983 resultados para Third generation therapies
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The thesis presents an overview of third generation of IP telephony. The architecture of 3G IP Telephony and its components are described. The main goal of the thesis is to investigate the interface between the Call Processing Server and Multimedia IP Networks. The interface functionality, proposed protocol stack and a general description are presented in the thesis. To provide useful services, 3G IP Telephony requires a set of control protocols for connection establishment, capabilities exchange and conference control. The Session Initiation Protocol (SIP) and the H.323 are two protocols that meet these needs. In the thesis these two protocols are investigated and compared in terms of Complexity, Extensibility, Scalability, Services, Resource Utilization and Management.
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Universal Mobile Telecommunication System (UMTS) on Third Generation Partnership Project (3GPP) –organisaation määrittelemä matkaviestinjärjestelmä. UMTS tukee sekä piiri- että pakettikytkentäistä tiedonsiirtoa ja mahdollistaa langattoman, suurinopeuksisen Internet-yhteyden. Diplomityön tarkoituksena on kuvata Nokia Research Center:n toteuttama kolmannen sukupolven 3GPP yhteensopiva pakettikytkentäinen koejärjestelmä. Työssä on käytetty uutta lähestymistapaa protokollakehitykseen, yhdistämällä eri työkaluilla tuotettuja protokollia yhdeksi kokonaisuudeksi. Liikenteen vaihtuessa lähitulevaisuudessa suurelta osin pakettikytkentäiseksi on mietittävä keinoja palvelunlaadun takaamiseksi. Näitä keinoja tutkittiin käyttämällä työssä toteutettua koejärjestelmää testialustana. Koejärjestelmää esiteltiin useissa konferensseissa ja se toimitettiin monille teleoperaattoreille.
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Projektin johtaminen informaatioaikakaudella merkitsee, yhä useammassa tapauksessa, virtuaalisen verkoston tietämyksen hallitsemista ja johtamista. Kolmannen sukupolven matkaviestinverkon rakentaminen on virtuaaliverkostoa hyväkseen käyttävä projekti, joka koostuu lukuisista osapuolista.Matkaviestinverkkoprojektien laajentuminen ja kilpailun kiristyminen alalla ovat nostaneet knowledge management -järjestelmien kysyntää. Kysyntä kohdistuu voimakkaimmin järjestelmiin, joiden avulla matkaviestinverkkotoimitusprojektin kaikki toiminnot pystytään käsittelemään yhdessä järjestelmässä. Tämän tutkimuksen pääasiallisena tavoitteena on ollut selvittää keskeisimmät vaatimukset kolmannen sukupolven matkaviestinverkon rakentamisprojektin knowledge management ?järjestelmälle. Tutkimus toteutettiin kirjallisuuden ja avoimien teemahaastattelujen avulla, käyttäen kvalitatiivisiä tutkimusmenetelmiä.Haastattelut osoittivat, että tärkeimmät vaatimukset kolmannen sukupolven matkaviestinverkkoja rakentavan projektiorganisaation knowledge management -järjestelmälle ovat: 1. Knowledge management -järjestelmän tulee toimia keskitettynä tietovarastona.2. Projektissa käsiteltävään tietoon on pystyttävä porautumaan vähintään prosessi- ja paikkatietoon pohjautuvista näkökulmista. 3. Pääsyn knowledge management -järjestelmään tulee olla mahdollista kaikille projektin osapuolille.4. Pääsyn knowledge management -järjestelmään tulee olla mahdollista mistä tahansa ja mihin kellonaikaan tahansa.5. Knowledge management -järjestelmän käyttöliittymän tulee olla mahdollisimman yksinkertainen. Järjestelmän tulee olla yhteydessä organisaatioiden muihin järjestelmiin.
Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer.
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The development of novel effective immunotherapeutic agents and early clinical data hinting at significant activity in non-small cell lung cancer (NSCLC) has introduced yet another player in the field of management of advanced disease. At present, first-line cytotoxic chemotherapy is generally withheld pending results of molecular testing for any actionable genetic alteration that could lead to targeted treatment, and in their absence chemotherapy is prescribed as a default therapy. Phase III trials comparing head-to-head immune checkpoint inhibitors with standard platinum-based doublet chemotherapy are underway. Second-line chemotherapy is likewise being challenged in phase III trials, one of which having recently reported positive results in advanced squamous cell carcinoma. In tumors harboring actionable transforming genetic alterations such as EGFR mutations and ALK rearrangements, second- and third-generation inhibitors allow for multiple lines of targeted treatment beyond initial resistance, postponing the use of cytotoxic chemotherapy to very late lines of therapy. Chemotherapy as a longstanding but still present standard of care capable of prolonging survival, improving quality of life, and relieving symptoms sees its role increasingly restricted to clinical, immunological, and molecular subsets of patients where its activity and efficacy have never been tested prospectively.
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Antifouling agents have been used on vessels and boats since ancient civilizations. Thus, a brief history on the three generations of antifouling paints was provided in the present review. Additionally, information about physic-chemical properties, environmental levels, toxicology and analytical methods was discussed for the 16 "new" booster biocides used as third-generation antifouling paints. The main problems, limitations and future trends related to this subject were also presented. Finally, actions were suggested in order to appraise the current status of the environmental impact caused by these compounds in South America.
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Coal, natural gas and petroleum-based liquid fuels are still the most widely used energy sources in modern society. The current scenario contrasts with the foreseen shortage of petroleum that was spread out in the beginning of the XXI century, when the concept of "energy security" emerged as an urgent agenda to ensure a good balance between energy supply and demand. Much beyond protecting refineries and oil ducts from terrorist attacks, these issues soon developed to a portfolio of measures related to process sustainability, involving at least three fundamental dimensions: (a) the need for technological breakthroughs to improve energy production worldwide; (b) the improvement of energy efficiency in all sectors of modern society; and (c) the increase of the social perception that education is a key-word towards a better use of our energy resources. Together with these technological, economic or social issues, "energy security" is also strongly influenced by environmental issues involving greenhouse gas emissions, loss of biodiversity in environmentally sensitive areas, pollution and poor solid waste management. For these and other reasons, the implementation of more sustainable practices in our currently available industrial facilities and the search for alternative energy sources that could partly replace the fossil fuels became a major priority throughout the world. Regarding fossil fuels, the main technological bottlenecks are related to the exploitation of less accessible petroleum resources such as those in the pre-salt layer, ranging from the proper characterization of these deep-water oil reservoirs, the development of lighter and more efficient equipment for both exploration and exploitation, the optimization of the drilling techniques, the achievement of further improvements in production yields and the establishment of specialized training programs for the technical staff. The production of natural gas from shale is also emerging in several countries but its production in large scale has several problems ranging from the unavoidable environmental impact of shale mining as well as to the bad consequences of its large scale exploitation in the past. The large scale use of coal has similar environmental problems, which are aggravated by difficulties in its proper characterization. Also, the mitigation of harmful gases and particulate matter that are released as a result of combustion is still depending on the development of new gas cleaning technologies including more efficient catalysts to improve its emission profile. On the other hand, biofuels are still struggling to fulfill their role in reducing our high dependence on fossil fuels. Fatty acid alkyl esters (biodiesel) from vegetable oils and ethanol from cane sucrose and corn starch are mature technologies whose market share is partially limited by the availability of their raw materials. For this reason, there has been a great effort to develop "second-generation" technologies to produce methanol, ethanol, butanol, biodiesel, biogas (methane), bio-oils, syngas and synthetic fuels from lower grade renewable feedstocks such as lignocellulosic materials whose consumption would not interfere with the rather sensitive issues of food security. Advanced fermentation processes are envisaged as "third generation" technologies and these are primarily linked to the use of algae feedstocks as well as other organisms that could produce biofuels or simply provide microbial biomass for the processes listed above. Due to the complexity and cost of their production chain, "third generation" technologies usually aim at high value added biofuels such as biojet fuel, biohydrogen and hydrocarbons with a fuel performance similar to diesel or gasoline, situations in which the use of genetically modified organisms is usually required. In general, the main challenges in this field could be summarized as follows: (a) the need for prospecting alternative sources of biomass that are not linked to the food chain; (b) the intensive use of green chemistry principles in our current industrial activities; (c) the development of mature technologies for the production of second and third generation biofuels; (d) the development of safe bioprocesses that are based on environmentally benign microorganisms; (e) the scale-up of potential technologies to a suitable demonstration scale; and (f) the full understanding of the technological and environmental implications of the food vs. fuel debate. On the basis of these, the main objective of this article is to stimulate the discussion and help the decision making regarding "energy security" issues and their challenges for modern society, in such a way to encourage the participation of the Brazilian Chemistry community in the design of a road map for a safer, sustainable and prosper future for our nation.
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Kandidaatintutkielmassa esitellään kolmannen sukupolven painevesireaktorilaitosten passiivisia turvallisuusjärjestelmiä.
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Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.
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Numerous studies have suggested a substantial genetic contribution in the etiology of the primary form of restless legs syndrome (RLS) and periodic leg movements (PLM). We describe the symptoms, the sleep profiles and physiological parameters of two families in which several members present RLS/PLM. The proband of family 1 is a 70-year-old woman and the proband of family 2 is a 57-year-old woman; both have exhibited the symptoms since the age of 20 years. All patients in both families were diagnosed with RLS according to the criteria of the International RLS Study Group. Polysomnographic recordings were performed to quantify and to describe PLM during sleep. Sleep parameters showed decreased sleep efficiency, increased sleep latency in the arousal index and the presence of PLM in all subjects. One of the families showed an exact profile of dominant inheritance with anticipation of age at onset. In the other family, the founders were blood relatives and there was no affected member in the third generation suggesting a recessive mode of inheritance. RLS/PLM is a prevalent sleep disorder affecting about 5 to 15% of the population and one that substantially impairs healthy sleep patterns. Efforts to understand the underlying pathophysiology will contribute to improve the sleep and life quality of these patients.
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A blend of 50% Potato Starch (PS), 35% Quality Protein Maize (QPM), and 15% Soybean Meal (SM) were used in the preparation of expanded pellets utilizing a laboratory extruder with a 1.5 × 20.0 × 100.0 mm die-nozzle. The independent variables analyzed were Barrel Temperature (BT) (75-140 °C) and Feed Moisture (FM) (16-30%). The effect of extrusion variables was investigated in terms of Expansion Index (EI), apparent density (ApD), Penetration Force (PF) and Specific Mechanical Energy (SME), viscosity profiles, DSC, crystallinity by X-ray diffraction, and Scanning Electronic Microscopy (SEM). The PF decreased from 30 to 4 kgf with the increase of both independent variables (BT and FM). SME was affected only by FM, and decreased with the increase in this variable. The optimal region showed that the maximum EI was found for BT in the range of 123-140 °C and 27-31% for FM, respectively. The extruded pellets obtained from the optimal processing region were probably not completely degraded, as shown in the structural characterization. Acceptable expanded pellets could be produced using a blend of PS, QPM, and SM by extrusion cooking.
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This thesis studies the collective memory of the Russian-speaking minority living in Estonia. The minority is exposed to two national narratives regarding the incorporation of Estonia into the Soviet Union in 1940. According to the Estonian narrative, Estonia was occupied and annexed by the Soviet Union while the Soviet-Russian narrative sees the actions to have been legal and voluntary. This thesis firstly examines thoughts the existence of these two opposing narratives evoke among the Russian-speaking minority and secondly it explores whether the views of the minority compare with the two official yet divergent narratives. The study focuses on the second and third generation minority members. The topic belongs to the field of memory studies. The objective is to understand the views the Russian minority have towards the controversial events of the years 1939-40. To accomplish the objectives set, a web-based survey using open-ended and multiple-choice questions was conducted. The open-ended questions addressed the main research questions while the multiple-choice questions contributed to forming a more comprehensive understanding of the subject in question. In order to interpret the data, qualitative content analysis has been applied. Based on the findings, the Russian-speaking minority respondents’ understanding of the events of 1939-40 could be described as fragmented, inconsistent and including viewpoints that resulted from the merger of different storylines. There is no single cohesive or coherent narrative of the past amongst the minority. In addition to that, their views do not generally comply with the narrative of the Russian Federation as often referred to in literature, even though the minority respondents do not want to see the Soviet involvement as critically as the Estonian narrative does. Many respondents conceive the events of 1939-40 as ambiguous revealing the ability to be tolerant and receptive in their views regarding the past.
