ZEBRAFISH AS AN INNOVATIVE MODEL TO SCREEN THE BEHAVIOURAL EFFECTS OF NOVEL DRUGS

Zebrafish (Danio rerio) is an emerging animal model alternative to rodents for studying human diseases. Its typical shoaling behaviour (tight aggregation of individuals) consisting of forming a tight group in which fish swim together, may represent an excellent model to study social behaviour. Zebrafish appear to be a good model to study learning and memory, too. The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) are two of the most-studied brain signaling molecules encoding information relevant to social behaviour. Isotocin (ISO) and vasotocin (AVT) are the equivalent neurohypophiseal hormones in fish, regulating reproductive and social behaviour. On this basis, we studied the effect of both OT and AVP in comparison with ISO and AVT, on shoaling, fear response to predator and learning and memory. Social behaviour was studied using mutant zebrafish Nacre. Since these peptides are known to affect anxiety in humans and rodents, the same compounds were also tested on fear response to predator, using Astronotus Ocellatus as stimulus fish. OT (2-40 ng/kg), ISO (0.1-10 ng/kg), AVP (0.5-40 ng/kg) and AVT (0.001-20 ng/kg) were given i.m. 10 min before each test. AVT/AVP were more potent to elicit anxiolytic than social effect while ISO and OT were equally potent. To investigate the mechanism of action, different antagonists were given 10 min before each peptide: the OT receptor antagonist Desgly (0.00001-1 ng/kg), the V1a receptor subtype AVP antagonist SR 49059 (0.00001-20 ng/kg) and the V1b receptor subtype antagonist SSR 149415 (0.00001-1 ng/kg). In both tests, treatment with all the peptides increased social preference and decreased fear response in a dose-dependent manner interpolated by symmetrical parabolas. Pre-treatment with SR 49059, SSR 149415 and Desgly dose-dependently blocked the pro-social and anxiolytic effect induced by each peptide. The less selective antagonist appeared to be SSR 149415. All the neuropeptides did not induce any change in swimming activity. Neuronal nicotinic acetylcholine receptors (nAChRs) play a modulatory role in cognition and zebrafish provide a preclinical model to study these cognitive processes. On the other hand, nicotinic receptor has been characterized in this teleost fish. Using a T-maze task, we investigated the effect of cholinergic drugs on spatial memory in zebrafish. Nicotine (0.0002-0.2 mg/kg), given i.p. 20 min before the test, improved the mean running time difference, showing an inverted U dose-response function. Selective and non selective nAChR antagonists, injected i.p. 10 min before nicotine, were used to study the receptor subunits, involved in spatial memory. Nicotine-induced cognitive enhancement was reduced by the selective nAChR subtype antagonists, MLA (0.01 mg/kg) for \u3b17 subunit, MII (0.1 mg/kg) for \u3b16\u3b22 subunit, Dh\u3b2E (0.01 mg/kg) for the \u3b14\u3b22 subunit, the non selective antagonist mecamylamine (0.1 mg/kg) and the muscarinic antagonist scopolamine (0.025 mg/kg), with Dh\u3b2E being more active than MLA or MII. No change in swimming activity was observed for all the nicotinic drugs. Another important cognitive process is the selective attention. It can be assessed in rodents with the novel object recognition (NOR) test. In the standard version of this test, the selection of objects to be used is critical. To overcome the limitation of NOR, we created a modified version of NOR, the virtual object recognition test (VORT) in mice where 3D objects were replaced with stationary geometrical 2D shapes and presented on two Ipods 3.5-inch widescreen displays. A comparable discrimination index as NOR was shown in VORT. 2D shapes that could be highly discriminated and some which could not, were identified. Mice were able to distinguish among different movements (horizontal, vertical or oblique). In fact, the shapes previously found not distinguishable when stationary were better discriminated when moving. Secondly, we focused our attention on zebrafish, which have a good capability to learn and a better visual acuity. Based on this abilities, we investigated in VORT if zebrafish, like mice, were able to discriminate different geometrical 2D shapes (circle, square or triangle), when presented on Ipod-screens, placed at the sides of a water tank. To evaluate the possibility that moving 2D shapes increased the attention of zebrafish, specific movements were applied to the same geometrical shapes. We found that zebrafish, like mice, were able to discriminate different geometrical 2D shapes both stationary and with different movements. In particular, the discrimination index of shapes, previously not discriminate, increased when they were moving. Finally, we investigated if memory performance could be improved by treatment with nicotine both in mice (0.1 mg/kg) and in zebrafish (0.02 mg/kg) or worsened by scopolamine (0.25 mg/kg for mice and 0.025 mg/kg for zebrafish) or by mecamylamine (1 mg/kg). Nicotine improved discrimination index for stationary shapes previously not discriminated while anticholinergic drugs impaired episodic memory in both species. Taken together, these findings showed the pro-social and anxiolytic properties of OT/AVP system mediated by different receptors and confirmed the important role of cholinergic system in the processes of acquisition and memory consolidation in zebrafish similar to mammals. Moreover, we showed, for the first time, both mice and zebrafish could discriminate not only geometrical shapes but also different movements in VORT, allowing a direct comparison between animal model and human to study attention. Zebrafish opens a new avenue of research to rapidly screen new compounds for the treatment of abnormal social behaviours (including autism or schizophrenia) and neurodegenerative diseases

From ten to four and back again: how to generalize the geometry

We discuss the four-dimensional N=1 effective approach in the study of warped type II flux compactifications with SU(3)x SU(3)-structure to AdS_4 or flat Minkowski space-time. The non-trivial warping makes it natural to use a supergravity formulation invariant under local complexified Weyl transformations. We obtain the classical superpotential from a standard argument involving domain walls and generalized calibrations and show how the resulting F-flatness and D-flatness equations exactly reproduce the full ten-dimensional supersymmetry equations. Furthermore, we consider the effect of non-perturbative corrections to this superpotential arising from gaugino condensation or Euclidean D-brane instantons. For the latter we derive the supersymmetry conditions in N=1 flux vacua in full generality. We find that the non-perturbative corrections induce a quantum deformation of the internal generalized geometry. Smeared instantons allow to understand KKLT-like AdS vacua from a ten-dimensional point of view. On the other hand, non-smeared instantons in IIB warped Calabi-Yau compactifications 'destabilize' the Calabi-Yau complex structure into a genuine generalized complex one. This deformation gives a geometrical explanation of the non-trivial superpotential for mobile D3-branes induced by the non-perturbative corrections.Comment: LaTeX, 47 pages, v2, references, hyperref added, v3, correcting small inaccuracies in eqs. (2.6a) and (5.16

Dirac equation for the supermembrane in a background with fluxes from a component description of the D=11 supergravity-supermembrane interacting system

We present a simple derivation of the 'Dirac' equation for the supermembrane fermionic field in a D=11 supergravity background with fluxes by using a complete but gauge-fixed description of the supergravity-supermembrane interacting system previously developed. We also discuss the contributions linear in the supermembrane fermions -the Goldstone fields for the local supersymmetry spontaneously broken by the superbrane- to the field equations of the supergravity-supermembrane interacting system. The approach could also be applied to more complicated dynamical systems such as those involving the M5-brane and the D=10 Dirichlet branes.Comment: 1+22 pages, JHEP style. v2: cosmetic changes and references added to conform to the JHEP published versio

Optimization of hybrid sol-gel coating for dropwise condensation of pure steam

We developed hybrid organic-inorganic sol-gel silica coatings with good durability in harsh environment (high temperatures, high vapor velocities) and with slightly hydrophobic behavior, sufficient to promote dropwise condensation (DWC) of pure steam. DWC is a very promising mechanism in new trends of thermal management and power generation systems to enhance the heat transfer during condensation as compared to film-wise condensation (FWC). The sol-gel coatings have been prepared from methyl triethoxy silane (MTES) and tetraethyl-orthosilicate (TEOS) and deposited on an aluminum substrate. The coatings were optimized in terms of precursor ratio and annealing temperature highlighting potentials and limits of such mixtures. A comprehensive surface characterization before and after saturated steam condensation tests has been performed and related to the thermal measurements for evaluating the heat transfer augmentation as compared to FWC obtained on untreated aluminum surfaces. The results showed that the developed hybrid organic-inorganic sol-gel silica coatings are promising DWC promoters

