931 resultados para 5-36


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There may be circumstances where it is necessary for microbiologists to compare variances rather than means, e,g., in analysing data from experiments to determine whether a particular treatment alters the degree of variability or testing the assumption of homogeneity of variance prior to other statistical tests. All of the tests described in this Statnote have their limitations. Bartlett’s test may be too sensitive but Levene’s and the Brown-Forsythe tests also have problems. We would recommend the use of the variance-ratio test to compare two variances and the careful application of Bartlett’s test if there are more than two groups. Considering that these tests are not particularly robust, it should be remembered that the homogeneity of variance assumption is usually the least important of those considered when carrying out an ANOVA. If there is concern about this assumption and especially if the other assumptions of the analysis are also not likely to be met, e.g., lack of normality or non additivity of treatment effects then it may be better either to transform the data or to carry out a non-parametric test on the data.

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Glucagon-like peptide-1(7-36)amide (GLP-1) possesses several unique and beneficial effects for the potential treatment of type 2 diabetes. However, the rapid inactivation of GLP-1 by dipeptidyl peptidase IV (DPP IV) results in a short half-life in vivo (less than 2 min) hindering therapeutic development. In the present study, a novel His7-modified analogue of GLP-1, N-pyroglutamyl-GLP-1 as well as N-acetyl-GLP-1 were synthesised and tested for DPP IV stability and biological activity. Incubation of GLP-1 with either DPP IV or human plasma resulted in rapid degradation of native GLP-1 to GLP-1(9-36)amide, while N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 were completely resistant to degradation. N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 bound to the GLP-1 receptor but had reduced affinities (IC50 values 32.9 and 6.7 nM, respectively) compared with native GLP-1 (IC50-37 nM). Similarly, both analogues stimulated cAMP production with EC50 values of 16.3 and 27 nM respectively compared with GLP-1 (EC50 4.7 nM). However, N-acetyl-GLP-1 and N-pyroglutamyl-GLP-1 exhibited potent insulinotropic activity in vitro at 5.6 mM glucose (P< 0.05 to P< 0.001) similar to native GLP-1. Both analogues (25 nM/kg body weight) lowered plasma glucose and increased plasma insulin levels when administered in conjunction with glucose (18 nM/kg body weight) to adult obese diabetic (ob/ob) mice. N-pyroglutamyl-GLP-1 was substantially better at lowering plasma glucose compared with the native peptide, while N-acetyl-GLP-1 was significantly more potent at stimulating insulin secretion. These studies indicate that N-terminal modification of GLP-1 results in DPP IV-resistant and biologically potent forms of GLP-1. The particularly powerful antihyperglycaemic action of N-pyroglutamyl-GLP-1 shows potential for the treatment of type 2 diabetes. © 2004 Society for Endocrinology.

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Although the incretin hormone glucagon-like peptide-1 (GLP-1) is a potent stimulator of insulin release, its rapid degradation in vivo by the enzyme dipeptidyl peptidase IV (DPP IV) greatly limits its potential for treatment of type 2 diabetes. Here, we report two novel Ala8-substituted analogues of GLP-1, (Abu8)GLP-1 and (Val8)GLP-1 which were completely resistant to inactivation by DPP IV or human plasma. (Abu8)GLP-1 and (Val8)GLP-1 exhibited moderate affinities (IC50: 4.76 and 81.1 nM, respectively) for the human GLP-1 receptor compared with native GLP-1 (IC50: 0.37 nM). (Abu8)GLP-1 and (Val8)GLP-1 dose-dependently stimulated cAMP in insulin-secreting BRIN BD11 cells with reduced potency compared with native GLP-1 (1.5- and 3.5-fold, respectively). Consistent with other mechanisms of action, the analogues showed similar, or in the case of (Val8)GLP-1 slightly impaired insulin releasing activity in BRIN BD11 cells. Using adult obese (ob/ob) mice, (Abu8 )GLP-1 had similar glucose-lowering potency to native GLP-1 whereas the action of (Val8)GLP-1 was enhanced by 37%. The in vivo insulin-releasing activities were similar. These data indicate that substitution of Ala8 in GLP-1 with Abu or Val confers resistance to DPP IV inactivation and that (Val8)GLP-1 is a particularly potent N-terminally modified GLP-1 analogue of possible use in type 2 diabetes.

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* The author is supported by a Return Fellowship from the Alexander von Humboldt Foundation.

