Wave response of the proposed harbor at Agat, Guam : numerical model investigation /

"March 1987."

Beḥinat ha-ḳabalah : ḥibur kolel s. Kol Sakhal ṿe-s. Shaʾagat Aryeh /

Added t.p.: Examen traditionis, duo inedita et poene incognita Leonis Mutinensis opuscula complectens quæ nunc primum edidit, annotationibus illustravit ... Isaacus Reggio.

Turismo de nichos : uma análise ao papel dos seniores como participantes ativos

Dissertação de Mestrado, Gestão do Turismo Internacional, 3 de Dezembro de 2015, Universidade dos Açores.

Denoising of LSFCM images with compensation for the photoblinking/photobleaching effects

Fluorescence confocal microscopy images present a low signal to noise ratio and a time intensity decay due to the so called photoblinking and photobleaching effects. These effects, together with the Poisson multiplicative noise that corrupts the images, make long time biological observation processes very difficult.

Using WorldFIP networks to support periodic and sporadic real-time traffic

In this paper we address the ability of WorldFIP to cope with the real-time requirements of distributed computer-controlled systems (DCCS). Typical DCCS include process variables that must be transferred between network devices both in a periodic and sporadic (aperiodic) basis. The WorldFIP protocol is designed to support both types of traffic. WorldFIP can easily guarantee the timing requirements for the periodic traffic. However, for the aperiodic traffic more complex analysis must be made in order to guarantee its timing requirements. This paper describes work that is being carried out to extend previous relevant work, in order to include the actual schedule for the periodic traffic in the worst-case response time analysis of sporadic traffic in WorldFIP networks

Troca de serviços e incentivos em sistemas P2P

Trabalho apresentado no âmbito do Mestrado em Engenharia Informática, como requisito parcial para obtenção do grau de Mestre em Engenharia Informática

Una reflexió historiogràfica sobre l'hospital com a espai de medicalització

El treball analitza la historiografia existent sobre les institucions hospitalàries com a espai de medicalització des de la segona meitat del s. XX. La finalitat és estudiar de quina manera diverses tendències historiogràfiques han percebut l’hospital com a espai de creació i difusió de coneixement científic. S'ha atorgat particular interès a les visions sobre el seu rol en la transformació de la medicina occidental i també als factors aliens a la medicina que, segons alguns historiadors, han, valgui la paradoxa, contribuït a transformar l’hospital en una institució mèdica.

A MODEL OF CREATINE DEFICIENCY SYNDROMES IN 3D BRAIN CELL CULTURES BY KNOCKDOWN OF GAMT AND SLC6A8 GENES

La créatine joue un rôle essentiel dans le métabolisme cellulaire par sa conversion, par la creatine kinase, en phosphocreatine permettant la régénération de l'ATP. La synthèse de créatine, chez les mammifères, s'effectue par une réaction en deux étapes impliquant Γ arginine: glycine amidinotransférase (AGAT) et la guanidinoacétate méthyltransférase (GAMT). L'entrée de créatine dans les cellules s'effectue par son transporteur, SLC6A8. Les déficiences en créatine, dues au déficit en GAMT, AGAT ou SLC6A8, sont fréquentes et caractérisées par une absence ou une forte baisse de créatine dans le système nerveux central. Alors qu'il est connu que AGAT, GAMT et SLC6A8 sont exprimés par le cerveau, les conséquences des déficiences en créatine sur les cellules nerveuses sont peu comprises. Le but de ce travail était de développer de nouveaux modèles expérimentaux des déficiences en Cr dans des cultures 3D de cellules nerveuses de rat en agrégats au moyen de l'interférence à l'ARN appliquée aux gènes GAMT et SLC6A8. Des séquences interférentes (shRNAs) pour les gènes GAMT et SLC6A8 ont été transduites par des vecteurs viraux AAV (virus adéno-associés), dans les cellules nerveuses en agrégats. Nous avons ainsi démontré une baisse de l'expression de GAMT au niveau protéique (mesuré par western blot), et ARN messager (mesuré par qPCR) ainsi qu'une variation caractérisitique de créatine et guanidinoacétate (mesuré par spectrométrie de masse). Après avoir validé nos modèles, nous avons montré que les knockdown de GAMT ou SLC6A8 affectent le développement des astrocytes et des neurones ou des oligodendrocytes et des astrocytes, respectivement, ainsi qu'une augmentation de la mort cellulaire et des modifications dans le pattern d'activation des voies de signalisation impliquant caspase 3 et p38 MAPK, ayant un rôle dans le processus d'apoptose. - Creatine plays essential roles in energy metabolism by the interconversion, by creatine kinase, to its phosphorylated analogue, phosphocreatine, allowing the regeneration of ATP. Creatine is synthesized in mammals by a two step mechanism involving arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT). Creatine is taken up by cells by a specific transporter, SLC6A8. Creatine deficiency syndromes, due to defects in GAMT, AGAT and SLC6A8, are among the most frequent inborn errors of metabolism, and are characterized by an absence or a severe decrease of creatine in central nervous system, which is the main tissue affected. While it is known that AGAT, GAMT and SLC6A8 are expressed in CNS, many questions remain on the specific effects of AGAT, GAMT and SLC6A8 deficiencies on brain cells. Our aim was to develop new experimental models of creatine deficiencies by knockdown of GAMT and SLC6A8 genes by RNAi in 3D organotypic rat brain cell cultures in aggregates. Specific shRNAs for the GAMT and SLC6A8 genes were transduced in brain cell aggregates by adeno-associated viruses (AAV). The AAV-transduced shRNAs were able to efficiently knockdown the expression of our genes of interest, as shown by a strong decrease of protein by western blotting, a decrease of mRNA by qPCR or characteristic variations of creatine and guanidinoacetate by tandem mass spectrometry. After having validated our experimental models, we have also shown that GAMT and SLC6A8 knockdown affected the development of astrocytes and neurons or oligodendrocytes and astrocytes, respectively. We also observed an increase of cell death and variations in activation pattern of caspase 3 and p38 MAPK pathways, involved in apoptosis, in our experimental model.

Creatine, central nervous system and creatine deficiency syndromes

It was long thought that most of brain creatine was of peripheral origin. However, recentworks have demonstrated that creatine crosses blood-brain barrier only with poor efficiency, and thatCNS must ensure parts of its creatine needs by its own creatine synthesis pathway, thank to the brainexpression of AGAT and GAMT (creatine synthesis) and SLC6A8 (creatine transporter). This newunderstanding of creatine metabolism and transport in CNS allows a better comprehension of creatinedeficiency syndromes, which are due to deficiencies in AGAT, GAMT and SLC6A8 and mainly affectthe brain of patients who show severe neurodevelopmental delay and present neurological symptomsin early infancy.

Motor Vehicle Accident Fatalities for the Week Ending, April 28, 2006

Record of the Fatalities for Motor Vehicle Accidents in Iowa per week.

Palosuojelumaksu, 2K

Puhe

Ammonia toxicity to the brain: effects on creatine metabolism and transport and protective roles of creatine.

Hyperammonemia can provoke irreversible damage to the developing brain, with the formation of cortical atrophy, ventricular enlargement, demyelination or gray and white matter hypodensities. Among the various pathogenic mechanisms involved, alterations in cerebral energy have been demonstrated. In particular, we could show that ammonia exposure generates a secondary deficiency in creatine in brain cells, by altering the brain expression and activity of the genes allowing creatine synthesis (AGAT and GAMT) and transport (SLC6A8). On the other hand, it is known that creatine administration can exert protective effects in various neurodegenerative processes. We could also show that creatine co-treatment under ammonia exposure can protect developing brain cells from some of the deleterious effects of ammonia, in particular axonal growth impairment. This article focuses on the effects of ammonia exposure on creatine metabolism and transport in developing brain cells, and on the potential neuroprotective properties of creatine in the brain exposed to ammonium.

Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency.

Hyperammonemic disorders in pediatric patients lead to poorly understood irreversible effects on the developing brain that may be life-threatening. We showed previously that some of these NH4+-induced irreversible effects might be due to impairment of axonal growth that can be protected under ammonium exposure by creatine co-treatment. The aim of the present work was thus to analyse how the genes of arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), allowing creatine synthesis, as well as of the creatine transporter SLC6A8, allowing creatine uptake into cells, are regulated in rat brain cells under NH4+ exposure. Reaggregated brain cell three-dimensional cultures exposed to NH4Cl were used as an experimental model of hyperammonemia in the developing central nervous system (CNS). We show here that NH4+ exposure differentially alters AGAT, GAMT and SLC6A8 regulation, in terms of both gene expression and protein activity, in a cell type-specific manner. In particular, we demonstrate that NH4+ exposure decreases both creatine and its synthesis intermediate, guanidinoacetate, in brain cells, probably through the inhibition of AGAT enzymatic activity. Our work also suggests that oligodendrocytes are major actors in the brain in terms of creatine synthesis, trafficking and uptake, which might be affected by hyperammonemia. Finally, we show that NH4+ exposure induces SLC6A8 in astrocytes. This suggests that hyperammonemia increases blood-brain barrier permeability for creatine. This is normally limited due to the absence of SLC6A8 from the astrocyte feet lining microcapillary endothelial cells, and thus creatine supplementation may protect the developing CNS of hyperammonemic patients.