2,867 research outputs found
Mathematical practice, crowdsourcing, and social machines
The highest level of mathematics has traditionally been seen as a solitary
endeavour, to produce a proof for review and acceptance by research peers.
Mathematics is now at a remarkable inflexion point, with new technology
radically extending the power and limits of individuals. Crowdsourcing pulls
together diverse experts to solve problems; symbolic computation tackles huge
routine calculations; and computers check proofs too long and complicated for
humans to comprehend.
Mathematical practice is an emerging interdisciplinary field which draws on
philosophy and social science to understand how mathematics is produced. Online
mathematical activity provides a novel and rich source of data for empirical
investigation of mathematical practice - for example the community question
answering system {\it mathoverflow} contains around 40,000 mathematical
conversations, and {\it polymath} collaborations provide transcripts of the
process of discovering proofs. Our preliminary investigations have demonstrated
the importance of "soft" aspects such as analogy and creativity, alongside
deduction and proof, in the production of mathematics, and have given us new
ways to think about the roles of people and machines in creating new
mathematical knowledge. We discuss further investigation of these resources and
what it might reveal.
Crowdsourced mathematical activity is an example of a "social machine", a new
paradigm, identified by Berners-Lee, for viewing a combination of people and
computers as a single problem-solving entity, and the subject of major
international research endeavours. We outline a future research agenda for
mathematics social machines, a combination of people, computers, and
mathematical archives to create and apply mathematics, with the potential to
change the way people do mathematics, and to transform the reach, pace, and
impact of mathematics research.Comment: To appear, Springer LNCS, Proceedings of Conferences on Intelligent
Computer Mathematics, CICM 2013, July 2013 Bath, U
A stagewise response to mitochondrial dysfunction in mitochondrial DNA maintenance disorders
\ua9 2024 The AuthorsMitochondrial DNA (mtDNA) deletions which clonally expand in skeletal muscle of patients with mtDNA maintenance disorders, impair mitochondrial oxidative phosphorylation dysfunction. Previously we have shown that these mtDNA deletions arise and accumulate in perinuclear mitochondria causing localised mitochondrial dysfunction before spreading through the muscle fibre. We believe that mito-nuclear signalling is a key contributor in the accumulation and spread of mtDNA deletions, and that knowledge of how muscle fibres respond to mitochondrial dysfunction is key to our understanding of disease mechanisms. To understand the contribution of mito-nuclear signalling to the spread of mitochondrial dysfunction, we use imaging mass cytometry. We characterise the levels of mitochondrial Oxidative Phosphorylation proteins alongside a mitochondrial mass marker, in a cohort of patients with mtDNA maintenance disorders. Our expanded panel included protein markers of key signalling pathways, allowing us to investigate cellular responses to different combinations of oxidative phosphorylation dysfunction and ragged red fibres. We find combined Complex I and IV deficiency to be most common. Interestingly, in fibres deficient for one or more complexes, the remaining complexes are often upregulated beyond the increase of mitochondrial mass typically observed in ragged red fibres. We further find that oxidative phosphorylation deficient fibres exhibit an increase in the abundance of proteins involved in proteostasis, e.g. HSP60 and LONP1, and regulation of mitochondrial metabolism (including oxidative phosphorylation and proteolysis, e.g. PHB1). Our analysis suggests that the cellular response to mitochondrial dysfunction changes depending on the combination of deficient oxidative phosphorylation complexes in each fibre
Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes
Proteasome-catalyzed peptide splicing represents an additional catalytic
activity of proteasomes contributing to the pool of MHC-class I-presented
epitopes. We here biochemically and functionally characterized a new melanoma
gp100 derived spliced epitope. We demonstrate that the gp100mel47–52/40–42
antigenic peptide is generated in vitro and in cellulo by a not yet described
proteasomal condensation reaction. gp100mel47–52/40–42 generation is enhanced
in the presence of the β5i/LMP7 proteasome-subunit and elicits a peptide-
specific CD8+ T cell response. Importantly, we demonstrate that different
gp100mel-derived spliced epitopes are generated and presented to CD8+ T cells
with efficacies comparable to non-spliced canonical tumor epitopes and that
gp100mel-derived spliced epitopes trigger activation of CD8+ T cells found in
peripheral blood of half of the melanoma patients tested. Our data suggest
that both transpeptidation and condensation reactions contribute to the
frequent generation of spliced epitopes also in vivo and that their immune
relevance may be comparable to non-spliced epitopes
Feasibility studies of the time-like proton electromagnetic form factor measurements with PANDA at FAIR
The possibility of measuring the proton electromagnetic form factors in the
time-like region at FAIR with the \PANDA detector is discussed. Detailed
simulations on signal efficiency for the annihilation of into a
lepton pair as well as for the most important background channels have been
performed. It is shown that precision measurements of the differential cross
section of the reaction can be obtained in a wide
angular and kinematical range. The individual determination of the moduli of
the electric and magnetic proton form factors will be possible up to a value of
momentum transfer squared of (GeV/c). The total cross section will be measured up to (GeV/c).
The results obtained from simulated events are compared to the existing data.
Sensitivity to the two photons exchange mechanism is also investigated.Comment: 12 pages, 4 tables, 8 figures Revised, added details on simulations,
4 tables, 9 figure
Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR
Simulation results for future measurements of electromagnetic proton form
factors at \PANDA (FAIR) within the PandaRoot software framework are reported.
The statistical precision with which the proton form factors can be determined
is estimated. The signal channel is studied on the basis
of two different but consistent procedures. The suppression of the main
background channel, , is studied.
Furthermore, the background versus signal efficiency, statistical and
systematical uncertainties on the extracted proton form factors are evaluated
using two different procedures. The results are consistent with those of a
previous simulation study using an older, simplified framework. However, a
slightly better precision is achieved in the PandaRoot study in a large range
of momentum transfer, assuming the nominal beam conditions and detector
performance
First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data
Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of
continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a
fully coherent search, based on matched filtering, which uses the position and rotational parameters
obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto-
noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch
between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have
been developed, allowing a fully coherent search for gravitational waves from known pulsars over a
fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of
11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial
outliers, further studies show no significant evidence for the presence of a gravitational wave signal.
Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of
the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for
the first time. For an additional 3 targets, the median upper limit across the search bands is below the
spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried
out so far
The COMPASS Experiment at CERN
The COMPASS experiment makes use of the CERN SPS high-intensitymuon and
hadron beams for the investigation of the nucleon spin structure and the
spectroscopy of hadrons. One or more outgoing particles are detected in
coincidence with the incoming muon or hadron. A large polarized target inside a
superconducting solenoid is used for the measurements with the muon beam.
Outgoing particles are detected by a two-stage, large angle and large momentum
range spectrometer. The setup is built using several types of tracking
detectors, according to the expected incident rate, required space resolution
and the solid angle to be covered. Particle identification is achieved using a
RICH counter and both hadron and electromagnetic calorimeters. The setup has
been successfully operated from 2002 onwards using a muon beam. Data with a
hadron beam were also collected in 2004. This article describes the main
features and performances of the spectrometer in 2004; a short summary of the
2006 upgrade is also given.Comment: 84 papes, 74 figure
Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector
A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino
Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector
A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13 TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV
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