11 research outputs found
Charming CP Violation and Dipole Operators from RS Flavor Anarchy
Recently the LHCb collaboration reported evidence for direct CP violation in
charm decays. The value is sufficiently large that either substantially
enhanced Standard Model contributions or non-Standard Model physics is required
to explain it. In the latter case only a limited number of possibilities would
be consistent with other existing flavor-changing constraints. We show that
warped extra dimensional models that explain the quark spectrum through flavor
anarchy can naturally give rise to contributions of the size required to
explain the the LHCb result. The D meson asymmetry arises through a sizable
CP-violating contribution to a chromomagnetic dipole operator. This happens
naturally without introducing inconsistencies with existing constraints in the
up quark sector. We discuss some subtleties in the loop calculation that are
similar to those in Higgs to \gamma\gamma. Loop-induced dipole operators in
warped scenarios and their composite analogs exhibit non-trivial dependence on
the Higgs profile, with the contributions monotonically decreasing when the
Higgs is pushed away from the IR brane. We show that the size of the dipole
operator quickly saturates as the Higgs profile approaches the IR brane,
implying small dependence on the precise details of the Higgs profile when it
is quasi IR localized. We also explain why the calculation of the coefficient
of the lowest dimension 5D operator is guaranteed to be finite. This is true
not only in the charm sector but also with other radiative processes such as
electric dipole moments, b to s\gamma, \epsilon'/\epsilon_K and \mu\ to
e\gamma. We furthermore discuss the interpretation of this contribution within
the framework of partial compositeness in four dimensions and highlight some
qualitative differences between the generic result of composite models and that
obtained for dynamics that reproduces the warped scenario.Comment: 14 page
The angiotensin type 1 receptor antagonist, eprosartan, attenuates the progression of renal disease in spontaneously hypertensive stroke-prone rats with accelerated hypertension
ABSTRACT The effects of the angiotensin type 1 (AT 1 ) receptor antagonist, eprosartan, were studied in a model of severe, chronic hypertension. Treatment of male spontaneously hypertensive stroke prone rats (SHR-SP) fed a high-fat, high-salt diet with eprosartan (60 mg/kg/day i.p.) for 12 weeks resulted in a lowering of blood pressure (250 Ϯ 9 versus 284 Ϯ 8 mm Hg), renal expression of transforming growth factor- mRNA (1.5 Ϯ 0.2 versus 5.4 Ϯ 1.4) and the matrix components: plasminogen activator inhibitor-1 (5.2 Ϯ 1.4 versus 31.4 Ϯ 10.7), fibronectin (2.2 Ϯ 0.6 versus 8.2 Ϯ 2.2), collagen I-␣1 (5.6 Ϯ 2.0 versus 23.8 Ϯ 7.3), and collagen III (2.7 Ϯ 0.9 versus 7.6 Ϯ 2.1). Data were corrected for rpL32 mRNA expression and expressed relative to Wistar Kyoto (WKY) rats [ϭ1.0]. Expression of fibronectin protein was also lowered by eprosartan (0.8 Ϯ 0.1 versus 1.9 Ϯ 0.5), relative to WKY rats. Eprosartan provided significant renoprotection to SHR-SP rats as measured by decreased proteinuria (22 Ϯ 2 versus 127 Ϯ 13 mg/day) and histological evidence of active renal damage (5 Ϯ 2 versus 195 Ϯ 6) and renal fibrosis (5.9 Ϯ 0.7 versus 16.4 Ϯ 1.9) in vehicle-versus eprosartantreated rats, respectively. Our results demonstrated that AT 1 receptor blockade with eprosartan can reduce blood pressure and preserve renal structure and function in this model of severe, chronic hypertension. These effects were accompanied by a decreased renal expression of transforming growth factor-1, plasminogen activator inhibitor-1, and several other extracellular matrix proteins compared with vehicle-treated SHR-SP. The renin-angiotensin system is a major regulator of blood pressure within the body, through the maintenance of vascular tone and sodium homeostasis. The renin-angiotensin system has, however, also been implicated in a number of diseases, characterized by remodeling and fibrosis, including forms of progressive renal disease. The generation of angiotensin II can lead to organ damage through both mitogenic activity and profibrotic remodeling. Eprosartan is a potent (K i ϭ 1.4 nM) angiotensin II receptor antagonist selective for the AT 1 subtype. AT 1 receptor antagonists have been shown to attenuate the effects of exogenous angiotensin II Materials and Methods Experimental Design. Male SHR-SP rats, progeny from the strain developed b
Warped dipole completed, with a tower of Higgs bosons
In the context of warped extra-dimensional models which address both the Planck-weak- and flavor-hierarchies of the Standard Model (SM), it has been argued that certain observables can be calculated within the 5D effective field theory only with the Higgs field propagating in the bulk of the extra dimension, just like other SM fields. The related studies also suggested an interesting form of decoupling of the heavy Kaluza-Klein (KK) fermion states in the warped 5D SM in the limit where the profile of the SM Higgs approaches the IR brane. We demonstrate that a similar phenomenon occurs when we include the mandatory KK excitations of the SM Higgs in loop diagrams giving dipole operators for SM fermions, where the earlier work only considered the SM Higgs (zero mode). In particular, in the limit of a quasi IR-localized SM Higgs, the effect from summing over KK Higgs modes is unsuppressed (yet finite), in contrast to the naive expectation that KK Higgs modes decouple as their masses become large. In this case, a wide range of KK Higgs modes have quasi-degenerate masses and enhanced couplings to fermions relative to those of the SM Higgs, which contribute to the above remarkable result. In addition, we find that the total contribution from KK Higgs modes in general can be comparable to that from the SM Higgs alone. It is also interesting that KK Higgs couplings to KK fermions of the same chirality as the corresponding SM modes have an unsuppressed overall contribution, in contrast to the result from the earlier studies involving the SM Higgs. Our studies suggest that KK Higgs bosons are generally an indispensable part of the warped 5D SM, and their phenomenology such as signals at the LHC are worth further investigation
