188 resultados para UDP-glucuronosyltransferase
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Il lavoro svolto in questa tesi fa parte di un progetto volto alla realizzazione di un sistema per svolgere test di guida di motoveicoli al banco a rulli, gestendo l’intera prova in remoto, ossia dall’esterno della cella. Tale sistema, denominato RideIT, è stato progettato da Alma Automotive per conto della nota casa motociclistica MV Augusta. Tramite il sistema RideIT, è possibile automatizzare la guida di motoveicoli sul banco a rulli, riproducendo via software, tramite un modello che governa degli attuatori, il comportamento del pilota per quel che riguarda gli azionamenti di acceleratore, frizione, cambio e freno durante un test. I vantaggi di questa soluzione riguardano soprattutto la sicurezza degli addetti, che possono effettuare tutte le prove del caso rimanendo al di fuori della sala prove, oltre alla possibilità di incrementare la ripetibilità e la riproducibilità dei risultati dei test, grazie all’eliminazione del fattore di soggettività legato al guidatore. Il sistema nasce con la specifica di poter eseguire test di omologazione al banco a rulli anche se, grazie alla flessibilità che è in grado di garantire, può essere perfettamente riconfigurato, anche in vista di futuri sviluppi del progetto.
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La presente tesi si pone come obiettivo quello di analizzare il protocollo LTP (in particolare in ION) e proporre dei miglioramenti utili al caso in cui siano presenti perdite elevate. Piu in dettaglio, una prima parte introduttiva motiva l'inefficacia del TCP/IP in ambito interplanetario e introduce l'architettura DTN Bundle Protocol (Cap.1). La tesi prosegue con la descrizione delle specifiche del protocollo LTP (Cap.2), in particolar modo evidenziando come un bundle venga incapsulato in un blocco LTP, come questo sia successivamente diviso in tanti segmenti LTP e come questi vengano successivamente inviati con il protocollo UDP o con un protocollo analogo. Viene quindi presentata un'approfondita analisi delle penalizzazioni dovute alle perdite dei segmenti LTP, sia di tipo dati che di segnalazione (Cap. 3). Quest'analisi permette di dimostrare la criticita degli effetti delle perdite, in particolare per quello che riguarda i segmenti LTP di segnalazione. Mentre in presenza di perdite basse tali effetti hanno in media un impatto minimo sul tempo di consegna di un blocco LTP (quindi del bundle in esso contenuto), in quanto avvengono raramente, in presenza di perdite elevate rappresentano un collo di bottiglia per il tempo di consegna di un blocco LTP. A tal proposito sono state proposte alcune modifiche che permettono di migliorare le prestazioni di LTP (Cap. 4) compatibilmente con le specifiche RFC in modo da garantire l'interoperabilita con le diverse implementazioni del protocollo. Successivamente nel Cap. 5 viene mostrato come sono state implementate le modifiche proposte in ION 3.4.1. Nel capitolo finale (Cap. 6) sono presenti i risultati numerici relativi ad alcuni test preliminari eseguiti confrontando la versione originale del protocollo con le versioni modificate contenenti i miglioramenti proposti. I test sono risultati molto positivi per elevate perdite, confermando cosi la validita dell'analisi e dei miglioramenti introdotti.
