Lepton flavour violation in the MSSM

We derive new constraints on the quantities delta_{XY}^{ij}, X,Y=L,R, which parametrise the flavour-off-diagonal terms of the charged slepton mass matrix in the MSSM. Considering mass and anomalous magnetic moment of the electron we obtain the bound |delta^{13}_{LL} delta^{13}_{RR}|<0.1 for tan beta=50, which involves the poorly constrained element delta^{13}_{RR}. We improve the predictions for the decays tau -> mu gamma, tau -> e gamma and mu -> e gamma by including two-loop corrections which are enhanced if tan beta is large. The finite renormalisation of the PMNS matrix from soft SUSY-breaking terms is derived and applied to the charged-Higgs-lepton vertex. We find that the experimental bound on BR(tau -> e gamma) severely limits the size of the MSSM loop correction to the PMNS element U_{e3}, which is important for the proper interpretation of a future U_{e3} measurement. Subsequently we confront our new values for delta^{ij}_{LL} with a GUT analysis. Further, we include the effects of dimension-5 Yukawa terms, which are needed to fix the Yukawa unification of the first two generations. If universal supersymmetry breaking occurs above the GUT scale, we find the flavour structure of the dimension-5 Yukawa couplings tightly constrained by mu -> e gamma.Comment: 37 pages, 15 figures; typo in Equation (35) and (49) correcte

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

A Comprehensive Analysis of Electric Dipole Moment Constraints on CP-violating Phases in the MSSM

We analyze the constraints placed on individual, flavor diagonal CP-violating phases in the minimal supersymmetric extension of the Standard Model (MSSM) by current experimental bounds on the electric dipole moments (EDMs) of the neutron, Thallium, and Mercury atoms. We identify the four CP-violating phases that are individually highly constrained by current EDM bounds, and we explore how these phases and correlations among them are constrained by current EDM limits. We also analyze the prospective implications of the next generation of EDM experiments. We point out that all other CP-violating phases in the MSSM are not nearly as tightly constrained by limits on the size of EDMs. We emphasize that a rich set of phenomenological consequences is potentially associated with these generically large EDM-allowed phases, ranging from B physics, electroweak baryogenesis, and signals of CP-violation at the CERN Large Hadron Collider and at future linear colliders. Our numerical study takes into account the complete set of contributions from one- and two-loop EDMs of the electron and quarks, one- and two-loop Chromo-EDMs of quarks, the Weinberg 3-gluon operator, and dominant 4-fermion CP-odd operator contributions, including contributions which are both included and not included yet in the CPsuperH2.0 package. We also introduce an open-source numerical package, 2LEDM, which provides the complete set of two-loop electroweak diagrams contributing to the electric dipole moments of leptons and quarks.Comment: 23 pages, 11 figures; v2: references added, minor change

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1β, INF-α and INF-β, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction

High-Resolution Melting Analysis as a Powerful Tool to Discriminate and Genotype Pseudomonas savastanoi Pathovars and Strains

Pseudomonas savastanoi is a serious pathogen of Olive, Oleander, Ash, and several other Oleaceae. Its epiphytic or endophytic presence in asymptomatic plants is crucial for the spread of Olive and Oleander knot disease, as already ascertained for P. savastanoi pv. savastanoi (Psv) on Olive and for pv. nerii (Psn) on Oleander, while no information is available for pv. fraxini (Psf) on Ash. Nothing is known yet about the distribution on the different host plants and the real host range of these pathovars in nature, although cross-infections were observed following artificial inoculations. A multiplex Real-Time PCR assay was recently developed to simultaneously and quantitatively discriminate in vitro and in planta these P. savastanoi pathovars, for routine culture confirmation and for epidemiological and diagnostical studies. Here an innovative High-Resolution Melting Analysis (HRMA)-based assay was set up to unequivocally discriminate Psv, Psn and Psf, according to several single nucleotide polymorphisms found in their Type Three Secretion System clusters. The genetic distances among 56 P. savastanoi strains belonging to these pathovars were also evaluated, confirming and refining data previously obtained by fAFLP. To our knowledge, this is the first time that HRMA is applied to a bacterial plant pathogen, and one of the few multiplex HRMA-based assays developed so far. This protocol provides a rapid, sensitive, specific tool to differentiate and detect Psv, Psn and Psf strains, also in vivo and against other related bacteria, with lower costs than conventional multiplex Real-Time PCR. Its application is particularly suitable for sanitary certification programs for P. savastanoi, aimed at avoiding the spreading of this phytopathogen through asymptomatic plants

Different SO(10) Paths to Fermion Masses and Mixings

Recently SO(10) models with type-II see-saw dominance have been proposed as a promising framework for obtaining Grand Unification theories with approximate Tri-bimaximal (TB) mixing in the neutrino sector. We make a general study of SO(10) models with type-II see-saw dominance and show that an excellent fit can be obtained for fermion masses and mixings, also including the neutrino sector. To make this statement more significant we compare the performance of type-II see-saw dominance models in fitting the fermion masses and mixings with more conventional models which have no built-in TB mixing in the neutrino sector. For a fair comparison the same input data and fitting procedure is adopted for all different theories. We find that the type-II dominance models lead to an excellent fit, comparable with the best among the available models, but the tight structure of this framework implies a significantly larger amount of fine tuning with respect to other approaches.Comment: 24 pages, References and minor wording changes adde

High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status

Family history of cancer (FHC) is a hallmark of cancer risk and an independent predictor of outcome, albeit with uncertain biologic foundations. We previously showed that FHC-high patients experienced prolonged overall (OS) and progression-free survival (PFS) following PD-1/PD-L1 checkpoint inhibitors. To validate our findings in patients with NSCLC, we evaluated two multicenter cohorts of patients with metastatic NSCLC receiving either first-line pembrolizumab or chemotherapy. From each cohort, 607 patients were randomly case–control matched accounting for FHC, age, performance status, and disease burden. Compared to FHC-low/negative, FHC-high patients experienced longer OS (HR 0.67 [95% CI 0.46–0.95], p = 0.0281), PFS (HR 0.65 [95% CI 0.48–0.89]; p = 0.0074) and higher disease control rates (DCR, 86.4% vs 67.5%, p = 0.0096), within the pembrolizumab cohort. No significant associations were found between FHC and OS/PFS/DCR within the chemotherapy cohort. We explored the association between FHC and somatic DNA damage response (DDR) gene alterations as underlying mechanism to our findings in a parallel cohort of 118 NSCLC, 16.9% of whom were FHC-high. The prevalence of ≥ 1 somatic DDR gene mutation was 20% and 24.5% (p = 0.6684) in FHC-high vs. FHC-low/negative, with no differences in tumor mutational burden (6.0 vs. 7.6 Mut/Mb, p = 0.6018) and tumor cell PD-L1 expression. FHC-high status identifies NSCLC patients with improved outcomes from pembrolizumab but not chemotherapy, independent of somatic DDR gene status. Prospective studies evaluating FHC alongside germline genetic testing are warranted