157 research outputs found
On theories of enhanced CP violation in B_s,d meson mixing
The DO collaboration has measured a deviation from the standard model (SM)
prediction in the like sign dimuon asymmetry in semileptonic b decay with a
significance of 3.2 sigma. We discuss how minimal flavour violating (MFV)
models with multiple scalar representations can lead to this deviation through
tree level exchanges of new MFV scalars. We review how the two scalar doublet
model can accommodate this result and discuss some of its phenomenology. Limits
on electric dipole moments suggest that in this model the coupling of the
charged scalar to the right handed u-type quarks is suppressed while its
coupling to the d-type right handed quarks must be enhanced. We construct an
extension of the MFV two scalar doublet model where this occurs naturally.Comment: 10 pages, 7 figures, v3 final JHEP versio
Theoretical and Phenomenological Constraints on Form Factors for Radiative and Semi-Leptonic B-Meson Decays
We study transition form factors for radiative and rare semi-leptonic B-meson
decays into light pseudoscalar or vector mesons, combining theoretical
constraints and phenomenological information from Lattice QCD, light-cone sum
rules, and dispersive bounds. We pay particular attention to form factor
parameterisations which are based on the so-called series expansion, and study
the related systematic uncertainties on a quantitative level. In this context,
we also provide the NLO corrections to the correlation function between two
flavour-changing tensor currents, which enters the unitarity constraints for
the coefficients in the series expansion.Comment: 52 pages; v2: normalization error in (29ff.) corrected, conclusion
about relevance of unitarity bounds modified; form factor fits unaffected;
references added; v3: discussion on truncation of series expansion added,
matches version to be published in JHEP; v4: corrected typos in Tables 5 and
Higgs-mediated FCNCs: Natural Flavour Conservation vs. Minimal Flavour Violation
We compare the effectiveness of two hypotheses, Natural Flavour Conservation
(NFC) and Minimal Flavour Violation (MFV), in suppressing the strength of
flavour-changing neutral-currents (FCNCs) in models with more than one Higgs
doublet. We show that the MFV hypothesis, in its general formulation, is more
stable in suppressing FCNCs than the hypothesis of NFC alone when quantum
corrections are taken into account. The phenomenological implications of the
two scenarios are discussed analysing meson-antimeson mixing observables and
the rare decays B -> mu+ mu-. We demonstrate that, introducing flavour-blind CP
phases, two-Higgs doublet models respecting the MFV hypothesis can accommodate
a large CP-violating phase in Bs mixing, as hinted by CDF and D0 data and,
without extra free parameters, soften significantly in a correlated manner the
observed anomaly in the relation between epsilon_K and S_psi_K.Comment: 27 pages, 4 figures. v3: minor modifications (typos corrected and few
refs. added), conclusions unchanged; journal versio
Protective Efficacy of Neutralizing Monoclonal Antibodies in a Nonhuman Primate Model of Ebola Hemorrhagic Fever
Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF
Limits on scalar leptoquark interactions and consequences for GUTs
A colored weak singlet scalar state with hypercharge 4/3 is one of the
possible candidates for the explanation of the unexpectedly large
forward-backward asymmetry in t tbar production as measured by the CDF and D0
experiments. We investigate the role of this state in a plethora of flavor
changing neutral current processes and precision observables of down-quarks and
charged leptons. Our analysis includes tree- and loop-level mediated
observables in the K and B systems, the charged lepton sector, as well as the Z
to b bbar decay width. We perform a global fit of the relevant scalar
couplings. This approach can explain the (g-2)_mu anomaly while tensions among
the CP violating observables in the quark sector, most notably the nonstandard
CP phase (and width difference) in the Bs system cannot be fully relaxed. The
results are interpreted in a class of grand unified models which allow for a
light colored scalar with a mass below 1TeV. We find that the renormalizable
SU(5) scenario is not compatible with our global fit, while in the SO(10) case
the viability requires the presence of both the 126- and 120-dimensional
representations.Comment: 26 pages, 7 figures; version as publishe
Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model
The alignment in flavour space of the Yukawa matrices of a general
two-Higgs-doublet model results in the absence of tree-level flavour-changing
neutral currents. In addition to the usual fermion masses and mixings, the
aligned Yukawa structure only contains three complex parameters, which are
potential new sources of CP violation. For particular values of these three
parameters all known specific implementations of the model based on discrete
Z_2 symmetries are recovered. One of the most distinctive features of the
two-Higgs-doublet model is the presence of a charged scalar. In this work, we
discuss its main phenomenological consequences in flavour-changing processes at
low energies and derive the corresponding constraints on the parameters of the
aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP.
