Emperor in the Byzantine Epigraphy (641-1204)

L’épigraphie byzantine est en science en construction dans le domaine de l’épigraphie médiévale. Ce travail repose sur la présentation d’un corpus de 229 inscriptions historiques comportant le nom de l’empereur byzantin, annotées et commentées, présenté par une étude globale du dossier. L’étude de la nature ainsi que de la répartition géographique et chronologique des inscriptions permet de souligner une nette domination de la capitale. En effet, la moitié du corpus est constitué des inscriptions de Constantinople, en particulier lors des périodes difficiles (VIIe-IXe siècles). La répartition chronologique est assez régulière mais avec une part assez importante des inscriptions d’époque macédonienne (867-1055). Les titulatures impériales sont à la fois stéréotypées et variées. Autour de la formule incontournable de pistos en Christos basileus autokrator, les épithètes correspondent souvent à l’idéologie impériale du moment ou du contexte, ce qui produit une assez grande variété des titres. Enfin, l’inscription est souvent incompréhensible pour des populations en majorité analphabètes. Du coup, en tant qu’objet elle est aussi un instrument idéologique qui permet de marquer le territoire de l’empreinte impériale, en particulier lors de la mise en défense d’une région, ou de la construction d’églises. En tant qu’objet présenté à la vue de tous, le texte inspire la crainte aux ennemis de l’Empire et le respect des populations locales envers leur empereur.The Byzantine epigraphy is a science under construction in the sphere of medieval epigraphy. This work is based on the presentation of a corpus of 229 historical inscriptions with the name of the Byzantine Emperor, annotated with commentary, presented by a comprehensive study of the file. The study of nature together with the geographical and chronological distribution of inscriptions allows to underline a clear domination of the capital. In fact, half of the corpus consists of Constantinople inscriptions, especially during difficult times (7th-9th centuries). The chronological distribution is fairly regular but with a sizeable part of the Macedonian inscriptions (867-1055). Imperial titulatures are both stereotypical and varied. Around the essential title pistos en Christos basileus autokrator, epithets often correspond to the imperial ideology of the moment or context, which produces a considerable variety of titles. Finally, inscription is often incomprehensible to the majority of the population, for the greater part illiterate. So, as an object, it is also an ideological instrument to mark out the territory of the imperial inprint, especially in the defense of a region, or when he building up of churches. As an object presented in plain sight, the text inflicts fear on the enemies of the Empire and generates respect of local people to their emperor

Influence of Non-Homogeneous Foundations On the Dynamic Responses of Railway Sleepers

International audienceIn a railway track, the sleeper’s responses on a non-homogeneous foundation have been investigated by researchers focusing on the foundation behavior along the rails. However, the foundation can also vary along the sleeper length, particularly when the track is newly tamped. The foundation at the sleeper center is often weaker than those under the rails and this non-homogeneity directly affects the sleeper responses. This paper presents a new model to calculate the influence of such foundations on the dynamic responses of the railway sleepers. This model is developed by combining a finite element model for the sleepers and foundation and a model of periodically supported beams subjected to moving loads for the rails. In this paper, the foundation contains three parts with different mechanical behaviors. The sleeper’s responses can be calculated by transforming the finite-element dynamic stiffness matrix to the one considering the boundary conditions and the relation between the rail seat forces and rail displacements governed by the beam model. This method reduces all the degrees of freedom of the railway track to its one period which gives a substantial reduction in computational time. The numerical applications show that the more homogeneous (so-called consolidated) the foundation is, the larger the sleeper strain is at its center. This result shows the potential application of the sleeper responses to estimating the consolidation level of the foundation

Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A

Growing evidence supports the implication of DYRK1A in the development of cognitive deficits seen in Down syndrome (DS) and Alzheimer's disease (AD). We here demonstrate that pharmacological inhibition of brain DYRK1A is able to correct recognition memory deficits in three DS mouse models with increasing genetic complexity [Tg(Dyrk1a), Ts65Dn, Dp1Yey], all expressing an extra copy of Dyrk1a. Overexpressed DYRK1A accumulates in the cytoplasm and at the synapse. Treatment of the three DS models with the pharmacological DYRK1A inhibitor leucettine L41 leads to normalization of DYRK1A activity and corrects the novel object cognitive impairment observed in these models. Brain functional magnetic resonance imaging reveals that this cognitive improvement is paralleled by functional connectivity remodelling of core brain areas involved in learning/memory processes. The impact of Dyrk1a trisomy and L41 treatment on brain phosphoproteins was investigated by a quantitative phosphoproteomics method, revealing the implication of synaptic (synapsin 1) and cytoskeletal components involved in synaptic response and axonal organization. These results encourage the development of DYRK1A inhibitors as drug candidates to treat cognitive deficits associated with DS and AD

Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis

International audience(R)-Roscovitine, a pharmacological inhibitor of kinases, is currently in phase II clinical trial as a drug candidate for the treatment of cancers, Cushing's disease and rheumatoid arthritis. We here review the data that support the investigation of (R)-roscovitine as a potential therapeutic agent for the treatment of cystic fibrosis (CF). (R)-Roscovitine displays four independent properties that may favorably combine against CF: (1) it partially protects F508del-CFTR from proteolytic degradation and favors its trafficking to the plasma membrane; (2) by increasing membrane targeting of the TRPC6 ion channel, it rescues acidification in phagolysosomes of CF alveolar macrophages (which show abnormally high pH) and consequently restores their bactericidal activity; (3) its effects on neutrophils (induction of apoptosis), eosinophils (inhibition of degranulation/induction of apoptosis) and lymphocytes (modification of the Th17/Treg balance in favor of the differentiation of anti-inflammatory lymphocytes and reduced production of various interleukins, notably IL-17A) contribute to the resolution of inflammation and restoration of innate immunity, and (4) roscovitine displays analgesic properties in animal pain models. The fact that (R)-roscovitine has undergone extensive preclinical safety/pharmacology studies, and phase I and II clinical trials in cancer patients, encourages its repurposing as a CF drug candidate