137 research outputs found
Model-Independent Searches for New Quarks at the LHC
New vector-like quarks can have sizable couplings to first generation quarks
without conflicting with current experimental constraints. The coupling with
valence quarks and unique kinematics make single production the optimal
discovery process. We perform a model-independent analysis of the discovery
reach at the Large Hadron Collider for new vector-like quarks considering
single production and subsequent decays via electroweak interactions. An early
LHC run with 7 TeV center of mass energy and 1 fb-1 of integrated luminosity
can probe heavy quark masses up to 1 TeV and can be competitive with the
Tevatron reach of 10 fb-1. The LHC with 14 TeV center of mass energy and 100
fb-1 of integrated luminosity can probe heavy quark masses up to 3.7 TeV for
order one couplings.Comment: 37 pages, 11 figures, 7 table
The role of the ER stress response protein PERK in rhodopsin retinitis pigmentosa
Mutations in rhodopsin, the light sensitive protein of rod cells, are the most common cause of dominant retinitis pigmentosa (RP), a type of inherited blindness caused by the dysfunction and death of photoreceptor cells. The P23H mutation, the most frequent single cause of RP in the USA, causes rhodopsin misfolding and induction of the unfolded protein response (UPR), an adaptive ER stress response and signalling network that aims to enhance the folding and degradation of misfolded proteins to restore proteostasis. Prolonged UPR activation, and in particular the PERK branch, can reduce protein synthesis and initiate cell death through induction of pro-apoptotic pathways. Here, we investigated the effect of pharmacological PERK inhibition on retinal disease process in the P23H-1 transgenic rat model of retinal degeneration. PERK inhibition with GSK2606414A led to an inhibition of eIF2α phosphorylation, which correlated with reduced ERG function and decreased photoreceptor survival at both high and low doses of PERK inhibitor. Additionally, PERK inhibition increased the incidence of inclusion formation in cultured cells overexpressing P23H rod opsin, and increased rhodopsin aggregation in the P23H-1 rat retina, suggesting enhanced P23H misfolding and aggregation. In contrast, treatment of P23H-1 rats with an inhibitor of eIF2α phosphatase, salubrinal, led to improved photoreceptor survival. Collectively, these data suggest the activation of PERK is part of a protective response to mutant rhodopsin that ultimately limits photoreceptor cell death
The Effective Lagrangian for Bulk Fermions in Models with Extra Dimensions
We compute the dimension 6 effective Lagrangian arising from the tree level
integration of an arbitrary number of bulk fermions in models with warped extra
dimensions. The coefficients of the effective operators are written in terms of
simple integrals of the metric and are valid for arbitrary warp factors, with
or without an infrared brane, and for a general Higgs profile. All relevant
tree level fermion effects in electroweak and flavor observables can be
computed using this effective Lagrangian.Comment: 22 pages. V2: typos corrected, matches published versio
Bounds and Decays of New Heavy Vector-like Top Partners
We study the phenomenology of new heavy vector-like fermions that couple to
the third generation quarks via Yukawa interactions, covering all the allowed
representations under the standard model gauge groups. We first review tree and
loop level bounds on these states. We then discuss tree level decays and
loop-induced decays to photon or gluon plus top. The main decays at tree level
are to W b and/or Z and Higgs plus top via the new Yukawa couplings. The
radiative loop decays turn out to be quite close to the naive estimate: in all
cases, in the allowed perturbative parameter space, the branching ratios are
mildly sensitive on the new Yukawa couplings and small. We therefore conclude
that the new states can be observed at the LHC and that the tree level decays
can allow to distinguish the different representations. Moreover, the
observation of the radiative decays at the LHC would suggest a large Yukawa
coupling in the non-perturbative regime.Comment: 32 pages, 2 tables, 10 figure
EWPD Constraints on Flavor Symmetric Vector Fields
Electroweak precision data constraints on flavor symmetric vector fields are
determined. The flavor multiplets of spin one that we examine are the complete
set of fields that couple to quark bi-linears at tree level while not initially
breaking the quark global flavor symmetry group. Flavor safe vector masses
proximate to, and in some cases below, the electroweak symmetry breaking scale
are found to be allowed. Many of these fields provide a flavor safe mechanism
to explain the t tbar forward backward anomaly, and can simultaneously
significantly raise the allowed values of the Standard Model Higgs mass
consistent with electroweak precision data.Comment: Matches version published in JHE
The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy
Inherited mutations in the rod visual pigment, rhodopsin, cause the degenerative blinding condition, retinitis pigmentosa (RP). Over 150 different mutations in rhodopsin have been identified and, collectively, they are the most common cause of autosomal dominant RP (adRP). Mutations in rhodopsin are also associated with dominant congenital stationary night blindness (adCSNB) and, less frequently, recessive RP (arRP). Recessive RP is usually associated with loss of rhodopsin function, whereas the dominant conditions are a consequence of gain of function and/or dominant negative activity. The in-depth characterisation of many rhodopsin mutations has revealed that there are distinct consequences on the protein structure and function associated with different mutations. Here we categorise rhodopsin mutations into seven discrete classes; with defects ranging from misfolding and disruption of proteostasis, through mislocalisation and disrupted intracellular traffic to instability and altered function. Rhodopsin adRP offers a unique paradigm to understand how disturbances in photoreceptor homeostasis can lead to neuronal cell death. Furthermore, a wide range of therapies have been tested in rhodopsin RP, from gene therapy and gene editing to pharmacological interventions. The understanding of the disease mechanisms associated with rhodopsin RP and the development of targeted therapies offer the potential of treatment for this currently untreatable neurodegeneration
Impact of massive neutrinos on the Higgs self-coupling and electroweak vacuum stability
The presence of right-handed neutrinos in the type I seesaw mechanism may
lead to significant corrections to the RG evolution of the Higgs self-coupling.
