81 research outputs found
Closed strings in Misner space: a toy model for a Big Bounce ?
Misner space, also known as the Lorentzian orbifold , is one
of the simplest examples of a cosmological singularity in string theory. In
this lecture, we review the semi-classical propagation of closed strings in
this background, with a particular emphasis on the twisted sectors of the
orbifold. Tree-level scattering amplitudes and the one-loop vacuum amplitude
are also discussed.Comment: 30 pages, 3 figures, to appear in the Proceedings of the NATO ASI and
EC Summer School ``String Theory: from Gauge Interactions to Cosmology'',
Cargese, France, June 7-19, 200
Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation
The current status of electric dipole moments of diamagnetic atoms which
involves the synergy between atomic experiments and three different theoretical
areas -- particle, nuclear and atomic is reviewed. Various models of particle
physics that predict CP violation, which is necessary for the existence of such
electric dipole moments, are presented. These include the standard model of
particle physics and various extensions of it. Effective hadron level combined
charge conjugation (C) and parity (P) symmetry violating interactions are
derived taking into consideration different ways in which a nucleon interacts
with other nucleons as well as with electrons. Nuclear structure calculations
of the CP-odd nuclear Schiff moment are discussed using the shell model and
other theoretical approaches. Results of the calculations of atomic electric
dipole moments due to the interaction of the nuclear Schiff moment with the
electrons and the P and time-reversal (T) symmetry violating
tensor-pseudotensor electron-nucleus are elucidated using different
relativistic many-body theories. The principles of the measurement of the
electric dipole moments of diamagnetic atoms are outlined. Upper limits for the
nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained
combining the results of atomic experiments and relativistic many-body
theories. The coefficients for the different sources of CP violation have been
estimated at the elementary particle level for all the diamagnetic atoms of
current experimental interest and their implications for physics beyond the
standard model is discussed. Possible improvements of the current results of
the measurements as well as quantum chromodynamics, nuclear and atomic
calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for
EPJ
Flow-based pipeline for systematic modulation and analysis of 3D tumor microenvironments
The cancer microenvironment, which incorporates interactions with stromal cells, extracellular matrix (ECM), and other tumor cells in a 3-dimensional (3D) context, has been implicated in every stage of cancer development, including growth of the primary tumor, metastatic spread, and response to treatment. Our understanding of the tumor microenvironment and our ability to develop new therapies would greatly benefit from tools that allow us to systematically probe microenvironmental cues within a 3D context. Here, we leveraged recent advances in microfluidic technology to develop a platform for high-throughput fabrication of tunable cellular microniches (“microtissues”) that allow us to probe tumor cell response to a range of microenvironmental cues, including ECM, soluble factors, and stromal cells, all in 3D. We further combine this tunable microniche platform with rapid, flow-based population level analysis (n > 500), which permits analysis and sorting of microtissue populations both pre- and post-culture by a range of parameters, including proliferation and homotypic or heterotypic cell density. We used this platform to demonstrate differential responses of lung adenocarcinoma cells to a selection of ECM molecules and soluble factors. The cells exhibited enhanced or reduced proliferation when encapsulated in fibronectin- or collagen-1-containing microtissues, respectively, and they showed reduced proliferation in the presence of TGF-β, an effect that we did not observe in monolayer culture. We also measured tumor cell response to a panel of drug targets and found, in contrast to monolayer culture, specific sensitivity of tumor cells to TGFβR2 inhibitors, implying that TGF-β has an anti-proliferative affect that is unique to the 3D context and that this effect is mediated by TGFβR2. These findings highlight the importance of the microenvironmental context in therapeutic development and that the platform we present here allows the high-throughput study of tumor response to drugs as well as basic tumor biology in well-defined microenvironmental niches.American Association for Cancer Research (Stand Up to Cancer Charitable Initiative)National Institute for Biomedical Imaging and Bioengineering (U.S.) (National Research Service Award Fellowship)National Science Foundation (U.S.) (Graduate Research Fellowship Program Grant 1122374)Howard Hughes Medical Institut
Full Factorial Analysis of Mammalian and Avian Influenza Polymerase Subunits Suggests a Role of an Efficient Polymerase for Virus Adaptation
