The outcome of the Notch pathway on proliferation depends on cellular context, being growth promotion in some, including several cancers, and growth inhibition in others. Such disparate outcomes are ...evident in Drosophila wing discs, where Notch overactivation causes hyperplasia despite having localized inhibitory effects on proliferation. To understand the underlying mechanisms, we have used genomic strategies to identify the Notch-CSL target genes directly activated during wing disc hyperplasia. Among them were genes involved in both autonomous and non-autonomous regulation of proliferation, growth and cell death, providing molecular explanations for many characteristics of Notch induced wing disc hyperplasia previously reported. The Notch targets exhibit different response patterns, which are shaped by both positive and negative feed-forward regulation between the Notch targets themselves. We propose, therefore, that both the characteristics of the direct Notch targets and their cross-regulatory relationships are important in coordinating the pattern of hyperplasia.
In the development of a conditioning process for cesium-bearing sorbents from the decontamination of aqueous waste streams, the treatment of a granular material composed of (Cs,K)2CuFe(CN)6 loaded ...onto mesoporous silica particles has been investigated in an additive-free two-step conditioning process involving (i) calcination at 1000 °C to remove volatile species and (ii) densification by spark plasma sintering. A 92.0 % dense pellet was obtained after 10 min sintering at 850 °C under 100 MPa. Density and microstructural measurements indicate that densification is first driven by the viscous flow of a vitreous phase containing Cs, formed during calcination. The density of the sample then increases further during sintering by grain boundary diffusion. However, a limited but non negligible part of cesium is lost during densification.
The in situ sintering of a powder of Pb
3(VO
4)
1.6(PO
4)
0.4 composition was performed in an Environmental Scanning Electron Microscope. The electric current induced by the electron beam was found ...to reduce the effective temperature of sintering as well as to accelerate the kinetics of shrinkage of a cluster composed of sub-micrometric grains of material. The presence of the residual current flow in the cluster during observation for in situ experiments helps to reduce the apparent sintering temperatures from 50 to 150
°C compared to conventional heating conditions without current.
► We studied the in situ sintering of a lead phosphovanadate (LPV) in an ESEM. ► Sintering temperature and kinetics are modified by the electronic beam. ► Sintering temperature of LPV is decreased by 100
°C in standard conditions. ► Current density increases the kinetics of the sintering. ► We conclude that ESEM could be a means to study sintering under current.
Electric taxi fleet simulation calls for a lot of uneasily accessible data. We learned from historical data in order to predict electric vehicle consumption and charging time. Although simulation was ...the main goal, the developed models will be used by the dispatching team of the company. Moreover, the data analysis process allowed us to discover flaws in the infrastructure (e.g., defective stations and defective batteries).
To test the metastatic response rate in stage 4 neuroblastoma, using dose-intensive induction chemotherapy in a multi-institutional setting.
From 1998 to 1999, 47 consecutive children were treated ...according to N7 protocol. Children received cyclophosphamide 140 mg/kg, doxorubicin 75 mg/m(2), and vincristine 0.066 mg/kg (CAV) in cycles 1, 2, 4, and 6, and cisplatinum 200 mg/m(2) and etoposide 600 mg/m(2) (P/VP) in cycles 3, 5, and 7. The International Neuroblastoma Staging system was used with an emphasis on skeletal evaluation by 123-iodine-metaiodobenzylguanidine (MIBG) scintigraphy. A phase II study evaluating the metastasis complete response rate after induction chemotherapy was conducted in patients who had positive metastatic sites on MIBG scans at diagnosis.
Forty-six patients were assessable for toxicity. Hematologic toxicity was the main toxicity observed. Neutropenia was more frequent after CAV than after P/VP (P < .001). A higher rate of thrombocytopenia was observed after P/VP (P = .03). Forty patients with positive MIBG were assessable for metastatic response, and complete regression of metastases was achieved in 17 patients (ie, 43%; 95% CI, 27% to 59%). Of all 47 patients, 21 achieved complete metastatic response.
The N7 induction chemotherapy protocol was feasible in a multicentric setting. The observed metastasis complete response rate was similar to that obtained in our previous studies and significantly lower than that published in a previous series using the same regimen. In our hands, escalating doses of cyclophosphamide and prolonging conventional chemotherapy with the same drugs failed to improve the metastasis complete response rate.
