Electroweak Precision Observables and the Unhiggs

We compute one-loop corrections to the S and T parameters in the Unhiggs scenario. In that scenario, the Standard Model Higgs is replaced by a non-local object, called the Unhiggs, whose spectral function displays a continuum above the mass gap. The Unhiggs propagator has effectively the same UV properties as the Standard Model Higgs propagator, which implies that loop corrections to the electroweak precision observables are finite and calculable. We show that the Unhiggs is consistent with electroweak precision tests when its mass gap is at the weak scale; in fact, it then mimics a light SM Higgs boson. We also argue that the Unhiggs, while being perfectly visible to electroweak precision observables, is invisible to detection at LEP.Comment: 13 pages; v2: references added, discussion of production cross-section expande

Soft-Wall Stabilization

We propose a general class of five-dimensional soft-wall models with AdS metric near the ultraviolet brane and four-dimensional Poincar\'e invariance, where the infrared scale is determined dynamically. A large UV/IR hierarchy can be generated without any fine-tuning, thus solving the electroweak/Planck scale hierarchy problem. Generically, the spectrum of fluctuations is discrete with a level spacing (mass gap) provided by the inverse length of the wall, similar to RS1 models with Standard Model fields propagating in the bulk. Moreover two particularly interesting cases arise. They can describe: (a) a theory with a continuous spectrum above the mass gap which can model unparticles corresponding to operators of a CFT where the conformal symmetry is broken by a mass gap, and; (b) a theory with a discrete spectrum provided by linear Regge trajectories as in AdS/QCD models.Comment: 27 pages, 6 figures, 1 table. v2: references added, version to appear in NJP Focus Issue on Extra Dimension

The Higgs as a Probe of Supersymmetric Extra Sectors

We present a general method for calculating the leading contributions to h -> gg and h -> gamma gamma in models where the Higgs weakly mixes with a nearly supersymmetric extra sector. Such mixing terms can play an important role in raising the Higgs mass relative to the value expected in the MSSM. Our method applies even when the extra sector is strongly coupled, and moreover does not require a microscopic Lagrangian description. Using constraints from holomorphy we fix the leading parametric form of the contributions to these Higgs processes, including the Higgs mixing angle dependence, up to an overall coefficient. Moreover, when the Higgs is the sole source of mass for a superconformal sector, we show that even this coefficient is often calculable. For appropriate mixing angles, the contribution of the extra states to h -> gg and h -> gamma gamma can vanish. We also discuss how current experimental limits already lead to non-trivial constraints on such models. Finally, we provide examples of extra sectors which satisfy the requirements necessary to use the holomorphic approximation.Comment: v4: 34 pages, 2 figures, typo corrected and clarification adde

Vector Bosons in the Randall-Sundrum 2 and Lykken-Randall models and unparticles

Unparticle behavior is shown to be realized in the Randall-Sundrum 2 (RS 2) and the Lykken-Randall (LR) brane scenarios when brane-localized Standard Model currents are coupled to a massive vector field living in the five-dimensional warped background of the RS 2 model. By the AdS/CFT dictionary these backgrounds exhibit certain properties of the unparticle CFT at large N_c and strong 't Hooft coupling. Within the RS 2 model we also examine and contrast in detail the scalar and vector position-space correlators at intermediate and large distances. Unitarity of brane-to-brane scattering amplitudes is seen to imply a necessary and sufficient condition on the positivity of the bulk mass, which leads to the well-known unitarity bound on vector operators in a CFT.Comment: 60 pages, 8 figure

Composite Higgs Search at the LHC

The Higgs boson production cross-sections and decay rates depend, within the Standard Model (SM), on a single unknown parameter, the Higgs mass. In composite Higgs models where the Higgs boson emerges as a pseudo-Goldstone boson from a strongly-interacting sector, additional parameters control the Higgs properties which then deviate from the SM ones. These deviations modify the LEP and Tevatron exclusion bounds and significantly affect the searches for the Higgs boson at the LHC. In some cases, all the Higgs couplings are reduced, which results in deterioration of the Higgs searches but the deviations of the Higgs couplings can also allow for an enhancement of the gluon-fusion production channel, leading to higher statistical significances. The search in the H to gamma gamma channel can also be substantially improved due to an enhancement of the branching fraction for the decay of the Higgs boson into a pair of photons.Comment: 32 pages, 16 figure

Chemotherapy of Skull Base Chordoma Tailored on Responsiveness of Patient-Derived Tumor Cells to Rapamycin1,2

Skull base chordomas are challenging tumors due to their deep surgical location and resistance to conventional radiotherapy. Chemotherapy plays a marginal role in the treatment of chordoma resulting from lack of preclinical models due to the difficulty in establishing tumor cell lines and valuable in vivo models. Here, we established a cell line from a recurrent clival chordoma. Cells were cultured for more than 30 passages and the expression of the chordoma cell marker brachyury was monitored using both immunohistochemistry and Western blot. Sensitivity of chordoma cells to the inhibition of specific signaling pathways was assessed through testing of a commercially available small molecule kinase inhibitor library. In vivo tumorigenicity was evaluated by grafting chordoma cells onto immunocompromised mice and established tumor xenografts were treated with rapamycin. Rapamycin was administered to the donor patient and its efficacy was assessed on follow-up neuroimaging. Chordoma cells main- tained brachyury expression at late passages and generated xenografts closely mimicking the histology and phe- notype of the parental tumor. Rapamycin was identified as an inhibitor of chordoma cell proliferation. Molecular analyses on tumor cells showed activation of the mammalian target of rapamycin signaling pathway and mutation of KRAS gene. Rapamycin was also effective in reducing the growth of chordoma xenografts. On the basis of these results, our patient received rapamycin therapy with about six-fold reduction of the tumor growth rate upon 10-month follow-up neuroimaging. This is the first case of chordoma in whom chemotherapy was tailored on the basis of the sensitivity of patient-derived tumor cells

Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant

Despite intense research and clinical efforts, patients affected by advanced colorectal cancer (CRC) have still a poor prognosis. The discovery of colorectal (CR) cancer stem cell (CSC) as the cell compartment responsible for tumor initiation and propagation may provide new opportunities for the development of new therapeutic strategies. Given the reduced sensitivity of CR-CSCs to chemotherapy and the ability of bone morphogenetic proteins (BMP) to promote colonic stem cell differentiation, we aimed to investigate whether an enhanced variant of BMP7 (BMP7v) could sensitize to chemotherapy-resistant CRC cells and tumors. Thirty-five primary human cultures enriched in CR-CSCs, including four from chemoresistant metastatic lesions, were used for in vitro studies and to generate CR-CSC-based mouse avatars to evaluate tumor growth and progression upon treatment with BMP7v alone or in combination with standard therapy or PI3K inhibitors. BMP7v treatment promotes CR-CSC differentiation and recapitulates the cell differentiation-related gene expression profile by suppressing Wnt pathway activity and reducing mesenchymal traits and survival of CR-CSCs. Moreover, in CR-CSC-based mouse avatars, BMP7v exerts an antiangiogenic effect and sensitizes tumor cells to standard chemotherapy regardless of the mutational, MSI, and CMS profiles. Of note, tumor harboring PIK3CA mutations were affected to a lower extent by the combination of BMP7v and chemotherapy. However, the addition of a PI3K inhibitor to the BMP7v-based combination potentiates PIK3CA-mutant tumor drug response and reduces the metastatic lesion size. These data suggest that BMP7v treatment may represent a useful antiangiogenic and prodifferentiation agent, which renders CSCs sensitive to both standard and targeted therapies

Gapped continuum Kaluza-Klein spectrum

We consider a warped ve-dimensional model with an ultraviolet (UV) brane and, on top of the Standard Model isolated modes, continua of KK modes with different mass gaps for all particles: gauge bosons, fermions, graviton, radion and Higgs boson. The model can be considered as a modelization in ve dimensions of gapped unparticles. The ve dimensional metric has a singularity, at a finite (infinite) value of the proper (conformal) coordinate, which is admissible as it supports finite temperature in the form of a black hole horizon. An infrared (IR) brane, with particular jumping conditions, is introduced to trigger correct electroweak breaking. The gravitational metric is AdS5 near the UV brane, to solve the hierarchy problem with a fundamental Planck scale, and linear, in conformal coordinates, near the IR, as in the linear dilaton and ve-dimensional clockwork models. The branes, and singularity, distances are fixed, à la Goldberger-Wise, by a bulk scalar field with brane potentials explicitly breaking the conformal symmetry. The bosonic continuum of KK modes with the smallest mass gap are those of gauge bosons, and so they are the most likely produced at the LHC. Mass gaps of the continuum of KK fermions do depend on their localization in the extra dimension. We have computed the spectral functions, and arbitrary Green's functions, and shown how they can modify some Standard Model processes.The work of EM is supported by the Spanish MINEICO under Grant FIS2017-85053-C2-1-P, by the Junta de Andalucía under Grant FQM-225, by the Consejería de Conocimiento, Investigación y Universidad of the Junta de Andalucía and European Regional Development Fund (ERDF) under Grant SOMM17/6105/UGR, and by the Spanish Consolider Ingenio 2010 Programme CPAN under Grant CSD2007-00042. The research of EM is also supported by the Ramón y Cajal Program of the Spanish MINEICO under Grant RYC-2016-20678. The work of MQ is partly supported by Spanish MINEICO (Grant FPA2017-88915-P), by the Catalan Government under Grant 2017SGR1069, and by Severo Ochoa Excellence Program of MINEICO (Grant SEV-2016-0588)

Phenotypic Diversity and Altered Environmental Plasticity in Arabidopsis thaliana with Reduced Hsp90 Levels

The molecular chaperone HSP90 aids the maturation of a diverse but select set of metastable protein clients, many of which are key to a variety of signal transduction pathways. HSP90 function has been best investigated in animal and fungal systems, where inhibition of the chaperone has exceptionally diverse effects, ranging from reversing oncogenic transformation to preventing the acquisition of drug resistance. Inhibition of HSP90 in the model plant Arabidopsis thaliana uncovers novel morphologies dependent on normally cryptic genetic variation and increases stochastic variation inherent to developmental processes. The biochemical activity of HSP90 is strictly conserved between animals and plants. However, the substrates and pathways dependent on HSP90 in plants are poorly understood. Progress has been impeded by the necessity of reliance on light-sensitive HSP90 inhibitors due to redundancy in the A. thaliana HSP90 gene family. Here we present phenotypic and genome-wide expression analyses of A. thaliana with constitutively reduced HSP90 levels achieved by RNAi targeting. HSP90 reduction affects a variety of quantitative life-history traits, including flowering time and total seed set, increases morphological diversity, and decreases the developmental stability of repeated characters. Several morphologies are synergistically affected by HSP90 and growth temperature. Genome-wide expression analyses also suggest a central role for HSP90 in the genesis and maintenance of plastic responses. The expression results are substantiated by examination of the response of HSP90-reduced plants to attack by caterpillars of the generalist herbivore Trichoplusia ni. HSP90 reduction potentiates a more robust herbivore defense response. In sum, we propose that HSP90 exerts global effects on the environmental responsiveness of plants to many different stimuli. The comprehensive set of HSP90-reduced lines described here is a vital instrument to further examine the role of HSP90 as a central interface between organism, development, and environment