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Perceived exertion: metrological approaches and applications to endurance performance in able-bodied and spinal cord injured populations.
Get PDFThe thesis contributes significantly to our understanding of perceived exertion (PE), paving the way for further investigation. By rectifying metrological issues, providing nuanced findings, and acknowledging limitations, it offers a foundation for future research in exercise science and sports performance.
Endurance training leads whether to improve performance and reduce PE, whether to impaired performance and a concurrent increase in the PE, or modifying either performance or PE with a specificity of training adaptation observed in relation to the modality of training used. PE reflects any psychophysiological stimuli that can affect performance. Through this lens, we can understand its relevance observed in our systematic review regarding the adaptation to any modification in fitness level. Hence, with the aim to monitor endurance training-induced adaptations, analyzing the PE with a method of production, estimation, or ratio is then a major addition.
Chapter 2 presents a pivotal metrological inquiry, uncovering a fundamental scientific error that has persisted for over six decades. This discovery challenges the validity of numerous studies in the field of PE and guides a reevaluation of subjective measurement methods. By addressing this error, the thesis establishes a scientific framework for accurately assessing PE in various interventions.
The subsequent sections of the thesis apply these insights in practical settings. The research explores novel aspects of PE, particularly its kinetics and relationship with physiological responses. Special attention is given to high-level athletes with spinal cord injuries, offering unique insights into their psychophysiological responses to exercise and longitudinal monitoring.
In summary, the thesis advances our understanding of PE by rectifying metrological errors, providing nuanced findings, and applying scientific rigor to subjective measurement methods. It underscores the importance of PE in training adaptations and offers valuable insights into the experiences of athletes with spinal cord injuries
Targeting the essential transcriptional regulator hp1043 for novel antimicrobial approaches in helicobacter pylori infection
No full textHelicobacter pylori is a highly prevalent and pathogenic bacterium that colonises the gastric mucosa and is responsible for various gastrointestinal disorders. Remarkably, the bacterium exhibits rapid development of resistance to standard antibiotics, reducing the effectiveness of therapies and eradication efforts. The growing challenge of antimicrobial resistance calls for new strategies. Innovative approaches are exploring the potential of targeting bacterial transcriptional regulators (TRs) modulating the expression of essential genes. Among the TRs in H. pylori, HP1043 was discovered as a crucial factor that has control key cellular processes. Playing a central role, hp1043 gene cannot be deleted, and the protein's level cannot be modulated. This intrinsic property renders it a challenging research subject yet places it as a potential focus for innovative antimicrobial strategies. In this study, we employed a gene reporter system to investigate HP1043's regulatory function in vivo and in vitro on a cluster of validated targets. This approach allows us also to study the effect of a variable distance between the HP1043 consensus sequence and the -10 Pribnow box element on its transcription regulation. In parallel, in silico screening and drug repositioning methods involving high-throughput-virtual-screening and molecular dynamics simulations were employed to identify candidate compounds that could inhibit HP1043's DNA-binding activity. Secondly, a crystal engineering approach aiming to reduce antibiotic dosage was employed to generate co-crystals capable of exploiting multiple mechanisms of action including the reported inhibitory activity on HP1043 binding. Finally, we explored the potential and versatility of peptide nucleic acids (PNAs) in modulating HP1043 expression. As short antisense oligomers, PNAs demonstrated to selectively block the translation of target genes, leveraging their precise gene knockdown capacity for antimicrobial purposes. This work represents the first examples of multi-targeting antimicrobial strategies against H. pylori, with a focus on the crucial regulator HP1043 and its regulatory mechanisms
Fast radiative transfer algorithms for atmospheric radiance computation in the presence of scattering
Get PDFThis thesis explores the implementation of fast scaling methodologies for the computation of mid and far-infrared spectrally resolved radiances in the presence of scattering. The study focuses on their application in operational satellite radiance data assimilation and remote sensing retrievals. In the first part of the work, two important scaling methodologies, Chou’s scaling and the similarity principle, initially developed for fluxes calculation, are considered. The assessment of their accuracy in reproducing spectrally resolved radiances in the mid and far-infrared is performed using a reference code in a nadir-looking geometry representative of the FORUM instrument (100-1600 cm−1). The results indicate good performance of the Chou method in reproducing radiances in the mid-infrared for water and ice clouds. However, limitations arise for ice clouds in the far-infrared, leading to overestimation of upwelling radiances. To address computational errors in the basic scaling method, a correction term is introduced based on the solution proposed by Tang et al. (2018). This correction term, originally derived for fluxes computation, is extended to spectrally resolved radiances through coefficient optimization. The application of this routine produces reduction in radiance residuals for various cloudy cases, especially for thin cirrus clouds targeted by the FORUM mission. However, challenges persist for medium-large optical depths and small effective radii. The radiative parameters needed for the Chou and Tang schemes are parametrized and integrated into the sigma-IASI/F2N code, a forward model for fast radiance and derivative calculations with respect to atmospheric and spectroscopic parameters. Finally, this thesis presents an improved approach for solving the radiative transfer equation efficiently. This new solution can be interpreted as an asymmetric adjusted scaling, and it excels in simulating spectrally resolved upwelling radiances in the presence of atmospheric diffusive layers, particularly for optically thin scattering layers like cirrus clouds
