ACETILACETOINO SINTASI DA Bacillus licheniformis NELLA SINTESI STEREOSELETTIVA DI ALCOLI TERZIARI POLIFUNZIONALI

In this PhD thesis the first application of acetylacetoin synthase (AAS), by B. licheniformis DSM 13, as a biocatalyst for the stereoselective formation of C-C bonds is described. AAS, a thiamine diphosphate (ThDP) dependent enzyme, catalyzes the condensation of dialkyl or alkyl-aryl-1,2-diketones into the corresponding α-hydroxy-β-diketones with the elimination of a carboxylic acid. The reactions were carried out using a single α-diketone as donor and acceptor (homo-coupling) or two different α-diketones (cross-coupling). The AAS enzymatic reaction of a new C-C bond formation is highly chemo-, regio- and enantioselective. The α-hydroxy-β-diketones obtained from the reactions of homo- and cross-coupling were reduced with acetylacetoin reductase (AAR), a dehydrogenase obtained from the same bacterium. The combined use of AAS and AAR allowed the preparation of a new range of optically pure α-alkyl-α,β-dihydroxyketones starting from commercial α-diketones. The stereochemistry of the enantiopure syn-α-alkyl-α,β-dihydroxyketones was assigned on the basis of NOE experiments, while their absolute configuration was determined transforming one of these compounds in the natural product (+)-citreodiol. The absolute configuration of α-alkyl-α, β-dihydroxyketones confirmed the S-stereospecificity of the AAR-reduction and R-stereospecificity of AAS homo and cross-coupling reactions. On the basis of the AAS activity, an alternative synthetic biomimetic route, reminiscent the ThDP-dependent enzymes activity, was studied. Both thiamine hydrochloride and its simplified analogue, thiazolium salt, act as pre-catalysts coupled with an appropriate basis and are able to activate α-diketones such as acyl-anion equivalents that can be transferred to enable ketonic acceptors as α-diketones and α-ketoesters. These carboligation reactions have been optimized in catalytic conditions using polyethylene glycol (PEG400), an eco-friendly reaction medium, that made easier the reaction workup allowing, in addition, the catalyst recycling. A further synthetic application of AAS was the chemo-enzymatic synthesis of the natural aroma of green tea. The chirality of this compound, closely related to its organoleptic properties, is actually studied in our laboratories. The versatility of AAS as biocatalyst for C-C bond forming reactions and the raised interest by its particular applications in organic synthesis promped us to purify the enzyme, with the ultimate goal of identifying the gene encoding for AAS in the genome of B. licheniformis DSM 13

Design and operation of the air-cooled beam dump for the extraction line of CERN's Proton Synchrotron Booster (PSB)

A new beam dump has been designed, built, installed and operated to withstand the future proton beam extracted from the Proton Synchrotron Booster (PSB) in the framework of the LHC Injector Upgrade (LIU) Project at CERN, consisting of up to 1E14 protons per pulse at 2 GeV, foreseen after the machine upgrades planned for CERN's Long Shutdown 2 (2019-2020). In order to be able to efficiently dissipate the heat deposited by the primary beam, the new dump was designed as a cylindrical block assembly, made out of a copper alloy and cooled by forced airflow. In order to determine the energy density distribution deposited by the beam in the dump, Monte Carlo simulations were performed using the FLUKA code, and thermo-mechanical analyses were carried out by importing the energy density into ANSYS. In addition, Computational Fluid Dynamics (CFD) simulations of the airflow were performed in order to accurately estimate the heat transfer convection coefficient on the surface of the dump. This paper describes the design process, highlights the constraints and challenges of integrating a new dump for increased beam power into the existing facility and provides data on the operation of the dump

A new laser device for ultra-rapid and sustainable aerosol sterilization

The current COVID-19 pandemic has highlighted the importance of aerosol-based transmission of human pathogens; this therefore calls for novel medical devices which are able to sterilize contaminated aerosols. Here we describe a new laser device able to sterilize droplets containing either viruses or bacteria. Using engineered viral particles, we determined the 10,600 nm wavelength as the most efficient and exploitable laser source to be manufactured in a commercial device. Given the lack of existing working models to reproduce a human aerosol containing living microbial particles, we developed a new system mimicking human droplet formation and preserving bacterial and viral viability. This evidenced the efficacy of 10,600 nm laser light to kill two aerosol transmitted human pathogens, Legionella pneumophila and SARS-CoV-2. The minimal exposure time of <15 ms was required for the inactivation of over 99% pathogens in the aerosol; this is a key element in the design of a device that is safe and can be used in preventing inter-individual transmission. This represents a major advantage over existing devices, which mainly aim at either purifying incoming air by filters or sterilizing solid surfaces, which are not the major transmission routes for airborne communicable diseases

