2,690 research outputs found
Discrete R-symmetries and Anomaly Universality in Heterotic Orbifolds
We study discrete R-symmetries, which appear in 4D low energy effective field
theory derived from hetetoric orbifold models. We derive the R-symmetries
directly from geometrical symmetries of orbifolds. In particular, we obtain the
corresponding R-charges by requiring that the couplings be invariant under
these symmetries. This allows for a more general treatment than the explicit
computations of correlation functions made previously by the authors, including
models with discrete Wilson lines, and orbifold symmetries beyond
plane-by-plane rotational invariance. Surprisingly, for the cases covered by
earlier explicit computations, the R-charges differ from the previous result.
We study the anomalies associated with these R-symmetries, and comment on the
results.Comment: 21 pages, 2 figures. Minor changes, typos corrected. Matches JHEP
published versio
Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells
Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34<sup>+</sup>38<sup>lo</sup>) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells <i>in vitro</i>. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34<sup>+</sup> cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease
Bulk Axions, Brane Back-reaction and Fluxes
Extra-dimensional models can involve bulk pseudo-Goldstone bosons (pGBs)
whose shift symmetry is explicitly broken only by physics localized on branes.
Reliable calculation of their low-energy potential is often difficult because
it requires details of the stabilization of the extra dimensions. In rugby ball
solutions, for which two compact extra dimensions are stabilized in the
presence of only positive-tension brane sources, the effects of brane
back-reaction can be computed explicitly. This allows the calculation of the
shape of the low-energy pGB potential and response of the extra dimensional
geometry as a function of the perturbing brane properties. If the
pGB-dependence is a small part of the total brane tension a very general
analysis is possible, permitting an exploration of how the system responds to
frustration when the two branes disagree on what the proper scalar vacuum
should be. We show how the low-energy potential is given by the sum of brane
tensions (in agreement with common lore) when only the brane tensions couple to
the pGB. We also show how a direct brane coupling to the flux stabilizing the
extra dimensions corrects this result in a way that does not simply amount to
the contribution of the flux to the brane tensions. We calculate the mass of
the would-be zero mode, and briefly describe several potential applications,
including a brane realization of `natural inflation,' and a dynamical mechanism
for suppressing the couplings of the pGB to matter localized on the branes.
Since the scalar can be light enough to be relevant to precision tests of
gravity (in a technically natural way) this mechanism can be relevant to
evading phenomenological bounds.Comment: 36 pages, JHEP styl
Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and proinflammatory dysregulation
Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM. We found that PAM were readily susceptible to initial infection with all five avian and mammalian influenza viruses but only avian viruses caused early and extensive apoptosis (by 6 h of infection) resulting in reduced virus progeny and moderated pro- inflammation. Full length viral PB1-F2 present only in avian influenza viruses is a virulence factor that targets AM for mitochondrial associated apoptotic cell death. With the use of reverse genetics on an avian H5N1 virus, we found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication. Taken together, we propose that early apoptosis of PAM limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process
Smooth tensionful higher-codimensional brane worlds with bulk and brane form fields
Completely regular tensionful codimension-n brane world solutions are
discussed, where the core of the brane is chosen to be a thin codimension-(n-1)
shell in an infinite volume flat bulk, and an Einstein-Hilbert term localized
on the brane is included (Dvali-Gabadadze-Porrati models). In order to support
such localized sources we enrich the vacuum structure of the brane by the
inclusion of localized form fields. We find that phenomenological constraints
on the size of the internal core seem to impose an upper bound to the brane
tension. Finite transverse-volume smooth solutions are also discussed.Comment: 1+14 pages, 2 figures; section 2.3 improved, typos corrected and
references added. Published versio
The Benefits of B ---> K* l+ l- Decays at Low Recoil
Using the heavy quark effective theory framework put forward by Grinstein and
Pirjol we work out predictions for B -> K* l+ l-, l = (e, mu), decays for a
softly recoiling K*, i.e., for large dilepton masses sqrt{q^2} of the order of
the b-quark mass m_b. We work to lowest order in Lambda/Q, where Q = (m_b,
sqrt{q^2}) and include the next-to-leading order corrections from the charm
quark mass m_c and the strong coupling at O(m_c^2/Q^2, alpha_s). The leading
Lambda/m_b corrections are parametrically suppressed. The improved Isgur-Wise
form factor relations correlate the B -> K* l+ l- transversity amplitudes,
which simplifies the description of the various decay observables and provides
opportunities for the extraction of the electroweak short distance couplings.
We propose new angular observables which have very small hadronic
uncertainties. We exploit existing data on B -> K* l+ l- distributions and show
that the low recoil region provides powerful additional information to the
large recoil one. We find disjoint best-fit solutions, which include the
Standard Model, but also beyond-the-Standard Model ones. This ambiguity can be
accessed with future precision measurements.Comment: 31 pages, 8 figures; Instability near minimal recoil from numerics
removed, Fig. 1 replaced and minor shifts in short distance uncertainties in
SM predictions; typos corrected and references added; main results and
conclusions unchange
Smc5/6: a link between DNA repair and unidirectional replication?
Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally. Here, we propose that unidirectional replication, combined with global Smc5/6 functions, can explain the apparent rDNA specificity
Non-Abelian discrete gauge symmetries in 4d string models
We study the realization of non-Abelian discrete gauge symmetries in 4d field
theory and string theory compactifications. The underlying structure
generalizes the Abelian case, and follows from the interplay between gaugings
of non-Abelian isometries of the scalar manifold and field identifications
making axion-like fields periodic. We present several classes of string
constructions realizing non-Abelian discrete gauge symmetries. In particular,
compactifications with torsion homology classes, where non-Abelianity arises
microscopically from the Hanany-Witten effect, or compactifications with
non-Abelian discrete isometry groups, like twisted tori. We finally focus on
the more interesting case of magnetized branes in toroidal compactifications
and quotients thereof (and their heterotic and intersecting duals), in which
the non-Abelian discrete gauge symmetries imply powerful selection rules for
Yukawa couplings of charged matter fields. In particular, in MSSM-like models
they correspond to discrete flavour symmetries constraining the quark and
lepton mass matrices, as we show in specific examples.Comment: 58 pages; minor typos corrected and references adde
TGF-beta(2)- and H2O2-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid
Background/Aims: The goal of the present study was to determine whether transforming growth factor-beta(2) (TGF-beta(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant alpha-lipoic acid (LA). Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-beta(2) for 24 h or 200 mu M hydrogen peroxide (H2O2) for 1 h. Lipid peroxidation was measured by a decrease in cis-pari-naric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-beta 2 or H2O2 exposure. Expressions of the heat shock protein (Hsp) alpha B-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis. Results: Both TGF-beta(2) and H2O2 increased lipid peroxidation. Treatment of astrocytes with TGF-beta(2) and H2O2 upregulated the expression of alpha B-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-beta(2)- and H2O2-stimulated gene expressions. Conclusion: We showed that TGF-beta(2)- and H2O2-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy. Copyright (C) 2012 S. Karger AG, Base
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