Periodic orbits near a heteroclinic loop formed by one dimensional orbit and a 2-dimensional manifold: application to the charged collinear 3-body problem

The paper is devoted to the study of a type of differential systems which appear usually in the study of some Hamiltonian systems with 2 degrees of freedom. We prove the existence of infinitely many periodic orbits on each negative energy level. All these periodic orbits pass near the total collision. Finally we apply these results to study the existence of periodic orbits in the charged collinear 3–body problem.

The loop group and the cobar construction

"Vegeu el resum a l'inici del document del fitxer adjunt."

Estudio y diseño de filtros pasobanda y en banda dual basados en resonadores microstrip open-loop acoplados

El proyecto está dedicado al estudio y diseño de filtros paso-banda y en banda dual con tecnología microstrip mediante estructuras resonantes de tipo open-loop. Se ha llevado a cabo el diseño de un filtro paso-banda con respuesta Chebyshev, un filtro pasobanda con ceros de transmisión y un filtro de banda dual para WCDMA y WiFi, empleado el método de diseño para filtros basados en resonadores inter-acoplados. Se presentan los modelos eléctricos de los filtros de RF simulados junto con sus respectivos layouts y se comparan las respuestas obtenidas de los dispositivos con las respuestas ideales. En el proyecto se realiza un estudio del comportamiento de los diferentes tipos de acoplamiento entre resonadores open-loop en función de la geometría de la estructura. Las tendencias de comportamiento de los acoplamientos permiten el diseño y colocación de los resonadores para satisfacer las especificaciones del filtro.

Understanding the two-component sensing System of virulent bacteria

Report for the scientific sojourn carried out at the l’ Institute for Computational Molecular Science of the Temple University, United States, from 2010 to 2012. Two-component systems (TCS) are used by pathogenic bacteria to sense the environment within a host and activate mechanisms related to virulence and antimicrobial resistance. A prototypical example is the PhoQ/PhoP system, which is the major regulator of virulence in Salmonella. Hence, PhoQ is an attractive target for the design of new antibiotics against foodborne diseases. Inhibition of the PhoQ-mediated bacterial virulence does not result in growth inhibition, presenting less selective pressure for the generation of antibiotic resistance. Moreover, PhoQ is a histidine kinase (HK) and it is absent in animals. Nevertheless, the design of satisfactory HK inhibitors has been proven to be a challenge. To compete with the intracellular ATP concentrations, the affinity of a HK inhibidor must be in the micromolar-nanomolar range, whereas the current lead compounds have at best millimolar affinities. Moreover, the drug selectivity depends on the conformation of a highly variable loop, referred to as the “ATP-lid, which is difficult to study by X-Ray crystallography due to its flexibility. I have investigated the binding of different HK inhibitors to PhoQ. In particular, all-atom molecular dynamics simulations have been combined with enhanced sampling techniques in order to provide structural and dynamic information of the conformation of the ATP-lid. Transient interactions between these drugs and the ATP-lid have been identified and the free energy of the different binding modes has been estimated. The results obtained pinpoint the importance of protein flexibility in the HK-inhibitor binding, and constitute a first step in developing more potent and selective drugs. The computational resources of the hosting institution as well as the experience of the members of the group in drug binding and free energy methods have been crucial to carry out this work.

Whole genome analysis of p38 SAPK-mediated gene expression upon stress

Background: Cells have the ability to respond and adapt to environmental changes through activation of stress-activated protein kinases (SAPKs). Although p38 SAPK signalling is known to participate in the regulation of gene expression little is known on the molecular mechanisms used by this SAPK to regulate stress-responsive genes and the overall set of genes regulated by p38 in response to different stimuli.Results: Here, we report a whole genome expression analyses on mouse embryonic fibroblasts (MEFs) treated with three different p38 SAPK activating-stimuli, namely osmostress, the cytokine TNFα and the protein synthesis inhibitor anisomycin. We have found that the activation kinetics of p38α SAPK in response to these insults is different and also leads to a complex gene pattern response specific for a given stress with a restricted set of overlapping genes. In addition, we have analysed the contribution of p38α the major p38 family member present in MEFs, to the overall stress-induced transcriptional response by using both a chemical inhibitor (SB203580) and p38α deficient (p38α-/-) MEFs. We show here that p38 SAPK dependency ranged between 60% and 88% depending on the treatments and that there is a very good overlap between the inhibitor treatment and the ko cells. Furthermore, we have found that the dependency of SAPK varies depending on the time the cells are subjected to osmostress. Conclusions: Our genome-wide transcriptional analyses shows a selective response to specific stimuli and a restricted common response of up to 20% of the stress up-regulated early genes that involves an important set of transcription factors, which might be critical for either cell adaptation or preparation for continuous extra-cellular changes. Interestingly, up to 85% of the up-regulated genes are under the transcriptional control of p38 SAPK. Thus, activation of p38 SAPK is critical to elicit the early gene expression program required for cell adaptation to stress.