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Nell'ottica di trovare modalità sempre più intuitive per movimentare manipolatori industriali l’obiettivo della tesi è quello di realizzare una mobile app su piattaforma Android in grado appunto di movimentare un generico manipolatore industriale. L'applicazione sviluppata fornisce all'utente un’interfaccia semplice e intuitiva che permette, dopo un’opportuna configurazione iniziale, di controllare il moto di un manipolatore industriale attraverso l’uso del touch screen e degli elementi grafici dell’interfaccia. Oltre a istruire un manipolatore l’applicazione offre anche delle funzionalità per il salvataggio e la gestione di determinate configurazioni che il manipolatore può assumere nello spazio. Il grande vantaggio dell’applicazione è quello di fornire un’interfaccia universale per la movimentazione di qualsiasi manipolatore. Si può affermare quindi che essa fornisce un livello di astrazione superiore. In questo progetto di tesi è stato effettuato il testing dell'applicazione sviluppata sia con il manipolatore industriale Comau Smart Six, robot antropomorfo a 6 gradi di libertà, sia con un manipolatore simulato in Unity 3D. Sono stati raccolti dei dati, in particolare dei grafici, che mettono in relazione i comandi impartiti al manipolatore e i dati ricevuti da questo, in modo da ricavarne dei parametri che misurano l'efficienza e la correttezza dell'applicazione.
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Fosfomycin targets the first step of peptidoglycan biosynthesis in Streptococcus pneumoniae catalyzed by UDP-N-acetylglucosamine enolpyruvyltransferase (MurA1). We investigated whether heteroresistance to fosfomycin occurs in S. pneumoniae. We found that of 11 strains tested, all but 1 (Hungary(19A)) displayed heteroresistance and that deletion of murA1 abolished heteroresistance. Hungary(19A) differs from the other strains by a single amino acid substitution in MurA1 (Ala364Thr). To test whether this substitution is responsible for the lack of heteroresistance, it was introduced into strain D39. The heteroresistance phenotype of strain D39 was not changed. Furthermore, no relevant structural differences between the MurA1 crystal structures of heteroresistant strain D39 and nonheteroresistant strain Hungary(19A) were found. Our results reveal that heteroresistance to fosfomycin is the predominant phenotype of S. pneumoniae and that MurA1 is required for heteroresistance to fosfomycin but is not the only factor involved. The findings provide a caveat for any future use of fosfomycin in the treatment of pneumococcal infections.
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After birth the development of appropriate detoxification mechanisms is important. Nuclear receptors (NR), such as constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-alpha (PPARalpha), retinoid receptors (RAR, RXR), and NR target genes are involved in the detoxification of exogenous and endogenous substances. We quantified abundances of hepatic mRNA of NR and several NR target genes (cytochromes, CYP; cytochrome P450 reductase, CPR; UDP-glucuronosyl transferase, UDP) in calves at different ages. Gene expression was quantified by real-time RT-PCR. Abundance of mRNA of CAR and PXR increased from low levels at birth in pre-term calves (P0) and full-term calves (F0) to higher levels in 5-day-old calves (F5) and in 159-day-old veal calves (F159), whereas mRNA levels of PPARalpha did not exhibit significant ontogenetic changes. RARbeta mRNA levels were higher in F5 and F159 than in F0, whereas no age differences were observed for RARalpha levels. Levels of RXRalpha and RXRbeta mRNA were lower in F5 than in P0 and F0. Abundance of CYP2C8 and CYP3A4 increased from low levels in P0 and F0 to higher levels in F5 and to highest levels in F159. Abundance of CPR was transiently decreased in F0 and F5 calves. Levels of UGT1A1 mRNA increased from low levels in P0 and F0 to maximal level in F5 and F159. In conclusion, mRNA levels of NR and NR target genes exhibited ontogenetic changes that are likely of importance for handling of xeno- and endobiotics with increasing age.
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BACKGROUND AND PURPOSE: There is a need to develop strategies to enhance the beneficial effects of motor training, including use-dependent plasticity (UDP), in neurorehabilitation. Peripheral nerve stimulation (PNS) modulates motor cortical excitability in healthy humans and could influence training effects in stroke patients. METHODS: We compared the ability of PNS applied to the (1) arm, (2) leg, and (3) idle time to influence training effects in the paretic hand in 7 chronic stroke patients. The end point measure was the magnitude of UDP. RESULTS: UDP was more prominent with arm stimulation (increased by 22.8%) than with idle time (by 2.9%) or leg stimulation (by 6.4%). CONCLUSIONS: PNS applied to the paretic limb paired with motor training enhances training effects on cortical plasticity in stroke patients.
