Performance of the H -> ZZ* -> 4 mu analysis with the CMS Phase-2 muon detector upgrade

A study of the performance of the Standard Model H(125 GeV) -> ZZ* -> 4 mu analysis with the upgraded CMS muon detector for the high luminosity operation (up to 7.5 x 10^{34} cm^{-2}s^{-1}) at the Large Hadron Collider (HL-LHC) has been carried out. The CMS Phase-2 muon detector upgrade, which will take place from 2024 to 2026, is crucial to efficiently exploit the data that will be collected at the HL-LHC, under very challenging experimental conditions, such as large number of overlapping collisions per event, up to 200 (referred to as pile-up). The H -> ZZ* -> 4 mu analysis essentially relies on the muon system to detect four muons in the final state; it therefore represents an important benchmark for the proposed muon detector upgrade, in particular the extension in pseudorapidity of the muon detector from |eta| < 2.4 to |eta| < 2.8 by introducing the ME0 (Muon Endcap 0) subdetector. The results presented here are obtained using simulated proton-proton collision events at sqrt{s} = 14 TeV with the full simulation of the upgraded CMS detector. The signal and background events are simulated with an average pile-up of 200. The analysis is performed assuming an integrated luminosity of 3000 fb^{-1} (expected in almost ten years of the HL-LHC operation) and follows the analysis of the 2016 data (Run-2). It is found that the signal selection efficiency remains immune to the high pile-up conditions and increases by 17% with the acceptance extension of the muon system

Epigenetic signature in persons with Down Syndrome

Persons affected by Down Syndrome show a heterogeneous phenotype that includes developmental defects and cognitive and haematological disorders. Premature accelerated aging and the consequent development of age associated diseases like Alzheimer Disease (AD) seem to be the cause of higher mortality late in life of DS persons. Down Syndrome is caused by the complete or partial trisomy of chromosome 21, but it is not clear if the molecular alterations of the disease are triggered by the specific functions of a limited number of genes on chromosome 21 or by the disruption of genetic homeostasis due the presence of a trisomic chromosome. As epigenomic studies can help to shed light on this issue, here we used the Infinium HumanMethilation450 BeadChip to analyse blood DNA methylation patterns of 29 persons affected by Down syndrome (DSP), using their healthy siblings (DSS) and mothers (DSM) as controls. In this way we obtained a family-based model that allowed us to monitor possible confounding effects on DNA methylation patterns deriving from genetic and environmental factors. We showed that defects in DNA methylation map in genes involved in developmental, neurological and haematological pathways. These genes are enriched on chromosome 21 but localize also in the rest of the genome, suggesting that the trisomy of specific genes on chromosome 21 induces a cascade of events that engages many genes on other chromosomes and results in a global alteration of genomic function. We also analysed the methylation status of three target regions localized at the promoter (Ribo) and at the 5’ sequences of 18S and 28S regions of the rDNA, identifying differently methylated CpG sites. In conclusion, we identified an epigenetic signature of Down Syndrome in blood cells that sustains a link between developmental defects and disease phenotype, including segmental premature aging

Precision measurements of the Higgs boson properties: from the H → ZZ* → 4l analysis with CMS at the LHC to the future large lepton colliders

The discussion of this thesis is dedicated to the precision measurements of the Higgs (H) boson properties, spanning from the study of the H boson decaying into four leptons with the CMS experiment at the Large Hadron Collider (LHC) to the future investigation of the H boson sector at large lepton colliders. The H → ZZ* → 4l (l=e,μ) decay channel offers an optimal way to study the H boson profile, playing a central role since the time of the discovery. Properties of the H boson are measured exploiting the total amount of data produced in proton-proton collisions at the LHC during Run 2. The dataset collected by the CMS experiment at a center-of-mass energy of 13 TeV corresponds to an integrated luminosity of 137 fb−1. The inclusive signal strength modifier and the signal strength modifiers for the main H boson production modes are reported. In addition, results within the framework of the Simplified Template Cross Sections are produced to explore the different H boson production mechanisms in specific kinematic regions of the phase space. The inclusive fiducial cross section for the H → 4l process is presented and the differential cross sections as a function of the transverse momentum and rapidity of the four-lepton system, the transverse momentum of the leading jet, and the jet multiplicity are shown. All results are found to be in agreement with the SM predictions. Along the way, the perspectives offered by future colliders in the exploration of the Higgs sector and an overview of the different projects of future machines and experiments are also presented. A large focus is reserved for the ongoing development of the design of a detector proposal called IDEA (Innovative Detector for Electron-positron Accelerators), specifically intended for the future H boson factory colliders

