Mass conservative and energy stable finite difference methods for the quasi-incompressible Navier–Stokes–Cahn–Hilliard system:Primitive variable and projection-type schemes

In this paper we describe two fully mass conservative, energy stable, finite difference methods on a staggered grid for the quasi-incompressible Navier-Stokes-Cahn-Hilliard (q-NSCH) system governing a binary incompressible fluid flow with variable density and viscosity. Both methods, namely the primitive method (finite difference method in the primitive variable formulation) and the projection method (finite difference method in a projection-type formulation), are so designed that the mass of the binary fluid is preserved, and the energy of the system equations is always non-increasing in time at the fully discrete level. We also present an efficient, practical nonlinear multigrid method - comprised of a standard FAS method for the Cahn-Hilliard equation, and a method based on the Vanka-type smoothing strategy for the Navier-Stokes equation - for solving these equations. We test the scheme in the context of Capillary Waves, rising droplets and Rayleigh-Taylor instability. Quantitative comparisons are made with existing analytical solutions or previous numerical results that validate the accuracy of our numerical schemes. Moreover, in all cases, mass of the single component and the binary fluid was conserved up to 10 to -8 and energy decreases in time

Towards Minimal S4 Lepton Flavor Model

We study lepton flavor models with the $S_4$ flavor symmetry. We construct simple models with smaller numbers of flavon fields and free parameters, such that we have predictions among lepton masses and mixing angles. The model with a $S_4$ triplet flavon is not realistic, but we can construct realistic models with two triplet flavons, or one triplet and one doublet flavons.Comment: 18 pages, 4 figures, references are adde

Thin accretion disk signatures of slowly rotating black holes in Ho\v{r}ava gravity

In the present work, we consider the possibility of observationally testing Ho\v{r}ava gravity by using the accretion disk properties around slowly rotating black holes of the Kehagias-Sfetsos solution in asymptotically flat spacetimes. The energy flux, temperature distribution, the emission spectrum as well as the energy conversion efficiency are obtained, and compared to the standard slowly rotating general relativistic Kerr solution. Comparing the mass accretion in a slowly rotating Kehagias-Sfetsos geometry in Ho\v{r}ava gravity with the one of a slowly rotating Kerr black hole, we verify that the intensity of the flux emerging from the disk surface is greater for the slowly rotating Kehagias-Sfetsos solution than for rotating black holes with the same geometrical mass and accretion rate. We also present the conversion efficiency of the accreting mass into radiation, and show that the rotating Kehagias-Sfetsos solution provides a much more efficient engine for the transformation of the accreting mass into radiation than the Kerr black holes. Thus, distinct signatures appear in the electromagnetic spectrum, leading to the possibility of directly testing Ho\v{r}ava gravity models by using astrophysical observations of the emission spectra from accretion disks.Comment: 12 pages, 15 figures. V2: 13 pages, clarifications and discussion added; version accepted for publication in Classical and Quantum Gravit

A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering

To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome. In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p < 1 × 10(-4) (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE. No new SNPs were found associated with statin response. The GRS was associated with reduced statin response: 0.0394 mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 × 10(-4)). The GRS was associated with statin response, but the small effect size (˜2% of the average low-density lipoprotein cholesterol reduction) limits applicabilit

The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model

Both Grand Unified symmetries and discrete flavour symmetries are appealing ways to describe apparent structures in the gauge and flavour sectors of the Standard Model. Both symmetries put constraints on the high energy behaviour of the theory. This can give rise to unexpected interplay when building models that possess both symmetries. We investigate on the possibility to combine a Pati-Salam model with the discrete flavour symmetry $S_4$ that gives rise to quark-lepton complementarity. Under appropriate assumptions at the GUT scale, the model reproduces fermion masses and mixings both in the quark and in the lepton sectors. We show that in particular the Higgs sector and the running Yukawa couplings are strongly affected by the combined constraints of the Grand Unified and family symmetries. This in turn reduces the phenomenologically viable parameter space, with high energy mass scales confined to a small region and some parameters in the neutrino sector slightly unnatural. In the allowed regions, we can reproduce the quark masses and the CKM matrix. In the lepton sector, we reproduce the charged lepton masses, including bottom-tau unification and the Georgi-Jarlskog relation as well as the two known angles of the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse hierarchy, and only allowing the neutrino parameters to spread into a range of values between $\lambda^{-2}$ and $\lambda^2$, with $\lambda\simeq0.2$. Finally, our model suggests that the reactor mixing angle is close to its current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for publication in JHE