Exploring the role of rare germline variants in non-coding regions of cancer predisposition genes in triple-negative breast cancer patients
Get PDFBRCA1 and BRCA2 are well-known genes that are associated with a significant increase in the risk of breast and ovarian cancers. However, current genetic screening is limited to BRCA1/2 exons and intron/exon boundaries, and limited information exists about the impact of variants in BRCA1/2 non-coding regions. As a result, the majority of variants identified in these regions remain unclassified, and about 80% of germline BRCA1/2 tests result in a "negative" diagnosis. Introns and proximal untranslated regions remain relatively unexplored, but evidence of non-coding variants' impact on cancer risk and response to treatment is beginning to emerge. The aim of this project was to investigate the prevalence of non-BRCA pathogenic germline variants in patients with triple-negative breast cancer and risk factors, the authors used an NGS custom panel of promoter regions of 62 genes involved in cancer predisposition. We enrolled 144 consecutive triple-negative breast cancer patients who were wild type for germline BRCA1/2 and identified 635 rare variants in non-coding regions of 28 genes, among the 144 patients. Clinical data were available for 75 patients, and these data were merged with the genomic dataset. Among these 75 patients, rare germline variants in BRCA2 were statistically significantly related to worse overall survival (p-value=0.017 HR=4.76 (1.32-17.15)). No differences in Disease-free survival and overall survival were found for other genes. CDH1's rare variants were related to the highest percentage of non-pathological complete response after neoadjuvant chemotherapy (p-value=0.0273); MLH1 and PALB2 rare variants were found to be both related to bilateral breast cancer (p-value=0.0146 and p=0.0005, respectively). Rare variants of the ATM gene were associated with a positive family history (p-value 0.0408). However, due to the small sample size, these analyses should be considered only exploratory, and further studies are needed to confirm these findings
From the identification of a draggable target for the Olanzapine-induced Metabolic Syndrome to the development of a new therapeutic approach using CRISPR/Cas7-11S.
Get PDFMetabolic Syndrome (MS) is a clinical condition characterized by multiple risk factors for cardiovascular diseases. Component features of MS include obesity, dyslipidemia, diabetes, and high blood pressure. Unbalanced diets, alcohol consumption, and reduced physical activity are the main risk factors for metabolic dysfunction. Moreover, MS represents one of the major side effects of commonly prescribed drugs like neuropsychiatric medications (antidepressants, antipsychotics, and mood stabilizers). Previously, using an unbiased approach, we identified the involvement of Histamine Receptor 1 (H1R) and Cannabinoid receptor 1 (CB1R) in the MS signature in hypothalamic gene expression in female mouse models of both diet and drug-induced MS. Here, we uncover the interplay between these two GPCRs in the pathophysiology of Olanzapine (OL) induced MS. Then, using the CRISPR-Cas9 approach, we demonstrate that the CB1R knockout in hypothalamic neurons is sufficient to reverse OL-induced MS while avoiding the side effects observed with Rimonabant treatment. This result underlines the need to develop a site-specific CB1R targeting therapy for MS. However, the stable changes in the genome using Cas9 as a therapeutic strategy in humans raise health concerns. To overcome this significant limitation and ensure a cell- and site-specific target of CB1R, the new RNA targeting CRISPR-Cas seems promising. Here, we developed a CRISPR-Cas7-11S toolbox for both in vitro and in vivo RNA targeting while designing and cloning spacer RNA sequences against CB1R RNA that would work for both human and mouse transcriptomes. Then, we screened the efficiency of CRISPR-Cas7-11S and single and multiple spacer RNAs compared with a non-targeting guide using the neuroblastoma cell lines. To provide a safety switch-off in case of undesired side effects of the CRISPR/Cas7-11S therapeutic system, the study aims to identify and test in vitro new ligands acting as cleavage breakers or complex formation inhibitors, arresting the enzymatic activity of CRISPR-Cas7-11S
Graphene based materials for water purification: characterization and application
Get PDFThis PhD thesis addresses the critical issue of water purification, an evolving field with increasing importance year by year, as highlighted by the recent revision of EU Drinking water directive (EU2020/2184). Current water treatment methods are insufficient for efficiently removing Emerging contaminants (ECs) and new materials and technologies are required.
Among these strategies, graphene-based materials, particularly Graphene Oxide (GO), have emerged as promising candidates for water purification. Key properties of GO are remarkable surface area, multi-site interaction with organic molecules and tailorable surface chemistry. The research objective was to assess GO effectiveness in different configurations (i.e., nanosheets, composites) as a sorbent of various ECs, such as pharmaceutical and personal care products, heavy metals, and Per- and Poly-Fluorinated Substances.
