| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Pemmasani, S. P., et al.
(author)
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Characterization of multilayer nitride coatings by electron microscopy and modulus mapping
- 2013
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In: Materials Characterization. - : Elsevier BV. - 1044-5803 .- 1873-4189. ; 81, s. 7-18
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Journal article (peer-reviewed)abstract
- This paper discusses multi-scale characterization of physical vapour deposited multilayer nitride coatings using a combination of electron microscopy and modulus mapping. Multilayer coatings with a triple layer structure based on TiAlN and nanocomposite nitrides with a nano-multilayered architecture were deposited by Cathodic arc deposition and detailed microstructural studies were carried out employing Energy Dispersive Spectroscopy, Electron Backscattered Diffraction, Focused Ion Beam and Cross sectional Transmission Electron Microscopy in order to identify the different phases and to study microstructural features of the various layers formed as a result of the deposition process. Modulus mapping was also performed to study the effect of varying composition on the moduli of the nano-multilayers within the triple layer coating by using a Scanning Probe Microscopy based technique. To the best of our knowledge, this is the first attempt on modulus mapping of cathodic arc deposited nitride multilayer coatings. This work demonstrates the application of Scanning Probe Microscopy based modulus mapping and electron microscopy for the study of coating properties and their relation to composition and microstructure. © 2013 Elsevier Inc.
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| 4. |
- Pemmasani, S. P., et al.
(author)
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Structure-property correlations in cathodic arc deposited tialn coatings
- 2012
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In: Materials Science Forum. - 0255-5476 .- 1662-9752. - 9783037852941 ; 702-703:1, s. 967-970
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Journal article (peer-reviewed)abstract
- PVD hard coatings, notably transition metal nitrides and carbides, are being increasingly used by industry for improving the life and machining speeds of cutting and forming tools. There has been an increasing trend towards use of complex coatings, based on ternary and even more complex multi-component systems, as well as in novel configurations such as multilayers, superlattices, nanolayers and graded coatings, to achieve superior properties in the tool as well as the finished product. The service properties of the coatings are known to be influenced by their microstructure, phase assembly and composition, apart from the orientation and stress states which can be suitably tailored for diverse applications. In the present study, a ternary coating based on Titanium Aluminum Nitride was deposited on high speed steel substrates by cathodic arc evaporation under varied bias voltage conditions. Asdeposited coatings were characterized by X-ray diffraction, Residual Stress Analysis, Scanning Electron Microscopy (SEM), EBSD and FIB. Mechanical and tribological characteristics of the coatings were evaluated by nanoindentation and nanoscratch testing, respectively. The variations in coating hardness and adhesion with the bias voltage were studied. The changes in coating microstructure as a consequence of variation in bias voltage were also examined. Results from the above investigations are presented to illustrate how a combination of electron microscopy with nanoindentation. © (2012) Trans Tech Publications, Switzerland.
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| 5. |
- Ramakrishna, Sarayu, et al.
