Global implementation of a cell culture change: Strategies, lessons learned and challenges

Post-approval changes for pharmaceuticals are necessary to maintain regulatory compliance, support continuous improvement and optimization of the manufacturing process, and ensure robust product supply. However, managing post-approval changes at the global scale can be complicated and time-consuming due to differences in regional procedures, timelines and health authority expectations. This talk will highlight challenges and strategies used to develop a global implementation plan for selected cell culture technical changes across multiples products and sites. In particular, the talk will discuss best practices and lessons learned related to quality risk management, validation and stability requirements to support process and product comparability, as well as change control, regulatory and supply chain strategies to maintain continuity of the supply during the implementation of the change

Spectre et g\'eom\'etrie conforme des vari\'et\'es compactes \`a bord

We prove that on any compact manifold $M^n$ with boundary, there exist a conformal class $C$ such that for any riemannian metric $g\in C$, $\lambda_1(M^n,g)Vol(M^n,g)^{2/n}< n.Vol(S^n,g_{\textrm{can}})^{2/n}$ and $\sigma_1(M,g,\rho)\mathcal M(\partial M)Vol(M)^{\frac{2-n}n}<n.Vol(S^n,g_{\textrm{can}})^{2/n}$, where $\lambda_1(M^n,g)$ denotes the first positive eigenvalue of the Neumann laplacian on $(M,g)$, $\sigma_1(M,g,\rho)$ the first positive Steklov eigenvalue for the density $\rho$ on $\partial M$, and $\mathcal M(\partial M)=\int_{\partial M}\rho dv_g$. The proof relies on a handle decomposition of the manifold. We also prove that the conformal volume of $(M,C)$ is $Vol(S^n,g_{\textrm{can}})$, and that the Friedlander-Nadirashvili and the M\"obius volume of $M$ are equal to those of the sphere. If $M$ is a domain in a space form, $C$ is the conformal class of the canonical metric.Comment: 19 pages, in French, 5 figure

Dynamic parameters of structures extracted from ambient vibration measurements: an aid for the seismic vulnerability assessment of existing buildings in moderate seismic hazard regions

During the past two decades, the use of ambient vibrations for modal analysis of structures has increased as compared to the traditional techniques (forced vibrations). The Frequency Domain Decomposition method is nowadays widely used in modal analysis because of its accuracy and simplicity. In this paper, we first present the physical meaning of the FDD method to estimate the modal parameters. We discuss then the process used for the evaluation of the building stiffness deduced from the modal shapes. The models considered here are 1D lumped-mass beams and especially the shear beam. The analytical solution of the equations of motion makes it possible to simulate the motion due to a weak to moderate earthquake and then the inter-storey drift knowing only the modal parameters (modal model). This process is finally applied to a 9-storey reinforced concrete (RC) dwelling in Grenoble (France). We successfully compared the building motion for an artificial ground motion deduced from the model estimated using ambient vibrations and recorded in the building. The stiffness of each storey and the inter-storey drift were also calculated

Multifunctional Devices and Logic Gates With Undoped Silicon Nanowires

We report on the electronic transport properties of multiple-gate devices fabricated from undoped silicon nanowires. Understanding and control of the relevant transport mechanisms was achieved by means of local electrostatic gating and temperature dependent measurements. The roles of the source/drain contacts and of the silicon channel could be independently evaluated and tuned. Wrap gates surrounding the silicide-silicon contact interfaces were proved to be effective in inducing a full suppression of the contact Schottky barriers, thereby enabling carrier injection down to liquid-helium temperature. By independently tuning the effective Schottky barrier heights, a variety of reconfigurable device functionalities could be obtained. In particular, the same nanowire device could be configured to work as a Schottky barrier transistor, a Schottky diode or a p-n diode with tunable polarities. This versatility was eventually exploited to realize a NAND logic gate with gain well above one.Comment: 6 pages, 5 figure

Monitoring computational clusters with OVIS.

Traditional cluster monitoring approaches consider nodes in singleton, using manufacturer-specified extreme limits as thresholds for failure ''prediction''. We have developed a tool, OVIS, for monitoring and analysis of large computational platforms which, instead, uses a statistical approach to characterize single device behaviors from those of a large number of statistically similar devices. Baseline capabilities of OVIS include the visual display of deterministic information about state variables (e.g., temperature, CPU utilization, fan speed) and their aggregate statistics. Visual consideration of the cluster as a comparative ensemble, rather than as singleton nodes, is an easy and useful method for tuning cluster configuration and determining effects of real-time changes

Agricultural Production and Externalities Simulator (APES) prototype to be used in Prototype 1 of SEAMLESS-IF

Production Economics,

Library of model components for process simulation relevant to production activities, Prototype 1 versions

Production Economics,

Metabarcoding data reveal vertical multitaxa variation in topsoil communities during the colonization of deglaciated forelands

Ice-free areas are expanding worldwide due to dramatic glacier shrinkage and are undergoing rapid colonization by multiple lifeforms, thus representing key environments to study ecosystem development. It has been proposed that the colonization dynamics of deglaciated terrains is different between surface and deep soils but that the heterogeneity between communities inhabiting surface and deep soils decreases through time. Nevertheless, tests of this hypothesis remain scarce, and it is unclear whether patterns are consistent among different taxonomic groups. Here, we used environmental DNA metabarcoding to test whether community diversity and composition of six groups (Eukaryota, Bacteria, Mycota, Collembola, Insecta, and Oligochaeta) differ between the surface (0–5 cm) and deeper (7.5–20 cm) soil at different stages of development and across five Alpine glaciers. Taxonomic diversity increased with time since glacier retreat and with soil evolution. The pattern was consistent across groups and soil depths. For Eukaryota and Mycota, alpha-diversity was highest at the surface. Time since glacier retreat explained more variation of community composition than depth. Beta-diversity between surface and deep layers decreased with time since glacier retreat, supporting the hypothesis that the first 20 cm of soil tends to homogenize through time. Several molecular operational taxonomic units of bacteria and fungi were significant indicators of specific depths and/or soil development stages, confirming the strong functional variation of microbial communities through time and depth. The complexity of community patterns highlights the importance of integrating information from multiple taxonomic groups to unravel community variation in response to ongoing global changes

Gas dynamics in tidal dwarf galaxies : disc formation at z=0

Tidal dwarf galaxies (TDGs) are recycled objects that form within the collisional debris of interacting/merging galaxies. They are expected to be devoid of non-baryonic dark matter, since they can form only from dissipative material ejected from the discs of the progenitor galaxies. We investigate the gas dynamics in a sample of six bona-fide TDGs around three interacting and post-interacting systems: NGC 4694, NGC 5291, and NGC 7252 ("Atoms for Peace"). For NGC 4694 and NGC 5291 we analyse existing HI data from the Very Large Array (VLA), while for NGC 7252 we present new HI observations from the Jansky VLA together with long-slit and integral-field optical spectroscopy. For all six TDGs, the HI emission can be described by rotating disc models. These HI discs, however, have undergone less than a full rotation since the time of the interaction/merger event, raising the question of whether they are in dynamical equilibrium. Assuming that these discs are in equilibrium, the inferred dynamical masses are consistent with the observed baryonic masses, implying that TDGs are devoid of dark matter. This puts constraints on putative "dark discs" (either baryonic or non-baryonic) in the progenitor galaxies. Moreover, TDGs seem to systematically deviate from the baryonic Tully-Fisher relation. These results provide a challenging test for alternative theories like MOND.Peer reviewe