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BACKGROUND: Reversible ischaemia/reperfusion (I/R) liver injury has been used to induce engraftment and hepatic parenchymal differentiation of exogenous beta2-microglubulin(-)/Thy1(+) bone marrow derived cells. AIM: To test the ability of this method of hepatic parenchymal repopulation, theoretically applicable to clinical practice, to correct the metabolic disorder in a rat model of congenital hyperbilirubinaemia. METHODS AND RESULTS: Analysis by confocal laser microscopy of fluorescence labelled cells and by immunohistochemistry for beta2-microglubulin, 72 hours after intraportal delivery, showed engraftment of infused cells in liver parenchyma of rats with I/R, but not in control animals with non-injured liver. Transplantation of bone marrow derived cells obtained from GFP-transgenic rats into Lewis rats resulted in the presence of up to 20% of GFP positive hepatocytes in I/R liver lobes after one month. The repopulation rate was proportional to the number of transplanted cells. Infusion of GFP negative bone marrow derived cells into GFP positive transgenic rats resulted in the appearance of GFP negative hepatocytes, suggesting that the main mechanism underlying parenchymal repopulation was differentiation rather than cell fusion. Transplantation of wild type bone marrow derived cells into hyperbilirubinaemic Gunn rats with deficient bilirubin conjugation after I/R damage resulted in 30% decrease in serum bilirubin, the appearance of bilirubin conjugates in bile, and the expression of normal UDP-glucuronyltransferase enzyme evaluated by polymerase chain reaction. CONCLUSIONS: I/R injury induced hepatic parenchymal engraftment and differentiation into hepatocyte-like cells of bone marrow derived cells. Transplantation of bone marrow derived cells from non-affected animals resulted in the partial correction of hyperbilirubinaemia in the Gunn rat.
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To interconnect a wireless sensor network (WSN) to the Internet, we propose to use TCP/IP as the standard protocol for all network entities. We present a cross layer designed communication architecture, which contains a MAC protocol, IP, a new protocol called Hop-to-Hop Reliability (H2HR) protocol, and the TCP Support for Sensor Nodes (TSS) protocol. The MAC protocol implements the MAC layer of beacon-less personal area networks (PANs) as defined in IEEE 802.15.4. H2HR implements hop-to-hop reliability mechanisms. Two acknowledgment mechanisms, explicit and implicit ACK are supported. TSS optimizes using TCP in WSNs by implementing local retransmission of TCP data packets, local TCP ACK regeneration, aggressive TCP ACK recovery, congestion and flow control algorithms. We show that H2HR increases the performance of UDP, TCP, and RMST in WSNs significantly. The throughput is increased and the packet loss ratio is decreased. As a result, WSNs can be operated and managed using TCP/IP.
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The exact mechanism for capillary occlusion in diabetic retinopathy is still unclear, but increased leukocyte-endothelial cell adhesion has been implicated. We examined the possibility that posttranslational modification of surface O-glycans by increased activity of core 2 transferase (UDP-Glc:Galbeta1-3GalNAcalphaRbeta-N-acetylglucoaminyltr ansferase) is responsible for increased adhesion of leukocytes to vascular endothelium in diabetes. The mean activity of core 2 transferase in polymorphonuclear leukocytes isolated from type 1 and type 2 diabetic patients was higher compared with age-matched control subjects (1,638 +/- 91 [n = 42] vs. 249 +/- 35 pmol x h(-1) x mg(-1) protein [n = 24], P = 0.00013; 1,459 +/- 194 [n = 58] vs. 334 +/- 86 [n = 11], P = 0.01). As a group, diabetic patients with retinopathy had significantly higher mean activity of core 2 transferase compared with individuals with no retinopathy. There was a significant association between enzyme activity and severity of retinopathy in type 1 and type 2 diabetic patients. There was a strong correlation between activity of core 2 transferase and extent of leukocyte adhesion to cultured retinal capillary endothelial cells for diabetic patients but not for age-matched control subjects. Results from transfection experiments using human myelocytic cell line (U937) demonstrated a direct relationship between increased activity of core 2 transferase and increased binding to cultured endothelial cells. There was no relationship between activity of core 2 transferase and HbA(1c) (P = 0.8314), serum advanced glycation end product levels (P = 0.4159), age of the patient (P = 0.7896), and duration of diabetes (P = 0.3307). On the basis that branched O-glycans formed by the action of core 2 transferase participate in leukocyte adhesion, the present data suggest the involvement of this enzyme in increased leukocyte-endothelial cell adhesion and the pathogenesis of capillary occlusion in diabetic retinopathy.
