Standardization of visible particles measurement in single-use systems, an advantage for the emerging applications

The use of single-use systems (SUS) in biopharmaceutical and biotechnological industries has recently become much more common. SUS assemblies include plastic bags, tube lines and components. As much as possible, SUS should be “essentially free” of visible particles (≥100µm). The presence of visible particles inside the SUS is a visual indicator regarding the quality of product. During the biopharmaceutical manufacturing process, interactions between the drug substance contained in the bag and visible particles might lead to product quality issues. However, SUS free of particles remains a challenge due to the SUS manufacturing process which requires several steps of assembly and the presence of different components. The adoption of SUS can be a solution for the emerging applications, like vaccines and cell and gene therapy, especially in the pandemic time with a need to have products quickly and with a particulates level very low. For this reason, it is important to be able to extract, measure, characterize, and reduce the particles. SUS manufacturers need to demonstrate continuous improvement of their manufacturing process in order to limit visible particulate matter. Due to the complexity of the SUS (bags, tube lines, components, transparency, size ...), it is difficult to do a visual inspection of the entire product. To overcome this issue, the development of a visible particle test method is necessary to assess the number of visible particles contained inside the SUS, which then allows assessment of any risks linked to particle matter. This method allows to extract, count and size the particles inside SUS, and to identify particles according to their shape, color and infrared and/or Raman spectrum. That is why Sartorius co-worked with ASTM to develop a standard practice [[i]] for the extraction of particulate matter from the surfaces of single-use components and assemblies designed for use in biopharmaceutical manufacturing

Role of evaporation rate on the particle organization and crack patterns obtained by drying a colloidal layer

International audience– A scientific hurdle in manufacturing solid films by drying colloidal layers is preventing them from fracturing. This paper examines how the drying rate of colloidal liquids influences the particle packing at the nanoscale in correlation with the crack patterns observed at the macroscale. Increasing the drying rate results in more ordered, denser solid structures, and the dried samples have more cracks.Yet, introducing a holding period (at a prescribed point) during the drying protocol results in a more disordered solid structure with significantly less cracks. To interpret these observations, this paper conjectures that a longer drying protocol favors the formation of aggregates. It is further argued that the number and size of the aggregates increase as the drying rate decreases. This results in the formation of a more disordered, porous film from the viewpoint of the particle packing, and a more resistant film, i.e. less cracks, from the macroscale viewpoint

Principe de minimisation d'énergie appliqué aux fissures fragiles en forme d'étoile

Les colonnes basaltiques, les septarias, les fissures d'impact en forme de toile d'araignée, les réseaux de fissures dans les boues, les peintures, les céramiques sont autant d'exemples de motifs de rupture faisant apparaitre des fissures en forme d'étoile. Est-il possible de prédire leur forme? La mécanique de la rupture fragile classique basée sur l'utilisation des facteurs d'intensité des contraintes, n'est pas en mesure de le faire. Mais nous verrons à travers une expérience modèle, que l'approche variationnelle de la rupture semble être une alternative rigoureuse pour relever ce challenge. Etant une extension du postulat énergétique de Griffith, cette approche est basée sur le principe que l'évolution quasi-statique d'une fissure est obtenue en minimisant la somme de l'énergie élastique et de l'énergie de rupture. Nous l'appliquerons à des expériences de séchage directionnel d'une suspension colloïdale dans un tube capillaire. Nous constaterons qu'elle est capable de prédire quantitativement les fissures en étoile qui y apparaissent. Enfin, nous l'appliquerons de façon inverse afin d'obtenir certaines informations sur l'origine de motifs naturels, colonnes basaltiques et septarias

Nanoindentation cartography in Al/Al-Cu-Fe composites: Correlation between chemical heterogeneities and mechanical properties

During the last two decades, nanoindentation testing has become a commonly used technique for measuring surface mechanical properties such as hardness or elastic modulus. With devices equipped with a motorized X-Y table, it is now possible to perform large regular nanoindentation arrays in order to make an accurate statistics of the mechanical properties. This method is particularly interesting to study heterogeneous materials. The statistical analysis, associated to mathematical deconvolution methods allows identifying the properties of each individual phase. Furthermore, hardness or elastic modulus maps can be then established and compared to other local properties such as microstructure, crystallographic orientation or chemical composition. The nanoindentation cartography method has been used to study the mechanical properties of a metal matrix composite (Aluminum matrix with ω-Al-Cu-Fe reinforcement particles, synthesized by sparking plasma sintering) (cf. figure 1). Emphasize has been placed on the Aluminum matrix properties, where the detailed analysis of the individual nanoindentation curves shows serrated behavior characteristic of Portevin-Le Chatelier effect associated to dislocation pinning by solute atoms. The comparison between chemical (SEM – EDXS analysis) and hardness maps as well as the quantitative analysis of the deformation curves gives evidence of a strong correlation between the chemical heterogeneities and mechanical properties of the Aluminum matrix