This paper examines the efficiency of two consolidation processing techniques: High Velocity Oxy-Fuel (HVOF) spray forming and Spark Plasma Sintering (SPS) to obtain bulk nanostructured materials ...from an Y
2O
3 reinforced Fe–40Al (at.%) milled powder. The microstructures of the sintered end-products were characterized by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) in order to gain new insights in their microstructure formation mechanisms. HVOF spray forming is more effective to retain fine nanograins, in particular within retained unmelted powder particles. The drawbacks of this technique are that it inevitably leads to a high fraction of porosity and, because of lack of wetting, large areas (the melted zones) without any Y
2O
3 oxide. Comparatively, SPS has a much higher potential to create sub-micrometer microstructures within which the oxides are more homogeneously distributed.
The gene
vestigial (
vg) plays a key role in indirect flight muscle (IFM) development. We show here that
vg is controlled by the Notch anti-myogenic signaling pathway in myoblasts and is regulated by ...a novel 822 bp enhancer during IFM differentiation. Interestingly, this muscle enhancer is activated in developing fibers and in a small number of myoblasts before the fusion of myoblasts with the developing muscle fibers. Moreover, we show that this enhancer is activated by
Drosophila Myocyte enhancing factor 2 (MEF2), Scalloped (SD) and VG but repressed by Twist, demonstrating a sensitivity to differentiation
in vivo.
In vitro experiments reveal that SD can directly bind this enhancer and MEF2 can physically interact with both SD and TWI. Cumulatively, our data reveal the interplay between different myogenic factors responsible for the expression of an enhancer activated during muscle differentiation.
•A thermal-electrical-mechanical model has been performed to simulate the SPS process.•With use of SPS tests, the behavior of the porous medium is identified.•Comparisons between SPS tests and ...simulations validate the approach.•The model is able to capture the stress, temperature and porosity fields in the sample.•Post mortem analyses confirm qualitatively the temperature field in the sample.
Spark Plasma Sintering is a non-conventional process of the powder metallurgy field which uses a high electrical current to rapidly produce fully dense materials. In the present paper, a thermal-electrical-mechanical model developed on ABAQUS Software is proposed to simulate the densification of a nickel disk. A compaction model, studied in Wolff, C., Mercier, S., Couque, H., Molinari, A., 2012. Modeling of conventional hot compaction and spark plasma sintering based on modified micromechanical models of porous materials. Mechanics of Materials 49 (0), 72–91. URL http://www.sciencedirect.com/science/article/pii/S0167663611002195, has been used to reproduce the densification of the sample. Two SPS experiments have been necessary to identify the parameters of the densification law. In order to evaluate the robustness of the present model, two other SPS experiments have been performed. The whole results of the simulation show a good agreement with the experimental data confirming the validity of the compaction model developed in Wolff, C., Mercier, S., Couque, H., Molinari, A., 2012. Modeling of conventional hot compaction and spark plasma sintering based on modified micromechanical models of porous materials. Mechanics of Materials 49 (0), 72–91. URL http://www.sciencedirect.com/science/article/pii/S0167663611002195.
Due to the spread of the H5N1 highly pathogenic strain of avian influenza virus across Europe, a preventive vaccination occurred in early 2006 among 135 French zoologic institutions. Approximately ...25,000 birds were vaccinated with a H5N2 inactivated vaccine. Among them, 4,369 birds were monitored by members of Association Francophone des Vétérinaires de Parc Zoologique regarding safety issues of the vaccination protocol. A total of 1,686 blood samples were collected before the first injection (n = 255), at the time of booster (n = 463), 60 day after the booster (n = 514), and 180 day (n = 229) and 330 day (n = 217) after the initial injection. Thus, sera of 126 species representing 15 different avian orders were tested using the hemagglutinin inhibition assay to evaluate seroconversion and the long-term serologic profile of selected anti-H5 antibody. Safety was considered satisfactory in all orders, and there were no deleterious effects on large-volume injection/body weight ratio. After the second injection, 71% of the birds developed a titer ≥32, with a mean titer of 558. Titers then decreased in all birds, with 42% of the remaining birds having a titer ≥32 at day 180 and only 26% at day 330. Results demonstrated that a booster 42 days after initial vaccination was mandatory to raise the titer above 32, considered to be the protective level in poultry, and to increase the number of seroconverted birds. Differences in the serologic responses among the orders and species of birds were detected and could be linked with the variation of vaccine dose injected per body weight or with species-specific immune response. The protocol for additional campaigns will be adjusted for some bird orders through the increase of injected dose or a half yearly booster to sustain better titers over the year. Vaccination is a useful tool, together with biosecurity, that should always be used as a primary method of preventing and controlling avian influenza outbreaks.
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