40 resultados para stable-like processes
Resumo:
Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P < 0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P < 0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P < 0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P < 0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P < 0.01). The total cholesterol concentration (P < 0.02), the low density lipoprotein cholesterol concentration (P < 0.02), and the VLDL cholesterol/VLDL apoB ratio (P < 0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P < 0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P < 0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.
Resumo:
We consider percolation properties of the Boolean model generated by a Gibbs point process and balls with deterministic radius. We show that for a large class of Gibbs point processes there exists a critical activity, such that percolation occurs a.s. above criticality. For locally stable Gibbs point processes we show a converse result, i.e. they do not percolate a.s. at low activity.
Resumo:
This paper examines the social impacts of weather extremes and the processes of social and communicative learning a society undertakes to find alternative ways to deal with the consequences of a crisis. In the beginning of the 20th Century hunger seemed to be expelled from Europe. Switzerland – like many other European countries – was involved in a global interdependent trade system, which provided necessary goods. But at the end of World War I very cold and wet summers in 1916/17 (causing crop failure) and the difficulties in war-trade led to malnutrition and enormous price risings of general living-standards in Switzerland, which shocked the people and caused revolutionary uprisings in 1918. The experience of malnutrition during the last two years of war made clear that the traditional ways of food supply in Switzerland lacked crisis stability. Therefore various agents in the field of food production, distribution and consumption searched for alternative ways of food supply. In that sense politicians, industrialists, consumer-groups, left-wing communitarians and farmers developed several strategies for new ways in food production. Traditionally there were political conflicts in Switzerland between farmers and consumers regarding price policies, which led mainly to the conflict in 1918. Consumers accused famers of holding back food to control extortionate prices while the farmers pointed to the bad harvest causing the price rising. The collaboration of these groups in search for new forms of food-stability made social integration possible again. In addition to other crisis-factors, weather extremes can have disastrous impacts and destroy a society’s self-confidence to its core. But even such crisis can lead to processes of substantial learning that allows a regeneration of confidence and show positive influence on political stabilization. The paper focuses on the process of learning and the alternative methods of food production that were suggested by various agents working in the field during the Interwar period. To achieve that goal documents of the various associations are analyzed and newspapers have been taken into consideration. Through the method of discourse-analysis of food-production during the Interwar period, possible solutions that crossed the minds of the agents should be brought to light.
Resumo:
The reconstruction of the stable carbon isotope evolution in atmospheric CO2 (δ13Catm), as archived in Antarctic ice cores, bears the potential to disentangle the contributions of the different carbon cycle fluxes causing past CO2 variations. Here we present a new record of δ13Catm before, during and after the Marine Isotope Stage 5.5 (155 000 to 105 000 yr BP). The dataset is archived on the data repository PANGEA® (www.pangea.de) under 10.1594/PANGAEA.817041. The record was derived with a well established sublimation method using ice from the EPICA Dome C (EDC) and the Talos Dome ice cores in East Antarctica. We find a 0.4‰ shift to heavier values between the mean δ13Catm level in the Penultimate (~ 140 000 yr BP) and Last Glacial Maximum (~ 22 000 yr BP), which can be explained by either (i) changes in the isotopic composition or (ii) intensity of the carbon input fluxes to the combined ocean/atmosphere carbon reservoir or (iii) by long-term peat buildup. Our isotopic data suggest that the carbon cycle evolution along Termination II and the subsequent interglacial was controlled by essentially the same processes as during the last 24 000 yr, but with different phasing and magnitudes. Furthermore, a 5000 yr lag in the CO2 decline relative to EDC temperatures is confirmed during the glacial inception at the end of MIS5.5 (120 000 yr BP). Based on our isotopic data this lag can be explained by terrestrial carbon release and carbonate compensation.
