Interaction between like-charged polyelectrolyte-colloid complexes in electrolyte solutions: a Monte Carlo simulation study in the Debye-H\"uckel approximation

We study the effective interaction between differently charged polyelectrolyte-colloid complexes in electrolyte solutions via Monte Carlo simulations. These complexes are formed when short and flexible polyelectrolyte chains adsorb onto oppositely charged colloidal spheres, dispersed in an electrolyte solution. In our simulations the bending energy between adjacent monomers is small compared to the electrostatic energy, and the chains, once adsorbed, do not exchange with the solution, although they rearrange on the particles surface to accomodate further adsorbing chains or due to the electrostatic interaction with neighbor complexes. Rather unexpectedly, when two interacting particles approach each others, the rearrangement of the surface charge distribution invariably produces anti-parallel dipolar doublets, that invert their orientation at the isoelectric point. These findings clearly rule out a contribution of dipole-dipole interactions to the observed attractive interaction between the complexes, pointing out that such suspensions can not be considered dipolar fluids. On varying the ionic strength of the electrolyte, we find that a screening length, short compared with the size of the colloidal particles, is required in order to observe the attraction between like charged complexes due to the non-uniform distribution of the electric charge on their surface ('patch attraction'). On the other hand, by changing the polyelectrolyte/particle charge ratio, the interaction between like-charged polyelectrolyte-decorated (pd) particles, at short separations, evolves from purely repulsive to strongly attractive. Hence, the effective interaction between the complexes is characterized by a potential barrier, whose height depends on the net charge and on the non-uniformity of their surface charge distribution.Comment: 24 pages, 9 figure

Long-term physical evolution of an elastomeric ultrasound contrast microbubble

Hypothesis: One of the main assets of crosslinked polymer-shelled microbubbles (MBs) as ultrasound-active theranostic agents is the robustness of the shells, combined with the chemical versatility in modifying the surface with ligands and/or drugs. Despite the long shelf-life, subtle modifications occur in the MB shells involving shifts in acoustic, mechanical and structural properties. Experiments: We carried out a long-term morphological and acoustic evolution analysis on elastomeric polyvinyl-alcohol (PVA)-shelled MBs, a novel platform accomplishing good acoustic and surface performances in one agent. Confocal laser scanning microscopy, acoustic spectroscopy and AFM nanomechanics were integrated to understand the mechanism of PVA MBs ageing. The changes in the MB acoustic properties were framed in terms of shell thickness and viscoelasticity using a linearised oscillation theory, and compared to MB morphology and to nanomechanical analysis. Findings: We enlightened a novel, intriguing ageing time evolution of the PVA MBs with double behaviour with respect to a crossover time of ∼50 days. Before, significant changes occur in MB stiffness and shell thickness, mainly due to a massive release of entangled PVA chains. Then, the MB resonance frequency increases together with shell thickening and softening. Our benchmark study is of general interest for emerging viscoelastomeric bubbles towards personalised medicine

Influence of space allowance on the welfare of weaned buffalo (Bubalus Bubalis) calves

Twenty weaned female buffalo calves were used to evaluate the effect of space allowance in relation to their body surface area on a range of behavioural and physiological parameters. Body surface area in m2 was calculated as 0.12 body weight0.60. Ten calves received 50% of body surface as space allocation (Group 50), 10 others received 90% of body surface area (Group 90). Animals in Group 50 lay with a lower number of outstretched legs than calves in Group 90. Buffaloes from Group 50 were observed standing more frequently than animals from Group 90 ( P < 0.001). The proportions of idling ( P < 0.01) and lying idle observations ( P < 0.001) were higher for Group 90 than for Group 50. Group 90 performed a higher number of non-agonistic interactions than Group 50 ( P < 0.01), whereas the opposite was observed for the number of agonistic interactions ( P < 0.01). When exposed to open field testing, Group 50 animals displayed an increased duration of movement, number of galloping events and more vocalisation. Neither immune responses to phytohemagglutinin and ovalbumin nor the cortisol response to exogenous ACTH were affected by treatment. It was concluded that 50% of body surface area may be an inadequate space allowance for weaned calves

The qualitative assessment of responsiveness to environmental challenge in horses and ponies.

