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Sökning: WFRF:(Heathcote P) > Tidskriftsartikel

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1.
  • Gusev, A, et al. (författare)
  • Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
  • 2016
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
  • Tidskriftsartikel (refereegranskat)abstract
    • Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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2.
  • Allum, F., et al. (författare)
  • A localized view on molecular dissociation via electron-ion partial covariance
  • 2022
  • Ingår i: Communications Chemistry. - : Springer Science and Business Media LLC. - 2399-3669. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Inner-shell photoelectron spectroscopy provides an element-specific probe of molecular structure, as core-electron binding energies are sensitive to the chemical environment. Short-wavelength femtosecond light sources, such as Free-Electron Lasers (FELs), even enable time-resolved site-specific investigations of molecular photochemistry. Here, we study the ultraviolet photodissociation of the prototypical chiral molecule 1-iodo-2-methylbutane, probed by extreme-ultraviolet (XUV) pulses from the Free-electron LASer in Hamburg (FLASH) through the ultrafast evolution of the iodine 4d binding energy. Methodologically, we employ electron-ion partial covariance imaging as a technique to isolate otherwise elusive features in a two-dimensional photoelectron spectrum arising from different photofragmentation pathways. The experimental and theoretical results for the time-resolved electron spectra of the 4d(3/2) and 4d(5/2) atomic and molecular levels that are disentangled by this method provide a key step towards studying structural and chemical changes from a specific spectator site. Coincidence experiments at free-electron lasers enable time resolved site-specific investigations of molecular photochemistry at high signal rates, but isolating individual dissociation processes still poses a considerable technical challenge. Here, the authors use electron-ion partial covariance imaging to isolate otherwise elusive chemical shifts in UV-induced photofragmentation pathways of the prototypical chiral molecule 1-iodo-2-methylbutane.
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5.
  • Garg, D., et al. (författare)
  • Fragmentation Dynamics of Fluorene Explored Using Ultrafast XUV-Vis Pump-Probe Spectroscopy
  • 2022
  • Ingår i: Frontiers in Physics. - : Frontiers Media SA. - 2296-424X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the use of extreme ultraviolet (XUV, 30.3 nm) radiation from the Free-electron LASer in Hamburg (FLASH) and visible (Vis, 405 nm) photons from an optical laser to investigate the relaxation and fragmentation dynamics of fluorene ions. The ultrashort laser pulses allow to resolve the molecular processes occurring on the femtosecond timescales. Fluorene is a prototypical small polycyclic aromatic hydrocarbon (PAH). Through their infrared emission signature, PAHs have been shown to be ubiquitous in the universe, and they are assumed to play an important role in the chemistry of the interstellar medium. Our experiments track the ionization and dissociative ionization products of fluorene through time-of-flight mass spectrometry and velocity-map imaging. Multiple processes involved in the formation of each of the fragment ions are disentangled through analysis of the ion images. The relaxation lifetimes of the excited fluorene monocation and dication obtained through the fragment formation channels are reported to be in the range of a few tens of femtoseconds to a few picoseconds.
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6.
  • Lee, J. W.L., et al. (författare)
  • Time-resolved relaxation and fragmentation of polycyclic aromatic hydrocarbons investigated in the ultrafast XUV-IR regime
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycyclic aromatic hydrocarbons (PAHs) play an important role in interstellar chemistry and are subject to high energy photons that can induce excitation, ionization, and fragmentation. Previous studies have demonstrated electronic relaxation of parent PAH monocations over 10-100 femtoseconds as a result of beyond-Born-Oppenheimer coupling between the electronic and nuclear dynamics. Here, we investigate three PAH molecules: fluorene, phenanthrene, and pyrene, using ultrafast XUV and IR laser pulses. Simultaneous measurements of the ion yields, ion momenta, and electron momenta as a function of laser pulse delay allow a detailed insight into the various molecular processes. We report relaxation times for the electronically excited PAH*, PAH(+*) and PAH(2+*) states, and show the time-dependent conversion between fragmentation pathways. Additionally, using recoil-frame covariance analysis between ion images, we demonstrate that the dissociation of the PAH(2+) ions favors reaction pathways involving two-body breakup and/or loss of neutral fragments totaling an even number of carbon atoms. Polycyclic aromatic hydrocarbons play an important role in interstellar chemistry, where interaction with high energy photons can induce ionization and fragmentation reactions. Here the authors, with XUV-IR pump-probe experiments, investigate the ultrafast photoinduced dynamics of fluorene, phenanthrene and pyrene, providing insight into their preferred reaction channels.
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7.
