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Computed tomographic features of renal morphology and ureteral course in cats
Con l’utilizzo della tomografia computerizzata (TC), uno strumento diagnostico avanzato e non invasivo, è stato possibile analizzare in dettaglio le condizioni renali e ureterali di un campione di 86 gatti.
Una delle patologie più frequenti nel gatto è la nefropatia cronica, con un tasso di incidenza del 53% nei gatti aventi età maggiore di 7 anni.
Questo studio retrospettivo svolto presso l’Ospedale Veterinario Universitario Didattico (OVUD) ha fornito informazioni sulla morfologia renale e le anomalie del decorso degli ureteri nella specie felina.
Molto spesso i gatti vanno incontro a infezioni ricorrenti, calcoli e lo sviluppo, quindi, della nefropatia cronica. Questo studio ha come obiettivo di valutare una possibile correlazione tra le alterazioni renali e le anomalie del decorso dell’uretere.
Un ulteriore obiettivo è quello di valutare la presenza di alterazioni della vena cava caudale e correlarle con una deviazione nel decorso dell’uretere.
I risultati ottenuti hanno dimostrato che le anomalie renali nel gatto sono frequentemente riscontrate nella specie felina, spesso correlate ad alterazioni ureterali. Sono spesso riscontrate alterazioni ureterali come l’uretere retrocavale, cubitato o tortuoso.
L’uretere retrocavale non predispone ad alterazioni renali mentre la cubitatura o tortuosità ureterale vanno ad alterare il parenchima renale.
Inoltre, è stata valutata anche la presenza di anomalie vascolari della vena cava caudale quali duplicazione, posta a sinistra, shunt porto-sistemici. Spesso questo tipo di alterazione va a modificare il decorso dell’uretere.
La densità del rene di sinistra risulta significativamente maggiore rispetto al rene destro.
Risulta esistere una correlazione tra la fase pre-contrasto e post-contrasto a livello di polo craniale del rene destro, così come a livello del margine laterale.Using computed tomography (CT), an advanced and non-invasive diagnostic tool, it was possible to analyze in detail the renal and ureteral conditions of a sample of 86 cats.
One of the most common diseases in cats is chronic kidney disease, with an incidence rate of 53% in cats over 7 years of age.
This retrospective study, conducted at the University Teaching Veterinary Hospital (OVUD), provided information on renal morphology and abnormalities in the course of the ureters in the feline species.
Cats often experience recurrent infections, kidney stones, and consequently, the development of chronic kidney disease. The objective of this study was to evaluate a possible correlation between renal alterations and abnormalities in the course of the ureters.
Another objective was to assess the presence of caudal vena cava anomalies and correlate them with deviations in the course of the ureters.
The results showed that renal anomalies in cats are frequently found in the species, often associated with ureteral abnormalities. Ureteral alterations such as retrocaval ureter, kinking, or tortuosity were often observed.
The retrocaval ureter does not predispose to renal alterations, while ureteral kinking or tortuosity affects the renal parenchyma.
Additionally, vascular anomalies of the caudal vena cava, such as duplication, left-sided positioning, and portosystemic shunts, were also evaluated. These types of anomalies often modify the course of the ureter.
The density of the left kidney was found to be significantly higher than that of the right kidney. A correlation was also observed between the pre-contrast and post-contrast phases at the cranial pole of the right kidney, as well as at the lateral margin
The memory in the eyes : a study on ocular behavior in the exploration of new and familiar images
Lo scopo di questo studio è indagare il fenomeno del “repetition effect” riferito al comportamento oculare. Con questo termine indichiamo il fenomeno per cui il comportamento oculare risulta modificarsi in funzione della famigliarità della scena osservata (Smith, Squire, 2017).
Questo fenomeno risulta caratterizzato dalla diminuzione del numero di fissazioni, dalla diminuzione dell’ampiezza delle saccadi, da minor aree esplorate e dalla presenza di uno scanpath totale minore per scene che sono state ripetute rispetto a scene nuove. Le scene già viste, che risultano famigliari al soggetto, vengono esplorate molto meno rispetto alle scene viste per la prima volta (Kaspar, König, 2011-a; Ryan, Althoff et al., 2000; Smith, Hopkins et al., 2006). Oltre a ciò, ci preponiamo di indagare se il comportamento oculare sia modulato anche dalla semantica della scena presentata.
Sulla base di questi studi abbiamo svolto un paradigma diviso in due fasi per andare a riprodurre ciò che abbiamo trovato in letteratura.
Nella fase di codifica i soggetti osservano delle scene naturali suddivise tra ripetute e non ripetute; le scene si differenziano anche per categoria semantica; sono presentate scene di animali e veicoli, immagini di frattali e scene con persone. Dopo una pausa di 10 minuti i soggetti continuano con la fase di test. In questa fase i soggetti devono riferire tramite tastiera se la scena che stanno osservando sia già stata vista o sia nuova. In questa fase sono mostrate ai soggetti solo immagini di animali e veicoli.
I dati raccolti hanno confermato che il comportamento oculare risulta modulato dalla ripetizione delle scene presentate. Nella fase di codifica è possibile notare come il comportamento si modifichi dopo 5/6 esposizioni alla scena; all’aumentare della ripetizione della scena il comportamento diventa più localizzato.
Nella fase di test è possibile notare la differenza tra il comportamento messo in atto per scene ripetute rispetto a quello per scene non ripetute e nuove, che invece risultano paragonabili. Il comportamento meno esplorativo viene messo in atto per le scene ripetute nonostante l’accuratezza nel riconoscimento sia ottimale anche per le scene non ripetute. Ciò sembra sottolineare che il “repetition effect” riferito ai movimenti oculari non dipende tanto dal riconoscere uno stimolo come già visto in precedenza, ma piuttosto dalla quantità di esposizione rivolta allo stimolo; quindi l’esperienza maturata nell’esplorarlo ovvero la famigliarità verso lo stesso. L’effetto ripetizione sembra dunque essere un fenomeno di natura inconscia, come suggerito da altri articoli in letteratura (Smith, Squire, 2017; Greene 2007).
Le scene con diversa semantica sono inoltre osservate in modo differente: le scene di veicoli mostrano un comportamento oculare più esplorativo mentre per le scene di animali il comportamento oculare risulta caratterizzato da uno scanpath totale inferiore.The purpose of this study is to investigate the phenomenon of the “repetition effect” in relation to eye movement behavior. This term refers to the phenomenon where eye movement behavior changes depending on the familiarity of the observed scene (Smith, Squire, 2017).
This phenomenon is characterized by a decrease in the number of fixations, a reduction in saccade amplitude, fewer areas explored, and a shorter overall scanpath. Familiar scenes, which are known to the subject, are explored much less compared to scenes viewed for the first time (Kaspar, König, 2011-a; Ryan, Althoff et al., 2000; Smith, Hopkins et al., 2006). Furthermore, we aim to investigate whether eye movement behavior is also influenced by the semantics of the presented scene.
Based on these studies, we designed a two-phase paradigm to replicate the findings in the literature. In the encoding phase, subjects observe natural scenes divided into repeated and non-repeated ones; the scenes also differ by semantic category. Scenes of animals and vehicles, fractal images, and scenes with people are presented. After a 10-minute break, subjects proceed to the test phase. In this phase, subjects must report via keyboard whether the scene they are observing has been seen before or is new. In this phase, only images of animals and vehicles are shown to the subjects.
The collected data confirmed that eye movement behavior is modulated by the repetition of the presented scenes. In the encoding phase, it is evident that behavior changes after 5-6 exposures to the scene; as the scene is repeated more, the behavior becomes more localized.
In the test phase, we can observe the difference in behavior between repeated scenes and new or non- repeated scenes, which instead show comparable behavior. Less exploratory behavior is adopted for repeated scenes, although recognition accuracy remains optimal even for non-repeated scenes. This seems to suggest that the “repetition effect” on eye movements does not depend on recognizing a stimulus as previously seen, but rather on the amount of exposure to the stimulus, i.e., the familiarity with it. The repetition effect thus appears to be an unconscious phenomenon, as suggested by other studies in the literature (Smith, Squire, 2017; Greene 2007).
Scenes with different semantics are also observed differently: vehicle scenes show more exploratory eye movement behavior, while animal scenes are characterized by a shorter overall scanpath
Alla ricerca di cosmologie non standard: il ruolo critico degli strumenti numerici
In this thesis we study the realm of non-standard cosmologies, with a particular emphasis on the role of numerical tools in probing beyond the standard Lambda Cold Dark Matter (LCDM) model. Despite the success of the LCDM model, questions persist regarding the true nature of dark matter (DM) and dark energy (DE). We investigate several candidates and mechanisms, including primordial black holes (PBHs) as a form of cold dark matter and the normal branch of Dvali-Gabadadze-Porrati (DGP) gravity as a dynamic DE mode.
A significant portion of this thesis is dedicated to studying PBHs, analyzing the constraints placed by cosmic microwave background (CMB) observations on matter accretion into PBHs, and considering the resulting emissions and their effect on the universe's thermal history. The work explores the complex interplay of accretion processes, outflows, and non-thermal emissions, which introduces considerable theoretical uncertainty in constraining PBH parameters.
In addressing the mystery of dark energy, we investigate the nDGP model using galaxy distribution data from the Baryon Oscillation Spectroscopic Survey (BOSS). Through the effective field theory of large-scale structure (EFTofLSS) and perturbative bias expansion, we establish limits on model parameters, showcasing the relationship between these parameters and their degeneracies.
Furthermore, the thesis contributes a novel adaptive interpolation tool, leveraging hydrodynamic simulations and the Optimized Kriging technique, to analyze the Lyman-alpha forest data. This allows for enhanced constraints on cosmological models, addressing tensions such as those in the amplitude of the linear power spectrum.
The prospective data from the Euclid satellite is anticipated to test the methodologies presented herein, offering a window into the fundamental properties of DM and DE.
This thesis underlines the potential of combining astrophysics, astroparticle physics, and cosmology, using numerical simulations and machine learning tools to test a plethora of non-standard cosmologies. The developed techniques stand as a testament to the evolving landscape of cosmological research, advocating for a synergistic approach to unravel the universe's most enigmatic constituents
Embodiment termico
In recent years technological improvements have brought great benefit to neuroprosthetic field. One of the main ones is the possibility of integrating sensory feedback, allowing amputees to increase the quality of their interaction with the surrounding environment and boost the embodiment of their prosthetic devices. Although there have been several successful attempts to restore haptic sensations in prosthetics, the dimension of temperature has commonly been neglected. Only recently a new device called “MiniTouch” has been developed to re-donate thermal feedback to upper-limb amputees. However, the actual ability of this device to trigger the embodiment of an artificial limb is still unknown. Here we show how, through a modified thermal version of the rubber hand illusion (RHI), we were able to trigger the embodiment of a silicon hand. This finding indicates that possible benefits, in terms of prostheses embodiment, could be achieved through the implementation of thermal feedback in prosthetic device. The role that gender and body mass index may have in shaping the illusion need further research and suggest directions for future works. Clarifying which individual differences can impact the embodiment process, will pave the way towards the implementation of personalized stimulations depending on individual characteristics
Migraine without aura : psychophysiological aspects of an epigenetic pathology
L’emicrania senz’aura è un disturbo neurologico fisiologicamente guidato da circuiti corticali disfunzionali, responsabili di modifiche cerebrali derivanti dalla ciclicità patologica, dalla predisposizione individuale, da fattori genetici, ambientali o da una loro combinazione. L’evoluzione di questa condizione può essere dovuta all’aumento del carico allostatico, mentre l’aggravarsi della frequenza degli attacchi e altri fattori contribuiscono a stati maladattivi nella vita dell’individuo affetto.
I nodi di tale patologia non sono, da ricercare solo nel soma, ma anche a livello psicologico e sociale; difatti è insita in essa una forte marcatura epigenetica.
Un ambiente incapace di accogliere le necessità di questi soggetti tende ad inasprirne la condizione di già non facile gestione e rende l’emicrania una delle principali cause di disabilità, risultando in un danno bidirezionale tra ambiente ed individuo.
Un’evoluzione della gestione economico-sanitaria, clinica e socio-culturale di questa complessa patologia renderebbe i cefalalgici capaci di estrinsecare le lor capacità in un giusto equilibrio tra il dare e il ricevere sociale.Migraine without aura is a neurological disorder physiologically driven by dysfunctional cortical circuits responsible for cerebral changes due to pathological cyclicity, individual predisposition, genetic and environmental factors, or their combination. The progression of this disorder can be attributed to increased allostatic load, while the worsening frequency of seizures and other factors contribute to maladaptive states in the life of the affected person.
The roots of this pathology are not only to be found in the body, but also on a psychological and social level; it is in fact strongly epigenetic. An environment that is unable to meet the needs of these people exacerbates an already difficult condition and makes migraine one of the most common causes of disability, leading to bidirectional damage between the environment and the individual.
Further development of the economic, health, clinical and socio-cultural management of this complex condition would enable migraine sufferers to develop their abilities in a balanced interplay between give and take in society
Biosensori elettrochimici smart per Point-of-Care testing
This PhD project aims at the development of smart electrochemical biosensors for Point-of-Care Testing. For all the devices, screen-printed electrodes functionalised with nanomaterials (gold nanoparticles, carbon nanotubes) were used as a platform and signal generation was provided by enzymatic reaction. In particular, smart immunosensors for COVID-19 diagnosis and for the assessment of immunity were developed. In the first case, the presence of Spike protein in nasopharyngeal swabs was tested, while immune response after vaccination or SARS-CoV-2 infection was tested with immunoassays to detect the presence of antibodies in serum samples. In this project, moreover, a highly sensitive magneto-genosensing assay based on PNA probes was developed to detect the presence of KRAS gene related mutation in liquid biopsy. For all the developed biosensors, the signal readout was performed using a smart, portable, battery-powered potentiostat based on a Wi-Fi protocol connected to a cloud that allows data acquisition, storage and sharing, making these devices consistent with the concept of Point-of-Care testing, as they can be brought to test patients in non-hospital settings. Finally, during a research period spent at Catalan Institute of Nanoscience and Nanotechnology (ICN2,Bellaterra, Barcelona, ES), the design of micropore nanoelectrodes to detect different-size molecules in blood samples was studied evaluating different parameters related to the fabrication of the devices.Lo sviluppo di biosensori elettrochimici smart per Point-of-Care testing è stato lo scopo principale di questo percorso di dottorato. Per tutti i dispositivi, sono stati utilizzati elettrodi screen-printed funzionalizzati con nanomateriali (nanoparticelle d’oro, nanotubi di carbonio) come piattaforma ed il segnale è stato generato da reazioni enzimatiche. In particolare, sono stati sviluppati immunosensori per la diagnosi di COVID-19 e per valutarne la risposta immunitaria. Nel primo caso, è stata testata la presenza di proteina Spike in tamponi rinofaringei, mentre la risposta immunitaria dopo la vaccinazione o l'infezione da SARS-CoV-2 è stata valutata con immunosaggi per rilevare la presenza di anticorpi nei campioni di siero. In questo progetto, inoltre, è stato messo a punto un genosaggio basato su microparticelle magnetiche e sonde PNA per rilevare la presenza di mutazioni correlate al gene KRAS nella biopsia liquida. Per tutti i biosensori sviluppati, la lettura del segnale è stata eseguita utilizzando un potenziostato smart, portatile, alimentato a batteria basato su un protocollo Wi-Fi e collegato a un cloud che consente l'acquisizione, la memorizzazione e la condivisione dei dati, che rendono questi dispositivi coerenti con il concetto di Point-of-Care testing, in quanto possono essere eseguiti al di fuori dell’ambiente ospedaliero in base alle necessità dei pazienti. Infine, nell'Istituto Catalano di Nanoscienze e Nanotecnologie (ICN2, Bellaterra, Barcellona, ES), è stato sviluppato un progetto riguardante la preparazione di nanoelettrodi con micropori per rilevare molecole di diverse dimensioni in campioni di sangue valutando diversi parametri relativi alla preparazione dei dispositivi
Settori distinti della corteccia prefrontale ventrolaterale codificano in modo diverso gli stimoli visivi a seconda delle regole del compito : uno studio elettrofisiologico sul macaco
Questo studio analizza i ruoli distinti delle aree prefrontali ventrolaterali (VLPF) nell'elaborazione delle informazioni visive in contesti diversi. L'attività dei singoli neuroni è stata registrata da scimmie che eseguivano un compito visivo passivo e compiti visuo-motori che prevedevano l'interazione con gli oggetti. Le aree della corteccia VLPF sono state suddivise in base alla connettività e sono state analizzate le risposte neuronali agli stimoli. Le aree caudali della corteccia VLPF hanno mostrato un maggiore coinvolgimento nell'elaborazione visiva, in particolare nelle risposte ai volti e agli oggetti afferrabili. È stata osservata una modulazione differenziale dell'attività neurale tra le varie condizioni, con le aree caudali che mostravano risposte più forti ai compiti legati all'azione. L'area 45A ha mostrato forti risposte agli stimoli visivi, probabilmente codificando le caratteristiche dell'oggetto o la difficoltà del compito. L'area caudale 12r ha mostrato una forte codifica dell'identità dell'oggetto, mentre l'area intermedia 46v ha codificato i risultati comportamentali. L'area caudale 46v ha mostrato risposte robuste durante la presentazione dello stimolo, forse riflettendo una pianificazione motoria precoce. L'area intermedia 12r era coinvolta nella codifica pragmatica dell'oggetto. Le aree rostrali hanno mostrato un coinvolgimento minore nelle funzioni studiate. Nel complesso, settori distinti della VLPF mostrano ruoli specifici nell'elaborazione delle informazioni visive e nella guida del comportamento, evidenziando i loro diversi contributi funzionali nei compiti cognitivi. This study investigates the distinct roles of ventrolateral prefrontal (VLPF) areas in
processing visual information within different contexts. Single-neuron activity was
recorded from monkeys performing a passive visual task and visuo-motor tasks
involving object interaction. VLPF areas were subdivided based on connectivity, and
neuronal responses to stimuli were analyzed. Caudal VLPF areas showed increased
involvement in visual processing, particularly in their responses to faces and graspable
objects. Differential modulation of neural activity was observed across conditions, with
caudal areas showing stronger responses to action-related tasks. Area 45A displayed
strong responses to visual stimuli, possibly encoding object features or task difficulty.
Caudal area 12r demonstrated strong coding of object identity, while middle area 46v
encoded behavioral outcomes. Caudal area 46v exhibited robust responses during
stimulus presentation, possibly reflecting early motor planning. Middle area 12r was
involved in pragmatic object coding. Rostral areas showed less involvement in the
studied functions. Overall, distinct VLPF sectors exhibit specific roles in processing
visual information and guiding behavior, highlighting their different functional
contributions in cognitive task
Cerimonie e festeggiamenti per le nozze di Isabella di Borbone e Giuseppe D’Asburgo-Lorena (Parma, 1760)
Il 7 settembre 1760 si celebrò a Parma il matrimonio fra Isabella di Borbone e l’arciduca Giuseppe principe ereditario di Ungheria, Boemia. Cerimonie e festeggiamenti, progettati in parziale collaborazione con Vienna, risposero a esigenze interne ed esterne allo Stato parmense di affermazione del potere sovrano, richiedendo attenzione per le tradizioni del passato e per i bisogni simbolici del presente. Sono stati interrogati documenti dell’Archivio di Stato di Parma e fonti narrative coeve
Reti corticali per la risonanza emotiva e motoria suscitata da espressioni facciali
Facial emotional expressions are one of the primary aspects of behavior through which an emotion manifests itself; hence, their perception has become one of our most refined visual abilities, allowing us to navigate within complex social dynamics, both verbal and non-verbal. The neural substrates underlying this perceptual process involve numerous brain territories, ranging from subcortical structures such as the amygdala to occipital, temporal, and frontal cortical areas. While the anatomical pathways and functional aspects of occipital and temporal territories involved in observing facial expressions have been described in detail for some time, only recently it was investigated the possible role of frontal and insular regions. In particular, a recent study (Del Vecchio et al., 2024), based on a multimodal approach involving electrophysiological recordings, electrical stimulations, and effective connectivity analyses, highlighted the involvement of 8 frontal areas and one insular area in this perceptual process. Based on their connectivity and their role in producing behavioral responses following the perception of emotional facial expressions, these regions were divided into 3 clusters: an emotional cluster, a cognitive-attentional cluster, and a motor cluster.
Since the effective connectivity used in the study by Del Vecchio et al. (2024) did not allow defining the anatomical pathways connecting the studied regions, the present study filled this gap by using tractography (DTI). Furthermore, to obtain a broader and more detailed view of the anatomo- functional circuitry of each studied area, their connectivity was also analyzed by using functional resting state (rfMRI), a method that allows the study of the connectivity aspects in a functional perspective. The results showed the involvement of specific bundles and functional networks for each cluster: the cingulum, uncinate, and anterior commissure bundles, and the default mode network characterize the emotional cluster; the inferior fronto-occipital and inferior longitudinal fasciculi, and the fronto-parietal network characterize the cognitive-attentional cluster; and finally, the aslant fasciculus and the somato-motor network characterize the motor cluster.
Overall, the results of this thesis suggest that within the context of observing facial expressions, although involved harmoniously and synergistically, these three clusters have relatively distinct roles: the emotional cluster would constitute the neural substrate underlying the emotional resonance that occurs when we observe emotional facial expressions; the motor cluster would constitute the neural substrate underlying exclusively motor resonance occurring when observing facial expressions of both emotional and neutral nature; and finally, the cognitive-attentional cluster would provide contextual information characterizing most social interactions.Le espressioni facciali emozionali sono uno dei principali aspetti del comportamento mediante cui
un’emozione si manifesta, per questo motivo la loro percezione è divenuta una delle nostre abilità
visive più raffinate, permettendoci di navigare all’interno di dinamiche sociali complesse sia di natura
verbale che non. I substrati neurali alla base di questo processo percettivo coinvolgono numerosi
territori cerebrali, a partire da strutture sottocorticali, come l’amigdala, fino ad aree corticali
occipitali, temporali e frontali. Se le vie anatomiche e gli aspetti funzionali dei territori occipitali e
temporali coinvolti nell’osservazione delle espressioni facciali sono stati descritti già da tempo ed in
modo dettagliato, solo recentemente è stato indagato il possibile ruolo delle regioni frontali ed insulari
in questo processo percettivo. In particolare, uno studio recente, (Del Vecchio e collaboratori 2024),
basato su un approccio multimodale che ha previsto registrazioni elettrofisiologiche, stimolazioni
elettriche ed analisi di connettività effettiva, ha evidenziato il coinvolgimento di 8 aree frontali ed
una insulare in questo processo percettivo; queste regioni sulla base della loro connettività e del loro
ruolo nella produzione delle risposte comportamentali che seguono la percezione delle espressioni
facciali emozionali, sono state suddivise in 3 clusters: un cluster emozionale, uno cognitivoattenzionale ed uno motorio.
Siccome la connettività effettiva utilizzata nello studio di Del Vecchio e collaboratori (2024) non ha
permesso di definire le vie anatomiche che connettono le regioni studiate, nel presente studio,
utilizzando la trattrografia, è stata colmata questa lacuna; inoltre, per ottenere una visione più ampia
e dettagliata della circuiteria anatomo-funzionale di ciascuna area studiata, la loro connettività è stata
analizzata anche mediante la functional resting state, una metodica che permette di studiare aspetti di
connettività di natura prettamente funzionale. I risultati hanno mostrato il coinvolgimento per ciascun
cluster di specifici fasci e network funzionali: i fascicoli del cingolo, dell’uncinato e della commisura
anteriore e il default mode network caratterizzano il cluster emozionale; i fascicoli fronto-occipitale
inferiore e longitudinale inferiore e il fronto-parietal network quello cognitivo-attenzionale; e, infine,
il fascicolo aslant e il network somato-motorio quello motorio. Nel complesso, i risultati della
presente tesi suggeriscono che, nel contesto del fenomeno dell'osservazione delle espressioni facciali,
questi tre cluster, sebbene coinvolti in modo armonico e sinergico, abbiano ruoli relativamente
distinti: il cluster emozionale costituirebbe il substrato neurale alla base della risonanza emotiva che
si verifica quando osserviamo espressioni facciali emozionali, il cluster motorio costituirebbe il
substrato neurale alla base della risonanza esclusivamente motoria che si verifica sia quando
osserviamo espressioni facciali di natura emozionale che neutre, ed infine il cluster cognitivoattenzionale fornirebbe le informazioni di carattere contestuale che caratterizzano la maggior parte
delle interazioni sociali
Experimental characterization and modelling of specialty optical fibres for bio-medical applications
Specialty optical fibers (SOF) which have at least one property different from standard ones are gaining more and more attention in bio-medical applications. These fibers include a wide group of liquid core fibers, photonic crystal fibers (PCFs), and active fibers.
Particularly during the last years, employing the PCFs as optical biosensors has received much attention in the scientific community. Generally speaking, optical biosensors are of special interest because of the increasing demand for biological and chemical analyte detection in a wide range of applications including clinical analysis \cite{haes2005detection}, food quality control \cite{khansili2018label}, defense and security \cite{kumar2013development}, and environmental monitoring \cite{giardi2009optical}. Briefly, a biosensor device is made of three main elements: the biorecognition element, the transducer, and the receiver.
There are different kinds of biosensors named electrochemical, thermometric, piezoelectric, and magnetic sensors \cite{andrews2015photonics, newman1992biosensors}. Among them, especially, optical biosensors look promising for point-of-care-based diagnosis \cite{haes2005detection} and food quality control \cite{khansili2018label}. These biosensors are modern analytical devices that employ light-guiding technologies as their transducer part and exploit the properties of light for bio/analyte detection. Changes in the optical properties of the light in contact with the bio/chemical analytes lead to changes in the output spectrum or the electrical signal recorded by the photodetector. Some of the advantages of optical biosensors compared with other sensors are the immunity of EM fields to electrical noises, higher sensitivity, simpler mechanism and detection protocol, more reliability, more flexibility, lower cost, and more compactness \cite{andrews2015photonics}.
Regarding the pros of being simple, compact, and usability with untrained personnel, particularly label-free optical biosensors are attracting more attention~\cite{andrews2015photonics}. In this scheme of detection, the bio/chemical analytes are directly detected without the laborious process of analyte molecule labeling \cite{zanchetta2017emerging,morales2019graphene, chamorro2022asymmetric}. Regarding their transducer part, optical biosensors are categorized into different groups resonator-based \cite{khozeymeh2018cylindrical,khozeymeh2019parallel, khozeymeh2019crystalline}, waveguide-based \cite{khozeymeh2018fast,khozeymeh2018sensitivity}, and interferometric-devices based \cite{nguyen2015interferometric, jiang2014high}. Although these optical sensors have demonstrated high sensitivities for both bulk and surface sensing measurements~\cite{cunningham2002enhancing, khozeymeh2019characteristics, talebifard2017optimized}, they still suffer from a critical issue. Indeed, the integration need of photonic and fluidic technologies \cite{gonzalez2016trends, ricciardi2015lab} envisages unified sensor devices. PCF-based biosensors are a group of optical biosensors that meet the need for effective integration between fluidics and photonics \cite{yang2011hollow, nasirifar2020hollow}. The integration of fluidics and photonics in these miniaturized structures may pave the way for lab-in-fiber technologies employing in vivo biosensing \cite{ricciardi2015lab}.
PCFs can be referred to the structures that confine the light inside a core surrounded by a microstructured cladding composed of air holes running along the length of the fiber \cite{yang2011hollow}. Thus, gas or liquid solutions can be infiltrated inside these air holes leading to the creation of biological layers on the dielectric inner walls of the fiber \cite{coscelli2009toward}. This advantage can be further exploited if HC-PCFs are considered thanks to the possibility of having a strong interaction between the sample and the light guided by the fiber. HC-PCFs can rely on two different transmission mechanisms: Photonic Band-gap (PBG) or inhibited coupling (IC) \cite{giovanardi2017inhibited}. The former presents disadvantages in terms of bandwidth and, moreover, this mechanism requires complicated microstructured cladding, while the latter allows covering a wider range of wavelengths. The transmission spectra of this kind of fiber are characterized by an alternating sequence of high and low transmission bands. In particular, there is high transmission when the coupling between the fundamental core mode and the cladding modes is prevented \cite{vincetti2010waveguiding}. The position of the transmission bands is defined by the thickness of the microstructured cladding which can be composed of much simpler structures and larger pitches with respect to PBG fibers, allowing easier infiltration of solutions.
So, HC-IC specialty fibers represent a promising platform for the development of label-free sensors for biological molecule detection \cite{giovanardi2017inhibited,giovanardi2019hollow}. The formation of a biological layer due to the molecular interaction of the target analyte with the suitably functionalized glass core surface is exploited for detection because it changes the thickness of cladding that is directly translated into a red shift in the transmission spectrum of the fiber without the use of additional transducers. In the first part of this thesis, we aim to demonstrate, as a proof of concept, the suitability of the HC-IC specialty fibers as a platform for DNA detection. For this purpose, two different kinds of HC-IC specialty fibers, tube-lattice (TL), and Kagome-lattice (KL) HC-IC fibers have been selected for DNA detection. Then precise functionalization process of the inner surface of the fiber has been performed. In the functionalization process, new steps have been added to increase the possibility of DNA detection. The experimental setup including optical and chemical parts, the methods, and the material are explained in Chapter 1, and the obtained results, their analysis, and reliability will be discussed in Chapter 2.
\par In Chapter 3, we will deal with another kind of specialty fiber used to develop yellow lasers for ophthalmology applications. These lasers have proven to be effective in treating a variety of retinal diseases. Recently, visible lasers with applications in medicine, biology, metrology, optical storage, and display technology have been interesting subjects for many research worldwide groups \cite{luke2019lasers}. For visible laser generation, there are several techniques based on gas lasers, Dye lasers, second harmonic generation (SHG), or optical parametric oscillator (OPO) techniques that can be adapted for visible laser development \cite{omatsu2009passively,fujimoto2011575, okamoto2010fundamentals}. Nevertheless, in general, these techniques suffer from low efficiency, complexity, and high costs. On the other hand, fiber lasers have the advantages of high beam quality, stability, excellent excitation efficiency, and an alignment-free design which enables low-cost and high-quality lasers. Particularly yellow fiber-based lasers emitting around 565-590 nm are of particular interest for their existing and potential applications in sodium laser guide star \cite{lavinsky2016nondamaging}, optical clock \cite{hong2005observation}, ophthalmology \cite{zhang2014versatile}, and in particular medical treatment for diabetic retinopathy (DR) \cite{aflalo2020theoretical}.
DR is the most common eye disease among diabetic patients which causes vision impairment and blindness. In the treatment of DR, experimental investigations on animals and humans, but also numerical analysis, have confirmed that yellow laser emission is the most suitable candidate, because it is effective with low power, and presents good clinical results with minimal collateral effects \cite{kapany1963retinal, aflalo2020theoretical, verdina2020role}. So far yellow emission has been possible with several techniques from copper bromide laser \cite {coutts1990efficient}, Ybdoped fiber \cite{ota2006high}, bifiber lasers \cite{dianov2007high}, optically pumped semiconductor lasers \cite{fallahi20085}. However, these techniques demand bulky structures with several free-space alignments, high maintenance, and tight limitations on the pump conditions. For accessing high-efficiency and simple direct yellow laser emission, particularly dysprosium Dydoped ZBLAN fiber lasers exploiting transition from to level, is a desirable candidate. Therefore, the design, modeling, and fabrication of compact and efficient Dydoped yellow fiber lasers are of critical importance.
In 2001 \cite{limpert2001laser}, the first CW yellow emission in a Dydoped ZBLAN fiber laser was demonstrated. Although Dydoped yellow fiber lasers have been analyzed in some other research works \cite{fujimoto2011575, bowman2012diode, bolognesi2014yellow}, still the reported slope efficiencies were less than 13.2. Indeed, in a considerable time, due to the lack of high-performance gain fibers and high-power GaN blue lasers as the pumping sources, no significant research progress has been observed in Dydoped fiber yellow lasers. In 2020, thanks to the breakthroughs of both Dydoped fluoride fibers and high-power blue GaN laser diodes, the first Dydoped ZBLAN fiber laser pumped by GaN laser diode, emitting at 445 nm, was reported \cite{amin2020yellow}. In that experiment, the maximum laser slope efficiency of 2.3 and 0.9 was reported for absorbed pump power in a Dydoped fiber with lengths of 0.6 m and 5.95 m. In 2021, the same researchers investigated the potential causes of the low experimental slope efficiency and found contributions from the background loss of the fiber and excited-state absorption (ESA) of the intracavity yellow light \cite{amin2021experimental}. They measured a maximum slope efficiency of 33 \cite{amin2021experimental}, which is still less than half of the Stokes limit which is about 78. Recently, Dydoped multi-component phosphate glass was examined and showed a strong yellow emission which was due to the high asymmetry and covalency of the local field and the high phonon energy \cite{tian2022silicate}. In that work, Dydoped multi-component phosphate core glass fiber was successfully drawn by using a rod-in-tube method. Furthermore in \cite{chen2023efficient}, another Dydoped NaLa(WO) glass ceramic fiber with good uniformity was fabricated using the molten core method, showing that it can be a very promising material candidate for tunable yellow lasers \cite{chen2023efficient}. Despite these positive results in the fabrication technology of new glasses, the most promising commercially available Dydoped fiber is the ZBLAN one produced by Le Verre Fluoré, France \cite{https}.
Interesting results have been obtained so far with this fiber \cite{amin2021experimental, amin2020yellow, zou2021direct}, even if the maximum reported slope efficiency is still quite low. Until now, few research works have dealt fully with the causes of the low slope efficiency in Dydoped fiber yellow lasers. Therefore, it is necessary to propose more numerical and analytical methods for further improvements in the performance of Dydoped ZBLAN fiber lasers.\\
In my thesis activity, it is proposed to use a Forward Time Centered Space (FTCS) method \cite{meyer2022fiber} and analytical methods for deep analysis and further understanding of Dydoped ZBLAN fiber laser properties. In this way, a suitable and comprehensive model is obtained that figures out the impact of different physical parameters, such as pump and signal overlap integrals with the doped region, as well as cavity parameters (active fiber length and mirror's reflectivity), on laser output performance.
On the other hand, the developed numerical method asses the impact of both ESA and amplified spontaneous emission (ASE) on the output power of the laser. Finally, the optimization criteria providing high slope efficiency (more than half of the Stokes limit) for yellow lasers, have been found. This in turn will pave the way for design, modeling, and employing the high slope efficiency Dydoped ZBLAN fiber lasers in DR treatments. The modeling and simulation of the yellow-fiber laser will be represented in Chapter 4.
Towards the final application of the yellow fiber lasers studied with numerical simulations, in Chapter 5, cell irradiation experiments are carried out, which obtain preliminary results.
Finally, in Chapter 6, we conclude our research studies