12 research outputs found

    Microstructure, magnetic and mechanical properties of Ni-Zn ferrites prepared by Powder Injection Moulding

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    Nowadays, the electronic industry demands small and complex parts as a consequence of the miniaturization of electronic devices. Powder injection moulding (PIM) is an emerging technique for the manufacturing of magnetic ceramics. In this paper, we analyze the sintering process, between 900 °C and 1300 °C, of Ni–Zn ferrites prepared by PIM. In particular, the densification behaviour, microstructure and mechanical properties of samples with toroidal and bar geometry were analyzed at different temperatures. Additionally, the magnetic behaviour (complex permeability and magnetic losses factor) of these compacts was compared with that of samples prepared by conventional powder compaction. Finally, the mechanical behaviour (elastic modulus, flexure strength and fracture toughness) was analyzed as a function of the powder loading of feedstock. The final microstructure of prepared samples was correlated with the macroscopic behaviour. A good agreement was established between the densities and population of defects found in the materials depending on the sintering conditions. In general, the final mechanical and magnetic properties of PIM samples were enhanced relative those obtained by uniaxial compaction

    Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase pairs

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    The design and synthesis of two Janus-type heterocycles with the capacity to simultaneously recognize guanine and uracyl in G-U mismatched pairs through complementary hydrogen bond pairing is described. Both compounds were conveniently functionalized with a carboxylic function and efficiently attached to a tripeptide sequence by using solid-phase methodologies. Ligands based on the derivatization of such Janus compounds with a small aminoglycoside, neamine, and its guanidinylated analogue have been synthesized, and their interaction with Tau RNA has been investigated by using several biophysical techniques, including UV-monitored melting curves, fluorescence titration experiments, and 1H NMR. The overall results indicated that Janus-neamine/guanidinoneamine showed some preference for the +3 mutated RNA sequence associated with the development of some tauopathies, although preliminary NMR studies have not confirmed binding to G-U pairs. Moreover, a good correlation has been found between the RNA binding affinity of such Janus-containing ligands and their ability to stabilize this secondary structure upon complexation

    Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

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    A straightforward methodology for the synthesis of conjugates between a cytotoxic organometallic ruthenium(II) complex and amino- and guanidinoglycosides, as potential RNA-targeted anticancer compounds, is described. Under microwave irradiation, the imidazole ligand incorporated on the aminoglycoside moiety (neamine or neomycin) was found to replace one triphenylphosphine ligand from the ruthenium precursor [(η6-p-cym)RuCl(PPh3)2]+, allowing the assembly of the target conjugates. The guanidinylated analogue was easily prepared from the neomycin-ruthenium conjugate by reaction with N,N′-di-Boc-N″-triflylguanidine, a powerful guanidinylating reagent that was compatible with the integrity of the metal complex. All conjugates were purified by semipreparative high-performance liquid chromatography (HPLC) and characterized by electrospray ionization (ESI) and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and NMR spectroscopy. The cytotoxicity of the compounds was tested in MCF-7 (breast) and DU-145 (prostate) human cancer cells, as well as in the normal HEK293 (Human Embryonic Kidney) cell line, revealing a dependence on the nature of the glycoside moiety and the type of cell (cancer or healthy). Indeed, the neomycin-ruthenium conjugate (2) displayed moderate antiproliferative activity in both cancer cell lines (IC50 ≈ 80 μM), whereas the neamine conjugate (4) was inactive (IC50 ≈ 200 μM). However, the guanidinylated analogue of the neomycin-ruthenium conjugate (3) required much lower concentrations than the parent conjugate for equal effect (IC50 = 7.17 μM in DU-145 and IC50 = 11.33 μM in MCF-7). Although the same ranking in antiproliferative activity was found in the nontumorigenic cell line (3 2 > 4), IC50 values indicate that aminoglycoside-containing conjugates are about 2-fold more cytotoxic in normal cells (e.g., IC50 = 49.4 μM for 2) than in cancer cells, whereas an opposite tendency was found with the guanidinylated conjugate, since its cytotoxicity in the normal cell line (IC50 = 12.75 μM for 3) was similar or even lower than that found in MCF-7 and DU-145 cancer cell lines, respectively. Cell uptake studies performed by ICP-MS with conjugates 2 and 3 revealed that guanidinylation of the neomycin moiety had a positive effect on accumulation (about 3-fold higher in DU-145 and 4-fold higher in HEK293), which correlates well with the higher antiproliferative activity of 3. Interestingly, despite the slightly higher accumulation in the normal cell than in the cancer cell line (about 1.4-fold), guanidinoneomycin-ruthenium conjugate (3) was more cytotoxic to cancer cells (about 1.8-fold), whereas the opposite tendency applied for neomycin-ruthenium conjugate (2). Such differences in cytotoxic activity and cellular accumulation between cancer and normal cells open the way to the creation of more selective, less toxic anticancer metallodrugs by conjugating cytotoxic metal-based complexes such as ruthenium(II) arene derivatives to guanidinoglycosides