References added. Discussion slightly extended. Conclusions unchange
Nuclear DNA content variation in life history phases of the Bonnemaisoniaceae (Rhodophyta)
Nuclear DNA content in gametophytes and sporophytes or the prostrate phases of the following species of Bonnemaisoniaceae (Asparagopsis armata, Asparagopsis taxiformis, Bonnemaisonia asparagoides, Bonnemaisonia clavata and Bonnemaisonia hamifera) were estimated by image analysis and static microspectrophotometry using the DNA-localizing fluorochrome DAPI (4′, 6-diamidino-2-phenylindole, dilactate) and the chicken erythrocytes standard. These estimates expand on the Kew database of DNA nuclear content. DNA content values for 1C nuclei in the gametophytes (spermatia and vegetative cells) range from 0.5 pg to 0.8 pg, and for 2C nuclei in the sporophytes or the prostrate phases range from 1.15-1.7 pg. Although only the 2C and 4C values were observed in the sporophyte or the prostrate phase, in the vegetative cells of the gametophyte the values oscillated from 1C to 4C, showing the possible start of endopolyploidy. The results confirm the alternation of nuclear phases in these Bonnemaisoniaceae species, in those that have tetrasporogenesis, as well as those that have somatic meiosis. The availability of a consensus phylogenetic tree for Bonnemaisoniaceae has opened the way to determine evolutionary trends in DNA contents. Both the estimated genome sizes and the published chromosome numbers for Bonnemaisoniaceae suggest a narrow range of values consistent with the conservation of an ancestral genome
Immunomodulation of murine collagen-induced arthritis by N, N-dimethylglycine and a preparation of Perna canaliculus
<p>Abstract</p> <p>Background</p> <p>Rheumatoid arthritis (RA) and its accepted animal model, murine collagen-induced arthritis (CIA), are classic autoimmune inflammatory diseases which require proinflammatory cytokine production for pathogenesis. We and others have previously used N, N-dimethylglycine (DMG) and extracts from the New Zealand green-lipped mussel <it>Perna canaliculus </it>(Perna) as potent immunomodulators to modify ongoing immune and/or inflammatory responses.</p> <p>Methods</p> <p>In our initial studies, we treated lipopolysaccahride (LPS) stimulated THP-1 monocytes <it>in vitro </it>with increasing concentrations of Perna extract or DMG. Additionally, we treated rat peripheral blood neutrophils with increasing concentrations of Perna extract and measured superoxide burst. In subsequent <it>in vivo </it>experiments, CIA was induced by administration of type II collagen; rats were prophylactically treated with either Perna or DMG, and then followed for disease severity. Finally, to test whether Perna and/or DMG could block or inhibit an ongoing pathologic disease process, we induced CIA in mice and treated them therapeutically with either of the two immunomodulators.</p> <p>Results</p> <p>Following LPS stimulation of THP-1 monocytes, we observed dose-dependent reductions in TNF-α and IL-12p40 production in Perna treated cultures. DMG treatment, however, showed significant increases in both of these cytokines in the range of 0.001–1 μM. We also demonstrate that <it>in vitro </it>neutrophil superoxide burst activity is dose-dependently reduced in the presence of Perna. Significant reductions in disease incidence, onset, and severity of CIA in rats were noted following prophylactic treatment with either of the two immunomodulators. More importantly, amelioration of mouse CIA was observed following therapeutic administration of Perna. In contrast, DMG appeared to have little effect in mice and may act in a species-specific manner.</p> <p>Conclusion</p> <p>These data suggest that Perna, and perhaps DMG, may be useful supplements to the treatment of RA in humans.</p
Tumour necrosis factor gene polymorphism: a predictive factor for the development of post-transplant lymphoproliferative disease
Epstein–Barr virus-positive post-transplant lymphoproliferative disease (PTLD) is a potentially lethal complication of iatrogenic immunosupression after transplantation. Predicting the development of PTLD allowing early and effective intervention is therefore of importance. Polymorphisms within cytokine genes are implicated in susceptibility to, and progression of, disease however the published data are often conflicting. We undertook investigation of polymorphic alleles within cytokine genes in PTLD and non-PTLD transplant cohorts to determine risk factors for disease.
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Methods:
SSP-PCR was used to analyse single nucleotide polymorphism within tumour necrosis factor (TNF)-α, interleukin- 1, -6, -10 and lymphotoxin-α genes. The TNF-α levels were measured by standard enzyme-linked immuno-absorbant assay.
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Results:
We show an association between variant alleles within the TNF-α promoter (−1031C (<i>P</i>=0.005)); −863A (<i>P</i>=0.0001) and TNF receptor I promoter regions (−201T (<i>P</i>=0.02)); −1135C (<i>P</i>=0.03) with the development of PTLD. We also show an association with TNF-α promoter haplotypes with haplotype-3 significantly increased (<i>P</i>=0.0001) and haplotype-1 decreased (P=0.02) in PTLD patients compared to transplant controls. Furthermore, we show a significant increase (<i>P</i>=0.02) in the level of TNF-α in PTLD patient plasma (range 0–97.97 pg ml<sup>−1</sup>) compared to transplant controls (0–8.147 pg ml<sup>−1</sup>), with the highest levels found in individuals carrying the variant alleles.
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Conclusion:
We suggest that genetic variation within TNF-α loci and the level of plasma cytokine could be used as a predictive risk factor for the development of PTLD
Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection.
Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity
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