403 research outputs found
Mixing-induced CP violating sources for electroweak baryogenesis from a semiclassical approach
The effects of flavor mixing in electroweak baryogenesis is investigated in a
generalized semiclassical WKB approach. Through calculating the nonadiabatic
corrections to the particle currents it is shown that extra CP violation
sources arise from the off-diagonal part of the equation of motion of particles
moving inside the bubble wall. This type of mixing-induced source is of the
first order in derivative expansion of the Higgs condensate, but is oscillation
suppressed. The numerical importance of the mixing-induced source is discussed
in the Minimal Supersymmetric Standard Model and compared with the source term
induced by semiclassical force. It is found that in a large parameter space
where oscillation suppression is not strong enough, the mixing-induced source
can dominate over that from the semiclassical force.Comment: 19 pp, 2 figs, 1 table, some comments added, to appear in
Eur.Phys.J.
Electroweak Baryogenesis and New TeV Fermions
New fermions, strongly coupled to the Standard Model Higgs boson provide a
well motivated extension of the Standard Model (SM). In this work we show that,
once new physics at heavier scales is added to stabilize the Higgs potential,
such an extension of the SM can strengthen the first order electroweak phase
transition and make the electroweak baryogenesis mechanism feasible. We propose
a SM extension with TeV Higgsinos, Winos and Binos that satisfy the following
properties: a) The electroweak phase transition is strong enough to avoid
sphaleron erasure in the broken phase for values of the Higgs mass mH < 300
GeV; b) It provides large CP-violating currents that lead to the observed
baryon asymmetry of the Universe for natural values of the CP-violating phase;
c) It also provides a natural Dark Matter candidate that can reproduce the
observed dark matter density; d) It is consistent with electroweak precision
measurements; e) It may arise from a softly broken supersymmetric theory with
an extra (asymptotically free) gauge sector; e) It may be tested by electron
electric dipole moment experiments in the near future.Comment: LateX, 40 pages, 12 embedded postscript figures. A discussion of the
stability of the Higgs potential and its connection to a possible ultraviolet
completion of the model has been adde
Improved Results in Supersymmetric Electroweak Baryogenesis
Electroweak baryogenesis provides a very attractive scenario to explain the
origin of the baryon asymmetry. The mechanism of electroweak baryogenesis makes
use of the baryon number anomaly and relies on physics that can be tested
experimentally. It is today understood that, if the Higgs mass is not larger
than 120 GeV, this mechanism may be effective within supersymmetric extensions
of the Standard Model. In this work, we reconsider the question of baryon
number generation at the electroweak phase transition within the context of the
minimal supersymmetric extension of the Standard Model. We derive the relevant
diffusion equations, give a consistent definition of the sources, and compare
our results with those appearing in the recent literature on this subjectComment: 19 pages, 2 figure
Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma
Osteosarcoma (OS) is the most common bone sarcoma in adolescents, and has poor
prognosis. A vicious cycle is established between OS cells and their microenvironment in
order to facilitate the tumor growth and cell spreading. The present work aims to better
characterize the tumor microenvironment in OS in order to identify new therapeutic targets
relating to metastatic process. Tissue microarrays of pre-chemotherapy OS biopsies were used
for characterizing the tumor niche by immunohistochemistry. Parameters studies included:
immune cells (M1, Mβ-subtypes of tumor-associated macrophages (TAM); T, B
lymphocytes; mast cells), vascularization (endothelial, perivascular cells), OPG, RANKL, and
mitotic index. Two groups of patients were defined, ββ localized OS (OS Meta-) and β8
metastatic OS (OS Meta+). The OS Meta- group was characterized by a higher infiltration of
INOS+ M1-polarized macrophages and upregulated OPG immunostaining. OS Meta+ tumors
showed a significant increase in CD146+
cells. INOS+
M1-macrophages were correlated with
OPG staining, and negatively with the presence of metastases. CD16γ+
Mβ-macrophages
were positively correlated with CD146+
cells. In multivariate analysis, INOS and OPG were
predictive factors for metastasis. An older age, non-metastatic tumor, good response to
chemotherapy, and higher macrophage infiltration were significantly associated with better
overall survival. TAMs are associated with better overall survival and a dysregulation of
M1/Mβ polarized-macrophages in favor of M1 subtype was observed in non-metastatic OS
Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution
We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking.</p