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Integrating physical objects (smart objects) and enterprise IT systems is still a labor intensive, mainly manual task done by domain experts. On one hand, enterprise IT backend systems are based on service oriented architectures (SOA) and driven by business rule engines or business process execution engines. Smart objects on the other hand are often programmed at very low levels. In this paper we describe an approach that makes the integration of smart objects with such backends systems easier. We introduce semantic endpoint descriptions based on Linked USDL. Furthermore, we show how different communication patterns can be integrated into these endpoint descriptions. The strength of our endpoint descriptions is that they can be used to automatically create REST or SOAP endpoints for enterprise systems, even if which they are not able to talk to the smart objects directly. We evaluate our proposed solution with CoAP, UDP and 6LoWPAN, as we anticipate the industry converge towards these standards. Nonetheless, our approach also allows easy integration with backend systems, even if no standardized protocol is used.
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Various applications for the purposes of event detection, localization, and monitoring can benefit from the use of wireless sensor networks (WSNs). Wireless sensor networks are generally easy to deploy, with flexible topology and can support diversity of tasks thanks to the large variety of sensors that can be attached to the wireless sensor nodes. To guarantee the efficient operation of such a heterogeneous wireless sensor networks during its lifetime an appropriate management is necessary. Typically, there are three management tasks, namely monitoring, (re) configuration, and code updating. On the one hand, status information, such as battery state and node connectivity, of both the wireless sensor network and the sensor nodes has to be monitored. And on the other hand, sensor nodes have to be (re)configured, e.g., setting the sensing interval. Most importantly, new applications have to be deployed as well as bug fixes have to be applied during the network lifetime. All management tasks have to be performed in a reliable, time- and energy-efficient manner. The ability to disseminate data from one sender to multiple receivers in a reliable, time- and energy-efficient manner is critical for the execution of the management tasks, especially for code updating. Using multicast communication in wireless sensor networks is an efficient way to handle such traffic pattern. Due to the nature of code updates a multicast protocol has to support bulky traffic and endto-end reliability. Further, the limited resources of wireless sensor nodes demand an energy-efficient operation of the multicast protocol. Current data dissemination schemes do not fulfil all of the above requirements. In order to close the gap, we designed the Sensor Node Overlay Multicast (SNOMC) protocol such that to support a reliable, time-efficient and energy-efficient dissemination of data from one sender node to multiple receivers. In contrast to other multicast transport protocols, which do not support reliability mechanisms, SNOMC supports end-to-end reliability using a NACK-based reliability mechanism. The mechanism is simple and easy to implement and can significantly reduce the number of transmissions. It is complemented by a data acknowledgement after successful reception of all data fragments by the receiver nodes. In SNOMC three different caching strategies are integrated for an efficient handling of necessary retransmissions, namely, caching on each intermediate node, caching on branching nodes, or caching only on the sender node. Moreover, an option was included to pro-actively request missing fragments. SNOMC was evaluated both in the OMNeT++ simulator and in our in-house real-world testbed and compared to a number of common data dissemination protocols, such as Flooding, MPR, TinyCubus, PSFQ, and both UDP and TCP. The results showed that SNOMC outperforms the selected protocols in terms of transmission time, number of transmitted packets, and energy-consumption. Moreover, we showed that SNOMC performs well with different underlying MAC protocols, which support different levels of reliability and energy-efficiency. Thus, SNOMC can offer a robust, high-performing solution for the efficient distribution of code updates and management information in a wireless sensor network. To address the three management tasks, in this thesis we developed the