Constraining General Two Higgs Doublet Models by the Evolution of Yukawa Couplings

We study how general two Higgs doublet models can be constrained by considering their properties under renormalization group evolution of the Yukawa couplings. We take into account both the appearance of a Landau pole as well as off-diagonal Yukawa couplings leading to flavour changing neutral currents in violation with experimental constraints at the electroweak scale. We find that the latter condition can be used to limit the amount of Z2 symmetry breaking allowed in a given model.Comment: 28 pages, 10 figures, added discussion of evolution from high to low scales, to be published in JHE

Revealing the electroweak properties of a new scalar resonance

One or more new heavy resonances may be discovered in experiments at the CERN Large Hadron Collider. In order to determine if such a resonance is the long-awaited Higgs boson, it is essential to pin down its spin, CP, and electroweak quantum numbers. Here we describe how to determine what role a newly-discovered neutral CP-even scalar plays in electroweak symmetry breaking, by measuring its relative decay rates into pairs of electroweak vector bosons: WW, ZZ, \gamma\gamma, and Z\gamma. With the data-driven assumption that electroweak symmetry breaking respects a remnant custodial symmetry, we perform a general analysis with operators up to dimension five. Remarkably, only three pure cases and one nontrivial mixed case need to be disambiguated, which can always be done if all four decay modes to electroweak vector bosons can be observed or constrained. We exhibit interesting special cases of Higgs look-alikes with nonstandard decay patterns, including a very suppressed branching to WW or very enhanced branchings to \gamma\gamma and Z\gamma. Even if two vector boson branching fractions conform to Standard Model expectations for a Higgs doublet, measurements of the other two decay modes could unmask a Higgs imposter.Comment: 23 pages, two figures; v2: minor revision and version to appear in JHE

Clusters of circulating tumor cells traverse capillary-sized vessels

Multicellular aggregates of circulating tumor cells (CTC clusters) are potent initiators of distant organ metastasis. However, it is currently assumed that CTC clusters are too large to pass through narrow vessels to reach these organs. Here, we present evidence that challenges this assumption through the use of microfluidic devices designed to mimic human capillary constrictions and CTC clusters obtained from patient and cancer cell origins. Over 90% of clusters containing up to 20 cells successfully traversed 5- to 10-μm constrictions even in whole blood. Clusters rapidly and reversibly reorganized into single-file chain-like geometries that substantially reduced their hydrodynamic resistances. Xenotransplantation of human CTC clusters into zebrafish showed similar reorganization and transit through capillary-sized vessels in vivo. Preliminary experiments demonstrated that clusters could be disrupted during transit using drugs that affected cellular interaction energies. These findings suggest that CTC clusters may contribute a greater role to tumor dissemination than previously believed and may point to strategies for combating CTC cluster-initiated metastasis

The zinc finger domain of Wilms' tumor 1 suppressor gene (WT1) behaves as a dominant negative, leading to abrogation of WT1 oncogenic potential in breast cancer cells

Abstract Introduction There is growing evidence that the Wilms' tumor 1 suppressor gene (WT1) behaves as an oncogene in some forms of breast cancer. Previous studies have demonstrated that the N-terminal domain of WT1 can act as a dominant negative through self-association. In the studies presented here we have explored the potential for the zinc finger domain (ZF) of WT1 to also have dominant-negative effects, and thus further our understanding of this protein. Methods Using full-length and ZF-only forms of WT1 we assessed their effect on the WT1 and c-myc promoter using luciferase and chromatin immunoprecipitation assays. The gene expression levels were determined by quantitative real-time RT-PCR, northern blot and western blot. We also assessed the effect of the ZF-only form on the growth of breast cancer cell lines in culture. Results Transfection with WT1–ZF plasmids resulted in a stronger inhibition of WT1 promoter than full-length WT1 in breast cancer cells. The WT1–ZF form lacking the lysine–threonine–serine (KTS) insert (ZF - KTS) can bind to the majority of WT1 consensus sites throughout the WT1 promoter region, while the ZF containing the insert (ZF + KTS) form only binds to sites in the proximal promoter. The abundances of endogenous WT1 mRNA and protein were markedly decreased following the stable expression of ZF - KTS in breast cancer cells. The expressions of WT1 target genes, including c-myc, Bcl-2, amphiregulin and TERT, were similarly suppressed by ZF - KTS. Moreover, WT1–ZF - KTS abrogated the transcriptional activation of c-myc mediated by all four predominant isoforms of WT1 (including or lacking alternatively spliced exons 5 and 9). Finally, WT1–ZF - KTS inhibited colony formation and cell division, but induced apoptosis in MCF-7 cells. Conclusion Our observations strongly argue that the WT1–ZF plasmid behaves as a dominant-negative regulator of the endogenous WT1 in breast cancer cells. The inhibition on proliferation of breast cancer cells by WT1–ZF - KTS provides a potential candidate of gene therapy for breast cancer

