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Showing 531 to 535 of 535 (0.037 seconds)Spelling suggestions: "subject:"aggregate""
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Modelování Huntingtonovy choroby a bněčná terapie při poškození míchy. / Huntington's disease modeling and stem cell therapy in spinal cord disorders and injuryHruška-Plocháň, Marián January 2013 (has links)
Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...
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Essays on monetary policy, saving and investmentLenza, Michèle 04 June 2007 (has links)
This thesis addresses three relevant macroeconomic issues: (i) why<p>Central Banks behave so cautiously compared to optimal theoretical<p>benchmarks, (ii) do monetary variables add information about<p>future Euro Area inflation to a large amount of non monetary<p>variables and (iii) why national saving and investment are so<p>correlated in OECD countries in spite of the high degree of<p>integration of international financial markets.<p><p>The process of innovation in the elaboration of economic theory<p>and statistical analysis of the data witnessed in the last thirty<p>years has greatly enriched the toolbox available to<p>macroeconomists. Two aspects of such a process are particularly<p>noteworthy for addressing the issues in this thesis: the<p>development of macroeconomic dynamic stochastic general<p>equilibrium models (see Woodford, 1999b for an historical<p>perspective) and of techniques that enable to handle large data<p>sets in a parsimonious and flexible manner (see Reichlin, 2002 for<p>an historical perspective).<p><p>Dynamic stochastic general equilibrium models (DSGE) provide the<p>appropriate tools to evaluate the macroeconomic consequences of<p>policy changes. These models, by exploiting modern intertemporal<p>general equilibrium theory, aggregate the optimal responses of<p>individual as consumers and firms in order to identify the<p>aggregate shocks and their propagation mechanisms by the<p>restrictions imposed by optimizing individual behavior. Such a<p>modelling strategy, uncovering economic relationships invariant to<p>a change in policy regimes, provides a framework to analyze the<p>effects of economic policy that is robust to the Lucas'critique<p>(see Lucas, 1976). The early attempts of explaining business<p>cycles by starting from microeconomic behavior suggested that<p>economic policy should play no role since business cycles<p>reflected the efficient response of economic agents to exogenous<p>sources of fluctuations (see the seminal paper by Kydland and Prescott, 1982}<p>and, more recently, King and Rebelo, 1999). This view was challenged by<p>several empirical studies showing that the adjustment mechanisms<p>of variables at the heart of macroeconomic propagation mechanisms<p>like prices and wages are not well represented by efficient<p>responses of individual agents in frictionless economies (see, for<p>example, Kashyap, 1999; Cecchetti, 1986; Bils and Klenow, 2004 and Dhyne et al. 2004). Hence, macroeconomic models currently incorporate<p>some sources of nominal and real rigidities in the DSGE framework<p>and allow the study of the optimal policy reactions to inefficient<p>fluctuations stemming from frictions in macroeconomic propagation<p>mechanisms.<p><p>Against this background, the first chapter of this thesis sets up<p>a DSGE model in order to analyze optimal monetary policy in an<p>economy with sectorial heterogeneity in the frequency of price<p>adjustments. Price setters are divided in two groups: those<p>subject to Calvo type nominal rigidities and those able to change<p>their prices at each period. Sectorial heterogeneity in price<p>setting behavior is a relevant feature in real economies (see, for<p>example, Bils and Klenow, 2004 for the US and Dhyne, 2004 for the Euro<p>Area). Hence, neglecting it would lead to an understatement of the<p>heterogeneity in the transmission mechanisms of economy wide<p>shocks. In this framework, Aoki (2001) shows that a Central<p>Bank maximizing social welfare should stabilize only inflation in<p>the sector where prices are sticky (hereafter, core inflation).<p>Since complete stabilization is the only true objective of the<p>policymaker in Aoki (2001) and, hence, is not only desirable<p>but also implementable, the equilibrium real interest rate in the<p>economy is equal to the natural interest rate irrespective of the<p>degree of heterogeneity that is assumed. This would lead to<p>conclude that stabilizing core inflation rather than overall<p>inflation does not imply any observable difference in the<p>aggressiveness of the policy behavior. While maintaining the<p>assumption of sectorial heterogeneity in the frequency of price<p>adjustments, this chapter adds non negligible transaction<p>frictions to the model economy in Aoki (2001). As a<p>consequence, the social welfare maximizing monetary policymaker<p>faces a trade-off among the stabilization of core inflation,<p>economy wide output gap and the nominal interest rate. This<p>feature reflects the trade-offs between conflicting objectives<p>faced by actual policymakers. The chapter shows that the existence<p>of this trade-off makes the aggressiveness of the monetary policy<p>reaction dependent on the degree of sectorial heterogeneity in the<p>economy. In particular, in presence of sectorial heterogeneity in<p>price adjustments, Central Banks are much more likely to behave<p>less aggressively than in an economy where all firms face nominal<p>rigidities. Hence, the chapter concludes that the excessive<p>caution in the conduct of monetary policy shown by actual Central<p>Banks (see, for example, Rudebusch and Svennsson, 1999 and Sack, 2000) might not<p>represent a sub-optimal behavior but, on the contrary, might be<p>the optimal monetary policy response in presence of a relevant<p>sectorial dispersion in the frequency of price adjustments.<p><p>DSGE models are proving useful also in empirical applications and<p>recently efforts have been made to incorporate large amounts of<p>information in their framework (see Boivin and Giannoni, 2006). However, the<p>typical DSGE model still relies on a handful of variables. Partly,<p>this reflects the fact that, increasing the number of variables,<p>the specification of a plausible set of theoretical restrictions<p>identifying aggregate shocks and their propagation mechanisms<p>becomes cumbersome. On the other hand, several questions in<p>macroeconomics require the study of a large amount of variables.<p>Among others, two examples related to the second and third chapter<p>of this thesis can help to understand why. First, policymakers<p>analyze a large quantity of information to assess the current and<p>future stance of their economies and, because of model<p>uncertainty, do not rely on a single modelling framework.<p>Consequently, macroeconomic policy can be better understood if the<p>econometrician relies on large set of variables without imposing<p>too much a priori structure on the relationships governing their<p>evolution (see, for example, Giannone et al. 2004 and Bernanke et al. 2005).<p>Moreover, the process of integration of good and financial markets<p>implies that the source of aggregate shocks is increasingly global<p>requiring, in turn, the study of their propagation through cross<p>country links (see, among others, Forni and Reichlin, 2001 and Kose et al. 2003). A<p>priori, country specific behavior cannot be ruled out and many of<p>the homogeneity assumptions that are typically embodied in open<p>macroeconomic models for keeping them tractable are rejected by<p>the data. Summing up, in order to deal with such issues, we need<p>modelling frameworks able to treat a large amount of variables in<p>a flexible manner, i.e. without pre-committing on too many<p>a-priori restrictions more likely to be rejected by the data. The<p>large extent of comovement among wide cross sections of economic<p>variables suggests the existence of few common sources of<p>fluctuations (Forni et al. 2000 and Stock and Watson, 2002) around which<p>individual variables may display specific features: a shock to the<p>world price of oil, for example, hits oil exporters and importers<p>with different sign and intensity or global technological advances<p>can affect some countries before others (Giannone and Reichlin, 2004). Factor<p>models mainly rely on the identification assumption that the<p>dynamics of each variable can be decomposed into two orthogonal<p>components - common and idiosyncratic - and provide a parsimonious<p>tool allowing the analysis of the aggregate shocks and their<p>propagation mechanisms in a large cross section of variables. In<p>fact, while the idiosyncratic components are poorly<p>cross-sectionally correlated, driven by shocks specific of a<p>variable or a group of variables or measurement error, the common<p>components capture the bulk of cross-sectional correlation, and<p>are driven by few shocks that affect, through variable specific<p>factor loadings, all items in a panel of economic time series.<p>Focusing on the latter components allows useful insights on the<p>identity and propagation mechanisms of aggregate shocks underlying<p>a large amount of variables. The second and third chapter of this<p>thesis exploit this idea.<p><p>The second chapter deals with the issue whether monetary variables<p>help to forecast inflation in the Euro Area harmonized index of<p>consumer prices (HICP). Policymakers form their views on the<p>economic outlook by drawing on large amounts of potentially<p>relevant information. Indeed, the monetary policy strategy of the<p>European Central Bank acknowledges that many variables and models<p>can be informative about future Euro Area inflation. A peculiarity<p>of such strategy is that it assigns to monetary information the<p>role of providing insights for the medium - long term evolution of<p>prices while a wide range of alternative non monetary variables<p>and models are employed in order to form a view on the short term<p>and to cross-check the inference based on monetary information.<p>However, both the academic literature and the practice of the<p>leading Central Banks other than the ECB do not assign such a<p>special role to monetary variables (see Gali et al. 2004 and<p>references therein). Hence, the debate whether money really<p>provides relevant information for the inflation outlook in the<p>Euro Area is still open. Specifically, this chapter addresses the<p>issue whether money provides useful information about future<p>inflation beyond what contained in a large amount of non monetary<p>variables. It shows that a few aggregates of the data explain a<p>large amount of the fluctuations in a large cross section of Euro<p>Area variables. This allows to postulate a factor structure for<p>the large panel of variables at hand and to aggregate it in few<p>synthetic indexes that still retain the salient features of the<p>large cross section. The database is split in two big blocks of<p>variables: non monetary (baseline) and monetary variables. Results<p>show that baseline variables provide a satisfactory predictive<p>performance improving on the best univariate benchmarks in the<p>period 1997 - 2005 at all horizons between 6 and 36 months.