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Vol. 21, Issue 36, 8 pages

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High-resolution pollen and dinoflagellate cyst records from sediment core M72/5-25-GC1 were used to reconstruct vegetation dynamics in northern Anatolia and surface conditions of the Black Sea between 64 and 20 ka BP. During this period, the dominance of Artemisia in the pollen record indicates a steppe landscape and arid climate conditions. However, the concomitant presence of temperate arboreal pollen suggests the existence of glacial refugia in northern Anatolia. Long-term glacial vegetation dynamics reveal two major arid phases ~64-55 and 40-32 ka BP, and two major humid phases ~54-45 and 28-20 ka BP, correlating with higher and lower summer insolation, respectively. Dansgaard-Oeschger (D-O) cycles are clearly indicated by the 25-GC1 pollen record. Greenland interstadials are characterized by a marked increase in temperate tree pollen, indicating a spread of forests due to warm/wet conditions in northern Anatolia, whereas Greenland stadials reveal cold and arid conditions as indicated by spread of xerophytic biomes. There is evidence for a phase lag of ~500 to 1500 yr between initial warming and forest expansion, possibly due to successive changes in atmospheric circulation in the North Atlantic sector. The dominance of Pyxidinopsis psilata and Spiniferites cruciformis in the dinocyst record indicates brackish Black Sea conditions during the entire glacial period. The decrease of marine indicators (marine dinocysts, acritarchs) at ~54 ka BP and increase of freshwater algae (Pediastrum, Botryococcus) from 32 to 25 ka BP reveals freshening of the Black Sea surface water. This freshening is possibly related to humid phases in the region, to connection between Caspian Sea and Black Sea, to seasonal freshening by floating ice, and/or to closer position of river mouths due to low sea level. In the southern Black Sea, Greenland interstadials are clearly indicated by high dinocyst concentrations and calcium carbonate content, as a result of an increase in primary productivity. Heinrich events show a similar impact on the environment in the northern Anatolia/Black Sea region as Greenland stadials.

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Concentrations of tin in sea water decreased from estuarine and shelf (0.02-0.04 µg/kg) to surface Atlantic waters (0.009 µg/kg). Mean contents (ppm) in other materials included: ultramafic rocks, 0.8; basalts, 1.7; silicic rocks, 2.5; red clays, 3.4; amphibolites, 1.2. Oceanic ferromanganese deposits contained from 0.2 to 5.8 ppm; tin and cobalt contents were correlated.

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Portuguese textbook has been the focus of many investigations, nevertheless, the theme still has much to be discussed, reflected and broadened. This conviction mobilized us to perform this research, seeking to answer three questions: (1) how does the author of the textbook induce the student to give his opinion in comprehension questions of text in Portuguese textbook of 4th and 5thgrade? Which enunciative links are used by the author of the textbook in comprehension questions of text concerning to the assumption of enunciative responsability? And (3) Which enunciative links are used by the author of the textbook in comprehension questions of text concerning to the non assumption of enunciative responsability? In this direction, we define as objective to id entify, describe, analyze and interpret how the (non) assumption of enunciative responsibility materializes itself in Portuguese textbooks. The theme is echoed in the guidelines of the Parâmetros Curriculares Nacionais PCN (1998; 2001), who assume that all education committed to citizenship need to create conditions in order the student can develop his discursive competence" (BRAZIL, 1998, p. 23). This assertion of PCN (1998; 2001) is closely related to our research object, and therefore, it has corroborated to the accomplishment of this study. So, we analyze the comprehension questions of the texts that are elaborated by the authors of Portuguese textbooks of the 4th and 5th grade, used at public schools in the city of Natal-RN in 2010. As a theoretical basis, we have considered the postulates of Textual Analysis of Discourses ATD and Enunciative Linguistics. Our research was mainly based on the studies of Adam (2011), Nølke (1994; 2001; 2006; 2009; 2013), Nølke, Fløttum e Norén (2004) Rabatel (2004; 2005; 2008; 2009), Guentchéva (1994; 1996). Our data analysis revealed that the authors of Portuguese textbooks explore the reading comprehension, inducing students to answer questions that may be categorized like: (1) induction to the assumption of enunciative responsibility, (2) induction for non assumption the enunciative responsibility, (3) orientation for the study of vocabulary and grammar and (4) orientation of extra themes. The results from the comparison of the books of 4th and 5th grade of the two analyzed collections, we observed through the links of (non) responsability Nølke (1994; 2001; 2006; 2009; 2013), Nølke, Fløttum e Norén (2004), which in 79% of the questions, the authors induce the decoding of a content objectively inscribed in the text. In this sense, the notion of understanding a text is compromised, since it is limited to copying contents or transcription exercises, failing to consider the interactive use of language, or rather, failing to expand the student's knowledge in the (re)construction of the text of the meanings. This shows that there is a lack in the deal with the text that includes the textual discursive resources in the reading activities in Portuguese textbooks. We recall, in this direction, the works of Marcuschi (2005), Antunes (2003, 2005), and Bunzen Rojo (2008), among others authors who contributed greatly to orient the choice of Portuguese textbooks. Finally, we believe that the study about the enunciative responsibility phenomenon in Portuguese texto oks offers, above all, instruments in order to the interlocutors identify the elements present in the enunciation and the effects that these elements bring to the (re) construction of the meanings in texts that they read and write in the classroom.