Teaching the Basics of Reactive Oxygen Species and their Relevance to Cancer Biology: Mitochondrial Reactive Oxygen Species Detection, Redox Signaling, and Targeted Therapies

Reactive oxygen species (ROS) have been implicated in tumorigenesis (tumor initiation, tumor progression, and metastasis). Of the many cellular sources of ROS generation, the mitochondria and the NADPH oxidase family of enzymes are possibly the most prevalent intracellular sources. In this article, we discuss the methodologies to detect mitochondria-derived superoxide and hydrogen peroxide using conventional probes as well as newly developed assays and probes, and the necessity of characterizing the diagnostic marker products with HPLC and LC-MS in order to rigorously identify the oxidizing species. The redox signaling roles of mitochondrial ROS, mitochondrial thiolperoxidases, and transcription factors in response to mitochondria-targeted drugs are highlighted. ROS generation and ROS detoxification in drug-resistant cancer cells and the relationship to metabolic reprogramming are discussed. Understanding the subtle role of ROS in redox signaling and in tumor proliferation, progression, and metastasis as well as the molecular and cellular mechanisms (e.g., autophagy) could help in the development of combination therapies. The paradoxical aspects of antioxidants in cancer treatment are highlighted in relation to the ROS mechanisms in normal and cancer cells. Finally, the potential uses of newly synthesized exomarker probes for in vivo superoxide and hydrogen peroxide detection and the low-temperature electron paramagnetic resonance technique for monitoring oxidant production in tumor tissues are discussed

2-[({2-[(2-Hy­droxy-5-meth­oxy­benzyl­idene)amino]­eth­yl}imino)­meth­yl]-4-meth­oxy­phenol

The asymmetric unit of the title compound, C18H20N2O4, contains one-half mol­ecule with an inversion center located at the centroid of the mol­ecule. In the crystal, mol­ecules are linked by C—H⋯π inter­actions, forming layers parallel to (101). An intra­molecular O—H⋯N hydrogen bond also occurs

Vers une pédagogie transculturelle des langues-cultures : l'émergence d'une parole qui fait sens pour les adolescents

This thesis questions the contribution of the school system to adolescent identity formation. Language is at the heart of this construction. However, in the French school landscape, the boundaries between the language of schooling, language families, the ELF and LVE are near hermetic and contribute to the fragmentation of identity. Compartmentalized teaching induces many dissociations (language and culture, body and mind) that hinder the development of ties between students and their environment. Vulnerable pupils accumulate difficulties and school becomes a place of social exclusion.Faced with the necessity of thinking pedagogy for pupils to experiencelinguistic and cultural otherness in terms of interrelatedness, this thesis proposes an analysis of the impact of artistic scenarios in English class. These scenarios were designed for students in a secondary school in Bobigny and they are based on their intercultural, transcultural and multilingual experiences and their interpretations of the world. They are built on co-reflection, co-writing, co- creation and co-feeling through dance and drama and open onto a space that offers the opportunity to verbalize their emotions. The analysis of pedagogical-artistic scenarios that are the subject of this work is based on a triple settings: ethnopsychological (transcultural psychotherapy, MR. Moro) psychological (creating a reassuring atmosphere which makes adolescents feel secure, B. Cyrulnik and cooperative learning, D. Johnson and R. Johnson) and pedagogical (incorporated learning, J. Aden). This triple setting offers a transcultural mediation as a method, to use the potential of artistic expression and creativity of adolescents. These three disciplines are complementary and the scenarios are designed among other things to restore a link between cognitive and emotional processes.A transcultural pedagogy allows us to rethink the class into an experiential community (interpretative and cooperative community, and a community of practice) while respecting and valuing the uniqueness of each pupil. At the heart of this pedagogy, the notion of shared experience and speech is central. The device is analyzed at the interface of collective and singular aesthetic experience and allows a shift in perspective on: self-representation, the representation of the other, the relationship between self and other, the relationship between oneself and his or her environment, the relationship between the others and their environment and in fine the awareness of self within the social matrix.This thesis is based on a mixed methodology and is at the interface of transcultural clinic, psychology and teaching of languages and cultures. It analyzes the impact of cross-cultural education through the voices of students collected during the project and in the longer term, three years after the experiment. The corpus is composed of class interactions in English and French, plays in English written and performed by students at the end of the year of the experimentation and qualitative interviews conducted afterwards.Cette thèse interroge le rôle de l'école dans la construction identitaire des adolescents. La langue est au cœur de cette construction identitaire. Cependant, dans le paysage scolaire français, les frontières entre la langue de scolarisation, les langues des familles, le FLE et les LVE sont quasi hermétiques et contribuent au morcellement identitaire. Les didactiques compartimentées induisent de nombreuses dissociations (langue et culture, corps et esprit) qui sont un frein à l'élaboration de liens entre l'élève et son environnement. Les élèves rendus vulnérables finissent par accumuler des difficultés et l'école devient un lieu d'exclusion sociale.Face à la nécessité de penser une pédagogie permettant aux élèves de vivre l'altérité linguistique et culturelle en termes de reliance, cette thèse propose l'analyse de l'impact de scénarios artistiques en classe d'anglais. Ces scénarios qui ont été conçus avec des élèves de troisième dans un collège de Bobigny s'appuient sur leurs expériences interculturelles et transculturelles, plurilingues ainsi que leurs interprétations du monde. Ils sont fondés sur la co-réflexion, la co-écriture, la co-création et le co-sentir à travers la danse et le théâtre et ouvrent sur un espace qui offre la possibilité de verbaliser ses émotions.L'analyse des scénarios pédagogico-didactiques qui font l'objet de ce travail s'appuie sur un triple ancrage : ethnopsychanalytique (clinique transculturelle, MR. Moro) psychologique (création d'une niche sécurisante à l'école (B. Cyrulnik) au travers d'un apprentissage coopératif, (D. Johnson et R. Johnson) et didactique, au travers d'une médiation artistique (apprentissage incorporé au travers des arts, J. Aden). Ces trois champs disciplinaires sont complémentaires et les scénarios visent à rétablir un lien entre les processus cognitifs et émotionnels.Une pédagogie transculturelle permet de repenser la classe en communauté « expérientielle » (communauté interprétative, coopérative et une communauté de pratique) tout en respectant et valorisant la singularité de chacun. Au cœur de cette pédagogie, la notion d'expérience et de parole partagée est centrale. Le dispositif analysé est à l'interface d'expériences esthétiques collectives et singulières et permet d'opérer un glissement de perspective sur : la représentation de soi, la représentation de l'autre, la relation entre soi et l'autre, la relation entre soi et son environnement, la relation entre l'autre et son environnement et, in fine, la prise de conscience de soi au sein de la matrice sociale.Cette thèse à visée exploratoire repose sur une méthodologie mixte à l'interface de la clinique transculturelle, de la psychologie et de la didactique des langues-cultures ; elle analyse les effets d'une pédagogie transculturelle au travers de la parole des élèves recueillie pendant le projet et à plus long terme, trois années après l'expérimentation. Le corpus est composé d'interactions de classe en anglais et en français, de pièces en anglais écrites et jouées par les élèves à la fin de l'année d'expérimentation ainsi que des entretiens qualitatifs réalisés a postériori visant à mesurer les impacts à moyen terme de cette expérience d'acteurs au sein d'une communauté expérientielle à un moment précis de l'adolescence