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The aim of this thesis is to explore the relationship between imagery, technology, and remote adult Aboriginal teacher candidates through the computer software Elluminate Live. It focuses on the implications that the role imagery plays in third generation distance education with these learners and the new media associated therein. The thesis honours the Medicine Wheel teachings and is presented within this cyclical framework that reflects Indigenous philosophies and belief systems. In accordance, Sharing Circle as methodology is used to keep the research culturally grounded, and tenets of narrative inquiry further support the study. Results indicate there are strong connections to curricula enhanced with imagery—most notably a spiritual connection. Findings also reveal that identity associated to geographical location is significant, as are supportive networks. Third generation distance education, such as Elluminate Live, needs to be addressed before Aboriginal communities open the doors to all it encompasses, and although previous literature peers into various elements, this study delves into why the graphical interface resonates with members of these communities. Of utmost importance is the insight this thesis lends to the pedagogy that may possibly evoke a transformative learning process contributing to the success rate of Aboriginal learners and benefit Aboriginal communities as a whole.
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The last will and testament of Peter Wright, dated December 18th, 1812. He was the father of Mary Wright, the first wife of Thomas Wilson (third generation). In the will, Peter states his executors as Lawrence Lemon, George Garner, and his wife Susannah Wright. There is also a transcript of the handwritten will.
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Dans cette thèse, nous construisons un modèle épidémiologique de la dissémina- tion de normes juridiques. L’objectif est d’expliquer la transmission de normes juridiques américaines régissant les tests de dépistages pour drogues au travail vers le Canada ainsi que la propagation subséquente de ces normes à travers la jurisprudence canadienne. La propagation des normes régissant les tests de dépistages pour drogues au travail sert donc à la fois de point de départ pour une réflexion théorique sur la transmission de normes juridiques et pour une étude de cas empirique. Nous partons de la prémisse que les explications du changement juridique, telles celle de la transplantation et celle de l’harmonisation, sont essentiellement métaphoriques. Ces métaphores explicatives fonctionnent en invitant des comparaisons entre les domaines connus et inconnus. Quand ce processus de comparaison est systématisé, la métaphore devient un modèle. Dans la thèse, nous appliquons cette procédure de systématisation afin de transformer la métaphore de la propagation virale en modèle épidémiologique. Après une revue de la littérature sur les épidémies sociales, nous décrivons les éléments pertinents de la théorie épidémiologique pour, ensuite, les transposer au domaine juridique. Le modèle est alors opérationnalisé en l’appliquant à une base de données composée de la jurisprudence pertinente (n=187). Les résultats soutiennent les hypothèses du modèle. 90 % des décisions qui citent les sources américaines sont infectées selon les critères du modèle, alors que seulement 64 % des décisions qui ne citent pas de sources américaines sont infectées. Cela soutient l’hypothèse d’une épidémie dite de « réservoir commun ». Nous avons également démontré une corrélation positive entre la référence à ces décisions et l’état d’infection! : 87 % des décisions qui citent des décisions qui réfèrent aux sources américaines sont infectées, alors que le taux d’infection parmi la population restante est de seulement 53 %. Les résultats semblables ont été obtenus pour les décisions de troisième génération. Cela soutient l’hypothèse selon laquelle il y a eu propagation à travers la jurisprudence suite aux contacts initiaux avec le réservoir commun. Des corrélations positives ont aussi été démontrées entre l’état d’infection et l’appartenance à l’une ou l’autre de sous-populations particulières qui seraient, par hypothèse, des points d’infection. En conclusion de la thèse, nous avançons que c’est seulement après avoir construit un modèle et d’avoir constaté ses limites que nous pouvons vraiment comprendre le rôle des métaphores et des modèles dans l’explication de phénomènes juridiques.