Single-Scale Natural SUSY
We consider the prospects for natural SUSY models consistent with current
data. Recent constraints make the standard paradigm unnatural so we consider
what could be a minimal extension consistent with what we now know. The most
promising such scenarios extend the MSSM with new tree-level Higgs interactions
that can lift its mass to at least 125 GeV and also allow for flavor-dependent
soft terms so that the third generation squarks are lighter than current bounds
on the first and second generation squarks. We argue that a common feature of
almost all such models is the need for a new scale near 10 TeV, such as a scale
of Higgsing or confinement of a new gauge group. We consider the question
whether such a model can naturally derive from a single mass scale associated
with supersymmetry breaking. Most such models simply postulate new scales,
leaving their proximity to the scale of MSSM soft terms a mystery. This
coincidence problem may be thought of as a mild tuning, analogous to the usual
mu problem. We find that a single mass scale origin is challenging, but suggest
that a more natural origin for such a new dynamical scale is the gravitino
mass, m_{3/2}, in theories where the MSSM soft terms are a loop factor below
m_{3/2}. As an example, we build a variant of the NMSSM where the singlet S is
composite, and the strong dynamics leading to compositeness is triggered by
masses of order m_{3/2} for some fields. Our focus is the Higgs sector, but our
model is compatible with a light stop (with the other generation squarks heavy,
or with R-parity violation or another mechanism to hide them from current
searches). All the interesting low-energy mass scales, including linear terms
for S playing a key role in EWSB, arise dynamically from the single scale
m_{3/2}. However, numerical coefficients from RG effects and wavefunction
factors in an extra dimension complicate the otherwise simple story.Comment: 32 pages, 3 figures; version accepted by JHE
QCD and strongly coupled gauge theories : challenges and perspectives
We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe
Detection of Late Intermediates in Virus Capsid Assembly by Charge Detection Mass Spectrometry
The
assembly of hundreds of identical proteins into an icosahedral
virus capsid is a remarkable feat of molecular engineering. How this
occurs is poorly understood. Key intermediates have been anticipated
at the end of the assembly reaction, but it has not been possible
to detect them. In this work we have used charge detection mass spectrometry
to identify trapped intermediates from late in the assembly of the
hepatitis B virus <i>T</i> = 4 capsid, a complex of 120
protein dimers. Prominent intermediates are found with 104/105, 110/111,
and 117/118 dimers. Cryo-EM observations indicate the intermediates
are incomplete capsids and, hence, on the assembly pathway. On the
basis of their stability and kinetic accessibility we have proposed
plausible structures. The prominent trapped intermediate with 104
dimers is attributed to an icosahedron missing two neighboring facets,
the 111-dimer species is assigned to an icosahedron missing a single
facet, and the intermediate with 117 dimers is assigned to a capsid
missing a ring of three dimers in the center of a facet
Renoprotective effects of carvedilol in hypertensive-stroke prone rats may involve inhibition of TGFβ expression
1. The effect of carvedilol on renal function, structure and expression of TGFβ and the matrix proteins fibronectin, collagen I and collagen III, was evaluated in spontaneously hypertensive stroke-prone (SHR-SP) rats fed a high fat, high salt diet. 2. Carvedilol treatment for 11 to 18 weeks did not alter systolic blood pressure in SHR-SP rats, however, it resulted in a significant reduction in heart rate. 3. Carvedilol treatment reduced renal fibrosis and total, active and chronic renal damage to levels approaching those of WKY rats on a normal diet. 4. Urinary protein excretion was higher in SHR-SP rats (51±10 mg day(−1)) than WKY rats (18±2 mg day(−1)) and this was further increased when SHR-SP rats were fed a high fat, high salt diet (251±120 mg day(−1)). Treatment with carvedilol resulted in significantly lower urinary protein excretion (37±15 mg day(−1)). 5. The expression of TGFβ mRNA was significantly higher in SHR-SP rats compared to WKY rats and a further increase was observed when rats were fed a high fat, high salt diet. Renal TGFβ expression was significantly reduced by treatment with carvedilol. The expression of fibronectin and collagen I and collagen III mRNA showed a pattern similar to that observed with TGFβ mRNA expression. Collagen I mRNA expression followed a pattern similar to renal fibrosis. 6. These data indicate that carvedilol can provide significant renal protection in the absence of any antihypertensive activity and that the mechanisms involved in this action may include reduced expression of profibrotic factors such as TGFβ
Discovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists
Elaboration of the oxazolidinedione
series led to replacement of
the exocyclic amides with substituted benzimidazoles. The structure–activity
relationship (SAR) exploration resulted in the discovery of potent
and selective nonsteroidal mineralocorticoid receptor (MR) antagonists
with significantly improved microsomal stability and pharmacokinetic
(PK) profile relative to the HTS hit <b>1a</b>. One compound <b>2p</b> possessed comparable efficacy as spironolactone (SPL) at
100 mg/kg (p.o.) in the rat natriuresis model. As such, this series
was validated as a lead series for further optimization