A MEMS-based solid propellant microthruster array for space and military applications

Since combustion is an easy way to achieve large quantities of energy from a small volume, we developed a MEMS based solid propellant microthruster array for small spacecraft and micro-air-vehicle applications. A thruster is composed of a fuel chamber layer, a top-side igniter with a micromachined nozzle in the same silicon layer. Layers are assembled by adhesive bonding to give final MEMS array. The thrust force is generated by the combustion of propellant stored in a few millimeter cube chamber. The micro-igniter is a polysilicon resistor deposited on a low stress SiO2/SiNx thin membrane to ensure a good heat transfer to the propellant and thus a low electric power consumption. A large range of thrust force is obtained simply by varying chamber and nozzle geometry parameters in one step of Deep Reactive Ion Etching (DRIE). Experimental tests of ignition and combustion employing home made (DB+x% BP) propellant composed of a Double-Base and Black-Powder. A temperature of 250 therefore degrees C, enough to propellant initiation, is reached for 40 mW of electric power. A combustion rate of about 3.4 mm/s is measured for DB+20% BP propellant and thrust ranges between 0.1 and 3,5 mN are obtained for BP ratio between 10% and 30% using a microthruster of 100 mu m of throat wide

Large Cross-Effect Dynamic Nuclear Polarisation Enhancements With Kilowatt Inverting Chirped Pulses at 94 GHz

Dynamic nuclear polarisation (DNP) is a process that transfers electron spin polarisation to nuclei by applying resonant microwave radiation, and has been widely used to improve the sensitivity of nuclear magnetic resonance (NMR). Here we demonstrate new levels of performance for static cross-effect proton DNP using high peak power chirped inversion pulses at 94 GHz to create a strong polarisation gradient across the inhomogeneously broadened line of the mono-radical 4-amino TEMPO. Enhancements of up to 340 are achieved at an average power of a few hundred mW, with fast build-up times (3 s). Experiments are performed using a home-built wideband kW pulsed electron paramagnetic resonance (EPR) spectrometer operating at 94 GHz, integrated with an NMR detection system. Simultaneous DNP and EPR characterisation of other mono-radicals and biradicals, as a function of temperature, leads to additional insights into limiting relaxation mechanisms and give further motivation for the development of wideband pulsed amplifiers for DNP at higher frequencies

Large cross-effect dynamic nuclear polarisation enhancements with kilowatt inverting chirped pulses at 94 GHz

This work was supported by UK Research Council EPSRC research grant EP/R13705/1 and Wellcome Trust 099149/Z/12/Z.Dynamic nuclear polarisation (DNP) is a process that transfers electron spin polarisation to nuclei by applying resonant microwave radiation, and has been widely used to improve the sensitivity of nuclear magnetic resonance (NMR). Here we demonstrate new levels of performance for static cross-effect proton DNP using high peak power chirped inversion pulses at 94 GHz to create a strong polarisation gradient across the inhomogeneously broadened line of the mono-radical 4-amino TEMPO. Enhancements of up to 340 are achieved at an average power of a few hundred mW, with fast build-up times (3 s). Experiments are performed using a home-built wideband kW pulsed electron paramagnetic resonance (EPR) spectrometer operating at 94 GHz, integrated with an NMR detection system. Simultaneous DNP and EPR characterisation of other mono-radicals and biradicals, as a function of temperature, leads to additional insights into limiting relaxation mechanisms and give further motivation for the development of wideband pulsed amplifiers for DNP at higher frequencies.Publisher PDFPeer reviewe