The responsiveness of 10 horses and 10 ponies to environmental challenge (represented by an open field test) was assessed using a qualitative approach based on free choice profiling methodology (FCP), which gives observers complete freedom to choose their own descriptive terms. Data were analysed with generalised Procrustes analysis (GPA), a multivariate statistical technique associated with FCP. A cross-validation of the outcomes of this approach to data recorded through quantitative behaviour analysis, and through a questionnaire given to the animals’ owner/riding instructor, was also performed using principal component analysis (PCA). Twelve undergraduate students generated their own descriptive vocabularies, by watching 20 horse/pony video clips lasting 2.5 min each. GPA showed that the consensus profile explained a high percentage of variation among the 12 observers, and differed significantly from the mean randomised profile ( p < 0.001). Two main dimensions of the consensus profile were identified, explaining 60% and 5.2% of the variation between animals, respectively. The 12 observer word charts interpreting these dimensions were semantically consistent, as they all converged towards the same meaning, albeit using different terms. The most used term to describe the positive end of axis 1 was ‘‘quiet’’, whereas ‘‘attentive’’ was the best positive descriptor of axis 2. The most frequently used descriptors for the negative ends of axes 1 and 2 were ‘‘nervous’’ and ‘‘bored’’, respectively. Thus, axis 1 was labelled as ‘‘quiet/nervous’’ and axis 2 was named as ‘‘attentive/bored’’. A marked effect of animal category was observed on the scores of the animals on the first dimension ( p < 0.001). Horses received significantly higher scores, and were thus assessed as more quiet and calm, than ponies. Conversely, ponies tended to receive lower scores on the second dimension ( p < 0.12), therefore they appeared less curious and attentive. The results of the PCA showed that the variables from different types of measurement clearly had meaningful relationships. For instance, the variables with the highest loading on the positive end of axis 1 were all indicative of tractable and docile animals, whereas axis 2 showed high loadings on the positive end for variables indicating attentive animals. Qualitative behaviour assessment proved to be an appropriate methodology for the study of horse behavioural responsiveness, in that it provided a multifaceted characterisation of horse behavioural expression that was in agreement with other quantitative and subjective assessments of the animals’ behaviour

Long-term response of stratospheric ozone and temperature to solar variability

The long-term variability in stratospheric ozone mass mixing ratio (O3) and temperature (T) from 1979 to 2013 is investigated using the latest reanalysis product delivered by the European Centre for Medium-Range Weather Forecasts (ECMWF), i.e., ERA-Interim. Moreover, using the Mg II index time series for the same time period, the response of the stratosphere to the 11-year Schwabe solar cycle is investigated. Results reveal the following features: (i) upward (downward) trends characterize zonally averaged O3 anomalies in the upper (middle to lower stratosphere) stratosphere, while prevailing downward trends affect the T field. Mg II index data exhibit a weaker 24th solar cycle (though not complete) when compared with the previous two; (ii) correlations between O3 and Mg II, T and Mg II, and O3 and T are consistent with photochemical reactions occurring in the stratosphere and large-scale transport; and (iii) wavelet cross-spectra between O3 and Mg II index show common power for the 11-year period, particularly in tropical regions around 30-50 hPa, and different relative phase in the upper and lower stratosphere. A comprehensive insight into the actual processes accounting for the observed correlation between ozone and solar UV variability would be gained from an improved bias correction of ozone measurements provided by different satellite instruments, and from the observations of the time behavior of the solar spectral irradiance

Differential effects on membrane permeability and viability of human keratinocyte cells undergoing very low intensity megasonic fields

Among different therapeutic applications of Ultrasound (US), transient membrane sonoporation (SP) - a temporary, non-lethal porosity, mechanically induced in cell membranes through US exposure - represents a compelling opportunity towards an efficient and safe drug delivery. Nevertheless, progresses in this field have been limited by an insufficient understanding of the potential cytotoxic effects of US related to the failure of the cellular repair and to the possible activation of inflammatory pathway. In this framework we studied the in vitro effects of very low-intensity US on a human keratinocyte cell line, which represents an ideal model system of skin protective barrier cells which are the first to be involved during medical US treatments. Bioeffects linked to US application at 1 MHz varying the exposure parameters were investigated by fluorescence microscopy and fluorescence activated cell sorting. Our results indicate that keratinocytes undergoing low US doses can uptake drug model molecules with size and efficiency which depend on exposure parameters. According to sub-cavitation SP models, we have identified the range of doses triggering transient membrane SP, actually with negligible biological damage. By increasing US doses we observed a reduced cells viability and an inflammatory gene overexpression enlightening novel healthy relevant strategies

