Challenges in the construction of a multi-product vaccine facility

A new multi-product vaccines facility in Sanofi Pasteur was designed and equipped with new state-of-the-art technologies. The construction of this building aims to increase capacity of producing pediatric vaccines and allowed to implement manufacturing process improvements, increase quality compliance level and addressed environmental, and safety concern. This new facility harbors three antigens processes from fermentation to purification and detoxification. The project has been challenging on different points: new equipment, process transfer issues, new qualification/validation strategy and regulatory registration. Apart from global feedbacks on costs, organization, resources, performance and authorities communication strategies, focus was also directed towards the resolution of a process issue during validation steps. A trouble- shooting group has been mobilized to work on the different axes with a specific method. Resolution of all the issues permitted the building registration, and therefore the vaccination of millions of children

Intermittency and regularity issues in 3D Navier-Stokes turbulence

Two related open problems in the theory of 3D Navier-Stokes turbulence are discussed in this paper. The first is the phenomenon of intermittency in the dissipation field. Dissipation-range intermittency was first discovered experimentally by Batchelor and Townsend over fifty years ago. It is characterized by spatio-temporal binary behaviour in which long, quiescent periods in the velocity signal are interrupted by short, active `events' during which there are violent fluctuations away from the average. The second and related problem is whether solutions of the 3D Navier-Stokes equations develop finite time singularities during these events. This paper shows that Leray's weak solutions of the three-dimensional incompressible Navier-Stokes equations can have a binary character in time. The time-axis is split into `good' and `bad' intervals: on the `good' intervals solutions are bounded and regular, whereas singularities are still possible within the `bad' intervals. An estimate for the width of the latter is very small and decreases with increasing Reynolds number. It also decreases relative to the lengths of the good intervals as the Reynolds number increases. Within these `bad' intervals, lower bounds on the local energy dissipation rate and other quantities, such as \|\bu(\cdot, t)\|_{\infty} and \|\nabla\bu(\cdot, t)\|_{\infty}, are very large, resulting in strong dynamics at sub-Kolmogorov scales. Intersections of bad intervals for $n\geq 1$ are related to Scheffer's potentially singular set in time. It is also proved that the Navier-Stokes equations are conditionally regular provided, in a given `bad' interval, the energy has a lower bound that is decaying exponentially in time.Comment: 36 pages, 3 figures and 6 Table

Investigations on the vulnerability of advanced CMOS technologies to MGy dose environments

This paper investigates the TID sensitivity of silicon-based technologies at several MGy irradiation doses to evaluate their potential for high TID-hardened circuits. Such circuits will be used in several specific applications suc as safety systems of current or future nuclear power plants considering various radiation environments including normal and accidental operating conditions, high energy physics instruments, fusion experiments or deep space missions. Various device designs implemented in well established bulk silicon and Partially Depleted SOI technologies are studied here up to 3 MGy. Furthermore, new insights are given on the vulnerability of more advanced technologies including planar Fully Depleted SOI and multiple-gate SOI transistors at such high dose. Potential of tested technologies are compared and discussed for stand-alone integrated circuits

Foisonnement de l'innovation agricole : quelques exemples d'initiatives en élevage herbivore

Les témoignages rassemblés pour illustrer le foisonnement des innovations agricoles émanent d'acteurs différents (agriculteurs, recherche, développement) mais sont tous caractérisés par des approches plutôt systémiques et des dynamiques de co-conception. Les thèmes abordés concernent la production (valorisation des surfaces avec des cultures dérobées, sélection d'espèce prairiales locales), l'appropriation de résultats de recherche (amélioration de la gestion des prairies), la conception d'itinéraires techniques (solutions pour limiter les pertes d'azote en rotation prairie - prairie), l'évaluation de systèmes (repérer des pratiques innovantes en mobilisant des principes de l'agroécologie) mais aussi l'amélioration des conditions de travail et la formation (communication « intergénérationnelle » entre des paysans herbagers et des élèves)

Assessing brain function in stressed healthy individuals following the use of a combination of green tea, Rhodiola, magnesium, and B vitamins: an fMRI study

IntroductionThis randomized, controlled, single-blinded trial assessed the effect of magnesium (Mg)-Teadiola (Mg, vitamins B6, B9, B12, Rhodiola, and green tea/L-theanine) versus placebo on the brain response to stressful thermal stimulus in chronically stressed, but otherwise healthy subjects. Impacts on stress-related quality-of-life parameters (depression, anxiety, sleep, and perception of pain) were also explored.MethodsThe study recruited a total of 40 adults (20 per group), suffering from stress for more than 1 month and scaling ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire at the time of inclusion. Individuals received oral Mg-Teadiola or placebo for 28 days (D). fMRI analysis was used to visualize the interplay between stress and pain cerebral matrices, using thermal stress model, at baseline (D0) and after D28.ResultsBased on blood-oxygen-level-dependent (BOLD) signal variations during the stress stimulation (before pain perception), a significantly increased activation between D0 and D28 was observed for left and right frontal area (p = 0.001 and p = 0.002, respectively), left and right anterior cingulate cortex (ACC) (p = 0.035 and p = 0.04, respectively), and left and right insula (p = 0.034 and p = 0.0402, respectively) in Mg-Teadiola versus placebo group. During thermal pain stimulation, a significantly diminished activation of the pain matrix was observed between D0 and D28, for left and right prefrontal area (both p = 0.001), left and right insula (p = 0.008 and p = 0.019, respectively), and left and right ventral striatum (both p = 0.001) was observed in Mg-Teadiola versus placebo group. These results reinforce the clinical observations, showing a perceived benefit of Mg-Teadiola on several parameters. After 1 month of treatment, DASS-42 stress score significantly decreased in Mg-Teadiola group [effect size (ES) −0.46 (−0.91; −0.01), p = 0.048]. Similar reductions were observed on D14 (p = 0.011) and D56 (p = 0.008). Sensitivity to cold also improved from D0 to D28 for Mg-Teadiola versus placebo [ES 0.47 (0.02; 0.92) p = 0.042].ConclusionSupplementation with Mg-Teadiola reduced stress on D28 in chronically stressed but otherwise healthy individuals and modulated the stress and pain cerebral matrices during stressful thermal stimulus

High Total Ionizing Dose and Temperature Effects on Micro- and Nano-Electronic Devices

This paper investigates the vulnerability of several micro- and nano-electronic technologies to a mixed harsh environment involving high total ionizing dose at MGy levels and high temperature. Such operating conditions emerge today for several applications like new security systems in existing or future nuclear power plants, fusion experiments, or deep space missions. In this work, the competing effects of ionizing radiations and temperature are characterized in elementary devices made of MOS transistors from several technologies. First, devices are irradiated using a radiation laboratory X-ray source up to MGy dose levels at room temperature. Devices are either grounded or biased during irradiation to simulate two major circuit cases: a circuit which waits for a wake up signal, representing most of the lifetime of an integrated circuit operating in a harsh environment, and a nominal circuit function. Devices are then annealed at several temperatures to discuss the post-irradiation behavior and to determine whether an elevated temperature is an issue or not for circuit function in mixed harsh environments