Compared to the Standard Model case, the Higgs mass window can become narrower,
and the cutoff scale become lower. Naively, these effects decrease with
decreasing right-handed neutrino mass. However, we point out that the unknown
Dirac Yukawa matrix may impact the vacuum stability constraints even in the low
scale seesaw case not far away from the electroweak scale, hence much below the
canonical seesaw scale of 10^15 GeV. This includes situations in which
production of right-handed neutrinos at colliders is possible. We illustrate
this within a particular parametrization of the Dirac Yukawas and with explicit
low scale seesaw models. We also note the effect of massive neutrinos on the
top quark Yukawa coupling, whose high energy value can be increased with
respect to the Standard Model case.Comment: 17 pages, 7 figures, minor revisions, version to appear in JHE
Flavor Violating Higgs Decays
We study a class of nonstandard interactions of the newly discovered 125 GeV
Higgs-like resonance that are especially interesting probes of new physics:
flavor violating Higgs couplings to leptons and quarks. These interaction can
arise in many frameworks of new physics at the electroweak scale such as two
Higgs doublet models, extra dimensions, or models of compositeness. We rederive
constraints on flavor violating Higgs couplings using data on rare decays,
electric and magnetic dipole moments, and meson oscillations. We confirm that
flavor violating Higgs boson decays to leptons can be sizeable with, e.g., h ->
tau mu and h -> tau e branching ratios of order 10% perfectly allowed by low
energy constraints. We estimate the current LHC limits on h -> tau mu and h ->
tau e decays by recasting existing searches for the SM Higgs in the tau-tau
channel and find that these bounds are already stronger than those from rare
tau decays. We also show that these limits can be improved significantly with
dedicated searches and we outline a possible search strategy. Flavor violating
Higgs decays therefore present an opportunity for discovery of new physics
which in some cases may be easier to access experimentally than flavor
conserving deviations from the Standard Model Higgs framework.Comment: 39 pages, 12 figures, 3 tables; v2: Improved referencing, updated mu
-> 3e bounds to include large loop contributions, corrected single top
constraints; conclusions unchanged; matches version to be published in JHEP;
v3: included 2-loop contributions in mu -> e conversion, improved discussion
of tau -> 3 mu and of EDM constraints on FV top-Higgs couplings; conclusions
unchange
Rescue of mutant rhodopsin traffic by metformin-induced AMPK activation accelerates photoreceptor degeneration
Protein misfolding caused by inherited mutations leads to loss of protein function and potentially toxic 'gain of function', such as the dominant P23H rhodopsin mutation that causes retinitis pigmentosa (RP). Here, we tested whether the AMPK activator metformin could affect the P23H rhodopsin synthesis and folding. In cell models, metformin treatment improved P23H rhodopsin folding and traffic. In animal models of P23H RP, metformin treatment successfully enhanced P23H traffic to the rod outer segment, but this led to reduced photoreceptor function and increased photoreceptor cell death. The metformin-rescued P23H rhodopsin was still intrinsically unstable and led to increased structural instability of the rod outer segments. These data suggest that improving the traffic of misfolding rhodopsin mutants is unlikely to be a practical therapy, because of their intrinsic instability and long half-life in the outer segment, but also highlights the potential of altering translation through AMPK to improve protein function in other protein misfolding diseases
The Custodial Randall-Sundrum Model: From Precision Tests to Higgs Physics
We reexamine the Randall-Sundrum (RS) model with enlarged gauge symmetry
SU(2)_L x SU(2)_R x U(1)_X x P_LR in the presence of a brane-localized Higgs
sector. In contrast to the existing literature, we perform the Kaluza-Klein
(KK) decomposition within the mass basis, which avoids the truncation of the KK
towers. Expanding the low-energy spectrum as well as the gauge couplings in
powers of the Higgs vacuum expectation value, we obtain analytic formulas which
allow for a deep understanding of the model-specific protection mechanisms of
the T parameter and the left-handed Z-boson couplings. In particular, in the
latter case we explain which contributions escape protection and identify them
with the irreducible sources of P_LR symmetry breaking. We furthermore show
explicitly that no protection mechanism is present in the charged-current
sector confirming existing model-independent findings. The main focus of the
phenomenological part of our work is a detailed discussion of Higgs-boson
couplings and their impact on physics at the CERN Large Hadron Collider. For
the first time, a complete one-loop calculation of all relevant Higgs-boson
production and decay channels is presented, incorporating the effects stemming
from the extended electroweak gauge-boson and fermion sectors.Comment: 74 pages, 13 figures, 3 tables. v2: Matches version published in JHE
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