On the effect of temperature on the reentrant condensation in polyelectrolyte-liposome complexation

In systems of highly charged linear polyelectrolytes and oppositely charged colloidal particles, long-lived clusters of polyelectrolyte-decorated particles form in an interval of concentrations around the isoelectric point, where reentrant condensation connected to charge inversion of cluster is observed. The mechanisms that drive the aggregation and stabilize, at the different polymer/particle ratios, a well defined size of the aggregates are not completely understood. Moreover, a central question still remains unanswered, i.e., whether the clusters are true equilibrium or metastable aggregates. To elucidate this point, in this work, we have investigated the effect of the temperature on the formation of the clusters. We employed liposomes built up by DOTAP lipid interacting with a simple anionic polyion, sodium polyacrylate, over an extended concentration range below and over the isoelectric condition. Our results show that the aggregation process can be described by a thermally-activated mechanism.Comment: Submitted Langmui

On non-linear baroclinic adjustment with the stratosphere

The effect of the stratosphere on the baroclinic adjustment of a nonlinear Eady model is presented. The classical linear Eady model has been modified by including an additional layer (the stratosphere), Ekman dissipation at the bottom boundary and a Newtonian cooling at the surface and the tropopause, respectively; non-linearity is introduced by wave-mean flow interaction for a single eddy mode. Results for the rigid-lid case and for small troposphere/stratosphere stratification ratio are compared with those for the linear Eady model with Ekman dissipation at the surface. For these cases model solutions consist of a steady zonal correction and an eddy field with a travelling constant amplitude wave. The equilibrated field, as a function of small stratification ratio, shows that the minimum amplitude of the eddy component raises to a height close to the tropopause (its steering level), denoting that the wave solution becomes vertical evanescent. When realistic values for the static stability in the stratosphere are considered, the zonal correction is no more time independent and reveals a degree of chaotic behaviour, while the eddy field is fully chaotic. Effects of changes in the zonal wind vertical shear and a further decreasing static stability in the stratosphere are also analysed. Results suggest that the minimum amplitude is, in average, higher than the one computed for the classical rigid lid with Ekman dissipation at the surface. Thus, as in the linear Eady model, the stratosphere induces a stabilising effect on the baroclinic dynamics. Finally, the model solutions are compared with the time behaviour of a simplified General Circulation Model

Emerging role of gefitinib in the treatment of non-small-cell lung cancer (NSCLC)

Most patients with non-small-cell lung cancer (NSCLC) present with advanced disease and their long-term prognosis remains poor. Epidermal growth factor receptor (EGFR)-targeted therapies, such as gefitinib, have been subjected to comprehensive clinical development. Several phase II and III trials evaluated the clinical efficacy of gefitinib as monotherapy in pretreated patients with advanced NSCLC, as well as both monotherapy and combined with chemotherapy in chemotherapy-naive patients. A phase III trial (ISEL) in heavily pretreated advanced NSCLC patients demonstrated some improvement in survival with gefitinib compared with placebo; however, the difference was not statistically significant within the overall population. A large phase III trial in pretreated patients (INTEREST) demonstrated the non-inferiority of gefitinib in comparison with docetaxel for overall survival, together with an improved quality of life and tolerability profiles. In a large phase III trial (IPASS) in Asian chemotherapy-naive, never or former light-smoker patients with adenocarcinoma, gefitinib was more effective than carboplatin–paclitaxel in prolonging progression-free survival, particularly in patients harboring EGFR gene mutations. Gefitinib was a generally well tolerated treatment, with skin rash and diarrhea being the most common treatment adverse events. As a result, gefitinib is expected to have a large impact on the management of patients with advanced NSCLC, in particular in EGFR mutated patients