Motivational effects of cannabinoids are mediated by μ-opioid and k-opioid receptor

Repeated THC administration produces motivational and somaticadaptive changes leading to dependence in rodents. Toinvestigate the molecular basis for cannabinoid dependenceand its possible relationship with the endogenous opioid system,we explored Δ9-tetrahydrocannabinol (THC) activity in mice lacking μ-, δ- or κ-opioid receptor genes. Acute THCinduced hypothermia, antinociception, and ypolocomotion remained unaffected in these mice, whereas THC tolerance and withdrawal were minimally modified in mutant animals. In contrast, profound phenotypic changes are observed in several place conditioning protocols that reveal both THC rewarding and aversive properties. Absence of μ receptors abolishes THC place preference. Deletion of κ receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of μ- and κ-opioid receptors in modulating reward pathways forms the basis for the dual euphoric–dysphoric activity of THC.

Defective TNF-alpha-mediated hepatocellular apoptosis and liver damage in acidic sphingomyelinase knockout mice

This study addressed the contribution of acidic sphingomyelinase (ASMase) in TNF-alpha-mediated hepatocellular apoptosis. Cultured hepatocytes depleted of mitochondrial glutathione (mGSH) became sensitive to TNF-alpha, undergoing a time-dependent apoptotic cell death preceded by mitochondrial membrane depolarization, cytochrome c release, and caspase activation. Cyclosporin A treatment rescued mGSH-depleted hepatocytes from TNF-alpha-induced cell death. In contrast, mGSH-depleted hepatocytes deficient in ASMase were resistant to TNF-alpha-mediated cell death but sensitive to exogenous ASMase. Furthermore, although in vivo administration of TNF-alpha or LPS to galactosamine-pretreated ASMase(+/+) mice caused liver damage, ASMase(-/-) mice exhibited minimal hepatocellular injury. To analyze the requirement of ASMase, we assessed the effect of glucosylceramide synthetase inhibition on TNF-alpha-mediated apoptosis. This approach, which blunted glycosphingolipid generation by TNF-alpha, protected mGSH-depleted ASMase(+/+) hepatocytes from TNF-alpha despite enhancement of TNF-alpha-stimulated ceramide formation. To further test the involvement of glycosphingolipids, we focused on ganglioside GD3 (GD3) because of its emerging role in apoptosis through interaction with mitochondria. Analysis of the cellular redistribution of GD3 by laser scanning confocal microscopy revealed the targeting of GD3 to mitochondria in ASMase(+/+) but not in ASMase(-/-) hepatocytes. However, treatment of ASMase(-/-) hepatocytes with exogenous ASMase induced the colocalization of GD3 and mitochondria. Thus, ASMase contributes to TNF-alpha-induced hepatocellular apoptosis by promoting the mitochondrial targeting of glycosphingolipids.

Clathrin Assembly Lymphoid Myeloid Leukemia (CALM) Protein: Localization in Endocytic-coated Pits, Interactions with Clathrin, and the Impact of Overexpression on Clathrin-mediated Traffic

The clathrin assembly lymphoid myeloid leukemia (CALM) gene encodes a putative homologue of the clathrin assembly synaptic protein AP180. Hence the biochemical properties, the subcellular localization, and the role in endocytosis of a CALM protein were studied. In vitro binding and coimmunoprecipitation demonstrated that the clathrin heavy chain is the major binding partner of CALM. The bulk of cellular CALM was associated with the membrane fractions of the cell and localized to clathrin-coated areas of the plasma membrane. In the membrane fraction, CALM was present at near stoichiometric amounts relative to clathrin. To perform structure-function analysis of CALM, we engineered chimeric fusion proteins of CALM and its fragments with the green fluorescent protein (GFP). GFP-CALM was targeted to the plasma membrane-coated pits and also found colocalized with clathrin in the Golgi area. High levels of expression of GFP-CALM or its fragments with clathrin-binding activity inhibited the endocytosis of transferrin and epidermal growth factor receptors and altered the steady-state distribution of the mannose-6-phosphate receptor in the cell. In addition, GFP-CALM overexpression caused the loss of clathrin accumulation in the trans-Golgi network area, whereas the localization of the clathrin adaptor protein complex 1 in the trans-Golgi network remained unaffected. The ability of the GFP-tagged fragments of CALM to affect clathrin-mediated processes correlated with the targeting of the fragments to clathrin-coated areas and their clathrin-binding capacities. Clathrin-CALM interaction seems to be regulated by multiple contact interfaces. The C-terminal part of CALM binds clathrin heavy chain, although the full-length protein exhibited maximal ability for interaction. Altogether, the data suggest that CALM is an important component of coated pit internalization machinery, possibly involved in the regulation of clathrin recruitment to the membrane and/or the formation of the coated pit.

