2,236 research outputs found

    Phase-space reconstruction of an atomic chaotic system

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    We consider the dynamics of a single atom submitted to periodic pulses of a far-detuned standing wave generated by a high-finesse optical cavity, which is an atomic version of the well-known ``kicked rotor''. We show that the classical phase-space map can be ``reconstructed'' by monitoring the transmission of the cavity. We also studied the effect of spontaneous emission on the reconstruction, and put limits to the maximum acceptable spontaneous emission rate.Comment: 5 figures, submitted to PR

    Ebv infections in Brazil III - infectious mononucleosis

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    Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys

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    A Bacille Calmette–Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provides limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime–boost regimen, to help the induction of a stronger cellular immune response

    The Synthesis and Reactivity of Naphthoquinonynes

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    AbstractThe first systematic exploration of the synthesis and reactivity of naphthoquinonynes is described. Routes to two regioisomeric Kobayashi‐type naphthoquinonyne precursors have been developed, and the reactivity of the ensuing 6,7‐ and 5,6‐aryne intermediates has been investigated. Remarkably, these studies have revealed that a broad range of cycloadditions, nucleophile additions and difunctionalizations can be achieved while maintaining the integrity of the highly sensitive quinone unit. The methodologies offer a powerful diversity oriented approach to C6 and C7 functionalized naphthoquinones, which are typically challenging to access. From a reactivity viewpoint, the study is significant because it demonstrates that aryne‐based functionalizations can be utilized strategically in the presence of highly reactive and directly competing functionality.</jats:p

    On the application of 3d metals for C-H activation toward bioactive compounds: The key step for the synthesis of silver bullets

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    Several valuable biologically active molecules can be obtained through C-H activation processes. However, the use of expensive and not readily accessible catalysts complicates the process of pharmacological application of these compounds. A plausible way to overcome this issue is developing and using cheaper, more accessible, and equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C-H activation processes to obtain potentially (or proved) biologically active compounds

    Agricultura orgânica em áreas urbanas e periurbanas com base na agroecologia.

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    A agricultura orgânica com base na agroecologia é o mote tecnológico adequado à realidade dos agroecossistemas urbanos. Este artigo ressalta a necessidade de se desenvolver tecnologias e insumos específicos. A partir de experiências com agricultura urbana em diferentes países em desenvolvimento, evidencia-se a necessidade de se buscar capacidades locais e apoio do poder público, especialmente nas iniciativas da sociedade organizada e mobilizada para a produção agrícola urbana

    It Takes Two to Tango, Part II : Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities

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    In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/seleniumcontaining triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of paranaphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango

    Microglia dysfunction caused by the loss of Rhoa disrupts neuronal physiology and leads to neurodegeneration

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    © 2020 The Author(s). Creative Commons Attribution (CC BY 4.0)Nervous tissue homeostasis requires the regulation of microglia activity. Using conditional gene targeting in mice, we demonstrate that genetic ablation of the small GTPase Rhoa in adult microglia is sufficient to trigger spontaneous microglia activation, producing a neurological phenotype (including synapse and neuron loss, impairment of long-term potentiation [LTP], formation of β-amyloid plaques, and memory deficits). Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated tumor necrosis factor (TNF) production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also find that the Rhoa/Src signaling pathway is disrupted in microglia of the APP/PS1 mouse model of Alzheimer disease and that low doses of Aβ oligomers trigger microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing Rho GTPase signaling in microglia can directly cause neurodegeneration.The authors acknowledge the support of the following i3S Scientific Platforms: Animal Facility, Translational Cytometry Unit (TraCy), BioSciences Screening (BS) and Advanced Light Microscopy (ALM), and members of the national infrastructure PPBI-Portuguese Platform of BioImaging (supported by POCI-01–0145-FEDER-022122). FCT Portugal ( PTDC/MED-NEU/31318/2017-031318 ) supported work in the J.B.R. lab. FCT Portugal , PEst ( UID/NEU/04539/2013 ), COMPETE-FEDER ( POCI-01-0145-FEDER-007440 ), Centro 2020 Regional Operational Programme ( CENTRO-01-0145-FEDER-000008 : BrainHealth 2020), and Strategic Project UIDB/04539/2020 and UIDP/04539/2020 (CIBB) supported work in the A.F.A. lab. C.C.P. and R.S. hold employment contracts financed by national funds through FCT (Fundação para a Ciência e a Tecnologia, I.P.) in the context of the program contract described in paragraphs 4, 5, and 6 of article 23 of law no. 57/2016, of August 29th, as amended by law no. 57/2017 of July 19th.info:eu-repo/semantics/publishedVersio
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