484 research outputs found
Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes
Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors
Molecular-orbital theory for the stopping power of atoms in the low velocity regime:the case of helium in alkali metals
A free-parameter linear-combination-of-atomic-orbitals approach is presented
for analyzing the stopping power of slow ions moving in a metal. The method is
applied to the case of He moving in alkali metals. Mean stopping powers for He
present a good agreement with local-density-approximation calculations. Our
results show important variations in the stopping power of channeled atoms with
respect to their mean values.Comment: LATEX, 3 PostScript Figures attached. Total size 0.54
Virus shapes and buckling transitions in spherical shells
We show that the icosahedral packings of protein capsomeres proposed by
Caspar and Klug for spherical viruses become unstable to faceting for
sufficiently large virus size, in analogy with the buckling instability of
disclinations in two-dimensional crystals. Our model, based on the nonlinear
physics of thin elastic shells, produces excellent one parameter fits in real
space to the full three-dimensional shape of large spherical viruses. The
faceted shape depends only on the dimensionless Foppl-von Karman number
\gamma=YR^2/\kappa, where Y is the two-dimensional Young's modulus of the
protein shell, \kappa is its bending rigidity and R is the mean virus radius.
The shape can be parameterized more quantitatively in terms of a spherical
harmonic expansion. We also investigate elastic shell theory for extremely
large \gamma, 10^3 < \gamma < 10^8, and find results applicable to icosahedral
shapes of large vesicles studied with freeze fracture and electron microscopy.Comment: 11 pages, 12 figure
Competition between Pauli and orbital effects in a charge-density wave system
We present angular dependent magneto-transport and magnetization measurements
on alpha-(ET)2MHg(SCN)4 compounds at high magnetic fields and low temperatures.
We find that the low temperature ground state undergoes two subsequent
field-induced density-wave type phase transitions above a critical angle of the
magnetic field with respect to the crystallographic axes. This new phase
diagram may be qualitatively described assuming a charge density wave ground
state which undergoes field-induced transitions due to the interplay of Pauli
and orbital effects.Comment: 11 pages, 4 figures, shown at the APS march meeting 2000, appears in
the Ph.D. thesis of J. S. Qualls (Florida State University, 1999), and
submitted to PR
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A multilevel neo-institutional analysis of infection prevention and control in English hospitals: coerced safety culture change?
Despite committed policy, regulative and professional efforts on healthcare safety, little is known about how such macro-interventions permeate organisations and shape culture over time. Informed by neo-institutional theory, we examined how inter-organisational influences shaped safety practices and inter-subjective meanings following efforts for coerced culture change. We traced macro-influences from 2000 to 2015 in infection prevention and control (IPC). Safety perceptions and meanings were inductively analysed from 130 in-depth qualitative interviews with senior- and middle-level managers from 30 English hospitals. A total of 869 institutional interventions were identified; 69% had a regulative component. In this context of forced implementation of safety practices, staff experienced inherent tensions concerning the scope of safety, their ability to be open and prioritisation of external mandates over local need. These tensions stemmed from conflicts among three co-existing institutional logics prevalent in the NHS. In response to requests for change, staff flexibly drew from a repertoire of cognitive, material and symbolic resources within and outside their organisations. They crafted 'strategies of action', guided by a situated assessment of first-hand practice experiences complementing collective evaluations of interventions such as 'pragmatic', 'sensible' and also 'legitimate'. Macro-institutional forces exerted influence either directly on individuals or indirectly by enriching the organisational cultural repertoire
A theorem proving framework for the formal verification of Web Services Composition
We present a rigorous framework for the composition of Web Services within a
higher order logic theorem prover. Our approach is based on the
proofs-as-processes paradigm that enables inference rules of Classical Linear
Logic (CLL) to be translated into pi-calculus processes. In this setting,
composition is achieved by representing available web services as CLL
sentences, proving the requested composite service as a conjecture, and then
extracting the constructed pi-calculus term from the proof. Our framework,
implemented in HOL Light, not only uses an expressive logic that allows us to
incorporate multiple Web Services properties in the composition process, but
also provides guarantees of soundness and correctness for the composition.Comment: In Proceedings WWV 2011, arXiv:1108.208
Cofactorization on Graphics Processing Units
We show how the cofactorization step, a compute-intensive part of the relation collection phase of the number field sieve (NFS), can be farmed out to a graphics processing unit. Our implementation on a GTX 580 GPU, which is integrated with a state-of-the-art NFS implementation, can serve as a cryptanalytic co-processor for several Intel i7-3770K quad-core CPUs simultaneously. This allows those processors to focus on the memory-intensive sieving and results in more useful NFS-relations found in less time
Demonstration of a novel technique to measure two-photon exchange effects in elastic scattering
The discrepancy between proton electromagnetic form factors extracted using
unpolarized and polarized scattering data is believed to be a consequence of
two-photon exchange (TPE) effects. However, the calculations of TPE corrections
have significant model dependence, and there is limited direct experimental
evidence for such corrections. We present the results of a new experimental
technique for making direct comparisons, which has the potential to
make precise measurements over a broad range in and scattering angles. We
use the Jefferson Lab electron beam and the Hall B photon tagger to generate a
clean but untagged photon beam. The photon beam impinges on a converter foil to
generate a mixed beam of electrons, positrons, and photons. A chicane is used
to separate and recombine the electron and positron beams while the photon beam
is stopped by a photon blocker. This provides a combined electron and positron
beam, with energies from 0.5 to 3.2 GeV, which impinges on a liquid hydrogen
target. The large acceptance CLAS detector is used to identify and reconstruct
elastic scattering events, determining both the initial lepton energy and the
sign of the scattered lepton. The data were collected in two days with a
primary electron beam energy of only 3.3 GeV, limiting the data from this run
to smaller values of and scattering angle. Nonetheless, this measurement
yields a data sample for with statistics comparable to those of the
best previous measurements. We have shown that we can cleanly identify elastic
scattering events and correct for the difference in acceptance for electron and
positron scattering. The final ratio of positron to electron scattering:
for GeV and
Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events
The - oscillation frequency has been measured with a sample of
23 million \B\bar B pairs collected with the BABAR detector at the PEP-II
asymmetric B Factory at SLAC. In this sample, we select events in which both B
mesons decay semileptonically and use the charge of the leptons to identify the
flavor of each B meson. A simultaneous fit to the decay time difference
distributions for opposite- and same-sign dilepton events gives ps.Comment: 7 pages, 1 figure, submitted to Physical Review Letter
Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum
We report a first measurement for ultra-high energy cosmic rays of the
correlation between the depth of shower maximum and the signal in the water
Cherenkov stations of air-showers registered simultaneously by the fluorescence
and the surface detectors of the Pierre Auger Observatory. Such a correlation
measurement is a unique feature of a hybrid air-shower observatory with
sensitivity to both the electromagnetic and muonic components. It allows an
accurate determination of the spread of primary masses in the cosmic-ray flux.
Up till now, constraints on the spread of primary masses have been dominated by
systematic uncertainties. The present correlation measurement is not affected
by systematics in the measurement of the depth of shower maximum or the signal
in the water Cherenkov stations. The analysis relies on general characteristics
of air showers and is thus robust also with respect to uncertainties in
hadronic event generators. The observed correlation in the energy range around
the `ankle' at differs significantly from
expectations for pure primary cosmic-ray compositions. A light composition made
up of proton and helium only is equally inconsistent with observations. The
data are explained well by a mixed composition including nuclei with mass . Scenarios such as the proton dip model, with almost pure compositions, are
thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray
flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report
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