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Summary Eukaryotic initiation factor 2 (eIF2), a heterotrimeric guanosine triphosphatase, has a central role in protein biosynthesis by supplying methionylated initiator tRNA to the ribosomal translation initiation complex and by serving as a target for translational control in response to stress. Recent work identified a novel step indispensable for eIF2 function: assembly of eIF2 from its three subunits by the cell proliferation protein Cdc123. We report the first crystal structure of a Cdc123 representative, that from Schizosaccharomyces pombe , both isolated and bound to domain III of Saccharomyces cerevisiae eIF2γ. The structures show that Cdc123 resembles enzymes of the ATP-grasp family. Indeed, Cdc123 binds ATP-Mg 2+ , and conserved residues contacting ATP-Mg 2+ are essential for Cdc123 to support eIF2 assembly and cell viability. A docking of eIF2αγ onto Cdc123, combined with genetic and biochemical experiments, allows us to propose a model explaining how Cdc123 participates in the biogenesis of eIF2 through facilitating assembly of eIF2γ to eIF2α. [ABSTRACT FROM AUTHOR]

Powder metallurgy processed Udimet 720 is a high creep strength nickel-based superalloy considered for high temperature turbine disks for nuclear gas cooled reactors working under 700 °C. Both fine-grained and coarse-grained microstructures have been obtained by applying respectively a subsolvus or a supersolvus solution treatments, followed by ageing treatments. In both microstructures, the distribution of the strengthening γ′ precipitates has been characterized by transmission electron microscopy (TEM). The creep curves of the coarse-grained microstructure show the three usual creep stages. On the contrary, the creep curves of the fine-grained microstructure show a transition directly from primary to apparent tertiary creep without any obvious steady state. According to TEM analyses, Orowan loops surround Udimet 720 CR γ′ and U720 HS γ′ at high stress whereas U720 HS γ′ are sheared at low stress. To describe the behavior of the superalloy Udimet 720, a specific creep model is developed on the basis of McLean and Dyson models including physical damage parameters. [Copyright &y& Elsevier]

During laser powder bed fusion (L-PBF), the protective atmosphere, normally argon, can become trapped in cavities formed during the process. We have demonstrated this by introducing ø0.5 mm pores in the CAD file (totalling 0.5% by volume) and measuring a threefold increase in argon content, versus an identical IN718 build-job without pores. For critical applications where the material is subjected to cyclic loading, any defects can act as stress raisers and initiate cracks. The pores that were introduced drastically reduced the fatigue performance of said material. However, after Hot Isostatic Pressing (HIP), the material regained its properties as if the pores were never introduced. Still, the argon remains after HIP according to measurements as it lacks solubility and thus cannot leave the material. Worth noting is that a small quantity of argon originates from gas-atomisation of the powder and thus does not leave entirely during the remelting in L-PBF. [ABSTRACT FROM AUTHOR]

High layer thicknesses for laser powder bed fusion are promising for productivity increase. However, these are associated with increased process instability, spatter generation and powder degradation, crucial for alloys sensitive to oxygen. The effect of increasing layer thickness from 30 to 60 µm is studied focusing on Ti-6Al-4V spatter formation during LPBF and its characterisation, with scanning and transmission electron microscopy, combustion analysis and X-ray photoelectron spectroscopy. Results indicate that spatters are covered with a uniform Ti-Al-based oxide layer and Al-rich oxide particulates, the thickness of which is about twice that present on virgin powder. The oxygen content was about 60% higher in spatters compared to the virgin powder. The study highlights that increasing the layer thickness to 60 µm permits to reduce the total generation of spatters by ∼40%, while maintaining similar spatter characteristics and static tensile properties. Hence, this allows to increase build rate without compromising process robustness. Highlights Increased layer thickness from 30 to 60 µm resulted in ∼40% lower amount of spatter generated per build Increased layer thickness from 30 to 60 µm resulted in ∼17% higher amount of generated spatter per scanned layer Increase in bulk oxygen content by >60% was registered for spatter compared to the virgin powder in both cases The oxide layer is about twice thicker on the spatter particles compared to virgin powder [ABSTRACT FROM AUTHOR]

[Display omitted] • The introduction of He in the build-atmosphere reduced the amount of generated spatters. • The oxygen content increased around 70 % from virgin to the spatter samples. • Thickness and nature of oxides on the surface of spatter varies and depends on the origin of spatter formation. • The oxidized spatters showed the growth of oxide particulates enriched with Al on a uniform Al-, Ti-based oxide layer. • The average oxide layer thickness almost doubled from virgin to spatter samples. The atmosphere is a vital factor influencing powder degradation during laser powder bed fusion. Particularly, its purity, density, and thermal conductivity, can strongly affect spatter generation, thermal history, and oxidation. It is critical to understand the atmosphere-spatter properties relationship to enhance powder recyclability and overall process sustainability. Herein, the effect of processing gases, among pure Ar, (Ar+He), and He, on spatter generation and oxidation during TiAl6V4 processing is investigated. To evaluate their influence on impurity pickup and morphology of spatters, bulk chemical analysis and scanning electron microscopy were conducted. The nature and thickness of surface oxides on spatters were comprehensively examined using surface analysis tools including X-ray photoelectron spectroscopy, Auger electron spectroscopy, and nano secondary ion mass spectroscopy. The bulk chemical analysis showed a 70% increase in oxygen content and a 3-fold increase in nitrogen content from virgin to spatter collected in standard argon atmosphere. The increase of impurities was substantially lower for the spatters generated in He and the mixture of (Ar+He). The surface analysis showed that the spatter surface was covered with a uniform Ti- and Al-rich oxide layer along with Al-based oxide particulates. Finally, this study discusses the nature of oxide on TiAl6V4 spatters. [ABSTRACT FROM AUTHOR]

