The efficient generation of multi-cycle coherent THz radiation is ofprimary importance to drive n... more The efficient generation of multi-cycle coherent THz radiation is ofprimary importance to drive novel table-top FELs. We explore thecascaded OPA, a new regime of OPA. We start from a home-builtYb:YLF amplifier at 1017-1020 nm temporally chirped to 800-ps. Wegenerate intra-band DFG in a PPLN crystal phase matched for 0.5THz. The interaction of the IR pulses with the THz pulses producesseveral spectrally cascaded orders, allowing for the generation of THzradiation beyond the Manley-Rowe limit. This technique promises IRto-THz conversion efficiencies in the order of 1-10%. After studying thesystem at room temperature, we explored the case of a crystal at 77 K,which provides much lower THz absorption. The experimental resultssupport the theoretical findings, and reveal that improvements in laserbandwidth and dispersion will lead to the calculated efficiencies.
Understanding the formation of massive stars is one of the unsolved problems in modern astronomy.... more Understanding the formation of massive stars is one of the unsolved problems in modern astronomy. The main difficulty is that the intense radiation from the high-luminosity stars and the thermal pressure from the resulting ionized gas (both insignificant for low-mass stars) may be able to reverse the accretion flow and prevent the star from accreting fresh material. Such feedback effects can naturally be mitigated if accretion proceeds through discs, which is the established mechanism to form sun-like stars. However, recent 3D MHD simulations have shown that accretion on 1000 au scales is through filaments rather than a large disc. This theoretical prediction has never been confirmed via observations owing to the poor linear resolution of previous studies (>1000 au). Here we present the first observational evidence that mass assembly in young high-mass stars forming in protoclusters is predominantly asymmetric and disordered. In particular, we observed the innermost regions aroun...
Cancer evolution is driven by natural selection acting upon phenotypic trait variation. However, ... more Cancer evolution is driven by natural selection acting upon phenotypic trait variation. However, the extent to which phenotypic variation within a tumour is a consequence of intra-tumour genetic heterogeneity remains undetermined. Here we show that colorectal cancer cells frequently have highly plastic phenotypic traitsin vivoin patient tumours. We measured the degree to which trait variation reflects genetic ancestry by quantifying the phylogenetic signal of gene expression across 297 samples with multi-region paired whole genome and transcriptome sequencing collected from 27 primary colorectal cancers. Within-tumour phylogenetic signal for genes and pathways was detected only infrequently, suggesting that the majority of intra-tumour variation in gene expression programmes was not strongly heritable. Expression quantitative trait loci analyses (eQTL) identified a small number of putative mechanisms of genetic control of gene expression due to thecis-acting coding, non-coding and s...
We present high spatial resolution (52 au) observations of the high-mass young stellar object (HM... more We present high spatial resolution (52 au) observations of the high-mass young stellar object (HMYSO) G345.4938+01.4677 made using the Atacama Large Millimeter/submillimeter Array. This O-type HMYSO is located at 2.38 kpc and is associated with a luminosity of 1.5 × 105 L ☉. We detect circumstellar emission from the H38β hydrogen recombination line showing a compact structure rotating perpendicularly to the previously detected radio jet. We interpret this emission as tracing a photoionized accretion disk around the HMYSO. While this disk-like structure seems currently too small to sustain continued accretion, the data present direct observational evidence of how disks can effectively survive the photoionization feedback from young high-mass stars. We also report the detection of a low-mass young stellar object in the vicinity of the HMYSO and suggest that it forms a high-mass and low-mass star binary system.
Natural selection shapes cancer genomes. Previous studies used signatures of positive selection t... more Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic. Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly con...
Tumors are composed of an evolving population of cells subjected to tissue-specific selection, wh... more Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian model for driver prediction. We demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolu...
A cryogenically cooled Yb:YAG amplifier with 4.7-ps laser pulses is employed to generate 100-GHz ... more A cryogenically cooled Yb:YAG amplifier with 4.7-ps laser pulses is employed to generate 100-GHz pulses in lithium niobate via optical rectification. We obtained a high efficiency ~0.05% at 300 K, close to the theoretical prediction.