Tenuous Correlation between Snow Depth or Sea Ice Thickness and C- or X-Band Backscattering in Nunavik Fjords of the Hudson Strait

Radar penetration in brine-wetted snow-covered sea ice is almost nil, yet reports exist of a correlation between snow depth or ice thickness and SAR parameters. This article presents a description of snow depth and first-year sea ice thickness distributions in three fjords of the Hudson Strait and of their tenuous correlation with SAR backscattering in the C- and X-band. Snow depth and ice thickness were directly measured in three fjords of the Hudson Strait from 2015 to 2018 in April or May. Bayesian linear regression analysis was used to investigate their relationship with RADARSAT-2 (C-band) or TerraSAR-X (X-band). Polarimetric ratios and the Cloude–Pottier decomposition parameters were explored along with the HH, HV and VV bands. Linear correlations were generally no higher than 0.3 except for a special case in May 2018. The co-polarization ratio did not perform better than the backscattering coefficients

IWGSC Sequence Repository: Moving towards tools to facilitate data integration for the reference sequence of wheat

URGI is a genomics and bioinformatics research unit at INRA (French National institute for Agricultural Research), dedicated to plants and crop parasites. We develop and maintain a genomic and genetic Information System called GnpIS that manages multiple types of wheat data. Under the umbrella of the IWGSC (International Wheat Genome Sequencing Consortium), we have set up a Sequence Repository on the Wheat@URGI website to store, browse and BLAST the data being generated by the wheat genome project: http://wheat-urgi.versailles.inra.fr/Seq-Repository. The repository holds the wheat physical maps, the chromosome survey sequence data for the individual chromosomes of breadwheat, draft sequences for diploid and tetraploid wheats and provides browsable access to the BAC-based reference sequence for chromosome 3B, the first of the chromosomes to be completed by the consortium. I will highlight the new features and data available in the Sequence Repository (e.g., new BLAST functionalities) and, in particular, present what we have done to address needs and concerns raised during the IWGSC S&P workshop last year. In addition, I will open the discussion about the future needs for tools to facilitate the integration of data to produce the reference sequence

Helicobacter pylori Counteracts the Apoptotic Action of Its VacA Toxin by Injecting the CagA Protein into Gastric Epithelial Cells

Infection with Helicobacter pylori is responsible for gastritis and gastroduodenal ulcers but is also a high risk factor for the development of gastric adenocarcinoma and lymphoma. The most pathogenic H. pylori strains (i.e., the so-called type I strains) associate the CagA virulence protein with an active VacA cytotoxin but the rationale for this association is unknown. CagA, directly injected by the bacterium into colonized epithelium via a type IV secretion system, leads to cellular morphological, anti-apoptotic and proinflammatory effects responsible in the long-term (years or decades) for ulcer and cancer. VacA, via pinocytosis and intracellular trafficking, induces epithelial cell apoptosis and vacuolation. Using human gastric epithelial cells in culture transfected with cDNA encoding for either the wild-type 38 kDa C-terminal signaling domain of CagA or its non-tyrosine-phosphorylatable mutant form, we found that, depending on tyrosine-phosphorylation by host kinases, CagA inhibited VacA-induced apoptosis by two complementary mechanisms. Tyrosine-phosphorylated CagA prevented pinocytosed VacA to reach its target intracellular compartments. Unphosphorylated CagA triggered an anti-apoptotic activity blocking VacA-induced apoptosis at the mitochondrial level without affecting the intracellular trafficking of the toxin. Assaying the level of apoptosis of gastric epithelial cells infected with wild-type CagA+/VacA+ H. pylori or isogenic mutants lacking of either CagA or VacA, we confirmed the results obtained in cells transfected with the CagA C-ter constructions showing that CagA antagonizes VacA-induced apoptosis. VacA toxin plays a role during H. pylori stomach colonization. However, once bacteria have colonized the gastric niche, the apoptotic action of VacA might be detrimental for the survival of H. pylori adherent to the mucosa. CagA association with VacA is thus a novel, highly ingenious microbial strategy to locally protect its ecological niche against a bacterial virulence factor, with however detrimental consequences for the human host

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Correction to: Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.

After publication of the original article [1], we were notified that columns in Table 2 were erroneously displayed