On the nonlinear stability of mKdV breathers

A mathematical proof for the stability of mKdV breathers is announced. This proof involves the existence of a nonlinear equation satisfied by all breather profiles, and a new Lyapunov functional which controls the dynamics of small perturbations and instability modes. In order to construct such a functional, we work in a subspace of the energy one. However, our proof introduces new ideas in order to attack the corresponding stability problem in the energy space. Some remarks about the sine-Gordon case are also considered.Comment: 7 p

A selective strategy for targeting primary hyperoxaluria diseases

Funding Information: Authors wish to thank the Centro de Instrumentación Científico-Técnica (CICT) of the University of Jaén, Spain, for partial financial support. A.A.-A. is grateful for the postdoctoral fellowship from Fundación Alfonso Martín Escudero. Authors acknowledge the use of the National Facility ELECMI ICTS, node “Laboratorio de Microscopias Avanzadas” at Universidad de Zaragoza. This research has also partially been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-098560-B-C22) and by the Andalusian Consejería de Economía y Conocimiento (FEDER program 2014-2020: grant number 1380682). This work was partially supported by the Associate Laboratory for Green Chemistry-LAQV, which is financed by national funds from FCT/MCTES (UIDB/50006/2020). Funding Information: This research has also partially been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (grant RTI2018-098560-B-C22) and by the Andalusian Consejería de Economía y Conocimiento (FEDER program 2014-2020: grant number 1380682). This work was partially supported by the Associate Laboratory for Green Chemistry-LAQV, which is financed by national funds from FCT/MCTES (UIDB/50006/2020). Funding Information: Authors wish to thank the Centro de Instrumentación Científico-Técnica (CICT) of the University of Jaén, Spain, for partial financial support. A.A.-A. is grateful for the postdoctoral fellowship from Fundación Alfonso Martín Escudero. Authors acknowledge the use of the National Facility ELECMI ICTS, node “Laboratorio de Microscopias Avanzadas” at Universidad de Zaragoza. Publisher Copyright: © 2022 The Author(s)Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism that result in an excess of oxalate production by the oxidation of glyoxylate by the human lactate dehydrogenase A enzyme (hLDHA). The selective liver inhibition of this enzyme is one of the therapeutic strategies followed in the treatment of this disease. Even though several efforts have been recently performed using gene silencing by the RNA interference approach, small-molecule inhibitors that selectively reach hepatocytes are preferred since they present the advantages of a lower production cost and better pharmacological properties. In that sense, the design, synthesis, and physicochemical characterization by NMR, FTIR, DLS and TEM of two nanocarriers based on chitosan conjugates (1, non-redox-sensitive; 2, redox-sensitive) have been performed to (i) achieve the selective transport of hLDHA inhibitors into hepatocytes and (ii) their disruption once they reach the hepatocytes cytosol. Polymer 2 self-assembled into micelles in water and showed high drug loadings (19.8–24.5 %) and encapsulation efficiencies (31.9–40.8%) for the hLDHA inhibitors (I-III) tested. The non-redox-sensitive micelle 1 remained stable under different glutathione (GSH) concentrations (10 μM and 10 mM), and just a residual release of the inhibitor encapsulated was observed (less than 10 %). On the other hand, micelle 2 was sufficiently stable under in vitro physiological conditions (10 μM, GSH) but it quickly disassembled under the simulated reducing conditions present inside hepatocytes (10 mM GSH), achieving a 60 % release of the hLDHA inhibitor encapsulated after 24 h, confirming the responsiveness of the developed carrier to the high levels of intracellular GSH.publishersversionpublishe

Controlled release of bupivacaine using hybrid thermoresponsive nanoparticles activated via photothermal heating

Near-infrared (NIR) responsive nanoparticles are of great interest in the biomedical field as antennas for photothermal therapy and also as triggers for on-demand drug delivery. The present work reports the preparation of hollow gold nanoparticles (HGNPs) with plasmonic absorption in the NIR region covalently bound to a thermoresponsive polymeric shell that can be used as an on-demand drug delivery system for the release of analgesic drugs. The photothermal heating induced by the nanoparticles is able to produce the collapse of the polymeric shell thus generating the release of the local anesthetic bupivacaine in a spatiotemporally controlled way. Those HGNPs contain a 10 wt.% of polymer and present excellent reversible heating under NIR light excitation. Bupivacaine released at physiological temperature (37 °C) showed a pseudo-zero order release that could be spatiotemporally modified on-demand after applying several pulses of light/temperature above and below the lower critical solution temperature (LCST) of the polymeric shell. Furthermore, the nanomaterials obtained did not displayed detrimental effects on four mammalian cell lines at doses up to 0.2 mg/mL. From the results obtained it can be concluded than this type of hybrid thermoresponsive nanoparticle can be used as an externally activated on-demand drug delivery system

