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

Gaugephobic Higgs Signals at the LHC

The Gaugephobic Higgs model provides an interpolation between three different models of electroweak symmetry breaking: Higgsless models, Randall-Sundrum models, and the Standard Model. At parameter points between the extremes, Standard Model Higgs signals are present at reduced rates, and Higgsless Kaluza-Klein excitations are present with shifted masses and couplings, as well as signals from exotic quarks necessary to protect the Zbb coupling. Using a new implementation of the model in SHERPA, we show the LHC signals which differentiate the generic Gaugephobic Higgs model from its limiting cases. These are all signals involving a Higgs coupling to a Kaluza-Klein gauge boson or quark. We identify the clean signal $p p \to W^(i) \to W H$ mediated by a Kaluza-Klein W, which can be present at large rates and is enhanced for even Kaluza-Klein numbers. Due to the very hard lepton coming from the W decay, this signature has little background, and provides a better discovery channel for the Higgs than any of the Standard Model modes, over its entire mass range. A Higgs radiated from new heavy quarks also has large rates, but is much less promising due to very high multiplicity final states.Comment: 16 pages, 8 figure

The hsp56 immunophilin component of steroid receptor heterocomplexes: Could this be the elusive nuclear localization signal-binding protein?

In many cells, the glucocorticoid receptor undergoes rapid steroid-mediated translocation from the cytoplasm to the nucleus, and this receptor is an excellent model for studying the mechanism of targeted protein movement through the cytoplasm. For such unidirectional movement to occur, the receptor must attach to a retrograde movement system in a manner that involves the nuclear localization signal. It is improbable that such attachment occurs via a direct protein-protein interaction between the receptor and the movement system; rather, one or more linker proteins are likely to be involved. As with other steroid receptors, the glucocorticoid receptor is associated with several other proteins in a heterocomplex. Two of these receptor-associated proteins are the heat shock proteins hsp90 and hsp56, and a third heat shock protein, hsp70, is required for assembly of the receptor heterocomplex. The hormone binding domain of the steroid receptors determines the interaction with both hsp90 and hsp70. Hsp56 is known to bind to hsp90, but its potential site, or sites, of interaction with the receptor are undefined. Hsp56 has recently been cloned and demonstrated to be an immunophilin of the FK506/rapamycin binding class. The immunophilins have peptidyl-prolyl isomerase activity but their cellular functions are unknown. Herein, we review the literature on the hsp56 immunophilin component of the receptor heterocomplex and present a rationale for hsp56 being the protein that determines the direction of receptor movement via a direct protein-protein interaction with the nuclear localization signal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30603/1/0000240.pd

Electroweak Symmetry Breaking in the DSSM

We study the theoretical and phenomenological consequences of modifying the Kahler potential of the MSSM two Higgs doublet sector. Such modifications naturally arise when the Higgs sector mixes with a quasi-hidden conformal sector, as in some F-theory GUT models. In the Delta-deformed Supersymmetric Standard Model (DSSM), the Higgs fields are operators with non-trivial scaling dimension 1 < Delta < 2. The Kahler metric is singular at the origin of field space due to the presence of quasi-hidden sector states which get their mass from the Higgs vevs. The presence of these extra states leads to the fact that even as Delta approaches 1, the DSSM does not reduce to the MSSM. In particular, the Higgs can naturally be heavier than the W- and Z-bosons. Perturbative gauge coupling unification, a large top quark Yukawa, and consistency with precision electroweak can all be maintained for Delta close to unity. Moreover, such values of Delta can naturally be obtained in string-motivated constructions. The quasi-hidden sector generically contains states charged under SU(5)_GUT as well as gauge singlets, leading to a rich, albeit model-dependent, collider phenomenology.Comment: v3: 40 pages, 3 figures, references added, typos correcte

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

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

Taking Ownership: Our Pledge to Educate All of Detroit's Children

Excellent Schools Detroit represents a broad and diverse cross section of Detroit's education, government, civic and community, parent, organized labor, and philanthropic leaders who are committed to ensuring that all Detroit children receive the great education they deserve. This citywide education plan reflects months of discussions and deliberations by coalition members, as well as a series of six community meetings in November and December, youth focus groups, small group discussions with multiple stakeholders, and other outreach efforts. We appreciate the thoughtful recommendations from the many Detroiters who are as passionate as we are about the need to prepare all students for college, careers, and life in the 21st century

Identification of DNA-Damage DNA-Binding Protein 1 as a Conditional Essential Factor for Cytomegalovirus Replication in Interferon-γ-Stimulated Cells

The mouse cytomegaloviral (MCMV) protein pM27 represents an indispensable factor for viral fitness in vivo selectively, antagonizing signal transducer and activator of transcription 2 (STAT2)-mediated interferon signal transduction. We wished to explore by which molecular mechanism pM27 accomplishes this effect. We demonstrate that pM27 is essential and sufficient to curtail the protein half-life of STAT2 molecules. Pharmacologic inhibition of the proteasome restored STAT2 amounts, leading to poly-ubiquitin-conjugated STAT2 forms. PM27 was found in complexes with an essential host ubiquitin ligase complex adaptor protein, DNA-damage DNA-binding protein (DDB) 1. Truncation mutants of pM27 showed a strict correlation between DDB1 interaction and their ability to degrade STAT2. SiRNA-mediated knock-down of DDB1 restored STAT2 in the presence of pM27 and strongly impaired viral replication in interferon conditioned cells, thus phenocopying the growth attenuation of M27-deficient virus. In a constructive process, pM27 recruits DDB1 to exploit ubiquitin ligase complexes catalyzing the obstruction of the STAT2-dependent antiviral state of cells to permit viral replication

Aurora A–Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy

Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by nonisoform–selective Aurora inhibitors, demonstrates the Aurora B/C-dominant cytokinesis failure and polyploidy phenotypes. Several Aurora inhibitors are in clinical trials for T/B-cell lymphoma, multiple myeloma, leukemia, lung, and breast cancers. Here, we describe an Aurora A–selective inhibitor, LY3295668, which potently inhibits Aurora autophosphorylation and its kinase activity in vitro and in vivo, persistently arrests cancer cells in mitosis, and induces more profound apoptosis than Aurora B or Aurora A/B dual inhibitors without Aurora B inhibition–associated cytokinesis failure and aneuploidy. LY3295668 inhibits the growth of a broad panel of cancer cell lines, including small-cell lung and breast cancer cells. It demonstrates significant efficacy in small-cell lung cancer xenograft and patient-derived tumor preclinical models as a single agent and in combination with standard-of-care agents. LY3295668, as a highly Aurora A–selective inhibitor, may represent a preferred approach to the current pan-Aurora inhibitors as a cancer therapeutic agent