(author)
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APOE4 affects basal and NMDAR mediated protein synthesis in neurons by perturbing calcium homeostasis
- 2021
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In: The Journal of Neuroscience. - 1529-2401. ; 41:42, s. 8686-8709
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Journal article (peer-reviewed)abstract
- Apolipoprotein E (APOE), one of the primary lipoproteins in the brain has three isoforms in humans - APOE2, APOE3, and APOE4. APOE4 is the most well-established risk factor increasing the pre-disposition for Alzheimer's disease. The presence of the APOE4 allele alone is shown to cause synaptic defects in neurons and recent studies have identified multiple pathways directly influenced by APOE4. However, the mechanisms underlying APOE4 induced synaptic dysfunction remain elusive. Here, we report that the acute exposure of primary cortical neurons or synaptoneurosomes to APOE4 leads to a significant decrease in global protein synthesis. Primary cortical neurons were derived from male and female embryos of Sprague-Dawley rats or C57BL/6J mice. Synaptoneurosomes were prepared from P30 male Sprague-Dawley rats. APOE4 treatment also abrogates the NMDA mediated translation response indicating an alteration of synaptic signaling. Importantly, we demonstrate that both APOE3 and APOE4 generate a distinct translation response which is closely linked to their respective calcium signature. Acute exposure of neurons to APOE3 causes a short burst of calcium through NMDARs leading to an initial decrease in protein synthesis which quickly recovers. Contrarily, APOE4 leads to a sustained increase in calcium levels by activating both NMDARs and L-VGCCs, thereby causing sustained translation inhibition through eEF2 phosphorylation, which in turn disrupts the NMDAR response. Thus, we show that APOE4 affects basal and activity mediated protein synthesis responses in neurons by affecting calcium homeostasis.SIGNIFICANCE STATEMENTDefective protein synthesis has been shown as an early defect in familial Alzheimer's disease. However, this has not been studied in the context of sporadic Alzheimer's disease, which constitutes the majority of cases. In our study, we show that APOE4, the predominant risk factor for Alzheimer's disease, inhibits global protein synthesis in neurons. APOE4 also affects NMDA activity mediated protein synthesis response, thus inhibiting synaptic translation. We also show that the defective protein synthesis mediated by APOE4 is closely linked to the perturbation of calcium homeostasis caused by APOE4 in neurons. Thus, we propose the dysregulation of protein synthesis as one of the possible molecular mechanisms to explain APOE4 mediated synaptic and cognitive defects. Hence, the study not only suggests an explanation for the APOE4 mediated pre-disposition to Alzheimer's disease, it also bridges the gap in understanding APOE4 mediated pathology.
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| 8. |
- Chandrasekaran, Abinaya, et al.
(author)
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Astrocytic reactivity triggered by defective autophagy and metabolic failure causes neurotoxicity in frontotemporal dementia type 3
- 2021
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In: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; , s. 2736-2751
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Journal article (peer-reviewed)abstract
- Frontotemporal dementia type 3 (FTD3), caused by a point mutation in the charged multivesicular body protein 2B (CHMP2B), affects mitochondrial ultrastructure and the endolysosomal pathway in neurons. To dissect the astrocyte-specific impact of mutant CHMP2B expression, we generated astrocytes from human induced pluripotent stem cells (hiPSCs) and confirmed our findings in CHMP2B mutant mice. Our data provide mechanistic insights into how defective autophagy causes perturbed mitochondrial dynamics with impaired glycolysis, increased reactive oxygen species, and elongated mitochondrial morphology, indicating increased mitochondrial fusion in FTD3 astrocytes. This shift in astrocyte homeostasis triggers a reactive astrocyte phenotype and increased release of toxic cytokines, which accumulate in nuclear factor kappa b (NF-κB) pathway activation with increased production of CHF, LCN2, and C3 causing neurodegeneration.
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| 9. |
- Ju, Young Seok, et al.
(author)
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Frequent somatic transfer of mitochondrial DNA into the nuclear genome of human cancer cells.
- 2015
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 25:6, s. 814-824
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Journal article (peer-reviewed)abstract
- Mitochondrial genomes are separated from the nuclear genome for most of the cell cycle by the nuclear double membrane, intervening cytoplasm, and the mitochondrial double membrane. Despite these physical barriers, we show that somatically acquired mitochondrial-nuclear genome fusion sequences are present in cancer cells. Most occur in conjunction with intranuclear genomic rearrangements, and the features of the fusion fragments indicate that nonhomologous end joining and/or replication-dependent DNA double-strand break repair are the dominant mechanisms involved. Remarkably, mitochondrial-nuclear genome fusions occur at a similar rate per base pair of DNA as interchromosomal nuclear rearrangements, indicating the presence of a high frequency of contact between mitochondrial and nuclear DNA in some somatic cells. Transmission of mitochondrial DNA to the nuclear genome occurs in neoplastically transformed cells, but we do not exclude the possibility that some mitochondrial-nuclear DNA fusions observed in cancer occurred years earlier in normal somatic cells.
