539 research outputs found
Fragile sites on human chromosomes - a personal odyssey
Unpublished paper. Uploaded with permission of Grant Sutherland 2020
Architecture of the Vibrio cholerae toxin-coregulated pilus machine revealed by electron cryotomography
Type IV pili (T4P) are filamentous appendages found on many Bacteria and Archaea. They are helical fibres of pilin proteins assembled by a multi-component macromolecular machine we call the basal body. Based on pilin features, T4P are classified into type IVa pili (T4aP) and type IVb pili (T4bP). T4aP are more widespread and are involved in cell motility, DNA transfer, host predation and electron transfer. T4bP are less prevalent and are mainly found in enteropathogenic bacteria, where they play key roles in host colonization. Following similar work on T4aP machines, here we use electron cryotomography to reveal the three-dimensional in situ structure of a T4bP machine in its piliated and non-piliated states. The specific machine we analyse is the Vibrio cholerae toxin-coregulated pilus machine (TCPM). Although only about half of the components of the TCPM show sequence homology to components of the previously analysed Myxococcus xanthus T4aP machine (T4aPM), we find that their structures are nevertheless remarkably similar. Based on homologies with components of the M. xanthus T4aPM and additional reconstructions of TCPM mutants in which the non-homologous proteins are individually deleted, we propose locations for all eight TCPM components within the complex. Non-homologous proteins in the T4aPM and TCPM are found to form similar structures, suggesting new hypotheses for their functions and evolutionary histories
Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids
Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann–Beller palladacycle was used to effect the key step during the synthesis of the natural products
Artemisinin Combination Therapies for Treatment of Uncomplicated Malaria in Uganda
OBJECTIVES: To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda. DESIGN: Randomized single-blind controlled trial. SETTING: Tororo, Uganda, an area of high-level malaria transmission. PARTICIPANTS: Children aged one to ten years with confirmed uncomplicated P. falciparum malaria. INTERVENTIONS: Amodiaquine + artesunate or artemether–lumefantrine. OUTCOME MEASURES: Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections. RESULTS: Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether–lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether–lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%–24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether–lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%–25.2%). Amodiaquine + artesunate and artemether–lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens. CONCLUSIONS: Amodiaquine + artesunate and artemether–lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether–lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated
Neutrinos below 100 TeV from the southern sky employing refined veto techniques to IceCube data
Many Galactic sources of gamma rays, such as supernova remnants, are expected
to produce neutrinos with a typical energy cutoff well below 100 TeV. For the
IceCube Neutrino Observatory located at the South Pole, the southern sky,
containing the inner part of the Galactic plane and the Galactic Center, is a
particularly challenging region at these energies, because of the large
background of atmospheric muons. In this paper, we present recent advancements
in data selection strategies for track-like muon neutrino events with energies
below 100 TeV from the southern sky. The strategies utilize the outer detector
regions as veto and features of the signal pattern to reduce the background of
atmospheric muons to a level which, for the first time, allows IceCube
searching for point-like sources of neutrinos in the southern sky at energies
between 100 GeV and several TeV in the muon neutrino charged current channel.
No significant clustering of neutrinos above background expectation was
observed in four years of data recorded with the completed IceCube detector.