    The effects of anticipatory fatigue and emotional symptomatology on perceived physical and cognitive fatigue

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    El objetivo de este estudio fue doble, primero, analizar los efec- tos de la fatiga anticipatoria, la sintomatología emocional y la pertenencia a un grupo clínico sobre la percepción de fatiga física y mental; segundo, ex- plorar el potencial efecto moderador de la anticipación de la fatiga en las re- laciones entre la sintomatología o la condición clínica y la sensación perci- bida de fatiga. Se analiza mediante un diseño ex post facto y correlacional los efectos parciales y condicionados de las variables predictivas mediante diferentes análisis de regresión jerárquica. Participaron 317 sujetos (29% procedentes de población clínica). Se evaluó la fatiga anticipatoria (Escala elaborada ad hoc), la experiencia percibida de fatiga (Escala de Fatiga de Chalder et al., 1993), y la sintomatología emocional (GHQ-28 de Goldberg, 1996). Los resultados mostraron efectos significativos de la fatiga anticipa- toria y la sintomatología emocional, predominantemente de la sintomatolo- gía depresiva sobre la percepción de fatiga física y mental. La pertenencia a un grupo clínico predecía de forma significativa y exclusiva la fatiga cogniti- va. Además, la fatiga anticipatoria moderaba el efecto del grupo (clínico versus general) sobre la fatiga cognitiva. En conclusión, la sintomatología, principalmente la depresiva, y la fatiga anticipatoria, tienen un valor predic- tivo significativo en la experiencia percibida de la fatiga física y mental. La anticipación de fatiga moderaba el efecto del grupo clínico sobre la expe- riencia de fatiga cognitiva una vez controlada la sintomatología depresiva.The two fold aim of this study was first, to analyze the effects of anticipatory fatigue, emotional symptomatology and belonging to a clinical group on the physical and cognitive perception of fatigue, and second, to explore the potential moderating effect of anticipatory fatigue on the rela- tionship between symptomatology or clinical condition and perceived fa- tigue. The conditional and partial effects of independent variables were analyzed by hierarchical regression in an ex-post-facto correlational design. The sample was composed of 317 participants (29% from a clinical popula- tion). Anticipatory fatigue (by an ad hoc scale), and perception of fatigue (by the Chalder Fatigue Scale) were measured. Emotional symptoms were as- sessed by Goldberg’s GHQ-28 questionnaire. Anticipatory fatigue and emotional symptoms (mainly depressive) had significant effects on cogni- tive and physical fatigue. Belonging to the clinical group significantly and exclusively predicted cognitive fatigue. Furthermore, anticipatory fatigue moderated between-group effects (clinical versus general) and cognitive fa- tigue. In brief, emotional symptoms (mainly depressive) and anticipatory fatigue significantly predicted perceived cognitive and physical fatigue. An- ticipation of fatigue moderated the effect of clinical group on cognitive fa- tigue after controlling for depressive symptomatology

    Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

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