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| 10. |
- Maniv, A., et al.
(author)
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Microscopic evidence for Mn-induced long range magnetic ordering in MAX phase compounds
- 2021
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In: Journal of Physics. - : IOP PUBLISHING LTD. - 0953-8984 .- 1361-648X. ; 33:2
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Journal article (peer-reviewed)abstract
- Zero and low field nuclear magnetic resonance measurements have been performed on MAX phase samples (Cr1-xMnx)(2)AC withA= Ge and Ga in order to obtain local microscopic information on the nature of magnetism in this system. Our results unambiguously provide evidence for the existence of long-range magnetic order in (Cr0.96Mn0.04)(2)GeC and for (Cr0.93Mn0.07)(2)GaC, but not for (Cr0.97Mn0.03)(2)GaC. We point to a possible dependence of long range magnetic order in these MAX phase compounds on theAatom.
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| 11. |
- Shanmugam, V., et al.
(author)
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Potential natural polymer-based nanofibres for the development of facemasks in countering viral outbreaks
- 2021
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In: Journal of Applied Polymer Science. - : Wiley. - 0021-8995 .- 1097-4628. ; 138:27
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Journal article (peer-reviewed)abstract
- The global coronavirus disease 2019 (COVID-19) pandemic has rapidly increased the demand for facemasks as a measure to reduce the rapid spread of the pathogen. Throughout the pandemic, some countries such as Italy had a monthly demand of ca. 90 million facemasks. Domestic mask manufacturers are capable of manufacturing 8 million masks each week, although the demand was 40 million per week during March 2020. This dramatic increase has contributed to a spike in the generation of facemask waste. Facemasks are often manufactured with synthetic materials that are non-biodegradable, and their increased usage and improper disposal are raising environmental concerns. Consequently, there is a strong interest for developing biodegradable facemasks made with for example, renewable nanofibres. A range of natural polymer-based nanofibres has been studied for their potential to be used in air filter applications. This review article examines potential natural polymer-based nanofibres along with their filtration and antimicrobial capabilities for developing biodegradable facemask that will promote a cleaner production.
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| 12. |
- Valleti, K., et al.
(author)
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Influence of substrate temperature and bias voltage on properties of chromium nitride thin films deposited by cylindrical cathodic arc deposition
- 2011
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In: Journal of Vacuum Science & Technology. A. Vacuum, Surfaces, and Films. - 0734-2101 .- 1520-8559. ; 29:5
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Journal article (peer-reviewed)abstract
- Chromium nitride (CrN) thin films have been deposited on high speed steel (HSS) substrates using rotating cylindrical cathodic arc deposition technique and the influence of substrate temperature (TSub) and bias voltage (VSub) on the physical/mechanical and corrosion resistance properties of the films comprehensively investigated. An increase in TSub was found to significantly influence the phase composition of films, which changed from a mixture of Cr CrxN CrN to predominantly CrN. This was also accompanied by an increase in droplet formation and columnar grain size. With increase in TSub over the range investigated (230 °C to 500 °C), an increase in adhesion strength by nearly 30 was observed. In contrast, change in VSub from -50 to -150 V resulted in the growth of highly dense (111) oriented CrN thin films but with relatively little change in phase constitution, adhesion strength or microdroplet formation. A change in TSub from 230 °C to 500 °C was accompanied by a nearly 50 fall in corrosion resistance, plausibly due to the concomitant decrease in pure Cr phase content and increase in macroscopic defect concentration with increase in TSub. In view of the above, CrN thin films deposited using cylindrical cathodic arc deposition technique yield better corrosion resistance and mechanical properties when grown at low TSub. © 2011 American Vacuum Society.
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