Project Management: metodologie Waterfall e Agile a confronto attraverso l’analisi di due casi studio

Il numero di progetti all'interno delle realtà aziendali è in continuo aumento e sempre più necessario, per garantire il successo di questi, è la diffusione di metodologie e best practice da poter usare nella gestione dei progetti. Scopo di questo elaborato è proprio quello di confrontare due dei modelli attualmente più diffusi nella gestione di progetti, ovvero la metodologia tradizionale, o Waterfall, e la metodologia Agile, in particolar modo il framework Scrum. L’obiettivo di questa tesi sarà supportato dall’analisi di due casi applicativi in ambito IT di una multinazionale di consulenza tecnologica, Modis Consulting S.r.l. L’elaborato si articola in quattro capitoli. Nella prima parte del primo capitolo viene data una definizione generale di progetto, di project management e dei vari cicli di vita che un progetto può assumere. Nella seconda parte, invece, si passa alla definizione della metodologia di gestione del progetto definita tradizionale, in cui vengono trattate le fasi, le caratteristiche principali e i vantaggi e gli svantaggi che ne derivano. Nel secondo capitolo viene trattata, invece, la seconda metodologia in questione, ovvero il modello Agile, soffermandosi principalmente sulle caratteristiche, le fasi, gli eventi e i ruoli del framework agile denominato Scrum. Alla fine del capitolo, sulla base delle caratteristiche e delle definizioni scritte in questi primi due capitoli, si passa ad un confronto tra il modello tradizionale e il modello Agile. Il terzo capitolo tratta lo studio del primo caso applicativo scelto, ovvero un progetto di natura IT nato a seguito di una richiesta di un cliente di Modis Consulting la cui gestione è avvenuta tramite la metodologia classica. Nell’ultimo capitolo, invece, si ha lo studio del secondo caso applicativo scelto, il quale nasce dalla volontà di digitalizzare alcuni processi aziendali interni di Modis in modo da supportare il business nello svolgimento di alcune attività

Synthesis and biological evaluation of bicyclic iminosugar derivatives as inhibitors of glycosidases

During this work, five pyrrolizidine derivatives and one isoxazolidine derivative have been synthetized in order to evaluate their biological activities towards glycosidases, related to their configurations and type of bridge functionalities between the bicyclic iminosugar moiety and the aromatic part of the molecules. The final pyrrolizidine derivatives have been synthetized through click reactions (urea forming reaction, thiourea forming reaction and CuAAC reaction) performed on a common amino-pyrrolizidine precursor. The final isoxazolidine derivative has been synthetized through a CuAAC reaction. In addition, an indolizidine scaffold was obtained through a ring-closing metathesis on a dialkenyl pyrrolidine. This bicyclic compound could be of interest as intermediate for the synthesis of indolizidine derivatives with potential as glycosidase inhibitors. Biological evaluation towards glycosidases of the final six compounds synthetized in this work revealed that all of these compounds show inhibition towards almonds’ β-glucosidase and/or jack beans’ α-mannosidase

Modulation of Neuroendocrine and Immunological Biomarkers Following Rehabilitation in Sarcopenic Patients

This study aimed to investigate if rehabilitation could down-regulated sarcopenia-associated inflammation by modulating the crosstalk between the neuroendocrine and immune systems, with the aim of ameliorating quality of life of sarcopenic subjects. A total of 60 sarcopenic patients (49 females and 11 males; median age 74.5, interquartile range 71–79), undergoing a personalized rehabilitation program, have been recruited and subjected to: (1) functional and physical evaluation (Short Physical Performance Battery (SPPB), Barthel Index and Tinetti Test); (2) pro-inflammatory IL-1β, TNF-α, IL-6, IL-18, and anti-inflammatory IL-10 cytokines plasmatic level measures; and (3) norepinephrine, epinephrine, dopamine, and serotonin neurotransmitter level evaluation at time of enrollment (T0) and once rehabilitation was concluded (1 month, T1). Rehabilitation combined a balance and strength training program with two daily sessions that were fine-tuned and personalized according to the ability of the patient. The results showed a significant increase at T1 in the plasmatic levels of IL-10 (p = 0.018) and of norepinephrine (p = 0.016)), whereas the concentration of IL-18 was significantly reduced (p = 0.012). Notably, changes in norepinephrine were positively correlated with clinical improvements (Tinetti and Barthel scores, p ≤ 0.0001; SPPB scores, p = 0.0002). These results show that efficient rehabilitation induces a reduction of inflammation, suggesting that this effect could be mediated by a modulation of the neuro-immune axis that results in an increase of norepinephrine

High g-glutamyl-transferase fractions as new markers to identify non-alcoholic fatty liver disease in childhood obesity

The system of advanced glycation end products (AGEs)AGEs and their soluble receptor (sRAGE) could play a role in the development of non-alcoholic fatty liver disease (NAFLD). Recently gamma-glutamyl-transferase (GGT) at values within the normal range, has been associated with evolution of atherosclerotic processes and predicts the onset and outcome of related diseases.The aim of the present study was to determine distinct GGT fractions in obese subjects with and without NAFLD and with serum GGT activity within the high-normal range. Moreover, we try to indentify relationships between the presence of steatosis with ALT, GGT and GGT fractions, hyperlipidemia, and sRAGE.28 obese children and adolescents (20 boys and 8 girls aged 11.9±2.77 years; height SDS 0.55±1.52; BMI SDS 3.11±0.55) were included in the study and were divided in Group 1 (14 with NAFLD) and Group 2 (14 no-NAFLD). Total GGT values were determined by enzyme kinetic assay. Separation of GGT fractions on the basis of their molecular weight was performed through liquid chromatography. sRAGE levels were determined using an ELISA kit.Tryglicerides, GGT, big-GGT (b-GGT), free-GGT (f-GGT) values were significantly higher in Group 1 than in Group 2, while sRAGE levels were significantly lower in Group 1. No other significant difference was found between groups [table1]. A significant negative correlation was demonstrated between sRAGE and GGT (r=-0.49), b-GGT (r=-0.39), small-GGT (s-GGT) (r=-0.47), f-GGT (r=-0.44). GGT activity was positively associated with total cholesterol (r=0.41) and triglycerides (r=0.42); the same significant correlation was demonstrated between the s-GGT fraction and total cholesterol (r=0.44) and triglycerides (r=0.42). f-GGT was the predominant fraction in Group 2, whereas in Group 1 we found a relative increase in s-GGT and b-GGT fractions. In obese NAFLD patients sRAGE significantly and negatively correlates only with s-GGT (r=-0.62).Our data demonstate that definition of specific predictive GGT fraction profile could be used to identify obese children with NAFLD that had higher GGT and lower sRAGE levels than their lean obese counterpart. It is conceivable that s-GGT they may be considered as primary marker of liver injury and as a surrogate for suspected fatty liver. Moreover, the AGEs-RAGE system could play a role in the pathogenesis of NAFLD in childhood obesity

Study of inflammations' markers and insulin resistance in obese children and adolescents with and without non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a serious problem in childhood obesity; hyperglycemia and oxidant stress lead to the accumulation of advanced glycation end products (AGEs) that with their soluble forms of receptor (sRAGE) could play a role in the pathogenesis of insulin resistance (IR) and the development of NAFLD.This study was planned to investigate the relationship between the presence of steatosis with anthropometric measurements, abnormal ALT and γ-glutamyl-transferase (GGT), hyperlipidemia, IR (HOMA-IR), and sRAGE in childhood obesity with and without NAFLD.28 obese children and adolescents (20 M and 8 F; 11.9±2.77 yr.; height SDS 0.55±1.52; BMI SDS 3.11±0.55) were included in the study and were divided in Group 1 (14 with NAFLD) and Group 2 (14 no-NAFLD). sRAGE levels were determined using an ELISA kit.Group 1 had significantly higher levels of tryglicerides and GGT and significantly lower concentrations of sRAGE than Group 2

A new device for measuring resting energy expenditure in severely obese children and adolescents with and without non-alcoholic fatty liver disease.