To investigate the adsorption mechanism of GO, a standardized protocol based on adsorption, kinetic and efficiency tests was employed together with molecular dynamics simulations. To fully exploit the adsorption capacity of GO as nanosheets, a two-step set-up was proposed (GO+MF), combining batch adsorption and microfiltration. Taking a step further in applicability of GO in water purification, Polysulfone-GO hollow fiber membranes (PSU-GO HFs) were developed by coextrusion. The composite exploit simultaneous adsorption and ultrafiltration capabilities in a single module, suitable for point of use application. In addition, the adsorption capacity of GO was selectively enhanced through covalent surface modification. GO modified with Amino acids (GO-AA), including L-glutamic acid, L-methionine, and Lysine. GO-AA exhibited significantly improved adsorption capacities towards select contaminants, and the role of grafting was deeply investigated.
These findings highlight GO potential in water purification, providing valuable perspectives for future applications
Subjective monitoring of professional soccer players: validation and application using big data analytics
Get PDFThe first aim of the research program reported in this thesis was to develop predictive models of daily and match-related fatigue and investigate the factors associated with subjective recovery in professional soccer players by analysing the commonly used wellness measures. The second aim was to explore the validity and reliability of five single-item scales widely used in research and practice to measure the subjective status of professional soccer players.
In the first study we found, using big data analytics, that daily and match-day fatigue can be predicted with reasonable accuracy in six professional soccer teams monitored throughout the entire season (53,294 observations). This study also shows that psychological factors like stress and mood are important predictors of fatigue (mental fatigue). In the second study of four professional soccer teams (36,381 observations), we found that subjective recovery is primarily associated with fatigue and muscle soreness, and that these variables mediate 55% of the relationship between training load and subjective recovery. Albeit correlative, our findings also suggest that reducing mental fatigue and muscle soreness may help subjective recovery and performance of professional soccer players. In the third study involving 186 Italian soccer players, we investigated the validity and reliability of single-item measures of subjective Fatigue, Sleep Quality, Muscle Soreness, Stress and Mood. Although correlated to their criterion measures, these scales do not show a convergent validity to the criterion measures themselves. In conclusion, these practical and inexpensive single-item scales commonly used to monitor soccer players daily, do not appear to be a valid assessment of the variable they purport to measure
The XENONnT neutron veto: design, construction and performance
Get PDFMany astrophysical and cosmological observations point to the presence of Dark Matter (DM) in the universe. Among the potential DM candidates, WIMPs emerge from theories beyond the SM. The XENON Dark Matter Project is one of the leading experiments for DM direct detection, employing a dual-phase xenon TPC. The current phase of the project, XENONnT, features a TPC with a sensitive liquid xenon mass of 5.9 t surrounded by a Gadolinium-loaded water Cherenkov Neutron Veto (NV). A critical challenge in DM detection is distinguishing WIMP-induced NR from the backgrounds.
In particular, neutrons emitted by detector materials can mimic WIMP signals, posing a significant threat to the sensitivity to DM. The NV plays a crucial role in mitigating this background by tagging the escaping neutrons through their delayed capture in water. The NV surrounds the TPC, with highly reflective panels and is instrumented with 120 PMTs. In the first two science runs the NV operated with pure water. In this setup, the NV achieved a neutron tagging efficiency of 53%, contributing significantly to the first WIMP analysis in the first XENONnT science run. A blind analysis over a total exposure of 1.1 tonne-year revealed no significant excess over the expected background, establishing the lowest upper limit to the WIMP-nucleon spin-independent cross-section of 2.58×10−47 cm2 for WIMPs of 28 GeV/c2 mass at a 90% confidence level
On the tomographic angular cluster clustering as a cosmological probe
No full textIn this Thesis, we present the study of the clustering properties of 1000 dark matter halo catalogues from the Pinocchio simulations.
In this Thesis, we also present the results published in Romanello et al. (2024)
Valorization of biomaterials from calcifying marine organism waste
Get PDFMarine aquaculture and fishery industries produce millions of tonnes of waste every year. According to FAO, global fish production reached about 179 million tonnes in 2018 and the 70 wt% of the processed seafood was discharged as waste. This waste is often just dumped in the sea or disposed in landfill in developing countries while in developed countries their disposal can be costly. Shells, in particular, represent the main marine waste but they also harbour useful chemicals such as chitin, protein and calcium carbonate. So, turning cast off shells into new materials, applying the concept of a circular economy, would benefit both the environment and the economy.
Mussel shells, for example, are mainly built up of single crystals of calcite and aragonite in an external and an internal layer, respectively. The recovery of these biomineral building units offers the possibility to overcome the synthetic difficulties in replicating the ability of organisms to act as crystal shapers and morphology modifiers.
Mollusk shells are a massive source of biogenic calcium carbonate (bCC) that can potentially substitute ground and precipitated calcium carbonate. These materials can be used as filler in polymeric matrices after a surface coating with hydrophobic molecules.
bCC may also be transformed into a new added-value material such as apatite with cytocompatible and osteoinductive properties for biomedical applications or it may be converted into nano-crystalline and amorphous calcium carbonate for applications that span from medical to material science.
bCC can also be extracted from crab and shrimp shells individually or in combination with other molecules such as proteins and chitin for potential applications as dye adsorbents.
Therefore, this thesis aimed to valorise seafood wastes from different calcifying marine organisms by recovering the biomaterials they are composed of and using them for different applications exploiting their unique features as biominerals