9 research outputs found

    Characterizing top gated bilayer graphene interaction with its environment by Raman spectroscopy

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    In this work we study the behavior of the optical phonon modes in bilayer graphene devices by applying top gate voltage, using Raman scattering. We observe the splitting of the Raman G band as we tune the Fermi level of the sample, which is explained in terms of mixing of the Raman (Eg) and infrared (Eu) phonon modes, due to different doping in the two layers. We theoretically analyze our data in terms of the bilayer graphene phonon self-energy which includes non-homogeneous charge carrier doping between the graphene layers. We show that the comparison between the experiment and theoretical model not only gives information about the total charge concentration in the bilayer graphene device, but also allows to separately quantify the amount of unintentional charge coming from the top and the bottom of the system, and therefore to characterize the interaction of bilayer graphene with its surrounding environment

    Towards optimal use of antithrombotic therapy of people with cancer at the end of life: a research protocol for the development and implementation of the SERENITY shared decision support tool Thrombosis Research

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    Background: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. Methods: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe.Results: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. Conclusions: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers

    Human 90 Kda Heat Shock Protein Hsp90 As A Target For Cancer Therapeutics

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    Protein misfolding causes a phenotype of disorders that is modulated by the action of multi-complexes formed by molecular chaperones and the proteasome machine. Hsp90 is a molecular chaperone involved in maintaining folding, stability and function of many proteins involved in apoptosis, signal-transduction pathways and cell-cycle regulation. Many of these proteins are usually deregulated in cancers and by keeping them active Hsp90 helps the stabilization of tumorogenic cells. Therefore, inhibition of Hsp90 will result in degradation of its client proteins via the proteasome followed by a down regulation of several properties of the malignant phenotype. As a consequence, Hsp90 has been considered to be an appealing target for cancer therapeutics because its inhibition can affect multiple oncogenic pathways simultaneously. Major efforts have generated Hsp90 inhibitors that passed Phase I clinical trials and have entered Phase II trials. 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    Mutant P53 Aggregates Into Prion-like Amyloid Oligomers And Fibrils: Implications For Cancer

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    Over 50% of all human cancers lose p53 function. To evaluate the role of aggregation in cancer, we asked whether wild-type (WT) p53 and the hot-spot mutant R248Q could aggregate as amyloids under physiological conditions and whether the mutant could seed aggregation of the wild-type form. The central domains (p53C) of both constructs aggregated into a mixture of oligomers and fibrils. R248Q had a greater tendency to aggregate than WT p53. Full-length p53 aggregated into amyloid-like species that bound thioflavin T. The amyloid nature of the aggregates was demonstrated using x-ray diffraction, electron microscopy, FTIR, dynamic light scattering, cell viabilility assay, and anti-amyloid immunoassay. The x-ray diffraction pattern of the fibrillar aggregates was consistent with the typical conformation of cross β-sheet amyloid fibers with reflexions of 4.7 Å and 10 Å. A seed of R248Q p53C amyloid oligomers and fibrils accelerated the aggregation of WT p53C, a behavior typical of a prion. The R248Q mutant co-localized with amyloid-like species in a breast cancer sample, which further supported its prion-like effect. A tumor cell line containing mutant p53 also revealed massive aggregation of p53 in the nucleus. We conclude that aggregation of p53 into a mixture of oligomers and fibrils sequestrates the native protein into an inactive conformation that is typical of a prionoid. This prion-like behavior of oncogenic p53 mutants provides an explanation for the negative dominance effect and may serve as a potential target for cancer therapy. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.287332815228162Vousden, K.H., Lane, D.P., p53 in health and disease (2007) Nat. Rev. Mol. Cell Biol., 8, pp. 275-283Joerger, A.C., Fersht, A.R., Structural biology of the tumor suppressor p53 (2008) Annu. Rev. 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    Accidental and experimental salinomycin poisoning in rabbits Intoxicações natural e experimental por salinomicina em coelhos

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    An outbreak of salinomycin poisoning in rabbits is described. At least 27 out of 2,000 rabbits reared on a farm died after the coccidiostatic drug sulfaquinoxaline was substituted by salinomycin in the feed. An average of 26.9ppm salinomycin was detected in the ration given to the rabbits. Clinical signs included anorexia, apathy and bradykinesia, which progressed to incoordination and recumbency. Gross lesions consisted of pale areas in the skeletal muscles. The histopathological findings showed severe necrotic degenerative myopathy in association with infiltration of neutrophils and macrophages. One rabbit exhibited similar alterations in the myocardium. Mineralization was observed in the affected skeletal muscles in some cases. In order to verify if the poisoning was due to salinomycin, 20 rabbits were divided into five groups and a ration containing the drug at doses of 10, 25, 50, 75 and 100ppm was given. The administration of doses higher than 50ppm resulted in manifestation of the clinical signs seen in the outbreak of poisoning. It was concluded, that probably an error related to the mixture of salinomycin in the feed was the cause of deaths in the spontaneous outbreak of poisoning on the rabbit farm.<br>Relata-se, pela primeira vez, um surto de intoxicação por salinomicina em coelhos. De 2000 animais, no mínimo 27 morreram após troca do coccidiostático sulfaquinoxalina pela salinomicina. A análise de parte da ração detectou 26,9ppm de salinomicina. Os sinais clínicos observados foram anorexia, apatia e lentidão com evolução para incoordenação dos movimentos e decúbito. As lesões macroscópicas consistiram de áreas pálidas na musculatura esquelética. O exame histopatológico evidenciou miopatia degenerativo-necrótica. Adicionalmente, verificou-se reação inflamatória constituída por neutrófilos e macrófagos. Um coelho apresentou lesões similares no miocárdio. Em alguns casos, mineralização estava presente nos músculos esqueléticos afetados. Vinte coelhos experimentais foram divididos em 5 grupos que receberam 10, 25, 50, 75 e 100ppm de salinomicina por via oral, com a finalidade de reproduzir a intoxicação. Os animais que receberam a partir de 50ppm de salinomicina apresentaram sinais clínicos semelhantes aos observados no surto espontâneo. Nossos resultados indicam que, provavelmente, erro na mistura da substância à ração causou a morte dos coelhos

    Ionizing radiation effects on food vitamins: a review

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    Ionizing radiation has been widely used in industrial processes, especially in the sterilization of medicals, pharmaceuticals, cosmetic products, and in food processing. Similar to other techniques of food processing, irradiation can induce certain alterations that can modify both the chemical composition and the nutritional value of foods. These changes depend on the food composition, the irradiation dose and factors such as temperature and presence or absence of oxygen in the irradiating environment. The sensitivity of vitamins to radiation is unpredictable and food vitamin losses during the irradiation are often substantial. The aim of this study was to discuss retention or loss of vitamins in several food products submitted to an irradiation process.<br>Assim como outras técnicas de processamento de alimentos, a irradiação induz certas alterações, que podem modificar a composição química e o valor nutritivo dos alimentos. A natureza e extensão destas mudanças dependem essencialmente da composição do alimento, da dose de irradiação e de fatores tais como a temperatura e a presença ou ausência do oxigênio do ar. Enquanto que algumas vitaminas, como a riboflavina, niacina e vitamina D são bastante estáveis, outras, como a tiamina e vitaminas A e E, são relativamente lábeis. O objetivo da presente revisão foi discutir as prováveis perdas de vitaminas de diversos produtos submetidos ao processo de irradiação
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