4,227 research outputs found
Localized magnetoplasmon modes arising from broken translational symmetry in semiconductor superlattices
The electromagnetic propagator associated with the localized collective
magnetoplasmon excitations in a semiconductor superlattice with broken
translational symmetry, is calculated analytically within linear response
theory. We discuss the properties of these collective excitations in both
radiative and non-radiative regimes of the electromagnetic spectra. We find
that low frequency retarded modes arise when the surface density of carriers at
the symmetry breaking layer is lower than the density at the remaining layers.
Otherwise a doublet of localized, high-frequency magnetoplasmon-like modes
occurs.Comment: Revtex file + separate pdf figure
Does a Theoretical Estimation of the Dust Size Distribution at Emission Suggest More Bioavailable Iron Deposition?
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95443/1/grl28895.pd
Turning Around the Sphaleron Bound: Electroweak Baryogenesis in an Alternative Post-inflationary Cosmology
The usual sphaleron bound and the statement of the impossibility of baryon
production at a second order phase transition or analytic cross-over are
reformulated in the first part of the paper as requirements of the expansion
rate of the Universe at the electroweak scale. With an (exact or effective)
additional contribution to the energy density scaling as 1/a^6, which dominates
until just before nucleosynthesis, the observed baryon asymmetry may be
produced at the electroweak scale in simple extensions of the Minimal Standard
Model, even in the case that the phase transition is not first order. We focus
our attention on one such cosmology, in which the Universe goes through a
period termed `kination' in which its energy is dominated by the kinetic energy
of a scalar field. The required kinetic energy dominated modes can occur either
as a field rolls down an exponential (or steeper) potential, or in the
oscillation of a field about the minimum of a steep power-law potential. We
implement in detail the former case with a single exponential field first
driving inflation, and then rolling into a kinetic energy dominated mode.
Reheating is achieved using an alternative to the usual mechanism due to
Spokoiny, in which the Universe is `reheated' by particle creation in the
expanding background. Density perturbations of the magnitude required for
structure formation may also be generated. We show that the analogous model for
the power-law potential cannot be consistently implemented. In models with
inflation driven by a second field and the usual mechanism of reheating (by
decay of the inflaton) the required kinetic energy dominated cosmology is
viable in both types of potential.Comment: 44 pages, ReVTeX, with 9 postscipt figures (included); minor
modifications to figure
Evaluation of the London Measure of Unplanned Pregnancy in a United States population of women
Copyright @ 2012 Morof et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Objective: To evaluate the reliability and validity of the London Measure of Unplanned Pregnancy (a U.K.-developed measure of pregnancy intention), in English and Spanish translation, in a U.S. population of women. Methods: A psychometric evaluation study of the London Measure of Unplanned Pregnancy (LMUP), a six-item, self-completion paper measure was conducted with 346 women aged 15–45 who presented to San Francisco General Hospital for termination of pregnancy or antenatal care. Analyses of the two language versions were carried out separately. Reliability (internal consistency) was assessed using Cronbach’s alpha and item-total correlations. Test-retest reliability (stability) was assessed using weighted Kappa. Construct validity was assessed using principal components analysis and hypothesis testing. Results: Psychometric testing demonstrated that the LMUP was reliable and valid in both U.S. English (alpha = 0.78, all item-total correlations .0.20, weighted Kappa = 0.72, unidimensionality confirmed, hypotheses met) and Spanish translation (alpha = 0.84, all item-total correlations .0.20, weighted Kappa = 0.77, unidimensionality confirmed, hypotheses met). Conclusion: The LMUP was reliable and valid in U.S. English and Spanish translation and therefore may now be used with U.S. women.The study was funded by an anonymous donation
Biosynthesis of the 15-membered ring depsipeptide neoantimycin
Antimycins are a family of natural products possessing outstanding biological activities and unique structures, which have intrigued chemists for over a half century. Of particular interest are the ring-expanded antimycins that show promising anti-cancer potential and whose biosynthesis remains uncharacterized. Specifically, neoantimycin and its analogs have been shown to be effective regulators of the oncogenic proteins GRP78/BiP and K-Ras. The neoantimycin structural skeleton is built on a 15-membered tetralactone ring containing one methyl, one hydroxy, one benzyl and three alkylmoieties, as well as an amide linkage to a conserved 3-formamidosalicylic acid moiety. Although the biosynthetic gene cluster for neoantimycins was recently identified, the enzymatic logic that governs the synthesis of neoantimycins has not yet been revealed. In this work, the neoantimycin gene cluster is identified and an updated sequence and annotation is provided delineating a non-ribosomal peptide synthetase/polyketide synthase (NRPS/PKS) hybrid scaffold. Using cosmid expression and CRISPR/Cas-based genome editing, several heterologous expression strains for neoantimycin production are constructed in two separate Streptomyces species. A combination of in vivo and in vitro analysis is further used to completely characterize the biosynthesis of neoantimycins including the megasynthases and trans-acting domains. This work establishes a set of highly tractable hosts for producing and engineering neoantimycins and their C11 oxidized analogs, paving the way for neoantimycin-based drug discovery and development
The Kondo Resonance in Electron Spectroscopy
The Kondo resonance is the spectral manifestation of the Kondo properties of
the impurity Anderson model, and also plays a central role in the dynamical
mean-field theory (DMFT) for correlated electron lattice systems. This article
presents an overview of electron spectroscopy studies of the resonance for the
4f electrons of cerium compounds, and for the 3d electrons of V_2O_3, including
beginning efforts at using angle resolved photoemission to determine the
k-dependence of the resonance. The overview includes the comparison and
analysis of spectroscopy data with theoretical spectra as calculated for the
impurity model and as obtained by DMFT, and the Kondo volume collapse
calculation of the cerium alpha-gamma phase transition boundary, with its
spectroscopic underpinnings.Comment: 32 pages, 11 figures, 151 references; paper for special issue of J.
Phys. Soc. Jpn. on "Kondo Effect--40 Years after the Discovery
STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer
BackgroundPoly (ADP-ribose) polymerase (PARP) inhibition (PARPi) has demonstrated potent therapeutic efficacy in patients with BRCA-mutant ovarian cancer. However, acquired resistance to PARPi remains a major challenge in the clinic.MethodsPARPi-resistant ovarian cancer mouse models were generated by long-term treatment of olaparib in syngeneic Brca1-deficient ovarian tumors. Signal transducer and activator of transcription 3 (STAT3)-mediated immunosuppression was investigated in vitro by co-culture experiments and in vivo by analysis of immune cells in the tumor microenvironment (TME) of human and mouse PARPi-resistant tumors. Whole genome transcriptome analysis was performed to assess the antitumor immunomodulatory effect of STING (stimulator of interferon genes) agonists on myeloid cells in the TME of PARPi-resistant ovarian tumors. A STING agonist was used to overcome STAT3-mediated immunosuppression and acquired PARPi resistance in syngeneic and patient-derived xenografts models of ovarian cancer.ResultsIn this study, we uncover an adaptive resistance mechanism to PARP inhibition mediated by tumor-associated macrophages (TAMs) in the TME. Markedly increased populations of protumor macrophages are found in BRCA-deficient ovarian tumors that rendered resistance to PARPi in both murine models and patients. Mechanistically, PARP inhibition elevates the STAT3 signaling pathway in tumor cells, which in turn promotes protumor polarization of TAMs. STAT3 ablation in tumor cells mitigates polarization of protumor macrophages and increases tumor-infiltrating T cells on PARP inhibition. These findings are corroborated in patient-derived, PARPi-resistant BRCA1-mutant ovarian tumors. Importantly, STING agonists reshape the immunosuppressive TME by reprogramming myeloid cells and overcome the TME-dependent adaptive resistance to PARPi in ovarian cancer. This effect is further enhanced by addition of the programmed cell death protein-1 blockade.ConclusionsWe elucidate an adaptive immunosuppression mechanism rendering resistance to PARPi in BRCA1-mutant ovarian tumors. This is mediated by enrichment of protumor TAMs propelled by PARPi-induced STAT3 activation in tumor cells. We also provide a new strategy to reshape the immunosuppressive TME with STING agonists and overcome PARPi resistance in ovarian cancer.Peer reviewe
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Enhanced Efficacy of Aurora Kinase Inhibitors in G2/M Checkpoint Deficient TP53 Mutant Uterine Carcinomas Is Linked to the Summation of LKB1-AKT-p53 Interactions.
Uterine carcinoma (UC) is the most common gynecologic malignancy in the United States. TP53 mutant UCs cause a disproportionate number of deaths due to limited therapies for these tumors and the lack of mechanistic understanding of their fundamental vulnerabilities. Here we sought to understand the functional and therapeutic relevance of TP53 mutations in UC. We functionally profiled targetable TP53 dependent DNA damage repair and cell cycle control pathways in a panel of TP53 mutant UC cell lines and patient-derived organoids. There were no consistent defects in DNA damage repair pathways. Rather, most models demonstrated dependence on defective G2/M cell cycle checkpoints and subsequent upregulation of Aurora kinase-LKB1-p53-AKT signaling in the setting of baseline mitotic defects. This combination makes them sensitive to Aurora kinase inhibition. Resistant lines demonstrated an intact G2/M checkpoint, and combining Aurora kinase and WEE1 inhibitors, which then push these cells through mitosis with Aurora kinase inhibitor-induced spindle defects, led to apoptosis in these cases. Overall, this work presents Aurora kinase inhibitors alone or in combination with WEE1 inhibitors as relevant mechanism driven therapies for TP53 mutant UCs. Context specific functional assessment of the G2/M checkpoint may serve as a biomarker in identifying Aurora kinase inhibitor sensitive tumors
Renormalized couplings and scaling correction amplitudes in the N-vector spin models on the sc and the bcc lattices
For the classical N-vector model, with arbitrary N, we have computed through
order \beta^{17} the high temperature expansions of the second field derivative
of the susceptibility \chi_4(N,\beta) on the simple cubic and on the body
centered cubic lattices. (The N-vector model is also known as the O(N)
symmetric classical spin Heisenberg model or, in quantum field theory, as the
lattice
O(N) nonlinear sigma model.) By analyzing the expansion of \chi_4(N,\beta) on
the two lattices, and by carefully allowing for the corrections to scaling, we
obtain updated estimates of the critical parameters and more accurate tests of
the hyperscaling relation d\nu(N) +\gamma(N) -2\Delta_4(N)=0 for a range of
values of the spin dimensionality N, including
N=0 [the self-avoiding walk model], N=1 [the Ising spin 1/2 model],
N=2 [the XY model], N=3 [the classical Heisenberg model]. Using the recently
extended series for the susceptibility and for the second correlation moment,
we also compute the dimensionless renormalized four point coupling constants
and some universal ratios of scaling correction amplitudes in fair agreement
with recent renormalization group estimates.Comment: 23 pages, latex, no figure
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