The study demonstrates a NAFLD prevalence similar to data reported in literature (range 20-77%) although lower than other populations suggesting different genetic and/or environmental factors SWA is an easy to handle and practical portable device for measuring REE. However, our results demonstrate that REE SWA measurements are significantly higher than those evaluated with IC, despite a positive significant correlation between SWA and IC; this data suggest the necessity to develop new obesity-specific algorithmsAlthough SWA probably may represent an acceptable device to measure REE in obese subjects, this evaluation do not allow to distinguish between NAFLD and non-NAFLD obese patient

Designing artificial metalloenzymes exploiting the Spy technology: study of a Cu(II)-Spy construct and perspectives

Metalloproteins promote several among the most complex biomolecular processes in Nature. The expanding demand for synthetic catalysts displaying enzyme-like activity is moving toward the development of ARTificial metalloenZYMES (ARTZYMES).[1] Protein redesign and de novo design are the two major strategies for the development of Artzymes, both having potentiality and drawbacks concerning the introduction of metal binding sites in a construct. Within the redesign approach, the so called ‘Trojan horse’ strategy involves the covalent or supramolecular grafting of a metal complex to a biomolecule,[2] to obtain the introduction of a metal ion into a known protein scaffold. We present here the original incorporation of a transition-metal binding site specifically designed on a small peptide component (SpyTag), onto a Spy-protein construct, thereby providing the Spy protein with a selective binding site for metal ions (Scheme 1). The Spy protein, redesigned by Howarth and colleagues,[3] comprises two components: a small beta-sandwich SpyCatcher (SC) protein component (ca. 110 residue), and the SpyTag (ST) peptide (13-16 residues). SC and ST incubated together in buffered aqueous solutions at neutral pH interact rapidly and selectively to form an isopeptide bond between a Lys (SC) and an Asp residue (ST). We redesigned the ST sequence by introducing an ATCUN sequence onto the Tag peptides. The ATCUN (Amino Terminal Cu and Ni binding site) fragment, characterized by a H2N-Xxx-Xxx-His sequence at the N-terminus, is known for its ability to bind Cu(II) and Ni(II) ions.[4] Additionally, the SC sequence was modified mutating two His residues into Gln to reduce the possibility of copper binding while preserving hydrogen bond interactions between residues. We were able to demonstrate that three different SpyTag-ATCUN peptides exhibit high binding affinity for Cu(II). Additionally, we confirm that the specific binding of Cu(II) at the ATCUN site of the ST sequence occurs in the presence of one equivalent of copper when SC is bound to ST. We observed this behaviour both with short ST peptides and when the ST sequence is expressed at the N-terminus of a natural protein, such as Thioredoxin. This engineered construct serves as an interesting proof-of-concept for novel metalloproteins, wherein the SpyTag peptide establishes the initial metal coordination sphere, while the SpyCatcher protein potentially contributes to the second coordination sphere. Starting from these results, this solid SC-ST metal binding construct could be employed studying its reactivity with different metals, as well as different metal binding groups with both natural and unnatural amino acids, introduced in the ST sequence via solid-phase peptide synthesis. Project ART2HYDROGEN “Artificial enzymes for the photocatalytic production of hydrogen in photosynthetic bacteria” funded under the National Recovery and Resilience Plan (NRRP), Mission 2 Component 2 Investment 3.5 - Call for tender No. 4 of March 23, 2022 of Italian Ministry of Ecologic Transition funded by the European Union – NextGenerationEU. Project code RSH2A_000009, Concession Decree 445 of December 29, 2022 adopted by the Italian Ministry of Environment and Energy Security

Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site

Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site