Electroluminiscence and optical amplification in silicon nanostructures: towards the integration of electronics and photonics

This line of research of my group intends to establish a Silicon technological platform in the field of photonics allowing the development of a wide set of applications. Particularly, what is still lacking in Silicon Photonics is an efficient and integrable light source such an LED or laser. Nanocrystals in silicon oxide or nitride matrices have been recently demonstrated as competitive materials for both active components (electrically and optically driven light emitters and optical amplifiers) and passive ones (waveguides and modulators). The final goal is the achievement of a complete integration of electronic and optical functions in the same CMOS chip. The first part of this paper will introduce the structural and optical properties of LEDs fabricated from silicon nanostructures. The second will treat the interaction of such nanocrystals with rare-earth elements (Er), which lead to an efficient hybrid system emitting in the third window of optical fibers. I will present the fabrication and assessment of optical waveguide amplifiers at 1.54 ¿m for which we have been able to demonstrate recently optical gain in waveguides made from sputtered silicon suboxide materials.

Matching at one loop for the four-quark operators in NRQCD

The matching coefficients for the four-quark operators in NRQCD (NRQED) are calculated at one loop using dimensional regularization for ultraviolet and infrared divergences. The matching for the electromagnetic current follows easily from our results. Both the unequal and equal mass cases are considered. The role played by the Coulomb infrared singularities is explained in detail.

Driving rate effects in avalanche-mediated first-order phase transitions

We study the driving-rate and temperature dependence of the power-law exponents that characterize the avalanche distribution in first-order phase transitions. Measurements of acoustic emission in structural transitions in Cu-Zn-Al and Cu-Al-Ni are presented. We show how the observed behavior emerges within a general framework of competing time scales of avalanche relaxation, driving rate, and thermal fluctuations. We confirm our findings by numerical simulations of a prototype model.

Loop bifurcation and magnetization rotation in exchange-biased Ni/FeF2

Exchange-biased Ni/FeF2 films have been investigated using vector coil vibrating-sample magnetometry as a function of the cooling field strength HFC . In films with epitaxial FeF2 , a loop bifurcation develops with increasing HFC as it divides into two sub-loops shifted oppositely from zero field by the same amount. The positively biased sub-loop grows in size with HFC until only a single positively shifted loop is found. Throughout this process, the negative and positive (sub)loop shifts maintain the same discrete value. This is in sharp contrast to films with twinned FeF2 where the exchange field gradually changes with increasing HFC . The transverse magnetization shows clear correlations with the longitudinal subloops. Interestingly, over 85% of the Ni reverses its magnetization by rotation, either in one step or through two successive rotations. These results are due to the single-crystal nature of the antiferromagnetic FeF2 , which breaks down into two opposite regions of large domains.

Particle orientation distribution in Y-Fe2O3magnetic tapes by Mössbauer and hysteresis loop measurements

The particle orientation in several Y-Fe2O3magnetic tapes has been quantitatively evaluated by using the data of both Mössbauer and hysteresis loop measurements performed in the three orthogonal directions. A texture function has been obtained as a development of real harmonics. The profile of the texture function gives the quality of the different magnetic tapes. A different degree of particle orientation at the surface of the tape is evidenced by means of conversion electron Mössbauer spectra.

Spatial patterns mediated by subcritical and supercritical thermal fluctuations in the splay Fréedericksz transition

The magnetically induced splay Fréedericksz transition is reexamined to look for pattern forming phenomena slightly above or below criticality. By using our traditional scheme of stochastic nematodynamic equations, situations are, respectively, found of transient and permanent predominance of transversal periodicities (wave numbers) along the direction perpendicular to the initial orientation within the sample. The relevance of these predictions in relation with recent observations in the electrically driven splay Fréedericksz transition, and in general with other pattern forming phenomena, is stressed.