before desorbing the filter with a water/methanol (50:50) solution. A significant decrease in the recovery of all evaluated drugs was found when worn plates were used. Additionally, the inter-personnel variability on drug recoveries during wiping procedures was evaluated. Significantly higher recoveries were achieved by the personnel with more training and experience versus personnel without prior experience. Finally, a laboratory stability test was developed to assess the degradation of the antineoplastic drugs during replicated shipping conditions. With the exception of vincristine sulfate which exhibited a significant (p?<?0.05) degradation after 48 h, all evaluated drugs were stable during the first 24–48 h. However, after 144 h, an increase in the degradation of all evaluated drugs was observed, with oxaliplatin and 5-fluorouracil exhibiting the most degradation.     

Contrasting confocal with defocusing microscale spatially offset Raman spectroscopy

The study compares and contrasts conventional confocal Raman microscopy/spectroscopy (CRM) with a recently developed micrometer scale defocusing spatially offset Raman spectroscopy (micro‐SORS), a method providing a new analytical capability for investigating non‐destructively the chemical composition of subsurface, micrometer‐scale‐thick diffusely scattering layers at depths beyond the reach of CRM. Because of close similarities between the two techniques and comparable embodiment of the instrumentations, but radically different interpretations of data, it is crucially important to recognise which type of method is pertinent to a specific measurement. The distinction comes principally from the nature of sample, whether turbid (micro‐SORS measurement) or transparent (CRM measurement) on the spatial scale of the axial (z‐)scan of the measurement. Which type of sample one deals with may not always be easily recognisable with micro‐scale thick layers, and the study therefore also presents a simple method for suggesting whether CRM or micro‐SORS methodology applies. This test relies on an axial (z‐)scan performed through the sample in both the positive and negative directions from the normal, imaged sample surface position using conventional CRM instrument. The absence or presence of symmetry or asymmetry of the intensity profiles of measured Raman signals around the imaged sample surface position as a function of sample axial displacement then suggests which interpretation could apply. The study paves a way for the development of micro‐SORS as a widely applicable analytical tool deployable on conventional Raman microscopes. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis,Characterization, and Biological Evaluation of a Dual-Action Ligand Targeting αvβ3 Integrin and VEGF Receptors

A dual-action ligand targeting both integrin α_Vβ₃ and vascular endothelial growth factor receptors (VEGFRs), was synthesized via conjugation of a cyclic peptidomimetic α_Vβ₃ Arg-Gly-Asp (RGD) ligand with a decapentapeptide. The latter was obtained from a known VEGFR antagonist by acetylation at the Lys13 side chain. Functionalization of the precursor ligands was carried out in solution and in the solid phase, affording two fragments: an alkyne VEGFR ligand and the azide integrin α_Vβ₃ ligand, which were conjugated by click chemistry. Circular dichroism studies confirmed that both the RGD and VEGFR ligand portions of the dual-action compound substantially adopt the biologically active conformation. In vitro binding assays on isolated integrin α_Vβ₃ and VEGFR-1 showed that the dual-action conjugate retains a good level of affinity for both its target receptors, although with one order of magnitude (10/20 times) decrease in potency. The dual-action ligand strongly inhibited the VEGF-induced morphogenesis in Human Umbilical Vein Endothelial Cells (HUVECs). Remarkably, its efficiency in preventing the formation of new blood vessels was similar to that of the original individual ligands, despite the worse affinity towards integrin α_Vβ₃ and VEGFR-1.     

Adsorption of chlorhexidine on synthetic hydroxyapatite and in vitro biological activity

The kinetic of chlorhexidine digluconate (CHXDG) uptake from aqueous solution by hydroxyapatite (HA) was investigated by ultraviolet (UV) analysis performed in HA powder (UV-solid) after the CHX adsorption. Adsorption isotherm of chlorhexidine (CHX) uptake was modeled by a combination of Languimir and Langmuir-Freundlich mechanisms. Strong molecule-molecule interactions and positive cooperativity predominated in the surface when CHX concentration was above 8.6 μg(CHX)/mg(HA). UV-solid spectra (shape, intensity and band position) of CHX bound to HA revealed that long-range molecular structures, such as aggregates or micelles, started to be formed at low CHX concentrations (1.52 μg(CHX)/mg(HA)) and predominated at high concentrations. Grazing-incidence X-ray diffraction (GIXRD) analysis from synchrotron radiation discarded the formation of crystalline structures on HA surface or precipitation of CHX crystalline salts, as suggested in previous works. The effect of the HA/CHX association on HA in vitro bioactivity, cytotoxicity and CHX antimicrobial activity was evaluated. It was shown that CHX did not inhibit the precipitation of a poorly crystalline apatite at HA/CHX surface after soaking in simulating body fluid (SBF). Cell viability studies after exposure to extracts of HA and HA/CHX showed that both biomaterials did not present significant in vitro toxicity. Moreover, HA/CHX inhibited Enterococcus faecalis growth for up to 6 days, revealing that binding to HA did not affect antimicrobial activity of CHX and reduced bacterial adhesion. These results suggested that HA/CHX association could result in a potential adjuvant antimicrobial system for clinical use.     

