839 resultados para Drugs - Side effects
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Is it conceivable to contemplate a future without the car as the center of an urban transportation system? Can emerging economies grow without concomitant growth in car usage? San Pedro Sula, Honduras, is one city at a critical decision point about the future of transportation and mobility. Will it be a sustainable transport future that balances economic, environmental and social needs or will it be the traditional “predict and provide” approach that attempts to expand the capacity of the road system to meet future travel demand. This paper provides some background into the issue for this Central American city by describing the current urban transport system, current plans for improvement and outlines a process for defining a vision for a sustainable transport future in San Pedro Sula. The paper concludes with a challenge to all cities that currently have low automobile ownership rates to consider a sustainable transport system in order to “thrive” with transport choices for all residents rather than “choke” on congestion and the negative side effects thereof.
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Cannabinoid receptors are members of the large family of G-protein coupled receptors. Two types of cannabinoid receptor have been discovered: CB1 and CB2. CB1 receptors are localised predominantly in the brain whereas CB2 receptors are more abundant in peripheral nervous system cells. CB1 receptors have been related with a number of disorders, including depression, anxiety, stress, schizophrenia, chronic pain and obesity. For this reason, several cannabinoid ligands were developed as drug candidates. Among these ligands, a prominent position is occupied by SR141716 (Rimonabant), which is a pyrazole derivative with inverse agonist activity discovered by Sanofi-Synthelabo in 1994. This compound was marketed in Europe as an anti-obesity drug, but subsequently withdrawn due to its side-effects. Since the relationship between the CB1 receptors’ functional modification, density and distribution, and the beginning of a pathological state is still not well understood, the development of radio-ligands suitable for in vivo PET (Positron Emission Tomography) functional imaging of CB1 receptors remains an important area of research in medicine and drug development. To date, a few radiotracers have been synthesised and tested in vivo, but most of them afforded unsatisfactory brain imaging results. A handful of radiolabelled CB1 PET ligands have also been submitted to clinical trials in humans. In this PhD Thesis the design, synthesis and characterization of three new classes of potential high-affinity CB1 ligands as candidate PET tracers is described.
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas
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Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
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Existing approaches for multirate multicast congestion control are either friendly to TCP only over large time scales or introduce unfortunate side effects, such as significant control traffic, wasted bandwidth, or the need for modifications to existing routers. We advocate a layered multicast approach in which steady-state receiver reception rates emulate the classical TCP sawtooth derived from additive-increase, multiplicative decrease (AIMD) principles. Our approach introduces the concept of dynamic stair layers to simulate various rates of additive increase for receivers with heterogeneous round-trip times (RTTs), facilitated by a minimal amount of IGMP control traffic. We employ a mix of cumulative and non-cumulative layering to minimize the amount of excess bandwidth consumed by receivers operating asynchronously behind a shared bottleneck. We integrate these techniques together into a congestion control scheme called STAIR which is amenable to those multicast applications which can make effective use of arbitrary and time-varying subscription levels.
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Weak references are references that do not prevent the object they point to from being garbage collected. Most realistic languages, including Java, SML/NJ, and OCaml to name a few, have some facility for programming with weak references. Weak references are used in implementing idioms like memoizing functions and hash-consing in order to avoid potential memory leaks. However, the semantics of weak references in many languages are not clearly specified. Without a formal semantics for weak references it becomes impossible to prove the correctness of implementations making use of this feature. Previous work by Hallett and Kfoury extends λgc, a language for modeling garbage collection, to λweak, a similar language with weak references. Using this previously formalized semantics for weak references, we consider two issues related to well-behavedness of programs. Firstly, we provide a new, simpler proof of the well-behavedness of the syntactically restricted fragment of λweak defined previously. Secondly, we give a natural semantic criterion for well-behavedness much broader than the syntactic restriction, which is useful as principle for programming with weak references. Furthermore we extend the result, proved in previously of λgc, which allows one to use type-inference to collect some reachable objects that are never used. We prove that this result holds of our language, and we extend this result to allow the collection of weakly-referenced reachable garbage without incurring the computational overhead sometimes associated with collecting weak bindings (e.g. the need to recompute a memoized function). Lastly we use extend the semantic framework to model the key/value weak references found in Haskell and we prove the Haskell is semantics equivalent to a simpler semantics due to the lack of side-effects in our language.