Cluster and virial expansions for the multi-species tonks gas
We consider a mixture of non-overlapping rods of different lengths ℓk moving in R or Z. Our main result are necessary and sufficient convergence criteria for the expansion of the pressure in terms of the activities zk and the densities ρk. This provides an explicit example against which to test known cluster expansion criteria, and illustrates that for non-negative interactions, the virial expansion can converge in a domain much larger than the activity expansion. In addition, we give explicit formulas that generalize the well-known relation between non-overlapping rods and labelled rooted trees. We also prove that for certain choices of the activities, the system can undergo a condensation transition akin to that of the zero-range process. The key tool is a fixed point equation for the pressure
Photoswitchable paclitaxel-based microtubule stabilisers allow optical control over the microtubule cytoskeleton
Small molecule inhibitors are prime reagents for studies in microtubule cytoskeleton research, being applicable across a range of biological models and not requiring genetic engineering. However, traditional chemical inhibitors cannot be experimentally applied with spatiotemporal precision suiting the length and time scales inherent to microtubule-dependent cellular processes. We have synthesised photoswitchable paclitaxel-based microtubule stabilisers, whose binding is induced by photoisomerisation to their metastable state. Photoisomerising these reagents in living cells allows optical control over microtubule network integrity and dynamics, cell division and survival, with biological response on the timescale of seconds and spatial precision to the level of individual cells within a population. In primary neurons, they enable regulation of microtubule dynamics resolved to subcellular regions within individual neurites. These azobenzene-based microtubule stabilisers thus enable non-invasive, spatiotemporally precise modulation of the microtubule cytoskeleton in living cells, and promise new possibilities for studying intracellular transport, cell motility, and neuronal physiology
Pathologies of the large-N limit for RP^{N-1}, CP^{N-1}, QP^{N-1} and mixed isovector/isotensor sigma-models
We compute the phase diagram in the N\to\infty limit for lattice RP^{N-1},
CP^{N-1} and QP^{N-1} sigma-models with the quartic action, and more generally
for mixed isovector/isotensor models. We show that the N=\infty limit exhibits
phase transitions that are forbidden for any finite N. We clarify the origin of
these pathologies by examining the exact solution of the one-dimensional model:
we find that there are complex zeros of the partition function that tend to the
real axis as N\to\infty. We conjecture the correct phase diagram for finite N
as a function of the spatial dimension d. Along the way, we prove some new
correlation inequalities for a class of N-component sigma-models, and we obtain
some new results concerning the complex zeros of confluent hypergeometric
functions.Comment: LaTeX, 88 pages, 33 figure
Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression
Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted
Analysis of FUS, PFN2, TDP-43, and PLS3 as potential disease severity modifiers in spinal muscular atrophy
Objective To investigate mutations in genes that are potential modifiers of spinal muscular atrophy (SMA) severity. Methods We performed a hypothesis-based search into the presence of variants in fused in sarcoma (FUS), transactive response DNA-binding protein 43 (TDP-43), plastin 3 (PLS3), and profilin 2 (PFN2) in a cohort of 153 patients with SMA types 1-4, including 19 families. Variants were detected with targeted next-generation sequencing and confirmed with Sanger sequencing. Functional effects of the identified variants were analyzed in silico and for PLS3, by analyzing expression levels in peripheral blood. Results We identified 2 exonic variants in FUS exons 5 and 6 (p.R216C and p.S135N) in 2 unrelated patients, but clinical effects were not evident. We identified 8 intronic variants in PLS3 in 33 patients. Five PLS3 variants (c.1511+82T>C; c.748+130 G>A; c.367+182C>T; c.891-25T>C (rs145269469); c.1355+17A>G (rs150802596)) potentially alter exonic splice silencer or exonic splice enhancer sites. The variant c.367+182C>T, but not RNA expression levels, corresponded with a more severe phenotype in 1 family. However, this variant or level of PLS3 expression did not consistently correspond with a milder or more severe phenotype in other families or the overall cohort. We found 3 heterozygous, intronic variants in PFN2 and TDP-43 with no correlation with clinical phenotype or effects on splicing. Conclusions PLS3 and FUS sequence variants do not modify SMA severity at the population level. Specific variants in individual patients or families do not consistently correlate with disease severity
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