Well-posedness and stability results for the Gardner equation

In this article we present local well-posedness results in the classical Sobolev space H^s(R) with s > 1/4 for the Cauchy problem of the Gardner equation, overcoming the problem of the loss of the scaling property of this equation. We also cover the energy space H^1(R) where global well-posedness follows from the conservation laws of the system. Moreover, we construct solitons of the Gardner equation explicitly and prove that, under certain conditions, this family is orbitally stable in the energy space.Comment: 1 figure. Accepted for publication in Nonlin.Diff Eq.and App

Chalcogenide nanoparticles and organic photosensitizers for synergetic antimicrobial photodynamic therapy

Synergistic antimicrobial effects were observed for copper sulfide (CuS) nanoparticles together with indocyanine green (ICG) in the elimination of wild type pathogenic bacteria (Staphylococcus aureusATCC 29213 andPseudomonas aeruginosaATCC 27853) and also opportunistic fungal infective yeast (Candida albicansATCC 10231). Furthermore, large antibacterial effects were observed for clinical isolates of Methicillin-resistantS. aureus(MRSA) PFGE strain-type USA300. This efficient antimicrobial action was attributed to the combined extra- and intracellular generation of reactive oxygen species upon light irradiation. Instead of the use of visible-light for the activation of common photosensitizers, both ICG and CuS nanoparticles can be activated in the near infrared (NIR)-region of the electromagnetic spectrum and therefore, superior tissue penetration would be expected in a potential elimination of pathogenic microorganisms not only on the skin but also in the soft tissue. In the different bacteria studied a 3-log reduction in the bacterial counts was achieved after only 6 min of NIR irradiation and treatment with ICG or CuS alone at concentrations of 40 and 160 µg mL-1, respectively. A maximum bactericidal effect againstS. aureusand USA300 strains was obtained for the combination of both photosensitizers at the same concentration. RegardingP. aeruginosa, a 4-log reduction in the CFU was observed for the combination of CuS and ICG at various concentrations. InCandida albicansthe combination of both ICG and CuS and light irradiation showed an antimicrobial dose-dependent effect with the reduction of at least 3-log in the cell counts for the combination of ICG + CuS at reduced concentrations. The observed antimicrobial effect was solely attributed to a photodynamic effect and any photothermal effect was avoided to discard any potential thermal injury in a potential clinical application. The generation of reactive oxygen species upon near infrared-light irradiation for those photosensitizers used was measured either alone or in combination. The cytocompatibility of the proposed materials at the doses used in photodynamic therapy was also demonstrated in human dermal fibroblasts and keratinocytes by cell culturing and flow cytometry studies. © The Royal Society of Chemistry 2021

Thermal and photochemical reactions of n-pyridinebenzopyrylium multistate of species (n = 2′,3′,4′). Exploring the synthetic potentialities from the unique reactivity of position 2′

Funding Information: This work was supported by the Associate Laboratory for Green Chemistry – LAQV (projects UIDB/50006/2020 and UIDP/ 50006/2020), the Research Unit on Applied Molecular Biosciences – UCIBIO (projects UIDP/04378/2020 and UIDB/ 04378/2020) and the Associate Laboratory Institute for Health and Bioeconomy – i4HB (project LA/P/0140/2020) which are financed by national funds from FCT/MCTES. FCT/MCTES is also acknowledged for supporting the National Portuguese NMR Network (ROTEIRO/0031/2013–PINFRA/22161/2016, cofinanced by FEDER through COMPETE 2020, POCI, PORL, and FCT through PIDDAC). A. C. acknowledges financing from Fundação Calouste Gulbenkian, grant no. 219201, and from the Angolan Embassy in Lisbon, Portugal, INAGBE grant. Dr. Ramesh Pandian is acknowledged for the initial acquisition and processing of single crystal X-ray data. Publisher Copyright: © 2023 The Author(s)The kinetics and thermodynamics of the pH-dependent multistate of species generated by the trans-chalcone of n-pyridinebenzopyrylium (n = 2′, 3′) were studied by UV–vis spectroscopy, 1H NMR and HPLC-MS, and the results compared with those reported for n = 4′. Due to the slow kinetics of the multistate species interconversion, the conjugation of these techniques has shown to be a powerful tool to investigate the behaviour of these systems. The species involved in the multistate are mutatis mutandis the same observed in anthocyanins and related compounds except for the flavylium cation, which was not observed in these systems even in very acidic medium. The rates of the interconversion of the multistate species upon pH stimuli are much slower than in anthocyanins. The compound bearing the pyridine nitrogen in position 2′ gives two novel products absorbing in the visible. Formation of the new products is particularly efficient from the thermal evolution of the photochemical products obtained upon light irradiation of the protonated trans-chalcone in a mixture of methanol:acidic water (1:1). This confirms the unique capacity of the substituents in position 2′ in giving intramolecular reactions involving the benzopyrylium core. Crystal structures for the three pyridine chalcone compounds (n = 2′, 3′, 4′) were obtained and the respective structures discussed.publishersversionpublishe