Resumo:
BACKGROUND The human waking EEG spectrum shows high heritability and stability and, despite maturational cortical changes, high test-retest reliability in children and teens. These phenomena have also been shown to be region specific. We examined the stability of the morphology of the wake EEG spectrum in children aged 11 to 13 years recorded over weekly intervals and assessed whether the waking EEG spectrum in children may also be trait-like. Three minutes of eyes open and three minutes of eyes closed waking EEG was recorded in 22 healthy children once a week for three consecutive weeks. Eyes open and closed EEG power density spectra were calculated for two central (C3LM and C4LM) and two occipital (O1LM and O2LM) derivations. A hierarchical cluster analysis was performed to determine whether the morphology of the waking EEG spectrum between 1 and 20 Hz is trait-like. We also examined the stability of the alpha peak using an ANOVA. RESULTS The morphology of the EEG spectrum recorded from central derivations was highly stable and unique to an individual (correctly classified in 85% of participants), while the EEG recorded from occipital derivations, while stable, was much less unique across individuals (correctly classified in 42% of participants). Furthermore, our analysis revealed an increase in alpha peak height concurrent with a decline in the frequency of the alpha peak across weeks for occipital derivations. No changes in either measure were observed in the central derivations. CONCLUSIONS Our results indicate that across weekly recordings, power spectra at central derivations exhibit more "trait-like" characteristics than occipital derivations. These results may be relevant for future studies searching for links between phenotypes, such as psychiatric diagnoses, and the underlying genes (i.e., endophenotypes) by suggesting that such studies should make use of more anterior rather than posterior EEG derivations.
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The spatial distributions of non-reactive natural tracers (anions, stable water isotopes, noble gases) in pore water of clay-rich formations were studied at nine sites. Regular curved profiles were identified in most cases. Transport modeling considering diffusion, advection and available constraints on the paleo-hydrogeological evolution indicates generally that diffusion alone can explain the observations, whereas a marked advective component would distort the profiles and so is not consistent with the data.
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The gladiator cemetery discovered in Ephesus (Turkey) in 1993 dates to the 2nd and 3rd century AD. The aim of this study is to reconstruct diverse diet, social stratification, and migration of the inhabitants of Roman Ephesus and the distinct group of gladiators. Stable carbon, nitrogen, and sulphur isotope analysis were applied, and inorganic bone elements (strontium, calcium) were determined. In total, 53 individuals, including 22 gladiators, were analysed. All individuals consumed C3 plants like wheat and barley as staple food. A few individuals show indication of consumption of C4 plants. The δ13C values of one female from the gladiator cemetery and one gladiator differ from all other individuals. Their δ34S values indicate that they probably migrated from another geographical region or consumed different foods. The δ15N values are relatively low in comparison to other sites from Roman times. A probable cause for the depletion of 15N in Ephesus could be the frequent consumption of legumes. The Sr/Ca-ratios of the gladiators were significantly higher than the values of the contemporary Roman inhabitants. Since the Sr/Ca-ratio reflects the main Ca-supplier in the diet, the elevated values of the gladiators might suggest a frequent use of a plant ash beverage, as mentioned in ancient texts.
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We review our recent work on protein-ligand interactions in vitamin transporters of the Sec-14-like protein. Our studies focused on the cellular-retinaldehyde binding protein (CRALBP) and the alpha-tocopherol transfer protein (alpha-TTP). CRALBP is responsible for mobilisation and photo-protection of short-chain cis-retinoids in the dim-light visual cycle or rod photoreceptors. alpha-TTP is a key protein responsible for selection and retention of RRR-alpha-tocopherol, the most active isoform of vitamin E in superior animals. Our simulation studies evidence how subtle chemical variations in the substrate can lead to significant distortion in the structure of the complex, and how these changes can either lead to new protein function, or be used to model engineered protein variants with tailored properties. Finally, we show how integration of computational and experimental results can contribute in synergy to the understanding of fundamental processes at the biomolecular scale.
