Flavour symmetries in the SMEFT

We analyse how $U(3)^5$ and $U(2)^5$ flavour symmetries act on the Standard Model Effective Field Theory, providing an organising principle to classify the large number of dimension-six operators involving fermion fields. A detailed counting of such operators, at different order in the breaking terms of both these symmetries, is presented. A brief discussion about possible deviations from these two reference cases, and a simple example of the usefulness of this classification scheme for high-$p_T$ analyses at the LHC, are also presented.Comment: 31 pages, 13 Table

HighPT: A Tool for high-pTp_T Drell-Yan Tails Beyond the Standard Model

HighPT is a Mathematica package for the analysis of high-energy data of semileptonic transitions at hadron colliders. It allows to compute high-$p_T$ tail observables for semileptonic processes, i.e. Drell-Yan cross sections, for dilepton and monolepton final states at the LHC. These observables can be calculated at tree level within the Standard Model Effective Field Theory, including the relevant operators up to dimension eight to ensure a consistent description of the cross section including terms of $\mathcal{O}(\Lambda^{-4})$ in the cutoff scale $\Lambda$. For New Physics models with new mediators that can be resolved at LHC energies, HighPT can also account for the full propagation effects of these new bosonic states at tree level. Using the available data from the high-$p_T$ tails in the relevant LHC run-II searches by the ATLAS and CMS collaborations, HighPT can also construct the corresponding likelihoods for all possible flavors of the leptonic final states. As an illustration, we derive and compare constraints on Wilson coefficients at different orders in the Effective Field Theory expansion, and we investigate lepton flavor violation for the $S_3$ leptoquark model. The HighPT code is publicly available at https://github.com/HighPT/HighPT.Comment: 34 page

Drell-Yan Tails Beyond the Standard Model

We investigate the high-$p_T$ tails of the $pp\to \ell \nu$ and $pp \to \ell \ell$ Drell-Yan processes as probes of New Physics in semileptonic interactions with an arbitrary flavor structure. For this purpose, we provide a general decomposition of the $2\to2$ scattering amplitudes in terms of form-factors that we match to specific scenarios, such as the Standard Model Effective Field Theory (SMEFT), including all relevant operators up to dimension-$8$, as well as ultraviolet scenarios giving rise to tree-level exchange of new bosonic mediators with masses at the TeV scale. By using the latest LHC run-II data in the monolepton ($e\nu$, $\mu\nu$, $\tau\nu$) and dilepton ($ee$, $\mu\mu$, $\tau\tau$, $e\mu$, $e\tau$, $\mu\tau$) production channels, we derive constraints on the SMEFT Wilson coefficients for semileptonic four-fermion and dipole operators with the most general flavor structure, as well as on all possible leptoquark models. For the SMEFT, we discuss the range of validity of the EFT description, the relevance of $\mathcal{O}(1/\Lambda^2)$ and $\mathcal{O}(1/\Lambda^4)$ truncations, the impact of $d=8$ operators and the effects of different quark-flavor alignments. Finally, as a highlight, we extract for several New Physics scenarios the combined limits from high-$p_T$ processes, electroweak pole measurements and low-energy flavor data for the $b\to c\tau\nu$ transition, showing the complementarity between these different observables. Our results are compiled in {\tt HighPT}, a package in {\tt Mathematica} which provides a simple way for users to extract the Drell-Yan tails likelihoods for semileptonic effective operators and for leptoquark models.Comment: 61 pages, 19 figure

Analysis of oxygenation and other risk factors of retinopathy of prematurity in preterm babies

