Transcorneal Permeation in a Corneal Device of Non-Steroidal Anti-Inflammatory Drugs in Drug Delivery Systems

This work is focused on the ex vivo study of corneal permeation of two anti-inflammatory drugs: diclofenac, and flurbiprofen (as a model of hydrophilic and lipophilic drug, respectively) loaded to cyclodextrins or polymeric nanoparticles in order to determine differences in their corneal permeation against free drug or commercial eye drops. These studies were carried out in a corneal device designed and developed in our laboratory. In this work the habitual conditions for the permeation studies were modified to reproduce the behaviour when eye drops were administered. For this reason a new tetracompartmental pharmacokinetic model was developed. The complex formation of diclofenac with cyclodextrins and the flurbiprofen loaded to polymeric nanoparticles has been shown as effective procedures to remarkably increase the bioavailability of the anti-inflammatory drugs. The efficiency of polymeric nanoparticles of Poly (D-L lactic-coglycolyc) acid and poly-ε-caprolacton as intraocular targeting of NSAIDs has also been proved, being the latter polymer more effective to increase the flurbiprofen corneal permeation. The apparent corneal permeability coefficient of samples has been calculated getting a low permeation values for free drugs

Activity in the brain's valuation and mentalizing networks is associated with propagation of online recommendations

Word of mouth recommendations influence a wide range of choices and behaviors. What takes place in the mind of recommendation receivers that determines whether they will be successfully influenced? Prior work suggests that brain systems implicated in assessing the value of stimuli (i.e., subjective valuation) and understanding others' mental states (i.e., mentalizing) play key roles. The current study used neuroimaging and natural language classifiers to extend these findings in a naturalistic context and tested the extent to which the two systems work together or independently in responding to social influence. First, we show that in response to text-based social media recommendations, activity in both the brain's valuation system and mentalizing system was associated with greater likelihood of opinion change. Second, participants were more likely to update their opinions in response to negative, compared to positive, recommendations, with activity in the mentalizing system scaling with the negativity of the recommendations. Third, decreased functional connectivity between valuation and mentalizing systems was associated with opinion change. Results highlight the role of brain regions involved in mentalizing and positive valuation in recommendation propagation, and further show that mentalizing may be particularly key in processing negative recommendations, whereas the valuation system is relevant in evaluating both positive and negative recommendations

The adaptive significance of human scleral brightness: an experimental study

Action Contro

Ecological factors are likely drivers of eye shape and colour pattern variations across anthropoid primates

Action Contro

Predicting the Amplitude of a Solar Cycle Using the North-South Asymmetry in the Previous Cycle: II. An Improved Prediction for Solar Cycle~24

Recently, using Greenwich and Solar Optical Observing Network sunspot group data during the period 1874-2006, (Javaraiah, MNRAS, 377, L34, 2007: Paper I), has found that: (1) the sum of the areas of the sunspot groups in 0-10 deg latitude interval of the Sun's northern hemisphere and in the time-interval of -1.35 year to +2.15 year from the time of the preceding minimum of a solar cycle n correlates well (corr. coeff. r=0.947) with the amplitude (maximum of the smoothed monthly sunspot number) of the next cycle n+1. (2) The sum of the areas of the spot groups in 0-10 deg latitude interval of the southern hemisphere and in the time-interval of 1.0 year to 1.75 year just after the time of the maximum of the cycle n correlates very well (r=0.966) with the amplitude of cycle n+1. Using these relations, (1) and (2), the values 112 + or - 13 and 74 + or -10, respectively, were predicted in Paper I for the amplitude of the upcoming cycle 24. Here we found that in case of (1), the north-south asymmetry in the area sum of a cycle n also has a relationship, say (3), with the amplitude of cycle n+1, which is similar to (1) but more statistically significant (r=0.968) like (2). By using (3) it is possible to predict the amplitude of a cycle with a better accuracy by about 13 years in advance, and we get 103 + or -10 for the amplitude of the upcoming cycle 24. However, we found a similar but a more statistically significant (r=0.983) relationship, say (4), by using the sum of the area sum used in (2) and the north-south difference used in (3). By using (4) it is possible to predict the amplitude of a cycle by about 9 years in advance with a high accuracy and we get 87 + or - 7 for the amplitude of cycle 24.Comment: 21 pages, 7 figures, Published in Solar Physics 252, 419-439 (2008

Software engineering techniques for the development of systems of systems

This paper investigates how existing software engineering techniques can be employed, adapted and integrated for the development of systems of systems. Starting from existing system-of-systems (SoS) studies, we identify computing paradigms and techniques that have the potential to help address the challenges associated with SoS development, and propose an SoS development framework that combines these techniques in a novel way. This framework addresses the development of a class of IT systems of systems characterised by high variability in the types of interactions between their component systems, and by relatively small numbers of such interactions. We describe how the framework supports the dynamic, automated generation of the system interfaces required to achieve these interactions, and present a case study illustrating the development of a data-centre SoS using the new framework

Lepton Flavour Violating Leptonic/Semileptonic Decays of Charged Leptons in the Minimal Supersymmetric Standard Model

We consider the leptonic and semileptonic (SL) lepton flavour violating (LFV) decays of the charged leptons in the minimal supersymmetric standard model (MSSM). The formalism for evaluation of branching fractions for the SL LFV charged-lepton decays with one or two pseudoscalar mesons, or one vector meson in the final state, is given. Previous amplitudes for the SL LFV charged-lepton decays in MSSM are improved, for instance the $\gamma$-penguin amplitude is corrected to assure the gauge invariance. The decays are studied not only in the model-independent formulation of the theory in the frame of MSSM, but also within the frame of the minimal supersymmetric SO(10) model within which the parameters of the MSSM are determined. The latter model gives predictions for the neutrino-Dirac Yukawa coupling matrix, once free parameters in the model are appropriately fixed to accommodate the recent neutrino oscillation data. Using this unambiguous neutrino-Dirac Yukawa couplings, we calculate the LFV leptonic and SL decay processes assuming the minimal supergravity scenario. A very detailed numerical analysis is done to constrain the MSSM parameters. Numerical results for SL LFV processes are given, for instance for tau -> e (mu) pi0, tau -> e (mu) eta, tau -> e (mu) eta', tau -> e (mu) rho0, tau -> e (mu) phi, tau -> e (mu) omega, etc.Comment: 36 pages, 3 tables, 5 .eps figure

A Pan-GTPase inhibitor as a molecular probe

Overactive GTPases have often been linked to human diseases. The available inhibitors are limited and have not progressed far in clinical trials. We report here a first-in-class small molecule pan-GTPase inhibitor discovered from a high throughput screening campaign. The compound CID1067700 inhibits multiple GTPases in biochemical, cellular protein and protein interaction, as well as cellular functional assays. In the biochemical and protein interaction assays, representative GTPases from Rho, Ras, and Rab, the three most generic subfamilies of the GTPases, were probed, while in the functional assays, physiological processes regulated by each of the three subfamilies of the GTPases were examined. The chemical functionalities essential for the activity of the compound were identified through structural derivatization. The compound is validated as a useful molecular probe upon which GTPase-targeting inhibitors with drug potentials might be developed