A model compound for pyridinechalcone-based multistate systems. Ring opening-closure as the slowest kinetic step of the multistate

UID/QUI/50006/2019. PTDC/QEQ-QFI/1971/2014. PTDC/QUI-COL/32351/2017. PTDC/QUI-QFI/30951/2017. grant no. 219201.Anthocyanins and related flavylium derivatives exist in aqueous solution as a pH-dependent mole fraction distribution of species (a multistate system) with known biological activity. Introduction of nitrogen heterocycles in the flavylium core can lead to multistates with different constitution and increased activity. Compound 1, a diethylamino derivative of 4-pyridinechalcone, was synthesized and characterized by X-ray crystallography, showing a pH-dependent reaction network similar to anthocyanins and related compounds. The several species present at the equilibrium multistate were fully characterized by 1H NMR and 13C NMR. The thermodynamics and kinetics of the multistate were studied through pH jumps followed by 1H NMR and UV-vis absorption including stopped-flow for the faster kinetic steps. In the parent 4-pyridinechalcone compound, protonation of the pyridine nitrogen for pH 4 prevents formation of the flavylium cation. In compound 1, the first protonation takes place in the diethylamino substituent and in acidic medium, two new flavylium derivatives, a single (2 pH 4) and a double (pH 1) positively charged species, in equilibrium with protonated hemiketal, cis and trans chalcones, have been characterized. Differently from anthocyanins and related compounds, experimental evidence for an unexpected very slow (0.0003 s-1) ring opening-closure between the hemiketal and the cis-chalcone (tautomerization) was achieved.publishe

Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase

During antibody affinity maturation, germinal center (GC) B cells cycle between affinity-driven selection in the light zone (LZ) and proliferation and somatic hypermutation in the dark zone (DZ). Although selection of GC B cells is triggered by antigen-dependent signals delivered in the LZ, DZ proliferation occurs in the absence of such signals. We show that positive selection triggered by T cell help activates the mechanistic target of rapamycin complex 1 (mTORC1), which promotes the anabolic program that supports DZ proliferation. Blocking mTORC1 prior to growth prevented clonal expansion, whereas blockade after cells reached peak size had little to no effect. Conversely, constitutively active mTORC1 led to DZ enrichment but loss of competitiveness and impaired affinity maturation. Thus, mTORC1 activation is required for fueling B cells prior to DZ proliferation rather than for allowing cell-cycle progression itself and must be regulated dynamically during cyclic re-entry to ensure efficient affinity-based selection. During germinal center selection, signals from Tfh cells in the light zone dictate the extent of B cell proliferation in the dark zone. Ersching et al. (2017) show that Tfh help induces mTORC1 activation in light zone B cells, leading to cell growth that sustains the subsequent dark zone proliferative burst

SNOM characterization of a potential low cost thin gold coated micro-structured grating using a commercial CD substrate

In this work near-field optical measurements of a corrugated grating coated with a 30 nm thick gold film are presented. The grating was made using the polycarbonate corrugated substrate of a commercially available recordable CD as template. This has been proved to be a versatile and low cost technique in producing large 1.6 μm period gratings. The study was carried out using a Scanning Near-Field Optical Microscope (SNOM) working in both collection and reflection modes at two different wavelengths, 532 nm and 633 nm. The results illustrate that the intensity patterns of near-field images are strongly polarization-dependent, even showing different periodicity of the localized fields for orthogonal polarization states. When electric field of the light is polarized parallel to the grooves, the periodicity of the SNOM images is coincident with the grating period, whereas when the light is polarized perpendicular to the grooves the SNOM pattern shows a periodicity twice that of the corresponding topography of the grating. Numerical simulations of the SNOM data based on a two-dimensional Finite Difference Time-Domain (2D-FDTD) model have been realized. The results of the simulations are in good agreement with the experimental data, emphasizing the need of performing numerical simulation for the correct interpretation of SNOM data

SP-0489: HPV-transformation in the cervix and at non-cervical sites

Pla general d'un dels panells horitzontals sobre espais verds de Barcelona a l'exposició Ciutat. Barcelona projecta a l'Edifici Fòrum. Exposició sobre la planificació urbanística i arquitectònica de Barcelon