Strong coupling, discrete symmetry and flavour

We show how two principles - strong coupling and discrete symmetry - can work together to generate the flavour structure of the Standard Model. We propose that in the UV the full theory has a discrete flavour symmetry, typically only associated with tribimaximal mixing in the neutrino sector. Hierarchies in the particle masses and mixing matrices then emerge from multiple strongly coupled sectors that break this symmetry. This allows for a realistic flavour structure, even in models built around an underlying grand unified theory. We use two different techniques to understand the strongly coupled physics: confinement in N=1 supersymmetry and the AdS/CFT correspondence. Both approaches yield equivalent results and can be represented in a clear, graphical way where the flavour symmetry is realised geometrically.Comment: 31 pages, 5 figures, updated references and figure

The minimal adjoint-SU (5) x Z(4) GUT model

An extension of the adjoint SU (5) model with a flavour symmetry based on the Z(4) group is investigated. The Z(4) symmetry is introduced with the aim of leading the up-and down-quark mass matrices to the Nearest-Neighbour-Interaction form. As a consequence of the discrete symmetry embedded in the SU (5) gauge group, the charged lepton mass matrix also gets the same form. Within this model, light neutrinos get their masses through type-I, type-III and one-loop radiative seesaw mechanisms, implemented, respectively, via a singlet, a triplet and an octet from the adjoint fermionic 24 fields. It is demonstrated that the neutrino phenomenology forces the introduction of at least three 24 fermionic multiplets. The symmetry SU (5) x Z(4) allows only two viable zero textures for the effective neutrino mass matrix. It is showed that one texture is only compatible with normal hierarchy and the other with inverted hierarchy in the light neutrino mass spectrum. Finally, it is also demonstrated that Z(4) freezes out the possibility of proton decay through exchange of coloured Higgs triplets at tree-level

Sex-Related Differences in Medically Treated Moderate Aortic Stenosis

BackgroundRecent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS.MethodsIn this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement.ResultsA total of 1895 patients with moderate AS (age 73 ± 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3- and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) (p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes.ConclusionsLV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed.</p

Computational Identification of Transcriptional Regulators in Human Endotoxemia

One of the great challenges in the post-genomic era is to decipher the underlying principles governing the dynamics of biological responses. As modulating gene expression levels is among the key regulatory responses of an organism to changes in its environment, identifying biologically relevant transcriptional regulators and their putative regulatory interactions with target genes is an essential step towards studying the complex dynamics of transcriptional regulation. We present an analysis that integrates various computational and biological aspects to explore the transcriptional regulation of systemic inflammatory responses through a human endotoxemia model. Given a high-dimensional transcriptional profiling dataset from human blood leukocytes, an elementary set of temporal dynamic responses which capture the essence of a pro-inflammatory phase, a counter-regulatory response and a dysregulation in leukocyte bioenergetics has been extracted. Upon identification of these expression patterns, fourteen inflammation-specific gene batteries that represent groups of hypothetically ‘coregulated’ genes are proposed. Subsequently, statistically significant cis-regulatory modules (CRMs) are identified and decomposed into a list of critical transcription factors (34) that are validated largely on primary literature. Finally, our analysis further allows for the construction of a dynamic representation of the temporal transcriptional regulatory program across the host, deciphering possible combinatorial interactions among factors under which they might be active. Although much remains to be explored, this study has computationally identified key transcription factors and proposed a putative time-dependent transcriptional regulatory program associated with critical transcriptional inflammatory responses. These results provide a solid foundation for future investigations to elucidate the underlying transcriptional regulatory mechanisms under the host inflammatory response. Also, the assumption that coexpressed genes that are functionally relevant are more likely to share some common transcriptional regulatory mechanism seems to be promising, making the proposed framework become essential in unravelling context-specific transcriptional regulatory interactions underlying diverse mammalian biological processes