MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution

Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution

Review of progress on fusion materials technology

SIGLELD:9091.9F(AERE-M--3170)(microfiche). / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Irradiation-induced embrittlement and precipitation in nimonic PE16

SIGLELD:9091.9F(AERE-R--10108)(microfiche). / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Beryllium irradiation embrittlement test programme. Material and specimen specification, manufacture and qualification

The report presents the specification, manufacture and qualification of the beryllium specimens to be irradiated in the BR2 reactor in Mol to investigate the effect of the neutron irradiation on the embrittlement as a function of temperature and beryllium oxide content. This work was been performed in the framework of the Nuclear Fusion Project of the Forschungszentrum Karlsruhe and is supported by the European Union within the European Fusion Technology Program. (orig.)16 refs.Available from TIB Hannover: ZA 5141(5778) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Berillium irradiation embrittlement test (BSBE) programme Assessment of the tensile and fracture toughness test data

Eine Auswertung der Zug- und Bruchzaehfestigkeitstests von sowohl unbestrahlten als auch bestrahlten Beryllium-Proben wurde durchgefuehrt. Bei den analysierten Proben handelt es sich um hot isostatic pressed (HIP) S-65 und vacuum hot pressed (VHP) S-200F Beryllium, die bei 200 C bzw. 400 C und 600 C bis zu einer Neutronenfluenz von 2.1 x 10"2"5 m"-"2 bestrahlt wurden. Der Einfluss der Herstellungsparameter (z.B. Herstellungsmethode, Verunreinigungen, Korngroesse usw.), sowie der Test- und Bestrahlungstemperatur auf die Materialeigenschaften wurde untersucht. Obwohl weitere und detaillierte mikrostrukturelle Untersuchungen notwendig sind, um das Material vollstaendig zu charakterisieren, zeigen die Analysen, dass die Streckgrenze und die Bruchfestigkeit des unbestrahlten Materials bei einer konstanten Temperatur mit der Quadratwurzel der Korngroesse zunehmen (Hall-Petch Gesetz). Das Material wird durch die Neutronenbestrahlung bei Bestrahlungstemperaturen unter 310 C stark versproedet. Eine kleine Wiedergewinnung der Streckbarkeit wurde jedoch bei Bestrahlungstemperaturen ueber 485 C beobachtet. Zusaetzlich vermindert die Bestrahlung stark die Bruchzaehfestigkeit des Materials bei allen Bestrahlungstemperaturen unter 600 C und nur bei 600 C wurde eine kleine Wiedergewinnung dieser Eigenschaft beobachtet. Alle Beryllium-Proben verhalten sich mehr oder weniger gleich bei niedrigen Bestrahlungstemperaturen und sind alle sproede. Die S-65 VHP und die S-200 HIP Beryllium-Proben sind jedoch bei Bestrahlungstemperaturen ueber 435 C etwas duktiler und zaeher. (orig.)An independent assessment has been made of the ambient and elevated temperature tensile and fracture toughness properties of unirradiated (reference), aged (#propor to#2000 h at temperatures in the range 185 to 605 C) and irradiated (2.1 x 10"2"5 nm"-"2 (>1 MeV) at 200, 400 and 600 C (nominal)) hot isostatic (HIP) and vacuum hot (VHP) pressed S-65 and S-200F beryllium grades as determined by SCK/CEN, Mol Belgium. The effects of material (powder consolidation method, beryllium oxide and elemental impurity contents and grain size), test (temperature) and irradiation (temperature, atom displacement dose and helium concentration) variables were analysed to further the development of composition - structure - property relationships for unirradiated and irradiated beryllium. Although detailed microstructural examinations of the unirradiated and irradiated materials and other investigations are required to clarify some of the present uncertainties, the results of the analysis demonstrate that the tensile proof and ultimate strengths of the reference and aged beryllium grades at a given test temperature increase with the inverse square root of the grain diameter (d) in accordance with the Hall-Petch relationship. The tensile yield strengths are also determined by the impurity elements and precipitates which increase the friction stress opposing the movement of free dislocations in the lattice. The ductilities of the reference and aged beryllium peak at 230-310 C whilst the non-uniform elongations generally decrease with increasing BeO (0.5 to 1.2%) and/or impurity contents at temperatures of 310 to 605 C. The beryllium grades are severely embrittled at irradiation/test temperatures of #<=#310 C but some recovery of the tensile ductility occurs at #>=#485 C. There is an increased tendency to cleavage fracture at the lower temperatures, the cleavage stress of the irradiated beryllium being dependent on d"-"("1"/"2"). The irradiated tensile samples fail by grain boundary and/or ductile dimple fracture at the higher temperatures, the intergranular fracture probably resulting from the stress-induced growth and coalescence of adjacent helium bubbles. The fracture toughness values for the reference and aged beryllium are broadly in agreement with the tensile strengths at low and intermediate temperatures and increase with increasing reductions of an area at the higher temperatures. Irradiation markedly reduces the fracture toughness at all temperatures but there is some recovery at #propor to#600 C; the irradiated fracture toughness correlates reasonably well with the tensile proof stress and/or reductionof area values. The beryllium grades do not differ significantly in their resistance to radiation damage at the lower test temperatures; however, the S-65 VHP and, in particular, the S-200F HIP grades are more ductile and marginally tougher at #>=#435 C. (orig.)Available from TIB Hannover: ZA 5141(6376) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Characterization and assessment of ferritic/martensitic steels

Ferritic/martensitic steels are candidate structural materials for a DEMO fusion reactor and are investigated intensively within the frame of the European Long Term Fusion Technology Programme. This report summarizes general features of ferritic/martensitic steels and gives a broad overview on the available data of the 9-12% CrMoVNb steels MANET I and II. The data include informations on the physical metallurgy, the transformation and hardening/tempering behaviour as well as results on tensile, creep, creep-rupture, isothermal and thermal fatigue, charpy impact and fracture toughness properties. Other topics are corrosion tests of helium or high pressure water coolants, compatibility with breeding and neutron multiplier materials, advanced welding techniques, and a short review on fabrication and technology of these steels. In the relevant temperature region from ambient temperatures to 450 C a widespread field of results on pre-, postirradiation and in-situ mechanical properties is available up to a few dpa and up to 500 appm helium. Special emphasis has been put on the recent world-wide optimization of these steels. New 7-10% CrWVTa steels have been developed with significantly improved impact and fracture toughness properties. Initial results from unirradiated and neutron irradiated charpy specimens from various heats are favourable and showed a general improvement of the fracture toughness properties. These ferritic/martensitic steels also satisfy the criteria of reduced long-term activation. The potential for fusion applications is discussed together with some guidelines for required R and D. (orig.)210 refs.SIGLEAvailable from TIB Hannover: ZA 5141(5626) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman