811 research outputs found
Self-designing networks and structural influences on safety: Developing a theory on the relation between organizational design and safety in temporary organizations that operate in a dynamic environment
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178382.pdf (Publisher’s version ) (Open Access)Delft University of Technology, 01 juni 2017Promotores : Ale, B.J.M., Kramer, E.H.213 p
Replenishing dopamine in Parkinson’s disease: Tyrosine hydroxylase Ser40 phosphorylation and phosphodiesterase inhibition
No full textThis thesis focuses on the biosynthesis machinery of the neurotransmitter dopamine and its therapeutic potential in the treatment of Parkinson's disease, a degenerative disorder caused by a deficiency in dopamine. Although L-DOPA is the current treatment for Parkinson's disease, it can lead to adverse effects and eventually lose effectiveness. As an alternative approach to replenish dopamine levels, this thesis suggests regulating the activity of tyrosine hydroxylase, the rate-limiting enzyme involved in dopamine production. By stimulating tyrosine hydroxylase activity, dopamine production can be increased, activating dopamine cells in the brain. The activity of tyrosine hydroxylase is regulated by Ser40 phosphorylation, a chemical reaction in which a phosphate group is added to an amino acid in the enzyme. This thesis explores the mechanisms that influence Ser40 phosphorylation and how they can be manipulated to increase the dopamine biosynthesis machinery in the dopamine neurons that are affected in Parkinson’s disease, specifically. The research findings indicate that cyclic nucleotide-mediated signaling plays a vital role in promoting Ser40 phosphorylation. Furthermore, the thesis investigates the impact of inhibiting phosphodiesterases, which break down cyclic nucleotides, on Ser40 phosphorylation. The results demonstrate that phosphodiesterase inhibition can upregulate tyrosine hydroxylase Ser40 phosphorylation and, as such, can stimulate the dopamine biosynthesis machinery. Overall, these findings suggest that manipulating tyrosine hydroxylase activity through phosphodiesterase inhibition could be a promising strategy to replenish dopamine levels and improve the quality of life for Parkinson's disease patients
Replenishing dopamine in Parkinson’s disease: Tyrosine hydroxylase Ser40 phosphorylation and phosphodiesterase inhibition
No full textThis thesis focuses on the biosynthesis machinery of the neurotransmitter dopamine and its therapeutic potential in the treatment of Parkinson's disease, a degenerative disorder caused by a deficiency in dopamine. Although L-DOPA is the current treatment for Parkinson's disease, it can lead to adverse effects and eventually lose effectiveness. As an alternative approach to replenish dopamine levels, this thesis suggests regulating the activity of tyrosine hydroxylase, the rate-limiting enzyme involved in dopamine production. By stimulating tyrosine hydroxylase activity, dopamine production can be increased, activating dopamine cells in the brain. The activity of tyrosine hydroxylase is regulated by Ser40 phosphorylation, a chemical reaction in which a phosphate group is added to an amino acid in the enzyme. This thesis explores the mechanisms that influence Ser40 phosphorylation and how they can be manipulated to increase the dopamine biosynthesis machinery in the dopamine neurons that are affected in Parkinson’s disease, specifically. The research findings indicate that cyclic nucleotide-mediated signaling plays a vital role in promoting Ser40 phosphorylation. Furthermore, the thesis investigates the impact of inhibiting phosphodiesterases, which break down cyclic nucleotides, on Ser40 phosphorylation. The results demonstrate that phosphodiesterase inhibition can upregulate tyrosine hydroxylase Ser40 phosphorylation and, as such, can stimulate the dopamine biosynthesis machinery. Overall, these findings suggest that manipulating tyrosine hydroxylase activity through phosphodiesterase inhibition could be a promising strategy to replenish dopamine levels and improve the quality of life for Parkinson's disease patients
'She must be a very good novelist':Rereading E.H. Young (1880-1949)
No full textE.H. Young was a popular but reclusive English author who published eleven novels between 1910 and 1947. Beginning with the very successful William (1925). Young focussed on middle-class domesticity. The history of Young's subtly iconoclastic novels is, on the one hand, paradigmatic of women writers between the wars who explored the home, and. on the other, instructive about the complexity and limitations of concepts such as middlebrow, canon formation, taste, and modernity. Reading Young's novels and analyzing their publication hsitory and reception raise intriguing questions concerning the nature of reading pleasure and the continuing wide appeal of novels of the everyday.</p
Asfalt in de waterbouw
No full textDit document bevat de vijfde brochure van de Vereniging voor Bitumineuze Werken (VBW) getiteld "Asfalt in de waterbouw". De brochure bevat een achttal artikelen m.b.t. dit onderwerp: - Totstandkoming van de leidraad voor toepassing van asfalt in de waterbouw; voorgeschiedenis, opzet en toekomstig gebruik; door ir. E.H. Ebbens - Overzicht asfalttoepassingen in de waterbouw; door Prof. ir. J.F. Agema - Materiaaltechnologie; door H.J.A.J. Gruis - Ontwerpen van waterbouwkundige asfaltbekledingen; door ir. J.A. van Herpen - Resultaten uit recent onderzoek; door ir. H. Roos - Uitvoering van bitumineuze dijkbekledingen; door ir. G.L.M. Mulders - Bouwen en beheren; door ir. W. Bandsma - Beheer en onderhoud van waterkeringen; door ing. L.A. Philips
Replenishing dopamine in Parkinson’s disease:Tyrosine hydroxylase Ser40 phosphorylation and phosphodiesterase inhibition
Full text linkThis thesis focuses on the biosynthesis machinery of the neurotransmitter dopamine and its therapeutic potential in the treatment of Parkinson's disease, a degenerative disorder caused by a deficiency in dopamine. Although L-DOPA is the current treatment for Parkinson's disease, it can lead to adverse effects and eventually lose effectiveness. As an alternative approach to replenish dopamine levels, this thesis suggests regulating the activity of tyrosine hydroxylase, the rate-limiting enzyme involved in dopamine production. By stimulating tyrosine hydroxylase activity, dopamine production can be increased, activating dopamine cells in the brain. The activity of tyrosine hydroxylase is regulated by Ser40 phosphorylation, a chemical reaction in which a phosphate group is added to an amino acid in the enzyme. This thesis explores the mechanisms that influence Ser40 phosphorylation and how they can be manipulated to increase the dopamine biosynthesis machinery in the dopamine neurons that are affected in Parkinson’s disease, specifically. The research findings indicate that cyclic nucleotide-mediated signaling plays a vital role in promoting Ser40 phosphorylation. Furthermore, the thesis investigates the impact of inhibiting phosphodiesterases, which break down cyclic nucleotides, on Ser40 phosphorylation. The results demonstrate that phosphodiesterase inhibition can upregulate tyrosine hydroxylase Ser40 phosphorylation and, as such, can stimulate the dopamine biosynthesis machinery. Overall, these findings suggest that manipulating tyrosine hydroxylase activity through phosphodiesterase inhibition could be a promising strategy to replenish dopamine levels and improve the quality of life for Parkinson's disease patients
Replenishing dopamine in Parkinson’s disease:Tyrosine hydroxylase Ser40 phosphorylation and phosphodiesterase inhibition
No full textThis thesis focuses on the biosynthesis machinery of the neurotransmitter dopamine and its therapeutic potential in the treatment of Parkinson's disease, a degenerative disorder caused by a deficiency in dopamine. Although L-DOPA is the current treatment for Parkinson's disease, it can lead to adverse effects and eventually lose effectiveness. As an alternative approach to replenish dopamine levels, this thesis suggests regulating the activity of tyrosine hydroxylase, the rate-limiting enzyme involved in dopamine production. By stimulating tyrosine hydroxylase activity, dopamine production can be increased, activating dopamine cells in the brain. The activity of tyrosine hydroxylase is regulated by Ser40 phosphorylation, a chemical reaction in which a phosphate group is added to an amino acid in the enzyme. This thesis explores the mechanisms that influence Ser40 phosphorylation and how they can be manipulated to increase the dopamine biosynthesis machinery in the dopamine neurons that are affected in Parkinson’s disease, specifically. The research findings indicate that cyclic nucleotide-mediated signaling plays a vital role in promoting Ser40 phosphorylation. Furthermore, the thesis investigates the impact of inhibiting phosphodiesterases, which break down cyclic nucleotides, on Ser40 phosphorylation. The results demonstrate that phosphodiesterase inhibition can upregulate tyrosine hydroxylase Ser40 phosphorylation and, as such, can stimulate the dopamine biosynthesis machinery. Overall, these findings suggest that manipulating tyrosine hydroxylase activity through phosphodiesterase inhibition could be a promising strategy to replenish dopamine levels and improve the quality of life for Parkinson's disease patients
Replenishing dopamine in Parkinson’s disease:Tyrosine hydroxylase Ser40 phosphorylation and phosphodiesterase inhibition
Full text linkThis thesis focuses on the biosynthesis machinery of the neurotransmitter dopamine and its therapeutic potential in the treatment of Parkinson's disease, a degenerative disorder caused by a deficiency in dopamine. Although L-DOPA is the current treatment for Parkinson's disease, it can lead to adverse effects and eventually lose effectiveness. As an alternative approach to replenish dopamine levels, this thesis suggests regulating the activity of tyrosine hydroxylase, the rate-limiting enzyme involved in dopamine production. By stimulating tyrosine hydroxylase activity, dopamine production can be increased, activating dopamine cells in the brain. The activity of tyrosine hydroxylase is regulated by Ser40 phosphorylation, a chemical reaction in which a phosphate group is added to an amino acid in the enzyme. This thesis explores the mechanisms that influence Ser40 phosphorylation and how they can be manipulated to increase the dopamine biosynthesis machinery in the dopamine neurons that are affected in Parkinson’s disease, specifically. The research findings indicate that cyclic nucleotide-mediated signaling plays a vital role in promoting Ser40 phosphorylation. Furthermore, the thesis investigates the impact of inhibiting phosphodiesterases, which break down cyclic nucleotides, on Ser40 phosphorylation. The results demonstrate that phosphodiesterase inhibition can upregulate tyrosine hydroxylase Ser40 phosphorylation and, as such, can stimulate the dopamine biosynthesis machinery. Overall, these findings suggest that manipulating tyrosine hydroxylase activity through phosphodiesterase inhibition could be a promising strategy to replenish dopamine levels and improve the quality of life for Parkinson's disease patients
First-order phase transitions and giant magnetocaloric effect
No full textModern society relies on cooling technology for food safety, comfort and medical applications. The solid-state cooling technology known as magnetic refrigeration is one of the most promising techniques to replace the current vapor-compression cooling technology. To date, the search for suitable materials with a large magnetocaloric effect (MCE) for domestic applications of magnetic refrigeration is still in progress. This thesis describes a study focused on magnetocaloric materials that can be used in magnetic refrigerators operating at room temperature. Understanding of the phase transition in these materials is of great important to create better materials. As a refrigerator is expected to operate at rather high cycle frequencies, large thermal hysteresis (?Thys) at the magnetic phase transition is the main obstacle to use a material for applications. We have been successful in tuning ?Thys of MnFe(P1-xGex) and related compounds to very small values, while maintaining a large MCE in a large range of working temperatures. These low-cost materials can be used as refrigerants working at high frequencies. This brings the use of practical magnetic cooling a step closer. On the other hand, we have discovered a near room-temperature giant MCE in a new class of magnetic materials based on the intermetallic MnCoGe alloy. The mechanism of manipulating the first-order magnetic phase transition in the MnCoGe-based alloys opens up new possibilities for searching novel magnetic refrigerants for room-temperature applications.Radiation Radionuclides ReactorsApplied Science
SAC on a Niagara T3-4 server: lessons and experiences
No full textThe Sparc T3-4 server provides up to 512 concurrent hardware threads, a degree of concurrency that is unprecedented in a single server system. This paper reports on how the automatically parallelising compiler of the data-parallel functional array language SAC copes with up to 512 execution units. We investigate three different numerical kernels that are representative for a wide range of applications: matrix multiplication, convolution and 3-dimensional FFT. We show both the high-level declarative coding style of SAC and the performance achieved on the T3-4 server. Last not least, we draw conclusions for improving our compiler technology in the future
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