Deformations of calibrated D-branes in flux generalized complex manifolds

We study massless deformations of generalized calibrated cycles, which describe, in the language of generalized complex geometry, supersymmetric D-branes in N=1 supersymmetric compactifications with fluxes. We find that the deformations are classified by the first cohomology group of a Lie algebroid canonically associated to the generalized calibrated cycle, seen as a generalized complex submanifold with respect to the integrable generalized complex structure of the bulk. We provide examples in the SU(3) structure case and in a `genuine' generalized complex structure case. We discuss cases of lifting of massless modes due to world-volume fluxes, background fluxes and a generalized complex structure that changes type.Comment: 52 pages, added references, added comment on ellipticity in appendix B, made minor changes according to instructions referee JHE

Fermions, T-duality and effective actions for D-branes in bosonic backgrounds

We find the effective action for any D-brane in a general bosonic background of supergravity. The results are explicit in component fields up to second order in the fermions and are obtained in a covariant manner. No interaction terms between fermions and the field $f=b+F$, characteristic of the bosonic actions, are considered. These are reserved for future work. In order to obtain the actions, we reduce directly from the M2-brane world-volume action to the D2-brane world-volume action. Then, by means of T-duality, we obtain the other Dp-brane actions. The resulting Dp-brane actions can be written in a single compact and elegant expression.Comment: 22 pages, latex, version published by JHEP plus typos corrected in eq.(44) and eq.(47

The general (2,2) gauged sigma model with three--form flux

We find the conditions under which a Riemannian manifold equipped with a closed three-form and a vector field define an on--shell N=(2,2) supersymmetric gauged sigma model. The conditions are that the manifold admits a twisted generalized Kaehler structure, that the vector field preserves this structure, and that a so--called generalized moment map exists for it. By a theorem in generalized complex geometry, these conditions imply that the quotient is again a twisted generalized Kaehler manifold; this is in perfect agreement with expectations from the renormalization group flow. This method can produce new N=(2,2) models with NS flux, extending the usual Kaehler quotient construction based on Kaehler gauged sigma models.Comment: 24 pages. v2: typos fixed, other minor correction

Wilson Loop, Regge Trajectory and Hadron Masses in a Yang-Mills Theory from Semiclassical Strings

We compute the one-loop string corrections to the Wilson loop, glueball Regge trajectory and stringy hadron masses in the Witten model of non supersymmetric, large-N Yang-Mills theory. The classical string configurations corresponding to the above field theory objects are respectively: open straight strings, folded closed spinning strings, and strings orbiting in the internal part of the supergravity background. For the rectangular Wilson loop we show that besides the standard Luescher term, string corrections provide a rescaling of the field theory string tension. The one-loop corrections to the linear glueball Regge trajectories render them nonlinear with a positive intercept, as in the experimental soft Pomeron trajectory. Strings orbiting in the internal space predict a spectrum of hadronic-like states charged under global flavor symmetries which falls in the same universality class of other confining models.Comment: 52 pages, latex 3 times, v3: references adde

Efficient and Consistent Recursive Filtering of Images with Reflective Extension

Recursive filters are commonly used in scale space construction for their efficiency and simple implementation. However these filters have an initialisation problem which either produces unusable results near the image boundaries or requires costly approximate solutions such as extending the boundary manually. In this paper, we describe a method for the recursive filtering of reflectively extended images for filters with symmetric denominator. We begin with an analysis of reflective extensions and their effect on non-recursive filtering operators. Based on the non-recursive case, we derive a formulation of recursive filtering on reflective domains as a linear but time-varying implicit operator. We then give an efficient method for decomposing and solving the linear implicit system. This decomposition needs to be performed only once for each dimension of the image. This yields a filtering which is both stable and consistent with the ideal infinite extension. The filter is efficient, requiring the same order of computation as the standard recursive filtering. We give experimental evidence to verify these claims