Brain metastases are a frequent feature of the course of non-small cell lung carcinoma (NSCLC). The potential usefulness of prophylactic cranial irradiation (PCI) has led to the search for target groups likely to derive benefit. This multivariate analysis looked for factors predictive of brain metastases in a group of stages I–III NSCLC patients under care of the thoracic oncology unit of Besançon University Hospital from 1977 to 2001. All the patients had the same follow-up. They were divided into two groups: BM+ when they had a brain metastasis as the first site of progression, whether solitary or not, and BM- otherwise. Variables analysed were age, gender, performance status (0–1 versus 2–3), weight-loss stage T-status, N-status, pathological type, type of treatment, administration of chemotherapy, use of cisplatin and response to treatment. Three hundred and five patients were eligible and there were 77 patients (25.25%) in the BM+ group. Median time to onset of brain metastases was 12 months (1–163 months) and median survival from the diagnosis of brain metastases was 6 months (1–65 months). Factors predictive of brain progression were age ≤62 years (RR: 2.5, 95% CI: 1.33–4.76 and P=0.004), T4 tumour status (RR: 3.75, 95% CI: 1.72–8.21 and P=0.0009), N2-3 (RR: 2.61, 95% CI: 1.32–5.15 and P=0.0057), and adenocarcinoma (RR: 3.39, 95% CI: 1.78–6.46 and P=0.0002). No aspect of treatment plays a role in the frequency of this type of metastasis. These factors predictive of brain progression could serve as a basis for the selection of patients with the aim of sitting of studies on prophylactic cranial irradiation in NSCLC. [Copyright &y& Elsevier]

One of the main challenges for some reactors components in austenitic stainless steels at high temperature in-service conditions is the demonstration of their behavior up to 60 years. The creep lifetimes of these stainless steels require on the one hand to carry out very long term creep tests and on the other hand to understand and to model the damage mechanisms in order to propose physically-based predictions toward 60 years of service. Different batches of austenitic stainless steels like-type 316L with low carbon and closely specified nitrogen content, 316L(N), are subjected to numerous creep tests carried out at various stresses and temperatures between 525 °C and 700 °C up to nearly 50 • 10 3 h. Interrupted creep tests show an acceleration of the creep deformation only during the last 15% of creep lifetime, which corresponds to macroscopic necking. The modeling of necking using the Norton viscoplastic power-law allows lifetime predictions in fair agreement with experimental data up to a transition time of about ten thousand hours which is temperature dependent. In fact, one experimental result together with literature ones, shows that the extrapolation of the ‘stress–lifetime’ curves obtained at high stress data leads to large overestimations of lifetimes at low stress. After FEG–SEM observations, these overestimates are mainly due to additional intergranular cavitation as often observed in many metallic materials in the long term creep regime. The modeling of cavity growth by vacancy diffusion along grain boundaries coupled with continuous nucleation proposed by Riedel is carried out. For each specimen, ten FEG–SEM images (about 250 observed grains) are analyzed to determine the rate of cavity nucleation assumed to be constant during each creep test in agreement with many literature results. This measured constant rate is the only measured parameter which is used as input of the Riedel damage model. Lifetimes for long term creep are rather fairly well evaluated by the lowest lifetime predicted by the necking model and the Riedel model predictions. This holds for experimental lifetimes up to 200,000 h and for temperatures between 525 °C and 700 °C. A transition time as well as a transition stress is defined by the intersection of the lifetime curves predicted by the necking and Riedel modelings. This corresponds to the change in damage mechanism. The scatter in lifetimes predicted by the Riedel model induced by the uncertainty of some parameter values is less than a factor of three, similar to experimental scatter. This model is also validated for various other austenitic stainless steels such as 304H, 316H, 321H (creep rupture data provided by NIMS). A transition from power-law to viscous creep deformation regime is reported in the literature at 650 °C–700 °C for steel 316H. Taking into account the low stress creep rate law, it allows us to predict lifetimes up to 200,000 h at very high temperature in fair agreement with experimental data. [ABSTRACT FROM AUTHOR]

Understanding molecular mechanisms of ribosomal translation sheds light on the emergence and evolution of protein synthesis in the three domains of life. Universally, ribosomal translation is described in three steps: initiation, elongation and termination. During initiation, a macromolecular complex assembled around the small ribosomal subunit selects the start codon on the mRNA and defines the open reading frame. In this review, we focus on the comparison of start codon selection mechanisms in eukaryotes and archaea. Eukaryotic translation initiation is a very complicated process, involving many initiation factors. The most widespread mechanism for the discovery of the start codon is the scanning of the mRNA by a pre-initiation complex until the first AUG codon in a correct context is found. In archaea, long-range scanning does not occur because of the presence of Shine-Dalgarno (SD) sequences or of short 5′ untranslated regions. However, archaeal and eukaryotic translation initiations have three initiation factors in common: e/aIF1, e/aIF1A and e/aIF2 are directly involved in the selection of the start codon. Therefore, the idea that these archaeal and eukaryotic factors fulfill similar functions within a common structural ribosomal core complex has emerged. A divergence between eukaryotic and archaeal factors allowed for the adaptation to the long-range scanning process versus the SD mediated prepositioning of the ribosome. [ABSTRACT FROM AUTHOR]