PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression

Sample and data collection were funded by Cancer Research UK. Analysis was funded by Breast Cancer Now, the Rosetrees Trust, Guys & St Thomas’ Charity (CanHelp) and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London

Genetic predisposition to ductal carcinoma in situ of the breast

Background: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. Methods: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Results: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10-8. Conclusion: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist

Multiscale Characterization of Microstructural Evolution in Powder Metallurgy and Ceramic Forming Processes

The microstructural evolution of materials during powder metallurgy and ceramic forming processes is a complex phenomenon that spans multiple length scales. In this study, we present a comprehensive multiscale characterization of the microstructural changes occurring during these processes. We employ a combination of advanced experimental techniques, including high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD), to investigate the microstructural features at various length scales. Our results reveal the intricate interplay between grain growth, phase transformation, and defect formation during sintering and forming processes. We observe a strong correlation between the initial powder characteristics, such as particle size and morphology, and the resulting microstructure. Furthermore, we employ phase-field modeling to simulate the microstructural evolution and validate our experimental findings. Our simulations provide insights into the kinetics of grain growth and the role of interfacial energy in governing microstructural changes. The results of this study have significant implications for the design and optimization of powder metallurgy and ceramic forming processes, enabling the tailoring of microstructures for specific applications. This work contributes to the fundamental understanding of microstructural evolution in these processes and paves the way for the development of advanced materials with tailored properties

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Not AvailableRice is the most important food crop both in value and volume for the Asian population. Frequent drought, flood and salinity stresses exacerbated by global climate change adversely affect rice production in more than fifty percent of the rice growing areas. Green revolution high yielding varieties carrying sd1 dwarfing gene have almost fully replaced the traditional climate resilient landraces and varieties of rice. However, these were bred primarily for yield under high input conditions and therefore are sensitive to adverse climatic conditions. Hence, there is urgent need to combine the high productivity with climate resilience. Knowledge of rice genome and genes for tolerance to different abiotic stresses provided us an opportunity to transfer favorable alleles of these genes into high yielding varieties through genomics-assisted backcross breeding through multi-institutional networks. Six consistent genomic regions (QTLs) for grain yield under drought; namely qDTY1.1, qDTY2.1, qDTY2.2, qDTY3.1, qDTY3.2 and qDTY12.1 have been transferred to flood tolerant versions of mega varieties of rice, Swarna, Samba Mahsuri and IR 64. To address the problem of flash flooding qSUB1 QTL has been transferred to nine popular rice varieties, namely ADT 46, Bahadur, Ranjit, HUR 105, Sarjoo 52, Pooja, Pratikshya MTU 1075 and Rajendra Mahsuri. Further, qSALTOL1 QTL for seedling stage salt tolerance and qSSISFH8.1 for reproductive stage salt tolerance have been transferred to six popular rice varieties, ADT 45, Gayatri, MTU 1010, PR 114, Pusa 44 and Sarjoo 52. We used foreground selection markers for the presence of desired gene/QTL and recombinant selection markers for reduction of linkage drag around these genes. Genotypic background selection was done after BC3F3 stage using a 50K SNP chip on a set of 20 advance lines obtained by phenotypic selection for closeness to the recipient parents. Near-isogenic lines (NILs) with more than 95% similarity to the recipient parent genome have been released and notified for commercial cultivation and are gaining fast popularity. These climate smart rice varieties will provide production stability in the adverse ecologies and support farmer’s income and livelihood.Not Availabl