<p>Remarkably, monetary variables provide a sensible improvement on<p>the performance of baseline variables at horizons above two years.<p>However, the analysis of the evolution of the forecast errors<p>reveals that most of the gains obtained relative to univariate<p>benchmarks of non forecastability with baseline and monetary<p>variables are realized in the first part of the prediction sample<p>up to the end of 2002, which casts doubts on the current<p>forecastability of inflation in the Euro Area.<p><p>The third chapter is based on a joint work with Domenico Giannone<p>and gives empirical foundation to the general equilibrium<p>explanation of the Feldstein - Horioka puzzle. Feldstein and Horioka (1980) found<p>that domestic saving and investment in OECD countries strongly<p>comove, contrary to the idea that high capital mobility should<p>allow countries to seek the highest returns in global financial<p>markets and, hence, imply a correlation among national saving and<p>investment closer to zero than one. Moreover, capital mobility has<p>strongly increased since the publication of Feldstein - Horioka's<p>seminal paper while the association between saving and investment<p>does not seem to comparably decrease. Through general equilibrium<p>mechanisms, the presence of global shocks might rationalize the<p>correlation between saving and investment. In fact, global shocks,<p>affecting all countries, tend to create imbalance on global<p>capital markets causing offsetting movements in the global<p>interest rate and can generate the observed correlation across<p>national saving and investment rates. However, previous empirical<p>studies (see Ventura, 2003) that have controlled for the effects<p>of global shocks in the context of saving-investment regressions<p>failed to give empirical foundation to this explanation. We show<p>that previous studies have neglected the fact that global shocks<p>may propagate heterogeneously across countries, failing to<p>properly isolate components of saving and investment that are<p>affected by non pervasive shocks. We propose a novel factor<p>augmented panel regression methodology that allows to isolate<p>idiosyncratic sources of fluctuations under the assumption of<p>heterogenous transmission mechanisms of global shocks. Remarkably,<p>by applying our methodology, the association between domestic<p>saving and investment decreases considerably over time,<p>consistently with the observed increase in international capital<p>mobility. In particular, in the last 25 years the correlation<p>between saving and investment disappears.<p> / Doctorat en sciences économiques, Orientation économie / info:eu-repo/semantics/nonPublished
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Synthesis of Thiophene-Vinyl-Benzothiazole Based Ligand Analogues for Detection of Aβ and Tau Pathology in Alzheimer's DiseaseJohansson, Joel January 2024 (has links)
As of today, Alzheimer’s disease is the leading cause of dementia among neurodegenerative disorders, affecting many millions of people worldwide. As the average life span of populations increase, more and more people succumb to the illness each year. Like other neurodegenerative disorders, Alzheimer’s disease can be attributed to the accumulation of protein aggregates in the brain. These amyloid-β peptides and tau proteins can presumably be detected in the brain many years before the onset of clinical symptoms. Development of fluorescent ligands, capable of binding to these neuropathological hallmarks and highlighting them, could serve as molecular diagnostic tools and facilitate an early diagnosis of the disease. The method could also be useful in studying disease progression and evaluating the effects of novel treatments. One such ligand is HS-259. The aim of this project was to synthetize different analogues of HS-259, and test their selectivity towards the aforementioned aggregates in brain tissue from an individual with Alzheimer’s disease. Staining of tissue samples with analogue solution enables visualization of aggregate sites through fluorescence imaging. In the end, five analogues were synthetized, albeit in relatively low overall yields. Synthetic methods included Suzuki-Miyara cross-couplings, Ullmann-type arylations and condensations. Liquid Chromatography-Mass Spectrometry (LC-MS) and Nuclear Magnetic Resonance (NMR) were used for analysis of the compounds. Two of the five analogues could be tested for staining of aggregates and assessed for photophysical characteristics, i.e. absorption- and emission spectra. One analogue stained both amyloid-β aggregates and some tau aggregates, whereas the other stained neither. Since only two analogues were tested and rendered inconsistent results, further studies are needed to assess the binding properties of HS-259 analogues in general.
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Action in Chronic Fatigue Syndrome: an Enactive Psycho-phenomenological and Semiotic Analysis of Thirty New Zealand Women's Experiences of Suffering and RecoveryHart, M J Alexandra January 2010 (has links)
This research into Chronic Fatigue Syndrome (CFS) presents the results of 60 first-person psycho-phenomenological interviews with 30 New Zealand women. The participants were recruited from the Canterbury and Wellington regions, 10 had recovered. Taking a non-dual, non-reductive embodied approach, the phenomenological data was analysed semiotically, using a graph-theoretical cluster analysis to elucidate the large number of resulting categories, and interpreted through the enactive approach to cognitive science.
The initial result of the analysis is a comprehensive exploration of the experience of CFS which develops subject-specific categories of experience and explores the relation of the illness to universal categories of experience, including self, ‘energy’, action, and being-able-to-do.
Transformations of the self surrounding being-able-to-do and not-being-able-to-do were shown to elucidate the illness process.
It is proposed that the concept ‘energy’ in the participants’ discourse is equivalent to the Mahayana Buddhist concept of ‘contact’. This characterises CFS as a breakdown of contact. Narrative content from the recovered interviewees reflects a reestablishment of contact.
The hypothesis that CFS is a disorder of action is investigated in detail.
A general model for the phenomenology and functional architecture of action is proposed. This model is a recursive loop involving felt meaning, contact, action, and perception and appears to be phenomenologically supported.
It is proposed that the CFS illness process is a dynamical decompensation of the subject’s action loop caused by a breakdown in the process of contact.
On this basis, a new interpretation of neurological findings in relation to CFS becomes possible. A neurological phenomenon that correlates with the illness and involves a brain region that has a similar structure to the action model’s recursive loop is identified in previous research results and compared with the action model and the results of this research. This correspondence may identify the brain regions involved in the illness process, which may provide an objective diagnostic test for the condition and approaches to treatment.
The implications of this model for cognitive science and CFS should be investigated through neurophenomenological research since the model stands to shed considerable light on the nature of consciousness, contact and agency.
Phenomenologically based treatments are proposed, along with suggestions for future research on CFS. The research may clarify the diagnostic criteria for CFS and guide management and treatment programmes, particularly multidimensional and interdisciplinary approaches.
Category theory is proposed as a foundation for a mathematisation of phenomenology.
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Streamlining Certification Management with Automation and Certification Retrieval : System development using ABP Framework, Angular, and MongoDB / Effektivisering av certifikathantering med automatisering och certifikathämtning : Systemutveckling med ABP Framework, Angular och MongoDBHassan, Nour Al Dine January 2024 (has links)
This thesis examines the certification management challenge faced by Integrity360. The decentralized approach, characterized by manual processes and disparate data sources, leads to inefficient tracking of certification status and study progress. The main objective of this project was to construct a system that automates data retrieval, ensures a complete audit, and increases security and privacy. Leveraging the ASP.NET Boilerplate (ABP) framework, Angular, and MongoDB, an efficient and scalable system was designed, developed, and built based on DDD (domain-driven design) principles for a modular and maintainable architecture. The implemented system automates data retrieval from the Credly API, tracks exam information, manages exam vouchers, and implements a credible authentication system with role-based access control. With the time limitations behind the full-scale implementation of all the planned features, such as a dashboard with aggregated charts and automatic report generation, the platform significantly increases the efficiency and precision of employee certification management. Future work will include these advanced functionalities and integrations with external platforms to improve the system and increase its impact on operations in Integrity360.
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