The efficient generation of multi-cycle coherent THz radiation is ofprimary importance to drive n... more The efficient generation of multi-cycle coherent THz radiation is ofprimary importance to drive novel table-top FELs. We explore thecascaded OPA, a new regime of OPA. We start from a home-builtYb:YLF amplifier at 1017-1020 nm temporally chirped to 800-ps. Wegenerate intra-band DFG in a PPLN crystal phase matched for 0.5THz. The interaction of the IR pulses with the THz pulses producesseveral spectrally cascaded orders, allowing for the generation of THzradiation beyond the Manley-Rowe limit. This technique promises IRto-THz conversion efficiencies in the order of 1-10%. After studying thesystem at room temperature, we explored the case of a crystal at 77 K,which provides much lower THz absorption. The experimental resultssupport the theoretical findings, and reveal that improvements in laserbandwidth and dispersion will lead to the calculated efficiencies.
Understanding the formation of massive stars is one of the unsolved problems in modern astronomy.... more Understanding the formation of massive stars is one of the unsolved problems in modern astronomy. The main difficulty is that the intense radiation from the high-luminosity stars and the thermal pressure from the resulting ionized gas (both insignificant for low-mass stars) may be able to reverse the accretion flow and prevent the star from accreting fresh material. Such feedback effects can naturally be mitigated if accretion proceeds through discs, which is the established mechanism to form sun-like stars. However, recent 3D MHD simulations have shown that accretion on 1000 au scales is through filaments rather than a large disc. This theoretical prediction has never been confirmed via observations owing to the poor linear resolution of previous studies (>1000 au). Here we present the first observational evidence that mass assembly in young high-mass stars forming in protoclusters is predominantly asymmetric and disordered. In particular, we observed the innermost regions aroun...
Cancer evolution is driven by natural selection acting upon phenotypic trait variation. However, ... more Cancer evolution is driven by natural selection acting upon phenotypic trait variation. However, the extent to which phenotypic variation within a tumour is a consequence of intra-tumour genetic heterogeneity remains undetermined. Here we show that colorectal cancer cells frequently have highly plastic phenotypic traitsin vivoin patient tumours. We measured the degree to which trait variation reflects genetic ancestry by quantifying the phylogenetic signal of gene expression across 297 samples with multi-region paired whole genome and transcriptome sequencing collected from 27 primary colorectal cancers. Within-tumour phylogenetic signal for genes and pathways was detected only infrequently, suggesting that the majority of intra-tumour variation in gene expression programmes was not strongly heritable. Expression quantitative trait loci analyses (eQTL) identified a small number of putative mechanisms of genetic control of gene expression due to thecis-acting coding, non-coding and s...
We present high spatial resolution (52 au) observations of the high-mass young stellar object (HM... more We present high spatial resolution (52 au) observations of the high-mass young stellar object (HMYSO) G345.4938+01.4677 made using the Atacama Large Millimeter/submillimeter Array. This O-type HMYSO is located at 2.38 kpc and is associated with a luminosity of 1.5 × 105 L ☉. We detect circumstellar emission from the H38β hydrogen recombination line showing a compact structure rotating perpendicularly to the previously detected radio jet. We interpret this emission as tracing a photoionized accretion disk around the HMYSO. While this disk-like structure seems currently too small to sustain continued accretion, the data present direct observational evidence of how disks can effectively survive the photoionization feedback from young high-mass stars. We also report the detection of a low-mass young stellar object in the vicinity of the HMYSO and suggest that it forms a high-mass and low-mass star binary system.
Natural selection shapes cancer genomes. Previous studies used signatures of positive selection t... more Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic. Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly con...
Tumors are composed of an evolving population of cells subjected to tissue-specific selection, wh... more Tumors are composed of an evolving population of cells subjected to tissue-specific selection, which fuels tumor heterogeneity and ultimately complicates cancer driver gene identification. Here, we integrate cancer cell fraction, population recurrence, and functional impact of somatic mutations as signatures of selection into a Bayesian model for driver prediction. We demonstrate that our model, cDriver, outperforms competing methods when analyzing solid tumors, hematological malignancies, and pan-cancer datasets. Applying cDriver to exome sequencing data of 21 cancer types from 6,870 individuals revealed 98 unreported tumor type-driver gene connections. These novel connections are highly enriched for chromatin-modifying proteins, hinting at a universal role of chromatin regulation in cancer etiology. Although infrequently mutated as single genes, we show that chromatin modifiers are altered in a large fraction of cancer patients. In summary, we demonstrate that integration of evolu...
A cryogenically cooled Yb:YAG amplifier with 4.7-ps laser pulses is employed to generate 100-GHz ... more A cryogenically cooled Yb:YAG amplifier with 4.7-ps laser pulses is employed to generate 100-GHz pulses in lithium niobate via optical rectification. We obtained a high efficiency ~0.05% at 300 K, close to the theoretical prediction.
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