Management Architecture for Wireless Sensor Networks (MARWIS). MARWIS is specifically designed for the management of heterogeneous wireless sensor networks. A distinguished feature of its design is the use of wireless mesh nodes as backbone, which enables diverse communication platforms and offloading functionality from the sensor nodes to the mesh nodes. This hierarchical architecture allows for efficient operation of the management tasks, due to the organisation of the sensor nodes into small sub-networks each managed by a mesh node. Furthermore, we developed a intuitive -based graphical user interface, which allows non-expert users to easily perform management tasks in the network. In contrast to other management frameworks, such as Mate, MANNA, TinyCubus, or code dissemination protocols, such as Impala, Trickle, and Deluge, MARWIS offers an integrated solution monitoring, configuration and code updating of sensor nodes. Integration of SNOMC into MARWIS further increases performance efficiency of the management tasks. To our knowledge, our approach is the first one, which offers a combination of a management architecture with an efficient overlay multicast transport protocol. This combination of SNOMC and MARWIS supports reliably, time- and energy-efficient operation of a heterogeneous wireless sensor network.
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A drinking experiment with participants suffering from Gilbert's syndrome was performed to study the possible influence of this glucuronidation disorder on the formation of ethyl glucuronide (EtG). Gilbert's syndrome is a rather common and, in most cases, asymptomatic congenital metabolic aberration with a prevalence of about 5 %. It is characterized by a reduction of the enzyme activity of the uridine diphosphate glucuronosyltransferase (UGT) isoform 1A1 up to 80 %. One of the glucuronidation products is EtG, which is formed in the organism following exposure to ethanol. EtG is used as a short-term marker for ethyl alcohol consumption to prove abstinence in various settings. After 2 days of abstinence from ethanol and giving a void urine sample, 30 study participants drank 0.1 L of sparkling wine (9 g ethanol). 3, 6, 12, and 24 h after drinking, urine samples were collected. 3 hours after drinking, an additional blood sample was taken, in which liver enzyme activities, ethanol, hematological parameters, and bilirubin were measured. EtG and ethyl sulfate (EtS), another short-term marker of ethanol consumption, were determined in the urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS); creatinine was measured photometrically. In all participants, EtG and EtS were detected in concentrations showing a wide range (EtG: 3 h sample 0.5-18.43 mg/L and 6 h sample 0.67-13.8 mg/L; EtS: 3 h sample 0.87-6.87 mg/L and 6 h sample 0.29-4.48 mg/L). No evidence of impaired EtG formation was found. Thus, EtG seems to be a suitable marker for ethanol consumption even in individuals with Gilbert's syndrome.
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Multiple osteochondromas (also called hereditary multiple exostoses) is an autosomal dominant disorder characterized by multiple cartilaginous tumors, which are caused by mutations in the genes for exostosin-1 (EXT1) and exostosin-2 (EXT2). The goal of this study was to elucidate the genetic alterations in a family with three affected members. Isolation of RNA from the patients' blood followed by reverse transcription and PCR amplification of selected fragments showed that the three patients lack a specific region of 90 bp from their EXT1 mRNA. This region corresponds to the sequence of exon 8 from the EXT1 gene. No splice site mutation was found around exon 8. However, long-range PCR amplification of the region from intron 7 to intron 8 indicated that the three patients contain a deletion of 4318 bp, which includes exon 8 and part of the flanking introns. There is evidence that the deletion was caused by non-homologous end joining because the breakpoints are not located within a repetitive element, but contain multiple copies of the deletion hotspot sequence TGRRKM. Exon 8 encodes part of the active site of the EXT1 enzyme, including the DXD signature of all UDP-sugar glycosyltransferases. It is conceivable that the mutant protein exerts a dominant negative effect on the activity of the EXT glycosyltransferase since it might interact with normal copies of the enzyme to form an inactive hetero-oligomeric complex. We suggest that sequencing of RNA might be superior to exome sequencing to detect short deletions of a single exon.