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

Decoupling property of the supersymmetric Higgs sector with four doublets

In supersymmetric standard models with multi Higgs doublet fields, selfcoupling constants in the Higgs potential come only from the D-terms at the tree level. We investigate the decoupling property of additional two heavier Higgs doublet fields in the supersymmetric standard model with four Higgs doublets. In particular, we study how they can modify the predictions on the quantities well predicted in the minimal supersymmetric standard model (MSSM), when the extra doublet fields are rather heavy to be measured at collider experiments. The B-term mixing between these extra heavy Higgs bosons and the relatively light MSSM-like Higgs bosons can significantly change the predictions in the MSSM such as on the masses of MSSM-like Higgs bosons as well as the mixing angle for the two light CP-even scalar states. We first give formulae for deviations in the observables of the MSSM in the decoupling region for the extra two doublet fields. We then examine possible deviations in the Higgs sector numerically, and discuss their phenomenological implications.Comment: 26 pages, 24 figures, text sligtly modified,version to appear in Journal of High Energy Physic

Inflation and dark matter in two Higgs doublet models

We consider the Higgs inflation in the extension of the Standard Model with two Higgs doublets coupled to gravity non-minimally. In the presence of an approximate global U(1) symmetry in the Higgs sector, both radial and angular modes of neutral Higgs bosons drive inflation where large non-Gaussianity is possible from appropriate initial conditions on the angular mode. We also discuss the case with single-field inflation for which the U(1) symmetry is broken to a Z_2 subgroup. We show that inflationary constraints, perturbativity and stability conditions restrict the parameter space of the Higgs quartic couplings at low energy in both multi- and single-field cases. Focusing on the inert doublet models where Z_2 symmetry remains unbroken at low energy, we show that the extra neutral Higgs boson can be a dark matter candidate consistent with the inflationary constraints. The doublet dark matter is always heavy in multi-field inflation while it can be light due to the suppression of the co-annihilation in single-field inflation. The implication of the extra quartic couplings on the vacuum stability bound is also discussed in the light of the recent LHC limits on the Higgs mass.Comment: (v1) 28 pages, 8 figures; (v2) 29 pages, a new subsection 3.3 added, references added and typos corrected, to appear in Journal of High Energy Physic

Characteristics of Mothers Caring for Children During Episodes of Homelessness

This study provides a description of the physical, psychological, and substance use problems of adult homeless women who are and are not caring for children. We also examined differences in the characteristics of these two groups of women. Interviews were conducted with 148 homeless women from three mid-sized U.S. cities, 24.3% of whom were caring for at least one child. Our results showed that women caring for children were more likely to be sheltered and have health insurance. Homeless women caring for children and solitary homeless women were generally similar in terms of substance abuse problems. However, rates of Borderline Personality Disorder were higher among women caring for children than among solitary homeless women. Our results are somewhat consistent with previous research, with the exception of substance abuse problems and mental health problems, which were shown to be equally problematic for all women, regardless of current caregiving status

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

Radiative contribution to neutrino masses and mixing in μν\mu\nuSSM

In an extension of the minimal supersymmetric standard model (popularly known as the $\mu\nu$SSM), three right handed neutrino superfields are introduced to solve the $\mu$-problem and to accommodate the non-vanishing neutrino masses and mixing. Neutrino masses at the tree level are generated through $R-$parity violation and seesaw mechanism. We have analyzed the full effect of one-loop contributions to the neutrino mass matrix. We show that the current three flavour global neutrino data can be accommodated in the $\mu\nu$SSM, for both the tree level and one-loop corrected analyses. We find that it is relatively easier to accommodate the normal hierarchical mass pattern compared to the inverted hierarchical or quasi-degenerate case, when one-loop corrections are included.Comment: 51 pages, 14 figures (58 .eps files), expanded introduction, other minor changes, references adde