Upper limits on the neutrino flux for a number of spectral hypotheses are
reported for a list of astrophysical objects in the southern hemisphere.Comment: 19 pages, 17 figures, 2 table
The IceCube Neutrino Observatory - Contributions to ICRC 2015 Part II: Atmospheric and Astrophysical Diffuse Neutrino Searches of All Flavors
Papers on atmospheric and astrophysical diffuse neutrino searches of all
flavors submitted to the 34th International Cosmic Ray Conference (ICRC 2015,
The Hague) by the IceCube Collaboration.Comment: 66 pages, 36 figures, Papers submitted to the 34th International
Cosmic Ray Conference, The Hague 2015, v2 has a corrected author lis
Advancing dendrochronological studies of fire in the United States
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Dendroecology is the science that dates tree rings to their exact calendar year of formation to study processes that influence forest ecology (e.g., Speer 2010 [1], Amoroso et al., 2017 [2]). Reconstruction of past fire regimes is a core application of dendroecology, linking fire history to population dynamics and climate effects on tree growth and survivorship. Since the early 20th century when dendrochronologists recognized that tree rings retained fire scars (e.g., Figure 1), and hence a record of past fires, they have conducted studies worldwide to reconstruct [2] the historical range and variability of fire regimes (e.g., frequency, severity, seasonality, spatial extent), [3] the influence of fire regimes on forest structure and ecosystem dynamics, and [4] the top-down (e.g., climate) and bottom-up (e.g., fuels, topography) drivers of fire that operate at a range of temporal and spatial scales. As in other scientific fields, continued application of dendrochronological techniques to study fires has shaped new trajectories for the science. Here we highlight some important current directions in the United States (US) and call on our international colleagues to continue the conversation with perspectives from other countries
A combined maximum-likelihood analysis of the high-energy astrophysical neutrino flux measured with IceCube
Evidence for an extraterrestrial flux of high-energy neutrinos has now been
found in multiple searches with the IceCube detector. The first solid evidence
was provided by a search for neutrino events with deposited energies
TeV and interaction vertices inside the instrumented volume. Recent
analyses suggest that the extraterrestrial flux extends to lower energies and
is also visible with throughgoing, -induced tracks from the Northern
hemisphere. Here, we combine the results from six different IceCube searches
for astrophysical neutrinos in a maximum-likelihood analysis. The combined
event sample features high-statistics samples of shower-like and track-like
events. The data are fit in up to three observables: energy, zenith angle and
event topology. Assuming the astrophysical neutrino flux to be isotropic and to
consist of equal flavors at Earth, the all-flavor spectrum with neutrino
energies between 25 TeV and 2.8 PeV is well described by an unbroken power law
with best-fit spectral index and a flux at 100 TeV of
.
Under the same assumptions, an unbroken power law with index is disfavored
with a significance of 3.8 () with respect to the best
fit. This significance is reduced to 2.1 () if instead we
compare the best fit to a spectrum with index that has an exponential
cut-off at high energies. Allowing the electron neutrino flux to deviate from
the other two flavors, we find a fraction of at Earth.
The sole production of electron neutrinos, which would be characteristic of
neutron-decay dominated sources, is rejected with a significance of 3.6
().Comment: 16 pages, 10 figures; accepted for publication in The Astrophysical
Journal; updated one referenc
Characterization of the Atmospheric Muon Flux in IceCube
Muons produced in atmospheric cosmic ray showers account for the by far
dominant part of the event yield in large-volume underground particle
detectors. The IceCube detector, with an instrumented volume of about a cubic
kilometer, has the potential to conduct unique investigations on atmospheric
muons by exploiting the large collection area and the possibility to track
particles over a long distance. Through detailed reconstruction of energy
deposition along the tracks, the characteristics of muon bundles can be
quantified, and individual particles of exceptionally high energy identified.
The data can then be used to constrain the cosmic ray primary flux and the
contribution to atmospheric lepton fluxes from prompt decays of short-lived
hadrons.
In this paper, techniques for the extraction of physical measurements from
atmospheric muon events are described and first results are presented. The
multiplicity spectrum of TeV muons in cosmic ray air showers for primaries in
the energy range from the knee to the ankle is derived and found to be
consistent with recent results from surface detectors. The single muon energy
spectrum is determined up to PeV energies and shows a clear indication for the
emergence of a distinct spectral component from prompt decays of short-lived
hadrons. The magnitude of the prompt flux, which should include a substantial
contribution from light vector meson di-muon decays, is consistent with current
theoretical predictions.Comment: 36 pages, 39 figure
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