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Karst aquifers are known for their wide distribution of water transfer velocities. From this observation, a multiple geochemical tracer approach seems to be particularly well suited to provide a significant assessment of groundwater flows, but the choice of adapted tracers is essential. In this study, several common tracers in karst aquifers such as physicochemical parameters, major ions, stable isotopes, and d13C to more specific tracers such as dating tracers – 14C, 3H, 3H–3He, CFC-12, SF6 and 85Kr, and 39Ar – were used, in a fractured karstic carbonated aquifer located in Burgundy (France). The information carried by each tracer and the best sampling strategy are compared on the basis of geochemical monitoring done during several recharge events and over longer time periods (months to years). This study’s results demonstrate that at the seasonal and recharge event time scale, the variability of concentrations is low for most tracers due to the broad spectrum of groundwater mixings. The tracers used traditionally for the study of karst aquifers, i.e., physicochemical parameters and major ions, efficiently describe hydrological processes such as the direct and differed recharge, but require being monitored at short time steps during recharge events to be maximized. From stable isotopes, tritium, and Cl� contents, the proportion of the fast direct recharge by the largest porosity was estimated using a binary mixing model. The use of tracers such as CFC-12, SF6, and 85Kr in karst aquifers provides additional information, notably an estimation of apparent age, but they require good preliminary knowledge of the karst system to interpret the results suitably. The CFC-12 and SF6 methods efficiently determine the apparent age of baseflow, but it is preferable to sample the groundwater during the recharge event. Furthermore, these methods are based on different assumptions such as regional enrichment in atmospheric SF6, excess air, and flow models among others. 85Kr and 39Ar concentrations can potentially provide a more direct estimation of groundwater residence time. Conversely, the 3H–3He method is inefficient in the karst aquifer for dating due to 3He degassing.
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A growing number of studies in humans demonstrate the involvement of vestibular information in tasks that are seemingly remote from well-known functions such as space constancy or postural control. In this review article we point out three emerging streams of research highlighting the importance of vestibular input: (1) Spatial Cognition: Modulation of vestibular signals can induce specific changes in spatial cognitive tasks like mental imagery and the processing of numbers. This has been shown in studies manipulating body orientation (changing the input from the otoliths), body rotation (changing the input from the semicircular canals), in clinical findings with vestibular patients, and in studies carried out in microgravity. There is also an effect in the reverse direction; top-down processes can affect perception of vestibular stimuli. (2) Body Representation: Numerous studies demonstrate that vestibular stimulation changes the representation of body parts, and sensitivity to tactile input or pain. Thus, the vestibular system plays an integral role in multisensory coordination of body representation. (3) Affective Processes and Disorders: Studies in psychiatric patients and patients with a vestibular disorder report a high comorbidity of vestibular dysfunctions and psychiatric symptoms. Recent studies investigated the beneficial effect of vestibular stimulation on psychiatric disorders, and how vestibular input can change mood and affect. These three emerging streams of research in vestibular science are—at least in part—associated with different neuronal core mechanisms. Spatial transformations draw on parietal areas, body representation is associated with somatosensory areas, and affective processes involve insular and cingulate cortices, all of which receive vestibular input. Even though a wide range of different vestibular cortical projection areas has been ascertained, their functionality still is scarcely understood.
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Abstract: Research on human values within the family focuses on value congruence between the family members (Knafo & Schwartz, 2004), based on the assumption that transmission of values is part of a child’s socialization process. Within the family, values are not only implicitly transmitted through this process but also explicitly conveyed through the educational goals of parents (Grusec et al., 2000; Knafo & Schwartz, 2003; 2004, 2009). However, there is a lack of empirical evidence on the role of family characteristics in the value transmission process, especially for families with young children. Thus, the study presented had multiple aims: Firstly, it analyzed the congruency between mothers’ and fathers’ values and their value-based educational goals. Secondly, it examined the influence of mothers’ and fathers’ socio-demographic characteristics on their educational goals. Thirdly, it analyzed the differences in parental educational goals in families with daughters and families with sons. Finally, it examined the congruency between children’s values and the value-based educational goals of their parents. The value transmission process within families with young children was analyzed using data from complete families (child, mother and father) in Switzerland (N = 265). The survey of children consisted of 139 boys and 126 girls aged between 7 and 9 years. Parents’ values and parental educational goals were assessed using the Portrait Value Questionnaire (PVQ-21) (Schwartz, 2005). Children’s’ values were assessed using the Picture-Based Value Survey for Children (PBVS-C) (Döring et al., 2010). Regarding the role of the family context in the process of shaping children’s values, the results of the study show that, on average, parents are similar not only with respect to their value profiles but also with regard to their notion as to which values they would like to transmit to their children. Our findings also suggest that children’s values at an early age are shaped more strongly by mothers’ values than by fathers’ values. Moreover, our results show differences in value transmission with respect to the child’s gender. In particular, they suggest that value transmission within the family has a greater influence on female than on male offspring.