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Ces travaux visent à étendre les applications de la résonance de plasmons de surface (SPR) L’objectif est d’offrir des outils diagnostics plus rapides, efficaces et simple d’utilisation pour diagnostiquer ou effectuer le suivi de conditions cliniques. Pour se faire, un nouveau type d’instrumentation SPR basé sur l’utilisation d’un prisme d’inversion (dove) a permis d’atteindre une limite de détection (LOD) de 10-6 unité d’indice de réfraction (RIU), une valeur comparable aux instruments commerciaux complexes tout en demeurant peu dispendieux, robuste et simple d’utilisation. Les travaux présentés dans cet ouvrage visent, dans un second temps, à réduire les interactions nonspécifiques (NSB) entre la surface des biocapteurs SPR et les composants de la matrice biologique complexe telles que: l’urine, le lysat cellulaire, le sérum et le sang. Ces dernières induisent des réponses empêchant l’utilisation de biocapteurs SPR en milieux complexes. Les acides aminés (AA) offrent une grande variété de propriétés physico-chimiques permettant la mise au point de monocouches auto-assemblées (SAM) aux propriétés diverses. Initialement, 19 des 20 acides aminés naturels ont été attachés à l’acide 3-mercaptopropionique (3-MPA) formant des SAMs peptidomimétiques. La quantité d’interactions nonspécifiques engendrées par ces différentes surfaces a été mesurée en exposant ces surfaces au sérum sanguin bovin complet variant de 400 ng/cm² jusqu’à 800 ng/cm². La détection à l’aide de ces surfaces de la β-lactamase (une enzyme responsable de la résistance aux antibiotiques au niveau μM) a démontré la possibilité d’employer ces surfaces pour bâtir des biocapteurs SPR. Des peptides de longueur allant de 2 à 5 résidus attachés à 3-MPA ont été synthétisés sur support solide. Cette étude a démontré que l’augmentation de la longueur des peptides formés d’AA résistants aux NBS accroit leur résistance jusqu’à 5 résidus. Le composé le plus performant de ce type (3-MPA-(Ser)5-OH) a permis d’atteindre 180 ng/cm². Cette valeur est similaire à celle des meilleures surfaces disponibles commercialement, notamment les surfaces de polyethylène glycol (PEG) à 100 ng/cm². Des surfaces de 3-MPA-(Ser)5-OH ont permis l’étalonnage de la β-lactamase et sa quantification directe dans un lysat cellulaire. La LOD pour ces biocapteurs est de 10 nM. Une troisième génération de surfaces peptidiques binaires a permis la réduction de la NSB jusqu’à un niveau de 23±10 ng/cm² une valeur comparable aux meilleures surfaces disponibles. Ces surfaces ont permis l’étalonnage d’un indicateur potentiel du cancer la metalloprotéinase-3 de matrice (MMP-3). Les surfaces formées de peptides binaires (3-MPA-H3D2-OH) ont permis la quantification directe de la MMP-3 dans le sérum sanguin complet. Une quatrième génération de surfaces peptidiques a permis de réduire davantage le niveau de NSB jusqu’à une valeur de 12 ± 11 ng/cm². Ces surfaces ont été modifiées en y attachant une terminaison de type acide nitriloacétique (NTA) afin d’y attacher des biomolécules marquées par six résidus histidines terminaux. Ces surfaces ont permis le développement d’une méthode rapide de balayage des ligands ciblant le « cluster of differenciation-36 » (CD36). L’étude d’électroformation des monocouches de peptide a permis de déterminer les conditions de formation optimales d’une couche de 3-MPA-HHHDD-OH permettant ainsi la formation de monocouches résistantes au NSB en moins de 6 minutes en appliquant un potentiel de formation de 200mV vs Ag/AgCl.