48 resultados para 12114


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The use of continuous glucose monitor changes the way patients manage their diabetes, as observed in the increased number of daily insulin bolus, the increased number of daily BG measurements, and the differences in the distribution of BG measurements throughout the day. Continuous monitoring also increases the interaction of patients with the information system and modifies their patterns of use.

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Contiene : Tom. I - Tom. III - Tom. IV.

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Mode of access: Internet.

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Five long piston cores collected from different subbasins of the Aegean Sea constitute the primary source of data for this PhD thesis. This study is the first to document a continuous paleoceanographic and paleoclimatic record of the Aegean Sea since the last interglacial. The chronostratigraphic reconstructions of the cored sediments based on organic carbon contents, stratigraphic position of known ash layers and oxygen isotopic curve matching collectively demonstrate the presence of sapropel S1 and MISS sapropels S3, S4 and S5 in the Aegean Sea subbasins. Generally, the organic carbon (TOC wt%) contents in sapropels range between 0.8% and 2% with highest concentrations of 9-13% in sapropels S4 and S5. Average sedimentation rates range between 4.7 and 11.8 cmlka with highest rates being observed in Euboea and North Ikaria basins (9.8 and 11.8 cm lka, respectively). The timing of the onset of sapropels S4 and S5 mostly predate those in the eastern Mediterranean with ages ranging from 106.4-105.6 and 128.6-128.4 ka BP, respectively. On the other hand, the initiation of the onset of sapropel S3 (i.e., 83.2-80.4 ka BP) seems to agree with its Mediterranean counterparts, which highlights the heterogeneity of the Aegean Sea subbasins in terms of rapid vs. lagged response to changing climatic conditions. The sapropel initiations appear to be synchronous across the Aegean Sea; whereas, the terminations display a wider temporal variability implying that the cessation of sapropels is controlled both by the amplitude of paleoclimatic changes and the physiography/location ofthe subbasins. Quantitative variations in the planktonic faunal assemblages exhibit a sequence of bioevents during the last -130,000 years which allow identification of four major biozones. The distributional patterns of the most significant taxa demonstrate similar trends among all core localities suggesting that the major changes in the planktonic foraminifera assemblages have taken place rather synchronously in the Aegean Sea. Sapropels S3, S4 and S5 were deposited under similar hydrographic conditions during which a distinct deep chlorophyll maximum (DCM) layer was established. This situation points to a stratified water column and increased export productivity during times of sapropel formation. On the other hand, the faunal contrast between Sl and older sapropels indicates that the former was developed in the absence of a DCM layer, lacking a deep phytoplankton assemblage. Under such conditions, oxygen advection via intermediate water flow must have been significantly reduced which implies significant stagnation. Sapropels are interpreted to have been deposited under normal marine conditions with temporary establishment of semi-euxinic bottom water conditions. Both marine and terrestrial organic matter contributed equally to MISS sapropels. In addition, organic carbon isotopic values across sapropels are more depleted than those in the eastern Mediterranean which, in tum, suggests enhanced riverine input during their deposition. Primary productivity calculations show that, particularly for sapropels with very high TOC values, both preservation and increased productivity are imperative in order to deposit sapropels with very high organic carbon contents (i.e., up to 13%).

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Histone deacetylases (HDACs) have been shown to play key roles in tumorigenesis, and

have been validated as effective enzyme target for cancer treatment. Largazole, a marine natural

product isolated from the cyanobacterium Symploca, is an extremely potent HDAC inhibitor that

has been shown to possess high differential cytotoxicity towards cancer cells along with excellent

HDAC class-selectivity. However, improvements can be made in the isoform-selectivity and

pharmacokinetic properties of largazole.

In attempts to make these improvements and furnish a more efficient biochemical probe

as well as a potential therapeutic, several largazole analogues have been designed, synthesized,

and tested for their biological activity. Three different types of analogues were prepared. First,

different chemical functionalities were introduced at the C2 position to probe the class Iselectivity profile of largazole. Additionally, docking studies led to the design of a potential

HDAC8-selective analogue. Secondly, the thiol moiety in largazole was replaced with a wide

variety of othe zinc-binding group in order to probe the effect of Zn2+ affinity on HDAC

inhibition. Lastly, three disulfide analogues of largazole were prepared in order to utilize a

different prodrug strategy to modulate the pharmacokinetic properties of largazole.

Through these analogues it was shown that C2 position can be modified significantly

without a major loss in activity while also eliciting minimal changes in isoform-selectivity. While

the Zn2+-binding group plays a major role in HDAC inhibition, it was also shown that the thiol

can be replaced by other functionalities while still retaining inhibitory activity. Lastly, the use of

a disulfide prodrug strategy was shown to affect pharmacokinetic properties resulting in varying

functional responses in vitro and in vivo.

v

Largazole is already an impressive HDAC inhibitor that shows incredible promise.

However, in order to further develop this natural product into an anti-cancer therapeutic as well as

a chemical probe, improvements in the areas of pharmacokinetics as well as isoform-selectivity

are required. Through these studies we plan on building upon existing structure–activity

relationships to further our understanding of largazole’s mechanism of inhibition so that we may

improve these properties and ultimately develop largazole into an efficient HDAC inhibitor that

may be used as an anti-cancer therapeutic as well as a chemical probe for the studying of

biochemical systems.

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With the need of the companies in becoming more competitive within the market, it arises an incessant search for selective human potential, with a high level of capacity and low rotativity, which motivation results in production raise, quality optimization and waste reduction. This scenario requires a strategy development which advantages the Human Resources Quality Management. This way, the model of the Human System Audit (HSA), developed by the Spanish researchers Ouijano and Navarro, presents itself as an important tool to diagnosis and evaluation, contemplating the environment where the organization is inserted, its strategies, its organizational design, its processes and its organizational effectiveness. In this sense, the present study has identified the existent relation between the professional satisfaction and the Organizational Culture, based in the model HSA. The research has been a quantitative-descriptive one and has had as population the technical-administrative workers from the Federal Center of Technical Education of Rio Grande do Norte (CEFET RN). The data collection has occurred during May, 2008, by means of the application of a questionnaire in the HSA model. The sample was composed by 167 subjects, distributed among the Five units of the institution. It was used the factorial analysis, with the extraction method of main components and orthogonal rotation varimax, in order to extract the dimensions of the satisfaction and of the organizational culture and the calculation of Cronbach s Alpha coefficient, to evaluate the reliability of these dimensions. The factorial analysis of the satisfaction indicators has identified four factors,, all of them showing significance: gratefulness and relationship , self-realization , stability and security and physical conditions and social benefits . The result of the factorial analysis with the indicators of the organizational culture has extracted four factors and among them, three of them have obtained significance: Personal Satisfaction Style , Competitive-Denial-Power Style and the Conventional-Dependent Style . After identifying the dimensions of the satisfaction and culture found at CEFET-RN, it has been notice the existence or not of relation among them, through the application of Pearson s coefficient. It has been verified that all of the dimensions of the Professional satisfaction are correlated with some dimension of the organizational culture, having in outstand position, with higher intensity, the relation between the culture style of Personal Satisfaction and the satisfaction factor referring to the self-realization

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Rezension von: Matthias Pilz (Hrsg.): Vorbereitung auf die Welt der Arbeit in Japan, Bildungssystem und Übergangsfragen, Wiesbaden: VS Verlag für Sozialwissenschaften 2011 (294 S.; ISBN 978-3-5311-8046-5)