  • Lee, J. W. L., et al. (författare)
  • The kinetic energy of PAH dication and trication dissociation determined by recoil-frame covariance map imaging
  • 2022
  • Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 24:38, s. 23096-23105
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the dissociation of dications and trications of three polycyclic aromatic hydrocarbons (PAHs), fluorene, phenanthrene, and pyrene. PAHs are a family of molecules ubiquitous in space and involved in much of the chemistry of the interstellar medium. In our experiments, ions are formed by interaction with 30.3 nm extreme ultraviolet (XUV) photons, and their velocity map images are recorded using a PImMS2 multi-mass imaging sensor. Application of recoil-frame covariance analysis allows the total kinetic energy release (TKER) associated with multiple fragmentation channels to be determined to high precision, ranging 1.94-2.60 eV and 2.95-5.29 eV for the dications and trications, respectively. Experimental measurements are supported by Born-Oppenheimer molecular dynamics (BOMD) simulations.
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8.
  • Damineli, Augusto, et al. (författare)
  • The Long-term Spectral Changes of Eta Carinae : Are they Caused by a Dissipating Occulter as Indicated by CMFGEN Models?
  • 2023
  • Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954
  • Tidskriftsartikel (refereegranskat)abstract
    • Eta Carinae (η Car) exhibits a unique set of P Cygni profiles with both broad and narrow components. Over many decades, the spectrum has changed-there has been an increase in observed continuum fluxes and a decrease in Fe II and H I emission-line equivalent widths. The spectrum is evolving toward that of a P Cygni star such as P Cygni itself and HDE 316285. The spectral evolution has been attributed to intrinsic variations such as a decrease in the mass-loss rate of the primary star or differential evolution in a latitudinal-dependent stellar wind. However, intrinsic wind changes conflict with three observational results: the steady long-term bolometric luminosity; the repeating X-ray light curve over the binary period; and the constancy of the dust-scattered spectrum from the Homunculus. We extend previous work that showed a secular strengthening of P Cygni absorptions by adding more orbital cycles to overcome temporary instabilities and by examining more atomic transitions. CMFGEN modeling of the primary wind shows that a time-decreasing mass-loss rate is not the best explanation for the observations. However, models with a small dissipating absorber in our line of sight can explain both the increase in brightness and changes in the emission and P Cygni absorption profiles. If the spectral evolution is caused by the dissipating circumstellar medium, and not by intrinsic changes in the binary, the dynamical timescale to recover from the Great Eruption is much less than a century, different from previous suggestions.
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9.
  • Heathcote, Robert J P, et al. (författare)
  • Male behaviour drives assortative reproduction during the initial stage of secondary contact.
  • 2016
  • Ingår i: Journal of evolutionary biology. - : Wiley. - 1420-9101 .- 1010-061X. ; 29:5, s. 1003-1015
  • Tidskriftsartikel (refereegranskat)abstract
    • Phenotypic divergence in allopatry can facilitate speciation by reducing the likelihood that individuals of different lineages hybridise during secondary contact. However, few studies have established the causes of reproductive isolation in the crucial early stages of secondary contact. Here we establish behavioural causes of assortative reproduction between two phenotypically divergent lineages of the European wall lizard (Podarcis muralis), which have recently come into secondary contact. Parentage was highly assortative in experimental contact zones. However, despite pronounced divergence in male phenotypes, including chemical and visual sexual signals, there was no evidence that females discriminated between males of the two lineages in staged interactions or under naturalistic free-ranging conditions. Instead, assortative reproduction was driven by male mate preferences and, to a lesser extent, male-male competition. The effects were more pronounced when the habitat structure promoted high lizard densities. These results emphasize that assortative reproduction can occur in the absence of female choice, and that male behaviour may play an important role in limiting hybridisation during the initial stages of secondary contact. This article is protected by copyright. All rights reserved.
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10.
  • Heathcote, Robert J. P., et al. (författare)
  • The scent of sun worship: basking experience alters scent mark composition in male lizards
  • 2014
  • Ingår i: Behavioral Ecology and Sociobiology. - : Springer Science and Business Media LLC. - 1432-0762 .- 0340-5443. ; 68:5, s. 861-870
  • Tidskriftsartikel (refereegranskat)abstract
    • Signals used in female choice should honestly advertise the benefits that males can provide, with direct benefits often argued as being more important than indirect benefits. However, the nature of direct benefits in species without paternal care or nuptial gifts is poorly understood. Previous studies on lizards suggest that females decide where to settle and assumedly who to mate with based on information contained in scent marks from territorial males. Access to high-quality thermal resources is crucial for female reproductive success. Females may therefore be able to detect and exploit thermal-induced variation in the chemical composition of male scent marks when assessing the quality of his territory. We show that the amount of time male wall lizards (Podarcis muralis) are allowed to bask significantly alters the chemical composition of their femoral secretions used in scent marking. The direction of the change is consistent with adaptive plasticity to maintain signalling efficacy under warm conditions that increase evaporation of femoral secretions. The compounds affected by basking experience included those previously associated with male quality or shown to mediate male-male competition in lizards. However, whilst female lizards could discriminate between scent marks of males that had experienced different basking conditions, they did not preferentially associate with the scent from males from high-quality thermal conditions. These results highlight the potential importance of a previously neglected environmental effect on chemical signalling. We suggest thermal effects may have significant consequences for scent-mark composition in variable environments, with potential repercussions on olfactory communication in lizards.
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