Resumo:
The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.
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BACKGROUND The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. METHODS/FINDINGS Key parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation. CONCLUSIONS FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.
Resumo:
The stable isotopic composition of fossil resting eggs (ephippia) of Daphnia spp. is being used to reconstruct past environmental conditions in lake ecosystems. However, the underlying assumption that the stable isotopic composition of the ephippia reflects the stable isotopic composition of the parent Daphnia, of their diet and of the environmental water have yet to be confirmed in a controlled experimental setting. We performed experiments with Daphnia pulicaria cultures, which included a control treatment conducted at 12 °C in filtered lake water and with a diet of fresh algae and three treatments in which we manipulated the stable carbon isotopic composition (δ13C value) of the algae, stable oxygen isotopic composition (δ18O value) of the water and the water temperature, respectively. The stable nitrogen isotopic composition (δ15N value) of the algae was similar for all treatments. At 12 °C, differences in algal δ13C values and in δ18O values of water were reflected in those of Daphnia. The differences between ephippia and Daphnia stable isotope ratios were similar in the different treatments (δ13C: +0.2 ± 0.4 ‰ (standard deviation); δ15N: −1.6 ± 0.4 ‰; δ18O: −0.9 ± 0.4 ‰), indicating that changes in dietary δ13C values and in δ18O values of water are passed on to these fossilizing structures. A higher water temperature (20 °C) resulted in lower δ13C values in Daphnia and ephippia than in the other treatments with the same food source and in a minor change in the difference between δ13C values of ephippia and Daphnia (to −1.3 ± 0.3 ‰). This may have been due to microbial processes or increased algal respiration rates in the experimental containers, which may not affect Daphnia in natural environments. There was no significant difference in the offset between δ18O and δ15N values of ephippia and Daphnia between the 12 and 20 °C treatments, but the δ18O values of Daphnia and ephippia were on average 1.2 ‰ lower at 20 °C than at 12 °C. We conclude that the stable isotopic composition of Daphnia ephippia provides information on that of the parent Daphnia and of the food and water they were exposed to, with small offsets between Daphnia and ephippia relative to variations in Daphnia stable isotopic composition reported from downcore studies. However, our experiments also indicate that temperature may have a minor influence on the δ13C, δ15N and δ18O values of Daphnia body tissue and ephippia. This aspect deserves attention in further controlled experiments.
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We present precise iron stable isotope ratios measured by multicollector-ICP mass spectrometry (MC-ICP-MS) of human red blood cells (erythrocytes) and blood plasma from 12 healthy male adults taken during a clinical study. The accurate determination of stable isotope ratios in plasma first required substantial method development work, as minor iron amounts in plasma had to be separated from a large organic matrix prior to mass-spectrometric analysis to avoid spectroscopic interferences and shifts in the mass spectrometer's mass-bias. The 56Fe/54Fe ratio in erythrocytes, expressed as permil difference from the “IRMM-014” iron reference standard (δ56/54Fe), ranges from −3.1‰ to −2.2‰, a range typical for male Caucasian adults. The individual subject erythrocyte iron isotope composition can be regarded as uniform over the 21 days investigated, as variations (±0.059 to ±0.15‰) are mostly within the analytical precision of reference materials. In plasma, δ56/54Fe values measured in two different laboratories range from −3.0‰ to −2.0‰, and are on average 0.24‰ higher than those in erythrocytes. However, this difference is barely resolvable within one standard deviation of the differences (0.22‰). Taking into account the possible contamination due to hemolysis (iron concentrations are only 0.4 to 2 ppm in plasma compared to approx. 480 ppm in erythrocytes), we model the pure plasma δ56/54Fe to be on average 0.4‰ higher than that in erythrocytes. Hence, the plasma iron isotope signature lies between that of the liver and that of erythrocytes. This difference can be explained by redox processes involved during cycling of iron between transferrin and ferritin.