777 research outputs found
An energy-stable time-integrator for phase-field models
We introduce a provably energy-stable time-integration method for general classes of phase-field models with polynomial potentials. We demonstrate how Taylor series expansions of the nonlinear terms present in the partial differential equations of these models can lead to expressions that guarantee energy-stability implicitly, which are second-order accurate in time. The spatial discretization relies on a mixed finite element formulation and isogeometric analysis. We also propose an adaptive time-stepping discretization that relies on a first-order backward approximation to give an error-estimator. This error estimator is accurate, robust, and does not require the computation of extra solutions to estimate the error. This methodology can be applied to any second-order accurate time-integration scheme. We present numerical examples in two and three spatial dimensions, which confirm the stability and robustness of the method. The implementation of the numerical schemes is done in PetIGA, a high-performance isogeometric analysis framework
Transcriptional analysis of Foxp3+ Tregs and functions of two identified molecules during resolution of ALI
Recovery from acute lung injury (ALI) is an active process. Foxp3+ Tregs contribute to recovery from ALI through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair. The current study investigates Treg transcriptional profiles during resolution of ALI in mice. Tregs from either lung or splenic tissue were isolated from uninjured mice or mice recovering from ALI and then examined for differential gene expression between these conditions. In mice with ALI, Tregs isolated from the lungs had hundreds of differentially expressed transcripts compared with those from the spleen, indicating that organ specificity and microenvironment are critical in Treg function. These regulated transcripts suggest which intracellular signaling pathways modulate Treg behavior. Interestingly, several transcripts having no prior recognized function in Tregs were differentially expressed by lung Tregs during resolution. Further investigation into 2 identified transcripts, Mmp12 and Sik1, revealed that Treg-specific expression of each plays a role in Treg-promoted ALI resolution. This study provides potentially novel information describing the signals that may expand resident Tregs, recruit or retain them to the lung during ALI, and modulate their function. The results provide insight into both tissue- and immune microenvironmentâspecific transcriptional differences through which Tregs direct their effects
Deterministic and stochastic descriptions of gene expression dynamics
A key goal of systems biology is the predictive mathematical description of
gene regulatory circuits. Different approaches are used such as deterministic
and stochastic models, models that describe cell growth and division explicitly
or implicitly etc. Here we consider simple systems of unregulated
(constitutive) gene expression and compare different mathematical descriptions
systematically to obtain insight into the errors that are introduced by various
common approximations such as describing cell growth and division by an
effective protein degradation term. In particular, we show that the population
average of protein content of a cell exhibits a subtle dependence on the
dynamics of growth and division, the specific model for volume growth and the
age structure of the population. Nevertheless, the error made by models with
implicit cell growth and division is quite small. Furthermore, we compare
various models that are partially stochastic to investigate the impact of
different sources of (intrinsic) noise. This comparison indicates that
different sources of noise (protein synthesis, partitioning in cell division)
contribute comparable amounts of noise if protein synthesis is not or only
weakly bursty. If protein synthesis is very bursty, the burstiness is the
dominant noise source, independent of other details of the model. Finally, we
discuss two sources of extrinsic noise: cell-to-cell variations in protein
content due to cells being at different stages in the division cycles, which we
show to be small (for the protein concentration and, surprisingly, also for the
protein copy number per cell) and fluctuations in the growth rate, which can
have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012
Effective theory of the Delta(1232) in Compton scattering off the nucleon
We formulate a new power-counting scheme for a chiral effective field theory
of nucleons, pions, and Deltas. This extends chiral perturbation theory into
the Delta-resonance region. We calculate nucleon Compton scattering up to
next-to-leading order in this theory. The resultant description of existing
p cross section data is very good for photon energies up to about 300
MeV. We also find reasonable numbers for the spin-independent polarizabilities
and .Comment: 29 pp, 9 figs. Minor revisions. To be published in PR
Approach to ergodicity in quantum wave functions
According to theorems of Shnirelman and followers, in the semiclassical limit
the quantum wavefunctions of classically ergodic systems tend to the
microcanonical density on the energy shell. We here develop a semiclassical
theory that relates the rate of approach to the decay of certain classical
fluctuations. For uniformly hyperbolic systems we find that the variance of the
quantum matrix elements is proportional to the variance of the integral of the
associated classical operator over trajectory segments of length , and
inversely proportional to , where is the Heisenberg
time, being the mean density of states. Since for these systems the
classical variance increases linearly with , the variance of the matrix
elements decays like . For non-hyperbolic systems, like Hamiltonians
with a mixed phase space and the stadium billiard, our results predict a slower
decay due to sticking in marginally unstable regions. Numerical computations
supporting these conclusions are presented for the bakers map and the hydrogen
atom in a magnetic field.Comment: 11 pages postscript and 4 figures in two files, tar-compressed and
uuencoded using uufiles, to appear in Phys Rev E. For related papers, see
http://www.icbm.uni-oldenburg.de/icbm/kosy/ag.htm
RAS/MAPK activation is associated with reduced Tumor-infiltrating lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
PURPOSE:
Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking.
EXPERIMENTAL DESIGN:
We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer.
RESULTS:
Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras-MAPK signaling were significantly correlated with lower TILs. MEK inhibition upregulated cell surface MHC expression and PD-L1 in TNBC cells both in vivo and in vitro. Moreover, combined MEK and PD-L1/PD-1 inhibition enhanced antitumor immune responses in mouse models of breast cancer.
CONCLUSIONS:
These data suggest the possibility that Ras-MAPK pathway activation promotes immune-evasion in TNBC, and support clinical trials combining MEK- and PD-L1-targeted therapies. Furthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors
Virtual Compton Scattering and Neutral Pion Electroproduction in the Resonance Region up to the Deep Inelastic Region at Backward Angles
We have made the first measurements of the virtual Compton scattering (VCS)
process via the H exclusive reaction in the nucleon resonance
region, at backward angles. Results are presented for the -dependence at
fixed GeV, and for the -dependence at fixed near 1.5 GeV.
The VCS data show resonant structures in the first and second resonance
regions. The observed -dependence is smooth. The measured ratio of
H to H cross sections emphasizes the different
sensitivity of these two reactions to the various nucleon resonances. Finally,
when compared to Real Compton Scattering (RCS) at high energy and large angles,
our VCS data at the highest (1.8-1.9 GeV) show a striking -
independence, which may suggest a transition to a perturbative scattering
mechanism at the quark level.Comment: 20 pages, 8 figures. To appear in Phys.Rev.
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
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