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En las décadas de 1950 y 1960, pese a las aparentes dificultades de comunicación con el exterior, la arquitectura española miró hacia fuera constantemente. La potencia de la arquitectura moderna latinoamericana, junto a las diferencias instrumentales y geográficas, la hacían difícilmente importable a un contexto materialmente escaso y excesivamente tradicional. Sin embargo, dicha producción interesó y se difundió notablemente durante ambas décadas. Este artículo pretende varias cosas a la vez. Por una parte, proporcionar una panorámica global sobre difusión de la arquitectura latinoamericana fuera de su continente. Para ello nos serviremos básicamente del que probablemente fue el medio más potente con el que contaron: las revistas especializadas de arquitectura. Pero también pretende ser una llamada de atención hacia las publicaciones periódicas españolas, mucho menos conocidas que otras europeas pero, sin embargo, repletas de buena arquitectura.
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En los países desarrollados el Internet de las Cosas (IoT) ya es una realidad. El mundo físico y el digital cada vez están más unidos, gracias a la reducción del tamaño, el descenso del coste de los sensores, la posibilidad de disponer de una conexión a Internet en todo momento y al desarrollo de las aplicaciones, que ponen en uso la gran cantidad de información generada por todos los objetos conectados. Los campos de aplicación del IoT son muy variados, lo que otorga grandes oportunidades a los fabricantes de cada uno de los diferentes sectores, y desafíos, en particular, a los desarrolladores de software de tecnologías móviles. Los Smartphone serán los ojos y los oídos de las aplicaciones y estarán comunicados con el resto de las cosas. Pero con la evolución de las aplicaciones y dispositivos ya no sólo se verá y escuchará la información enviada por los sensores conectados a internet, sino que además, también existirá una comunicación completa entre los dispositivos y el SmartPhone. Este proyecto tiene por objetivo la realización de una aplicación móvil, para el sistema operativo móvil iOS, que cubra la posibilidad de comunicarse, controlar e interaccionar con un sistema de control para aumentar así la calidad y el bienestar del usuario. Para ello, se parte de una situación determinada en la que ya existe un modelado de dispositivos que incorporan la tecnología necesaria para recibir órdenes y contestar, y de un servidor que dispone de una comunicación directa con estos dispositivos y que a su vez gestiona un sistema de licencias con el cual se controla qué usuario tiene acceso a qué dispositivo. El futuro de la aplicación pasa por la posibilidad de comunicarse con el dispositivo directamente mediante una red WiFi propia, generada por él mismo, o bien, mediante bluetooh, o llamada perdida si el dispositivo incorporara una tarjeta SIM. La comunicación del SmartPhone con el servidor será mediante protocolo UDP. Mientras que la comunicación directa entre el SmartPhone y el dispositivo sería mediante TCP, siendo similar a la que ya existe entre el servidor y el dispositivo. La aplicación incorporará tres grandes bloques a nivel de control que se desarrollan a lo largo del trabajo. Un bloque de comunicación, un bloque de protocolos de estado y un bloque de modelaje de los mensajes que la aplicación intercambia con el servidor. Para dotar de una mayor seguridad a la aplicación, se hará que los mensajes que se intercambian con el servidor vayan cifrados y firmados de forma digital, lo que permitirá al receptor determinar el origen del mensaje (autenticación de origen y no repudio), y confirmar que dicho mensaje no haya sufrido alteraciones desde que fue firmado (integridad y confidencialidad)