Amongst all the internal gene segments (PB2. PB1, PA, NP, M and NS), the avian PB1 segment is the only one which was reassorted into the human H2N2 and H3N2 pandemic strains. This suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. To test this hypothesis, we tested the compatibility between PB2, PB1, PA and NP derived from a H5N1 virus and a mammalian H1N1 virus. All 16 possible combinations of avian-mammalian chimeric viral ribonucleoproteins (vRNPs) were characterized. We showed that recombinant vRNPs with a mammalian PB2 and an avian PB1 had the strongest polymerase activities in human cells at all studied temperature. In addition, viruses with this specific PB2-PB1 combination could grow efficiently in cell cultures, especially at a high incubation temperature. These viruses were potent inducers of proinflammatory cytokines and chemokines in primary human macrophages and pneumocytes. Viruses with this specific PB2-PB1 combination were also found to be more capable to generate adaptive mutations under a new selection pressure. These results suggested that the viral polymerase activity might be relevant for the genesis of influenza viruses of human health concern
Planck 2013 results. XXII. Constraints on inflation
We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0:9603 _ 0:0073, ruling out exact scale invariance at over 5_: Planck establishes an upper bound on the tensor-to-scalar ratio of r < 0:11 (95% CL). The Planck data thus shrink the space of allowed standard inflationary models, preferring potentials with V00 < 0. Exponential potential models, the simplest hybrid inflationary models, and monomial potential models of degree n _ 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns=dln k = 0:0134 _ 0:0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by __2 e_ _ 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the _2 e_ by approximately 4 as a result of slightly lowering the theoretical prediction for the ` <_ 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions
Status of low energy SUSY models confronted with the LHC 125 GeV Higgs data
Confronted with the LHC data of a Higgs boson around 125 GeV, different
models of low energy SUSY show different behaviors: some are favored, some are
marginally survived and some are strongly disfavored or excluded. In this note
we update our previous scan over the parameter space of various low energy SUSY
models by considering the latest experimental limits like the LHCb data for
B_s->\mu^+\mu^- and the XENON 100(2012) data for dark matter-neucleon
scattering. Then we confront the predicted properties of the SM-like Higgs
boson in each model with the combined 7 TeV and 8 TeV Higgs search data of the
LHC. For a SM-like Higgs boson around 125 GeV, we have the following
observations: (i) The most favored model is the NMSSM, whose predictions about
the Higgs boson can naturally (without any fine tuning) agree with the
experimental data at 1-sigma level, better than the SM; (ii) The MSSM can fit
the LHC data quite well but suffer from some extent of fine tuning; (iii) The
nMSSM is excluded at 3-sigma level after considering all the available Higgs
data; (iv) The CMSSM is quite disfavored since it is hard to give a 125 GeV
Higgs boson mass and at the same time cannot enhance the di-photon signal rate.Comment: more comprehensive (table and figs showing chi-square added
Small molecule compounds targeting the p53 pathway: are we finally making progress?
Loss of function of p53, either through mutations in the gene or through mutations to other members of the pathway that inactivate wild-type p53, remains a critically important aspect of human cancer development. As such, p53 remains the most commonly mutated gene in human cancer. For these reasons, pharmacologic activation of the p53 pathway has been a highly sought after, yet unachieved goal in developmental therapeutics. Recently progress has been made not only in the discovery of small molecules that target wild-type and mutant p53, but also in the initiation and completion of the first in-human clinical trials for several of these drugs. Here, we review the current literature of drugs that target wild-type and mutant p53 with a focus on small-molecule type compounds. We discuss common means of drug discovery and group them according to their common mechanisms of action. Lastly, we review the current status of the various drugs in the development process and identify newer areas of p53 tumor biology that may prove therapeutically useful
Simultaneous observations of PKS 2155-304 with H.E.S.S., Fermi, RXTE and ATOM: spectral energy distributions and variability in a low state
We report on the first simultaneous observations that cover the optical,
X-ray, and high energy gamma-ray bands of the BL Lac object PKS 2155-304. The
gamma-ray bands were observed for 11 days, between 25 August and 6 September
2008, jointly with the Fermi Gamma-ray Space Telescope and the H.E.S.S.
atmospheric Cherenkov array, providing the first simultaneous MeV-TeV spectral
energy distribution with the new generation of gamma-ray telescopes. The ATOM
telescope and the RXTE and Swift observatories provided optical and X-ray
coverage of the low-energy component over the same time period. The object was
close to the lowest archival X-ray and Very High Energy state, whereas the
optical flux was much higher. The light curves show relatively little (~30%$)
variability overall when compared to past flaring episodes, but we find a clear
optical/VHE correlation and evidence for a correlation of the X-rays with the
high energy spectral index. Contrary to previous observations in the flaring
state, we do not find any correlation between the X-ray and VHE components.
Although synchrotron self-Compton models are often invoked to explain the SEDs
of BL Lac objects, the most common versions of these models are at odds with
the correlated variability we find in the various bands for PKS 2155-304.Comment: Accepted for publication in the Astrophysical Journa
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