Influence of mixed thiolate/thioether versus dithiolate coordination on the accessibility of the uncommon +I and +III oxidation states for the nickel ion: an experimental and computational study

Sulfur-rich nickel metalloenzymes are capable of stabilizing Ni(I) and Ni(III) oxidation states in catalytically relevant species. In an effort to better understand the structural and electronic features that allow the stabilization of such species, we have investigated the electrochemical properties of two mononuclear N(2)S(2) Ni(II) complexes that differ in their sulfur environment. Complex 1 features aliphatic dithiolate coordination ([NiL], 1), and complex 2I is characterized by mixed thiolate/thioether coordination ([NiL(Me)]I, 2I). The latter results from the methylation of a single sulfur of 1. The X-ray structure of 2I reveals a distorted square planar geometry around the Ni(II) ion, similar to what was previously reported by us for 1. The electrochemical investigation of 1 and 2(+) shows that the addition of a methyl group shifts the potentials of both redox Ni(II)/Ni(I) and Ni(III)/Ni(II) redox couples by about 0.7 and 0.6 V to more positive values. Through bulk electrolyses, only the mononuclear dithiolate [Ni(I)L](-) (1(-)) and the mixed thiolate/thioether [Ni(III)L(Me)](2+) (2(2+)) complexes were generated, and their electronic properties were investigated by UV-vis and EPR spectroscopy. For 1(-) (Ni(I), d(9) configuration) the EPR data are consistent with a d(x(2))(-)(y(2)) based singly occupied molecular orbitals (SOMOs). However, DFT calculations suggest that there is also pronounced radical character. This is consistent with the small g-anisotropy observed in the EPR experiments. The spin population (Mulliken analysis) analysis of 1(-) reveals that the main contribution to the SOMO (64%) is due to the bipyridine unit. Time dependent density functional theory (TD-DFT) calculations attribute the most prominent features observed in the electronic absorption spectrum of 1(-) to metal to ligand charge transfer (MLCT) transitions. Concerning 2(2+), the EPR spectrum displays a rhombic signal with g(x) = 2.236, g(y) = 2.180, and g(z) = 2.039 in CH(3)CN. The g(iso) value is larger than 2.0, which is consistent with metal based oxidation. The unpaired electron (Ni(III), d(7) configuration) occupies a Ni-d(z(2)) based molecular orbital, consistent with DFT calculations. Nitrogen hyperfine structure is observed as a triplet in the g(z) component of the EPR spectrum with A(N) = 51 MHz. This result indicates the coordination of a CH(3)CN molecule in the axial position. DFT calculations confirm that the presence of a fifth ligand in the coordination sphere of the Ni ion is required for the metal-based oxidation process. Finally, we have shown that 1 exhibits catalytic reductive dehalogenation activity below potentials of -2.00 V versus Fc/Fc(+) in CH(2)Cl(2).     

Effect of quenched size polydispersity on the fluid-solid transition in charged colloidal suspensions

We study the effect of quenched size polydispersity on the phase behavior of charged colloidal suspensions using free-energy calculations in Monte Carlo simulations. The colloids are assumed to interact with a hard-core repulsive Yukawa (screened-Coulomb) interaction with constant surface potential, so that the particles are polydisperse both in size and charge. In addition, we take the size distribution to be fixed in both the fluid and crystal phase (no size fractionation is allowed). We study the fluid-solid transition for various screening lengths and surface potentials, finding that upon increasing the size polydispersity the freezing transition shifts toward higher packing fractions and the density discontinuity between the two coexisting phases diminishes. Our results provide support for a terminal polydispersity above which the freezing transition disappears.     

HMGB1–Carbenoxolone Interactions: Dynamics Insights from Combined Nuclear Magnetic Resonance and Molecular Dynamics

The interplay of protein dynamics and molecular recognition is of fundamental importance in biological processes. Atomic‐resolution insights into these phenomena may provide new opportunities for drug discovery. Herein, we have combined NMR relaxation experiments and residual dipolar coupling (RDC) measurements with molecular dynamics (MD) simulations to study the effects of the anti‐inflammatory drug carbenoxolone (CBNX) on the conformational properties and on the internal dynamics of a subdomain (box A) of high‐mobility group B protein (HMGB1). ¹⁵N relaxation data show that CBNX binding enhances the fast pico‐ to nanosecond motions of a loop and partially removes the internal motional anisotropy of the first two helices of box A. Dipolar wave analysis of amide RDC data shows that ligand binding induces helical distortions. In parallel, increased mobility of the loop upon ligand binding is highlighted by the essential dynamics analysis (EDA) of MD simulations. Moreover, simulations detect two possible orientations for CBNX, which induces two possible conformations of helix H3, one being similar to the free form and the second one causing a partial helical distortion. Finally, we introduce a new approach for the analysis of the internal coordination of protein residues that is consistent with experimental data and allows us to pinpoint which substructures of box A are dynamically affected by CBNX. The observations reported here may be useful for understanding the role of protein dynamics in binding at atomic resolution.     

First direct measurement of the total cross-section of 12C(α,γ)16O

The total cross-section of ¹²C(α,γ)¹⁶O was measured for the first time by a direct and ungated detection of the ¹⁶O recoils. This measurement in inverse kinematics using the recoil mass separator ERNA in combination with a windowless He gas target allowed to collect data with high precision in the energy range E = 1.9 to 4.9 MeV. The data represent new information for the determination of the astrophysical S(E) factor.     

Atmospheric temperature time series analysis at Mt. Cimone Observatory, Italy, 1946–1991

Summary Observations of atmospheric temperature have been uninterruptedly carried out at Mt. Cimone (2165 m s.l.) since January 1946. Four decades and a half of homogeneous measurements are presented in this paper giving particular emphasis to long-term change: in the yearly temperature averages there is no evidence for secular trend as well as in the winter and summer temperature averages. On the contrary the spring averages show a decreasing long-term trend, while the autumn averages reveal an increasing long-term trend. We find, for the spring season, a global decrease of about −1°C and, for the autumn season, a global increase of about +1°C. A temperature correlation analysis between Mt. Cimone and an area-box of about (200×700) km², exceeding the Po Valley, just to the North of Mt. Cimone, is presented. Results show how long-term temperature change, representing the mentioned area, could be powerfully monitored by operating a single station as Mt. Cimone.