Maintaining adequate and stable blood oxygen level is important for preterm babies to avoid the risk of brain, lung and retinal injury such as retinopathy of prematurity (ROP). However, wide disparities in policies and practices of oxygenation in preterm babies exist among neonatal care providers as it is still unclear which best method of monitoring and what features of oxygen measurements are important to clinician’s interpretations for assessing preterm babies at risk of developing severe ROP or unstable health condition. This thesis consists of two projects: NZ-ROP that examines multiple factors of severe ROP including summary statistics (mean, standard deviation (SD), coefficient of variation (CV) and desaturation) for oxygen saturation (OS) features in very extreme preterm babies, and NZ-LP that investigates the efficacy of some of these statistics for health monitoring of late preterm babies. The OS data in NZ-ROP were recorded using modified oximeters that have offsets and inherent software artefact, both of which mask the actual saturation for certain OS ranges and may complicate the choice of methods in the analyses. Therefore, novel algorithms involving linear and quadratic interpolations are developed, implemented on the New Zealand data, and validated using the data of a UK preterm baby, as recorded from offsets and non-offsets oximeters. For all data sets, the algorithms produced saturation distributions that were very close to those obtained from the non-offset oximeter. The algorithms perform within the recommended standards of commercial oximeters currently used in the clinical practice. ROP is a multifactorial disease, with oxygenation fluctuations as one of the key contributors. The all-subsets logistic regression, robust and generalised additive statistical modelling, along with a model averaging approach, are applied in NZ-ROP to determine the relationship of variability and level of OS with severe ROP, and the extent of contribution of various clinical predictors to the severity of this eye disease. Desaturation, as a measure of OS variability, has the strongest association with severe ROP among all OS statistics, in particular, the risk of severe ROP is almost three times higher in babies that exhibit greater occurrences of desaturation episodes. Additionally, this study identifies longer periods of ventilation support, frequent desaturation events, extreme prematurity and low birth weight as the most important factors that substantially exacerbate the severity of ROP, and therefore signify babies’ underlying condition of being severely ill. Persistent cardiorespiratory instabilities prior to hospital discharge may expose preterm babies to a greater risk of neuro-developmental impairments. In NZ-LP, the statistical summaries of mean, SD and CV are computed from the OS measurements of healthy stable and unstable babies, and the performance of these statistics in detecting the unstable babies is evaluated using an extremeness index for outlying data and a hierarchical clustering technique. With SD and CV, the clinically unstable babies were very well separated from the group of stable babies, wherein, the separation was even more apparent with the use of CV. These suggest that measures of variability could be better than saturation level for highlighting babies’ underlying instability due to immature physiological systems, but the combination of variability and level through the CV are believed to be even better. Identification and summarisation of useful OS features quantitatively hold great promise for improved monitoring of oxygenation instability and diagnosis of severe ROP for preterm babies

Live Imaging at the Onset of Cortical Neurogenesis Reveals Differential Appearance of the Neuronal Phenotype in Apical versus Basal Progenitor Progeny

The neurons of the mammalian brain are generated by progenitors dividing either at the apical surface of the ventricular zone (neuroepithelial and radial glial cells, collectively referred to as apical progenitors) or at its basal side (basal progenitors, also called intermediate progenitors). For apical progenitors, the orientation of the cleavage plane relative to their apical-basal axis is thought to be of critical importance for the fate of the daughter cells. For basal progenitors, the relationship between cell polarity, cleavage plane orientation and the fate of daughter cells is unknown. Here, we have investigated these issues at the very onset of cortical neurogenesis. To directly observe the generation of neurons from apical and basal progenitors, we established a novel transgenic mouse line in which membrane GFP is expressed from the beta-III-tubulin promoter, an early pan-neuronal marker, and crossed this line with a previously described knock-in line in which nuclear GFP is expressed from the Tis21 promoter, a pan-neurogenic progenitor marker. Mitotic Tis21-positive basal progenitors nearly always divided symmetrically, generating two neurons, but, in contrast to symmetrically dividing apical progenitors, lacked apical-basal polarity and showed a nearly randomized cleavage plane orientation. Moreover, the appearance of beta-III-tubulin–driven GFP fluorescence in basal progenitor-derived neurons, in contrast to that in apical progenitor-derived neurons, was so rapid that it suggested the initiation of the neuronal phenotype already in the progenitor. Our observations imply that (i) the loss of apical-basal polarity restricts neuronal progenitors to the symmetric mode of cell division, and that (ii) basal progenitors initiate the expression of neuronal phenotype already before mitosis, in contrast to apical progenitors

miRNA-Dependent Translational Repression in the Drosophila Ovary

Background: The Drosophila ovary is a tissue rich in post-transcriptional regulation of gene expression. Many of the regulatory factors are proteins identified via genetic screens. The more recent discovery of microRNAs, which in other animals and tissues appear to regulate translation of a large fraction of all mRNAs, raised the possibility that they too might act during oogenesis. However, there has been no direct demonstration of microRNA-dependent translational repression in the ovary. Methodology/Principal Findings: Here, quantitative analyses of transcript and protein levels of transgenes with or without synthetic miR-312 binding sites show that the binding sites do confer translational repression. This effect is dependent on the ability of the cells to produce microRNAs. By comparison with microRNA-dependent translational repression in other cell types, the regulated mRNAs and the protein factors that mediate repression were expected to be enriched in sponge bodies, subcellular structures with extensive similarities to the P bodies found in other cells. However, no such enrichment was observed. Conclusions/Significance: Our results reveal the variety of post-transcriptional regulatory mechanisms that operate in the Drosophila ovary, and have implications for the mechanisms of miRNA-dependent translational control used in the ovary.This work was supported in part by NIH grant GM54409 and in part by Research Grant No. 1-FY08-445. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Cellular and Molecular Biolog

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)