CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

In order to identify potential markers of renal cancer, the plasma membrane protein content of renal cell carcinoma (RCC)-derived cell lines was annotated using a proteomics process. One unusual protein identified at high levels in A498 and 786-O cells was CD70 (TNFSF7), a type II transmembrane receptor normally expressed on a subset of B, T and NK cells, where it plays a costimulatory role in immune cell activation. Immunohistochemical analysis of CD70 expression in multiple carcinoma types demonstrated strong CD70 staining in RCC tissues. Metastatic tissues from eight of 11 patients with clear cell RCC were positive for CD70 expression. Immunocytochemical analysis demonstrated that binding of an anti-CD70 antibody to CD70 endogenously expressed on the surface of A498 and 786-O cell lines resulted in the rapid internalisation of the antibody–receptor complex. Coincubation of the internalising anti-CD70 antibody with a saporin-conjugated secondary antibody before addition to A498 cells resulted in 50% cell killing. These data indicate that CD70 represents a potential target antigen for toxin-conjugated therapeutic antibody treatment of RCC

Time-resolved single-crystal X-ray crystallography

In this chapter the development of time-resolved crystallography is traced from its beginnings more than 30 years ago. The importance of being able to “watch” chemical processes as they occur rather than just being limited to three-dimensional pictures of the reactant and final product is emphasised, and time-resolved crystallography provides the opportunity to bring the dimension of time into the crystallographic experiment. The technique has evolved in time with developments in technology: synchrotron radiation, cryoscopic techniques, tuneable lasers, increased computing power and vastly improved X-ray detectors. The shorter the lifetime of the species being studied, the more complex is the experiment. The chapter focusses on the results of solid-state reactions that are activated by light, since this process does not require the addition of a reagent to the crystalline material and the single-crystalline nature of the solid may be preserved. Because of this photoactivation, time-resolved crystallography is often described as “photocrystallography”. The initial photocrystallographic studies were carried out on molecular complexes that either underwent irreversible photoactivated processes where the conversion took hours or days. Structural snapshots were taken during the process. Materials that achieved a metastable state under photoactivation and the excited (metastable) state had a long enough lifetime for the data from the crystal to be collected and the structure solved. For systems with shorter lifetimes, the first time-resolved results were obtained for macromolecular structures, where pulsed lasers were used to pump up the short lifetime excited state species and their structures were probed by using synchronised X-ray pulses from a high-intensity source. Developments in molecular crystallography soon followed, initially with monochromatic X-ray radiation, and pump-probe techniques were used to establish the structures of photoactivated molecules with lifetimes in the micro- to millisecond range. For molecules with even shorter lifetimes in the sub-microsecond range, Laue diffraction methods (rather than using monochromatic radiation) were employed to speed up the data collections and reduce crystal damage. Future developments in time-resolved crystallography are likely to involve the use of XFELs to complete “single-shot” time-resolved diffraction studies that are already proving successful in the macromolecular crystallographic field.</p

Rapport I.3. Valorisation de l’information hydrologique à partir de l’information pluviométrique

Rainfall estimates are relatively accurate for the whole of France, and there is much to be gained from making use of this information to amplify available hydrological data, which frequently fall short of the necessary duration. The following are examples of annual and monthly discharge, flood and low water determination methods which were developed from the Allier river basin survey (D.G.R.S.T.) : (i) Simple and spatial correlations. (ii) Single and double renewal methods. (iii) Monthly and daily deterministic methods. Examples are also given of the introduction of qualitative physical factors to amplify rainfall data where no observed data are available.A peu près partout en France existe une estimation relativement bonne de la pluviométrie, il est donc avantageux d’utiliser cette dernière pour valoriser l’information hydrométrique de durée souvent trop courte. Exemples de diverses méthodes tirées de l’étude du bassin de l’Ailier réalisée sous contrat D.G.R.S.T. : — corrélations (au niveau simple et spatial) ; — modèles de renouvellement simples ou doubles ; — modèles déterministes mensuels ou journaliers en matière de débits annuels, mensuels, crues et étiages. Exemples d’introduction des facteurs qualitatifs physiques pour valoriser l’information pluviométrique en cas d’absence de mesures.Cormary Y. Rapport I.3. Valorisation de l’information hydrologique à partir de l’information pluviométrique. In: Utilisation des ressources en eau d'un bassin dans le cadre de l'aménagement du territoire. Compte rendu des onzièmes journées de l'hydraulique; Paris, 22-24 septembre 1970. Tome 1, 1971

Rapport IV.1. Étude des écoulements urbains. Conception des réseaux d’assainissement

In order to face a quickened town-planning, a separating sgstem including storm basins seem to be a flexible and adequate means. Computation of such complex systems cannot be carried out without modeling runoff processes ; models will clearly show up the played part by these processes on town-planning. After an analysis of the connected with town growth problems, a streaming simple model, tested according to experimental data, is discribed and discussed thereafter.Pour faire face à une urbanisation accélérée, les réseaux séparatifs avec bassins d’orage semblent un moyen souple et efficace. Le calcul de tels réseaux complexes ne peut se faire que par une modélisation des processus d’écoulement, mettant clairement en évidence le rôle joué par l’urbanisation sur ces processus. Après une analyse des problèmes liés à l’urbanisation, un modèle de ruissellement simple, testé sur des données expérimentales, est décrit et discuté ci-après.Cormary Y., Desbordes Michel. Rapport IV.1. Étude des écoulements urbains. Conception des réseaux d’assainissement. In: Influence des activités de l'homme sur le cycle hydrométéorologique. Compte-rendu des treizièmes journées de l'hydraulique. Paris, 16-18 septembre 1974. Tome 2, 1975

Can Swallowing Cerebral Neurophysiology Be Evaluated during Ecological Food Intake Conditions? A Systematic Literature Review

Swallowing is a complex function that relies on both brainstem and cerebral control. Cerebral neurofunctional evaluations are mostly based on functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), performed with the individual laying down; which is a non-ecological/non-natural position for swallowing. According to the PRISMA guidelines, a review of the non-invasive non-radiating neurofunctional tools, other than fMRI and PET, was conducted to explore the cerebral activity in swallowing during natural food intake, in accordance with the PRISMA guidelines. Using Embase and PubMed, we included human studies focusing on neurofunctional imaging during an ecologic swallowing task. From 5948 unique records, we retained 43 original articles, reporting on three different techniques: electroencephalography (EEG), magnetoencephalography (MEG) and functional near infra-red spectroscopy (fNIRS). During swallowing, all three techniques showed activity of the pericentral cortex. Variations were associated with the modality of the swallowing process (volitional or non-volitional) and the substance used (mostly water and saliva). All techniques have been used in both healthy and pathological conditions to explore the precise time course, localization or network structure of the swallowing cerebral activity, sometimes even more precisely than fMRI. EEG and MEG are the most advanced and mastered techniques but fNIRS is the most ready-to-use and the most therapeutically promising. Ongoing development of these techniques will support and improve our future understanding of the cerebral control of swallowing