Methodology to investigate interference using off-the-shelf LiDARs

With the increase of assisted and automated functions provided on new vehicles and some automotive manufacturers starting to equip high end vehicles with LiDARs, there is a need to consider and analyse the effects of having LiDAR sensors on different vehicles interacting with each other in close proximity (e.g. cities, highways, crossroads, etc.). This paper investigates interference between 360 degree scanning LiDARs, which are one of the common typologies of automotive LiDARs. One LiDAR was selected as the victim, and 5 different LiDARs were used one by one as offenders. The victim and offending LiDARs were placed in a controlled environment to reduce sources of noise, and several sets of measurements were carried out and repeated at least four times. When the attacker and victim LiDARs were turned on at the same time some variations in the signals were observed, however the statistical variation was too low to be able to identify interference. As a result, this work highlights that there is no obvious effect of interference witnessed between the selected off-the-shelf 360 degree LiDAR sensors; this lack of interference can be attributed to the working principle of this type of LiDAR and low probability of having directly interfering beams, and also to the focusing and filtering optical circuits that the LiDARs have by design. The presented results confirm that mechanical scanning LiDAR can be used safely for assisted and automated driving even in situations with multiple LiDARs

Analytics dei testi riflessivi scritti dai docenti neoassunti nel portfolio digitale

In this paper, we present the preliminary results of the analysis performed on 50,000texts written by the Newly Qualified Teachers to reflect on their practice. The Italian InductionProgramme for NQT includes online activities to be carried out in the E-portfoliomanaged by Indire. As part of the training monitoring with the aim to evaluate our supportand to improve instructional scaffolding to teachers, we analysed teachers’ reflectivewriting mixing a new developed framework for teachers’ reflective writing andNatural Language Processing (NLP) techniques. In providing a case study of a large-scaleanalysis of textual teachers’ data in an institutional setting, this paper wants to contributeto the field of learning analytics. We will describe the context, the characteristics of thedata analysed, how all of this has shaped the analytics design. We will describe its implementationand therefore the procedures, tools and metrics developed to representthe content of the teachers’ reflective writing, and we will try to evaluate if and howthese preliminary results can help us to reach the research goals and to understand thestrengths and weaknesses of different methodologies.Presentiamo i risultati preliminari e l’analisi svolta su circa 50.000 testi scritti dai docentineo nominati in ruolo per riflettere su due attività didattiche svolte con gli studenti, nelcontesto del percorso dell’anno di formazione e prova 2016/17. Il percorso prevede attivitàin presenza e attività a distanza completate sul portfolio digitale, ospitato nell’ambienteonline gestito dall’Indire. Nell’ambito del monitoraggio della formazione, con il fine di ottimizzaregli strumenti e il supporto fornito, abbiamo interrogato i dati testuali prodottidai docenti nell’interazione con l’ambiente per capire se i testi presentassero evidenze riconducibilialle scritture riflessive. Obiettivi dell’indagine sono stati la definizione di unoschema per la classificazione dei testi sulla base del livello di riflessività evidenziato e l’impiego di strumenti di Trattamento Automatico del Linguaggio (TAL) per l’analisi dell’interocorpus testuale prodotto dai docenti. Descriveremo il contesto scientifico e progettuale,le caratteristiche dei dati analizzati, come questo abbia determinato il disegno d’indagine;descriveremo inoltre la sua implementazione e dunque le procedure, gli strumenti e lemetriche adottate o elaborate per rappresentare il contenuto dei dati; infine discuteremoi primi risultati e alcuni vantaggi e limiti dell’approccio adottato

Imported arboviral infections in Italy, July 2014-October 2015: A National Reference Laboratory report

BACKGROUND: Imported cases of infections due to Dengue (DENV) and Chikungunya (CHIKV) viruses and, more recently, Zika virus (ZIKV) are commonly reported among travelers returning from endemic regions. In areas where potentially competent vectors are present, the risk of autochthonous transmission of these vector-borne pathogens is relatively high. Laboratory surveillance is crucial to rapidly detect imported cases in order to reduce the risk of transmission. This study describes the laboratory activity performed by the National Reference Laboratory for Arboviruses (NRLA) at the Italian National Institute of Health in the period from July 2014 to October 2015. METHODS: Samples from 180 patients visited/hospitalized with a suspected DENV/CHIKV/ZIKV infection were sent to the NRLA from several Italian Hospitals and from Regional Reference Laboratories for Arboviruses, in agreement with the National Plan on human surveillance of vector-borne diseases. Both serological (ELISA IgM test and Plaque Reduction Neutralization Test-PRNT) and molecular assays (Real Time PCR tests, RT-PCR plus nested PCR and sequencing of positive samples) were performed. RESULTS: DENV infection was the most frequently diagnosed (80 confirmed/probable cases), and all four genotypes were detected. However, an increase in imported CHIKV cases (41 confirmed/probable cases) was observed, along with the detection of the first ZIKV cases (4 confirmed cases), as a consequence of the recent spread of both CHIKV and ZIKV in the Americas. CONCLUSIONS: Main diagnostic issues highlighted in our study are sensitivity limitations of molecular tests, and the importance of PRNT to confirm serological results for differential diagnosis of Arboviruses. The continuous evaluation of diagnostic strategy, and the implementation of laboratories networks involved in surveillance activities is essential to ensure correct diagnosis, and to improve the preparedness for a rapid and proper identification of viral threats

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/ 27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis