Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-β-Rhamnoside Isolated from Parrotia persica

Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae) in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3-O-β-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica, followed by an analysis of the biological effects of myricetin-3-O-β-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3-O-β-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 µg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3-O-β-rhamnoside at 10 µg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3-O-β-rhamnoside and chlorogenic acid

The Impact of Oil Shocks on Exchange Rates: The Case of Selected OPEC Countries

OPEC countries are heavily dependent on oil dollar revenues through which impact on exchange rates. The purpose of this study is to investigate the effect of oil shocks on the real exchange rates for selected OPEC countries for the period 1980-2018. The oil shocks are first obtained using the vector auto-regression model and then their effects on the exchange rates are estimated using a panel quantile regression model. The results show that effect of oil shocks on exchange rates varies across quantiles. The oil specific-demand shock and global demand shock have a negative and significant effect on the real exchange rates while the oil supply shock has a positive and significant effect on the real exchange rates in OPEC countries. Furthermore, oil specific-demand shock has the most impact on the real exchange rates

Genetic, magnetic resonance imaging and body fluid biomarker associations with severity of multiple sclerosis

Multiple sclerosis is a chronic and progressive neuroinflammatory disease that leads to demyelination and neurodegeneration in the central nervous system (CNS). Previous research has identified a wide range of environmental, lifestyle and genetic factors which increase MS susceptibility. However, the pathomechanisms that influence the severity of MS are largely unknown, and adequate biomarkers of disease severity are consequently lacking. Therefore, the aim of my thesis was to; 1) assess associations between the nerve injury biomarker neurofilament light (NfL) and brain atrophy and lesion volumes; 2) assess which brain/lesion volume measures show the strongest longitudinal association with clinical MS disability measures and to what degree these associations were affected by age; and to 3) identify genetic variants associated with brain atrophy, lesion volumes and plasma NfL (pNfL) levels in persons with MS. In Study I, we assessed how cerebrospinal fluid (CSF) and pNfL levels were associated with T1- and T2-lesion volumes as well as whole-brain, cortical and subcortical grey matter, white matter and thalamic volume fractions of total intracranial volume based on magnetic resonance imaging (MRI). High baseline CSF and pNfL levels were associated with lower whole-brain, subcortical grey matter, thalamic, white matter and corpus callosal volume fractions over time. A further analysis showed that there was an association between baseline pNfL and baseline cortical grey matter fractions also in absence of radiological signs of inflammatory disease activity. A topographic analysis of cortical thickness showed that loss of cortical volume preferentially involved frontotemporal cortical regions. These findings indicate that NfL levels contribute information about MS severity not provided by traditional MRI lesion metrics. In Study II, we showed that associations between baseline MRI variables, and baseline physical disability and self-reported impact of MS rapidly increased in strength in individuals beyond approximately 40-50 years of age. In separate longitudinal analyses using linear mixed-effects models, we showed that among the recorded brain volume measures, cortical and subcortical grey matter and thalamic volume fractions at baseline were the strongest predictors of future worsening in clinical disability over a median of approximately ten years’ follow-up time. They were also stronger predictors than T1- and T2-lesion volumes. In Study III, we assessed if a weighted risk score comprising 12 known MS risk human leukocyte antigen (HLA) alleles was associated with baseline and longitudinal MRI measures as described in Studies I and II. While this risk score was not significantly associated with baseline MRI measures, we found that a high score was associated with lower cortical grey matter fractions longitudinally. A further analysis showed that this effect was primarily driven by the HLA-DRB1*15:01 allele. These results suggest that MS HLA risk variants not only affect inflammatory, but also neurodegenerative aspects of the disease. In Studies IV and V, we performed genome-wide association studies of pNfL levels and whole-brain volume fractions, respectively, in persons with MS (and controls in Study IV). While no genome-wide significant associations were found in Study IV, gene set analyses highlighted a neural crest and odontogenesis development pathway in the regulation of pNfL levels, and a weighted MS susceptibility polygenic risk score was associated with higher pNfL levels in MS with statistical significance. These findings suggest that there is some degree of genetic regulation of pNfL levels, which partially overlap with MS risk. In Study V, we identified a genome-wide significant locus upstream of the glycerol kinase 2 (GK2) gene, previously implicated in the propensity for tobacco smoking, which is a known MS risk and severity factor. Gene set analyses in Study V also implicated Hypoxia Inducible Factor-1 (HIF1) in the regulation of whole-brain volume fractions, indicating that iron metabolism and response to hypoxia play a role in the neurodegenerative processes in MS

The Effect of Financial Leverage on the Growth of the Companies Listed in Tehran Stock Exchange

This study examines the effect of financial leverage on the growth of companies listed in Tehran Stock Exchange. The study population includes pharmaceutical companies listed in Tehran Stock Exchange. The study interval is 2010-2014. Using variable data software brings a new approach, and is calculated by Excel. Variables of the study were calculated by data of Rahavard Novin Software and Excel. Data was analyzed by SPSS using descriptive and inferential statistics such as the Kolmogorov-Smirnov test, Pearson correlation and linear regression in order to test hypotheses of the study. According to the tests and analyses, it could be concluded that hypotheses were accepted. Thus, we can claim that there was an inverse relationship between leverage and company's growth

Cold spray coating: process evaluation and wealth of applications; from structural repair to bioengineering

Il processo di spruzzatura a freddo, più comunemente indicato come Cold Spray (CS), consiste nell’accelerare delle polveri attraverso un ugello di de Laval verso un substrato. Se la velocità di impatto supera un valore di soglia, le particelle plasticizzano e aderiscono alla superficie. Molti materiali, quali metalli, ceramiche, compositi e polimeri possono essere depositati con il Cold Spray, creando molteplici opportunità per ottenere proprietà particolari. Il CS è una nuova e interessante tecnologia per ottenere rivestimenti superficiali. Offre diversi vantaggi tecnologici rispetto ai processi di spruzzatura termica (thermal spray) in quanto utilizza energia cinetica e non termica per la deposizione delle polveri. Ciò permette di evitare tensioni residue di trazione, ossidazione e reazioni chimiche indesiderate. Lo sviluppo di nuovi sistemi di materiali con proprietà migliorate e personalizzate in funzione dell’applicazione, dai motori a combustione interna alle biotecnologie, rende appetibile l’applicazione del cold spray per la definizione di differenti combinazioni di materiali che permettono di enfatizzare le proprietà volute. La presente tesi s’inserisce in questo contesto e i suoi principali obiettivi possono essere divisi in due categorie: Il primo è lo studio del processo e la conoscenza delle sue principali caratteristiche. A tal fine, l’attenzione è stata focalizzata su due aspetti: la determinazione della velocità critica e di quella di erosione e lo studio del comportamento meccanico dei rivestimenti ottenuti con il CS sotto l’azione di azioni d’indentazione e di come questo differisca dai processi tecnologici tradizionali. Durante la deposizione del rivestimento tramite CS, l’adesione è ottenuta quando la velocità delle particelle eccede un valore minimo, chiamato velocità critica, ma è, allo stesso tempo, inferiore a un valore massimo, che comporta l’erosione della superficie. È stato proposto un nuovo modello, ibrido in quanto frutto della combinazione di risultati numerici e soluzioni analitiche. Rispetto a precedenti modelli reperibili in bibliografia, nel modello sviluppato si tengono in considerazione sia la porosità delle particelle che i fenomeni di adesione tra le polveri e il substrato. I risultati ottenuti risultano essere in buon accordo con i dati sperimentali a disposizione. Il modello è basato su un approccio energetico. Tuttavia, diversi sono diversi gli indici fisici o meccanici che sono stati proposti come indicatori dell’adesione e della crescita del rivestimento generato con il CS. Ciò su cui la maggior parte degli approcci riconosce è che durante l’impatto delle particelle ad elevata velocità si formano getti di materiale. Avere un’accurata comprensione di cosa accade durante l’impatto nei getti di materiale potrebbe essere la via per capire i meccanismi di adesione nel CS. Tuttavia, in un modello a elementi finiti, eccessive deformazioni/distorsioni degli elementi che schematizzano i getti rendono i risultati della simulazione estremamente dipendenti dalla mesh. Si è quindi anche proposto un approccio di simulazione, semplificato ma efficace, per la simulazione della formazione dei getti di materiale. A tal fine, si è utilizzato l’approccio Euleriano nel quale gli elementi sono fissi e il materiale può scorrere in essi. Con tale strumento è stata, quindi, studiata con risultati promettenti l’evoluzione dello stato di deformazione di sei materiali Ta, Cu, Ni, Al2024, Ti6Al4V e SS304. Si sono determinate le variazioni di temperatura e l’evoluzione della deformazione così come la genesi delle condizioni di instabilità con conseguente formazione dei getti di materiale. Tale parte della tesi termina con una discussione sulla velocità critica dei materiali. Dopo aver studiato il fenomeno dell'impatto durante il CS, si è esplorato il comportamento meccanico del rivestimento consolidato durante l’applicazione di carichi di indentazione, variabili dal nano al micro regime, è stato osservato un comportamento peculiare. I rivestimenti depositati con il CS, a differenza dei materali monolitici, mostrano una forte dipendenza rispetto alla scala di indentazione rispetto al tipico compartamento alla Nix-Gao. La durezza improvvisamente diminuisce in regime micro in confronto al regime di nano indentazione. Ciò è stato messo in relazione all’esistenza di difetti macroscopici come i bordi inter-particella che portano alla generazione di microcricche e anche a porosità. Per interpretare le osservazioni sperimentali è stato costruito un modello a elementi finiti che ha considerato il danneggiamento inter-particella. A tal fine si è utilizzato un modello di danneggiamento duttile in combinazione con modelli di evoluzione del danno lineari. E’ stata, quindi, studiata la deviazione delle curve carico-spostamento nel materiale con difetti inter-particelle in confronto al materiale base monolitico ed è stato proposto un parametro di riduzione della capacità di resistenza al carico per valutare l’escursione dei dati carico-profondità dell’indentazione. Le analisi e le prove eseguite in questa sono state accompagnate da due esaurienti discussioni critiche dello stato dell’arte. La prima di queste riguarda i differenti sistemi di materiali ad oggi utilizzati per il CS così come le possibili prossime potenziali applicazioni innovative. Lo studio comprende materiali metallici, polimeriic, compositi a matrice metallica, materiali ceramici e termina con una discussione sul futuro di questa tecnologia. La seconda riguarda l’impiego del CS per alleviare la corrosione e comprende l’applicazione del CS per conferire una superiore resistenza alla corrosione depositando materiali più nobili del substrato così come rivestimenti anodici da sacrificare. Attenzione speciale è stata data alla comprensione di come i parametri e le condizioni di CS possono influenzare il comportamento a corrosione del rivestimento. E’ stato discusso l’effetto della temperatura di deposizione, della pressione, della dimensione delle particelle, del gas accelerante, dei trattamenti post-CS e della co-deposizione di polveri miste metallo-ceramiche sul comportamento a corrosione. Sono, inoltre, presentati alcuni esempi di applicazione del CS contro la corrosione in diversi settori (biomed, navale, elettronica,..) insieme a possibili prospettive di impieghi futuri. Il secondo obiettivo della tesi è lo studio delle applicazioni emergenti del CS, soprattutto per riparare elementi danneggiati e per ottenere rivestimenti e parti con migliore biocompatibilità. Per quanto riguarda il primo aspetto, già ci sono stati alcuni tentativi di utilizzare il CS per riparare elementi elicotteristici o stampi danneggiati. Tuttavia, la maggior parte delle volte si sono eseguite solo ispezioni visive, in quanto non era possibile simulare condizioni di carico realistiche. Inoltre, non sono molti gli studi di base e sistematici al riguardo. Nella presente ricerca si è eseguito uno studio sistematico delle forme dei difetti e della capacità del CS di riempire le cavità, a loro volta studiate in modo da ottimizzare l’adesione del rivestimento. Un altro requisito richiesto è che la riparazione eseguita con il CS abbia proprietà che permettano al pezzo la stessa resistenza meccanica del pezzo monolitico. In particolare, la fatica rappresenta uno dei meccanismo di danno più pericolosi per le i particolari strutturali. Si è quindi studiata la resistenza a fatica di reirivestimenti ottenuti con il CS ed è stato presentato un modello per la valutazione del limite di fatica di provini rivestiti con il CS. Tale modello è risultato in buon accordo con i risultati sperimentali. Inoltre, in questa fase si è investigato il miglioramento della vita a fatica che si può ottenere con trattamenti ibridi, quali la pallinatura (shot peening, SP) e la pallinatura severa (severe shot peening, SSP), applicati sia come pre che come post trattamento rispetto al CS. Il materiale indagato è, in questo caso, la lega Al 6082: i risultati sperimentali indicano entrambi i trattamenti hanno un notevole effetto benefico se eseguiti prima del CS. In particolare il miglior risultato è stato ottenuto con la sequenza SSP+CS, che ha permesso di incrementare la resistenza a fatica di circa il 26% rispetto ai provini non trattati e non rivestiti. Per quanto riguarda, infine, le applicazioni biomediche del CS, si propongono delle linee guida per la deposizione di rivestimenti porosi. L’impianto con rivestimento poroso, infatti, può essere stabilizzato grazie alla crescita dell’osso piuttosto che con l’applicazione di cemento. Questo può migliorare il fissaggio dell’impianto e ridurre il rischio di allentamento. Tale applicazione del CS è inusuale e originale, oltre che, a prima vista contraddittoria, in quanto è generalmente utilizzato per ottenere rivestimenti ad elevata densità e ridotta porosità. A tal fine, nella tesi il CS è utilizzato con parametri non convenzionali (poveri di dimensioni piuttosto elevate e alta velocita`di spruzzo) per geenrare un rivestimento poroso di lega i Titanio per applicazioni strutturali di impianti bio-med. Il risultato di questa parte dello studio è la generazione di rivestimenti porosi (fino al 29% di porosità) che costituiscono la base per un approfondimento e sviluppo della tematica.Cold spray (CS) is a process in which solid powders are accelerated in a de Laval nozzle toward a substrate. If the impact velocity exceeds a threshold value, particles endure plastic deformation and adhere to the surface. Different materials such as metals, ceramics, composites and polymers can be deposited using cold spray, creating a wealth of interesting opportunities towards harvesting particular properties. Cold spray is a novel and promising technology to obtain surface coating. It offers several technological advantages over thermal spray since it utilizes kinetic rather than thermal energy for deposition. As a result, tensile residual stresses, oxidation and undesired chemical reactions can be avoided. Development of new material systems with enhanced properties covering a wide range of required functionalities of surfaces and interfaces, from internal combustion engines to biotechnology, brought forth new opportunities to the cold spraying with a rich variety of material combinations. This thesis goal can be divided into two main categories: The first is process evaluation and understanding the fundamental features of the cold spray. In this regard, the focus was on two issues: assessment of critical and erosion velocities and also the mechanical behavior of cold spray coating under indentation loading condition and how it differs from the conventional manufacturing processes. During cold spray deposition, bonding is obtained when the impact velocity of small particles exceeds a critical value called critical velocity, but it is less than an upper limit beyond which erosion happens. A new model is proposed, combination of numerical and analytical solutions, to calculate not only the critical velocity but also erosion velocity. Compared with previous studies, porosity of particles and adherence phenomena between particle and the substrate is taken into account as a novelty. The results of the proposed approach is compared with experimental data and good agreement is found. This model was based on energy approach. To reveal the phenomenological characteristic of interface bonding in cold spray, severe and localized plastic deformation and material jet formation at the impacting interface should be studied. However, excessive deformation/distortion of elements in the material jet makes it extremely mesh dependent in simulation. A simplified but effective simulation of material jet formation and growth during cold spray is proposed. To this end, Eulerian framework is used in which elements are fixed and material can flow. Six metals and alloys e.g. Ta, Cu, Ni, Al2024, Ti6Al4V and SS304 are examined to cover a wide range of physical, thermal and mechanical properties. General deformation, induced plastic strain, temperature rise in the particle and in particular in the material jet is presented and discussed. It is found that to ensure shear instability for all metals and alloys, material flow velocity in the jet should reach very close to the shear wave velocity. It is also found that the maximum velocity of material flow is linearly proportional to the impact velocity, with the same slope for all materials. It is accordingly proposed that critical velocity of metals and alloys can be simply expressed as a constant times the shear wave velocity. For 25 micrometer particle diameter in room temperature, critical velocity in cold spray is approximately 20% of shear wave velocity: Vcr = 0.2(G/ρ)^0.5. After studying the impact phenomenon during cold spray, mechanical behavior of consolidated coating under indentation loading condition is also explored. During the experiments for characterizing cold spray coating in a wide indentation load range, from nano to micro indentation region, a peculiar behavior was observed. Cold spray deposited coatings, unlike bulk materials, show strong dependency on the indentation size scale different from the typical Nix-Gao behavior. The hardness suddenly decreases in micro indentation region in comparison to nano indentation region. This was related to the existence of macroscopic defects such as interparticle boundaries and subsequent splat’s boundary cracking and also the porosities. To interpret the experimental observation, a finite element model was developed. The interparticle damage was taken into consideration. Ductile damage initiation in combination with the linear damage evolution models was used. The deviation of load-displacement curves in the material with inter particle defects in comparison to bulk material was studied. A load bearing reduction parameter was proposed to evaluate the excursion of load-depth data. The first two studies were efforts to study the fundamentals of the cold spray process and most influencing parameters on subsequent loading conditions. This phase of the thesis was accomplished with two comprehensive reviews. First on different material systems that have been cold sprayed. The review covers different material systems that have been studied up to now with a view on potential innovative applications. This includes metallic, ceramic, metal matrix composite (MMC), polymer (both as substrate and coating) and nano structured powders. A critical discussion on the future of this technology is provided. The second review is on cold spray to mitigate corrosion. The review includes application of cold spray to provide superior corrosion resistance by depositing more noble materials than substrate as well as sacrificial protection. Special attention is given to understand how cold spray parameters and conditions could affect the resulting corrosion behavior of the coating. The effect of deposition temperature and pressure, particle size, carrier gas, post-treatment and co-deposition of metals and ceramic particles on corrosion behavior is discussed. A few examples of cold spray applications against corrosion in various fields (biomedical, naval, electronics and hot corrosion) are presented. A discussion with possible future perspective is also given. The second goal of the research is investigating the application of cold spray coating mainly on repairing damaged parts and biomedical engineering. There has been some efforts in repairing structural parts such as rotorcraft components or damaged mold surface using cold spray technology. Most of the time only visual inspection has been performed since simulating real loading conditions for these parts are not possible. Moreover, not many fundamental studies have been done in this regard. In the present investigation, a systematic study of defect shape and ability of cold spray to fill it and shape optimization for maximum bond strength is done. Furthermore, repaired part must retain bulk material properties to withstand service loads. Fatigue represents one of the most intricate types of the damage to which structural parts are subjected in service. The effect of cold spray deposition on fatigue life of coated specimen is studied. A model to predict the fatigue limit of the cold sprayed specimen is proposed and has good agreement with experimental results. The enhancement of fatigue life by means of hybrid treatments is also investigated. Shot peening which is a surface treatment that can enhance the fatigue life by inducing near-surface compressive residual stresses is considered. The effect of severe shot peening (SSP) and conventional shot peening (SP) as pre and post treatment on mechanical and fatigue behavior of cold sprayed aluminum alloy 6082 is experimentally evaluated. It was found that conventional and severe shot peening are most efficient to improve fatigue behavior if they are performed prior to cold spray deposition. The best results were obtained for SSP+CS which increased the fatigue strength up to 26 % in comparison to as received condition. For biomedical application of CS coating, guidelines are proposed for one-step deposition of porous coatings without any subsequent heat treatment. Experiments were carried out at under-critical impact conditions, using rather coarse powders and fast gun traverse speeds. The e_ect of substrate material and spray parameters on the strength and porosity of the coating is investigated. Thick, macro rough, sufficiently high strength coatings, suitable for implant applications, with porosity of up to about 30% was successfully deposited using marginally low impact conditions.DIPARTIMENTO DI MECCANICAMachine and vehicle design27COLOMBO, GIORGIOCOLOSIMO, BIANCA MARI

Underground Mining Monitoring and Communication Systems based on ZigBee and GIS

ZigBee as a wireless sensor network (WSN) was developed for underground mine monitoring and communication systems. The radio wave attenuations between ZigBee nodes were investigated to measure underground communication distances. Various sensor node arrangements of ZigBee topologies were evaluated. A system integration of a WSN-assisted GIS for underground mining monitoring and communication from a surface office was proposed. The controllable and uncontrollable parameters of underground environments were assessed to establish a reliable ZigBee network