Volatilità e stagionalità nelle commodity con applicazione del metodo Cos

LAUREA MAGISTRALELe commodity energetiche sono richieste in maniera differente durante le stagioni dell'anno. Questo è facile da immaginare in quanto la corrente elettrica o il gas sono più utilizzati nella stagione invernale, per via del fatto che la luce del giorno dura meno ore e le basse temperature richiedono l'azionamento del riscaldamento. La prima conseguenza di ciò è che anche il prezzo segue il passare delle stagioni, sarà più alto quando la richiesta è maggiore e più basso quando la richiesta è minore. Un effetto simile lo si può osservare sulla volatilità. Infatti, si può notare come la volatilità presenti una forma sinusoidale e tenda ad aumentare il suo valore al ridursi del time to maturity. \\ Le commodity sono una parte importante delle securities scambiate sui mercati finanziari. I principali prodotti scambiati in mercati regolamentati sono futures e opzioni. I futures sono strumenti che permettono di fissare al momento della stipula il prezzo di un certo sottostante, che sarà scambiato in una data successiva. Una caratteristica importante di questi prodotti, che non verrà considerata nello sviluppo dei modelli sottostanti, è che avviene uno scambio di denaro corrispondente alla differenza del Fair Value del futures rispetto all'ultima data di scambio (clearing). I futures, nonostante la loro semplicità, sono strumenti fondamentali in quanto per molte commodity non esiste un valore spot. Questo deriva dal fatto che la maggior parte dei mercati in cui si comprano commodity, il sottostante corrisponde alla commodity fisica, che risulta impossibile da muovere istantaneamente. I futures sono anche utilizzati come strumenti di hedging di un'esposizione al rischio di prezzo oppure per speculazione, per esempio chiudendo un margine dovuto ad un acquisto e a una vendita a prezzi differenti. Le opzioni sono strumenti più complessi, il detentore ha il diritto, ma non l'obbligo, di acquistare/vendere una certo sottostante ad un prezzo concordato in precedenza, dietro il pagamento di un premio al momento della stipula. Allo stesso modo dei futures, le opzioni posso essere utilizzate a fini di hedging o di speculazione. Se il sottostante di questi strumenti finanziari è una commodity energetica, allora il valore deve seguire lo stesso effetto stagionale. È quindi fondamentale considerare la stagionalità nel momento in cui si sviluppa un modello per valutare questi strumenti finanziari. Infine, dato che la volatilità forzerà il calcolo del valore delle opzioni attraverso la funzione caratteristica del sottostante, verrà proposta l'applicazione del metodo Cos.The energy commodities are asked differently during the year. This is simple to understand since power or natural gas are more needed in the cold season, due to the short daylight or the cold temperature which requires the heating activation. On consequence, the price will follow the seasonality of the year, will raise when the demand is higher and fall when is shorter. A similar effect can be observed in the volatility. Indeed the volatility shows a sinusoidal form and tend to rise when the instrument approaches the maturity. \\ Commodities are an important part of the securities exchanged in the financial markets. The principal products, exchanged in the regulated markets, are futures and options. Futures are financial instruments which allow to fix at the moment of the conclusion of the contract the price of a certain underlying, which will be exchanged later. An important characteristic of these products, that will not be considered in the development of the models later on, is that the difference in the fair value must be paid periodically during the life of the contract (clearing). Futures, despite their simplicity, are fundamental because for most of the commodities there aren't any spot price. This comes from the fact that in a great number of exchange, where commodities can be bough or sold, the underlying is a physical commodity, which is very difficult to move instantaneously. Futures are also used as hedging instruments of a market price exposure or in term of speculation, for example closing a margin after buying and selling to different prices. Options are more complicated instruments, the buyer has the right, but not the obligation, to buy/sell a certain underlying to a strike price established before, provided that a premium form the buyer to the seller is paid. As for the futures, optins can be used as hedging or speculation instruments. If the underlying is an energy commodity, then the value of the underlying must follow the same stagionality effect. It is then fundamental to consider such effect in the development of a model to value these options. Finaly, since the volatility model will force the calculus trough the characteric function of the underlying, the application of the Cos method will be proposed

Targeting dementias through cancer kinases inhibition

The failures in Alzheimer's disease (AD) therapy strongly suggest the importance of reconsidering the research strategies analyzing other mechanisms that may take place in AD as well as, in general, in other neurodegenerative dementias. Taking into account that in AD a variety of defects result in neurotransmitter activity and signaling efficiency imbalance, neuronal cell degeneration and defects in damage/repair systems, aberrant and abortive cell cycle, glial dysfunction, and neuroinflammation, a target may be represented by the intracellular signaling machinery provided by the kinome. In particular, based on the observations of a relationship between cancer and AD, we focused on cancer kinases for targeting neurodegeneration, highlighting the importance of targeting the intracellular pathways at the intersection between cell metabolism control/duplication, the inhibition of which may stop a progression in neurodegeneration

insights into the definition of terms in european medical device regulation

ABSTRACTIntroduction: Medical devices comprise apparatus/instruments, software, and materials with therapeutic activities obtained by principal mechanisms of action different from pharmacological, immunological and metabolic, which are proper of medicinal products. In this context the key for the distinction between medicinal products and devices lies in the correct interpretation of these terms, which, although defined in a guideline, are still not univocally interpreted.Areas covered: This article discusses the definitions of pharmacological and non-pharmacological mechanisms of action, such as the chemical and physical means. The aim is to give insights on the correct definition these terms in order to contribute to build the desired synergy between scientific and regulatory fields and promote a correct interpretation of the European regulatory framework as well as sustainable health and innovation.Expert commentary: We propose a series of definitions and a method to interpret those definitions within ..

Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?

p53 transcriptional activity depends mainly on posttranslational modifications and protein/protein interaction. Another important mechanism that controls p53 function is its conformational stability since p53 is an intrinsically unstable protein. An altered conformational state of p53, independent from point mutations, has been reported in tissues from patients with Alzheimer's disease (AD), leading to an impaired and dysfunctional response to stressors. Recent evidence shows that one of the activators that induces p53 posttranslational modification and wild-type conformational stability is homeodomain interacting protein kinase 2 (HIPK2). Hence, conditions that induce HIPK2 deregulation would result in a dysfunctional response to stressors by affecting p53 activity. Discovering the mechanisms of HIPK2 activation/inhibition and the ways to manipulate HIPK2 activity are an interesting option to affect several biological pathways, including those underlying AD. Soluble beta-amyloid peptides have recently been involved in HIPK2 degradation, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus, before triggering the amyloidogenic cascade. Here we discuss about these findings and the potential relevance of HIPK2 as a target for AD and highlight the existence of a novel amyloid-based mechanism in AD potentially leading to the survival of injured dysfunctional cells

Role of hormones in the regulation of RACK1 expression as a signaling checkpoint in immunosenescence

Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopolysaccharide (LPS) stimulation and cytokine release. The lack of PKC activation seems to be dependent on the reduced expression of the receptor for activated C kinase 1 (RACK1), a scaffolding protein involved in multiple signal transduction cascades. The defective expression of RACK1 may be dependent on age-related alteration of the balance between the adrenal hormones cortisol and dehydroepiandrosterone (DHEA). DHEA levels reduce with aging, while cortisol levels remain substantially unchanged, resulting in an overall increase in the cortisol:DHEA ratio. These hormonal changes are significant in the context of RACK1 expression and signaling function because DHEA administration in vivo and in vitro can restore the levels of RACK1 and the function of the PKC signaling cascade in aged animals and in human cells. In contrast, there is evidence that cortisol can act as a negative transcriptional regulator of RACK1 expression. The rack1 gene promoter contains a glucocorticoid responsive element that is also involved in androgen signaling. Furthermore DHEA may have an indirect influence on the post-transcriptional regulation of the functions of the glucocorticoid receptor. In this review, we will examine the role of the hormonal regulation of rack1 gene transcriptional regulation and the consequences on signaling and function in immune cells and immunosenescence

Homeodomain Interacting Protein Kinase 2: A Target for Alzheimer's Beta Amyloid Leading to Misfolded p53 and Inappropriate Cell Survival

BACKGROUND: Homeodomain interacting protein kinase 2 (HIPK2) is an evolutionary conserved serine/threonine kinase whose activity is fundamental in maintaining wild-type p53 function, thereby controlling the destiny of cells when exposed to DNA damaging agents. We recently reported an altered conformational state of p53 in tissues from patients with Alzheimer's Disease (AD) that led to an impaired and dysfunctional response to stressors. METHODOLOGY/PRINCIPAL FINDINGS: Here we examined the molecular mechanisms underlying the impairment of p53 activity in two cellular models, HEK-293 cells overexpressing the amyloid precursor protein and fibroblasts from AD patients, starting from recent findings showing that p53 conformation may be regulated by HIPK2. We demonstrated that beta-amyloid 1-40 induces HIPK2 degradation and alters HIPK2 binding activity to DNA, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus. Expression of HIPK2 was analysed by western blot experiments, whereas HIPK2 DNA binding was examined by chromatin immunoprecipitation analysis. In particular, we evaluated the recruitment of HIPK2 onto some target promoters, including hypoxia inducible factor-1alpha and metallothionein 2A. CONCLUSIONS/SIGNIFICANCE: These results support the existence of a novel amyloid-based pathogenetic mechanism in AD potentially leading to the survival of injured dysfunctional cells

Разработка способов ремонта трубопроводов, проложенных способов ННБ

Секция IV. ОБЕСПЕЧЕНИЕ НАДЕЖНОСТИ И БЕЗОПАСНОСТИ ПРИ СООРУЖЕНИИ, РЕКОНСТРУКЦИИ, МОДЕРНИЗАЦИИ И РЕМОНТЕ ОБЪЕКТОВ МАГИСТРАЛЬНОГО ТРУБОПРОВОДНОГО ТРАНСПОРТ

Experimental Paradigm for the Assessment of the Non-pharmacological Mechanism of Action in Medical Device Classification: The Example of Glycerine as Laxative

The evolution of medical devices has led to the introduction of medical devices that include “substances” and which, due to their presentation and sites of application may resemble medicinal products. The difference between substance-based medical devices and medicinal products lies in the proper definition of the principal mechanism of action. The major problem at the moment is the lack of a proper procedure for the demonstration of a mechanism that is “not pharmacological, immunological or metabolic.” We aimed to design an experimental set up to demonstrate the difference between the mechanism of action of two substances used commonly for the treatment of constipation, lubiprostone (example of medicinal product) and glycerine (example of medical device). By implementing cellular models and molecular analyses we demonstrate the difference in their mechanism of action. This set up can be considered an example on the possibility to define a paradigm for the case by case study of the mechanism of action of substances and combination of substances in medical devices