Emergency Laser Treatment of a Tracheobronchial Carcinoid during ECMO

Early diagnosis of endobronchial carcinoids is challenging, as they often mimic other common acute respiratory conditions at first presentation. Increasing consensus favours surgical resection over endoscopic management of bronchial carcinoids whenever possible. ECMO has been reported to be an effective supportive strategy in many cases of elective and urgent surgical or endoscopic airway procedures. However, it has never been described as a supportive technique for the emergency endoscopic management of an endobronchial carcinoid. Herein we report the case of a 17 year-old girl presenting with spontaneous pneumomediastinum and an almost complete endotracheal obstruction at the level of the main carina, due to a typical carcinoid that was treated successfully by endoscopic laser disruption under veno-venous extracorporeal circulation in an emergency scenario

Epigenetic Variability across Human Populations: A Focus on DNA Methylation Profiles of the KRTCAP3, MAD1L1 and BRSK2 Genes

Natural epigenetic diversity has been suggested as a key mechanism in microevolutionary processes due to its capability to create phenotypic variability within individuals and populations. It constitutes an important reservoir of variation potentially useful for rapid adaptation in response to environmental stimuli. The analysis of population epigenetic structure represents a possible tool to study human adaptation and to identify external factors that are able to naturally shape human DNA methylation variability. The aim of this study is to investigate the dynamics that create epigenetic diversity between and within different human groups. To this end, we first used publicly available epigenome-wide data to explore population-specific DNA methylation changes that occur at macro-geographic scales. Results from this analysis suggest that nutrients, UVA exposure and pathogens load might represent the main environmental factors able to shape DNA methylation profiles. Then, we evaluated DNA methylation of candidate genes (KRTCAP3, MAD1L1, and BRSK2), emerged from the previous analysis, in individuals belonging to different populations from Morocco, Nigeria, Philippines, China, and Italy, but living in the same Italian city. DNA methylation of the BRSK2 gene is significantly different between Moroccans and Nigerians (pairwise t-test: CpG 6 P-value = 5.2*10 (-) (3); CpG 9 P-value = 2.6*10 (-) (3); CpG 10 P-value = 3.1*10 (-) (3); CpG 11 P-value = 2.8*10 (-) (3)). Comprehensively, these results suggest that DNA methylation diversity is a source of variability in human groups at macro and microgeographical scales and that population demographic and adaptive histories, as well as the individual ancestry, actually influence DNA methylation profiles

A meta-analysis on age-associated changes in blood DNA methylation: Results from an original analysis pipeline for Infinium 450k data

open18noAging is characterized by a profound remodeling of the epigenetic architecture in terms of DNA methylation patterns. To date the most effective tool to study genome wide DNA methylation changes is Infinium HumanMethylation450 BeadChip (Infinium 450k). Despite the wealth of tools for Infinium 450k analysis, the identification of the most biologically relevant DNA methylation changes is still challenging. Here we propose an analytical pipeline to select differentially methylated regions (DMRs), tailored on microarray architecture, which is highly effective in highlighting biologically relevant results. The pipeline groups microarray probes on the basis of their localization respect to CpG islands and genic sequences and, depending on probes density, identifies DMRs through a single-probe or a regioncentric approach that considers the concomitant variation of multiple adjacent CpG probes. We successfully applied this analytical pipeline on 3 independent Infinium 450k datasets that investigated age-associated changes in blood DNA methylation. We provide a consensus list of genes that systematically vary in DNA methylation levels from 0 to 100 years and that have a potentially relevant role in the aging process.This work was supported by the European Union's Seventh Framework Programme (grant agreement no. 259679 “IDEAL”, grant agreement no. 266486 “NU-AGE”, grant agreement no. 305280), by CARISBO foundation and by the Italian Ministry of Health, Progetto Ricerca Finalizzata 2008, convenzione 35: “An integrated approach to identify functional, biochemical and genetic markers for diagnostic and prognostic purposes in the elderly, in the centenarians and in people with dementia, Alzheimer's disease, mild cognitive impairment”.openBacalini MG; Boattini A; Gentilini D; Giampieri E; Pirazzini C; Giuliani C; Fontanesi E; Remondini D; Capri M; Del Rio A; Luiselli D; Vitale G; Mari D; Castellani G; Di Blasio AM; Salvioli S; Franceschi C; Garagnani P.Bacalini MG; Boattini A; Gentilini D; Giampieri E; Pirazzini C; Giuliani C; Fontanesi E; Remondini D; Capri M; Del Rio A; Luiselli D; Vitale G; Mari D; Castellani G; Di Blasio AM; Salvioli S; Franceschi C; Garagnani P

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| &lt; 0.03 at 95% confidence level. [Figure not available: see fulltext.

Measurement of t(t)over-bar normalised multi-differential cross sections in pp collisions at root s=13 TeV, and simultaneous determination of the strong coupling strength, top quark pole mass, and parton distribution functions

Peer reviewe