In Austria, two recent eParticipation projects focused on adolescent citizens. The first project, “mitmachen.at - move your future” was to provide initial experiences with an eParticipation tool. The second project, “Jugend2help”, applied the lessons learned from the “mitmachen.at” project to improve the Austrian public administration web portal for adolescent citizens. In both projects, the results indicate that web portals and eParticpation seems to suit the adolescents’ information and communication needs. Involving the users is central to the development of an eParticipation process or platform so that the users’ specific characteristics (age, skills), needs and interests are included appropriately. The target users’ characteristics are also important for developing a marketing strategy which is able to reach them. Other issues which must also be considered in eParticipation are accessibility, inclusion and possibly gender.
Die Aktivität von Galaxien ist eine relativ seltene und offenbar kurzlebige Erscheinung, die sich vor allem durch eine verstärkte Abstrahlung, oft über das ganze Spektrum hinweg, vom Röntgen- bis zum Radiobereich, bemerkbar macht. Dabei wird auf neue Befunde an Infrarotgalaxien eingegangen, die dafür sprechen, daß die gravitative Wechselwirkung zwischen Galaxien eine wesentliche Rolle spielt. Das Buch ist eine zusammenfassende Darstellung des heutigen Kenntnisstandes über "Aktive Galaxien", ein Thema, das gegenwärtig im Zentrum des astronomischen Interesses und der aktuellen Forschung steht. Nach einem Überblick über die seit längerem bekannten Phänomene und die Probleme ihrer Deutung wird auf neue, am Max-Planck-Institut für Astronomie mit den Teleskopen der Calar Alto Sternwarte (Südspanien) gewonnene, Ergebnisse eingegangen.
Die Aktivität von Galaxien ist eine relativ seltene und offenbar kurzlebige Erscheinung, die sich vor allem durch eine verstärkte Abstrahlung, oft über das ganze Spektrum hinweg, vom Röntgen- bis zum Radiobereich, bemerkbar macht. Dabei wird auf neue Befunde an Infrarotgalaxien eingegangen, die dafür sprechen, daß die gravitative Wechselwirkung zwischen Galaxien eine wesentliche Rolle spielt. Das Buch ist eine zusammenfassende Darstellung des heutigen Kenntnisstandes über "Aktive Galaxien", ein Thema, das gegenwärtig im Zentrum des astronomischen Interesses und der aktuellen Forschung steht. Nach einem Überblick über die seit längerem bekannten Phänomene und die Probleme ihrer Deutung wird auf neue, am Max-Planck-Institut für Astronomie mit den Teleskopen der Calar Alto Sternwarte (Südspanien) gewonnene, Ergebnisse eingegangen.
Hermann Abich was born in 1806 in Berlin and died in 1886 in Graz. He grew up in a wealthy family which had friendly relations with famous scientists like Alexander von Humboldt, Leopold von Buch or Carl Ritter. After his studies in Heidelberg and Berlin he turned to extended fieldwork at the volcanoes of Italy. In 1833 1834 he published excellent petrological/chemical results and got soon a good scientific reputation. Thus he was nominated as Professor for Geology and Mineralogy of the prestigious Russian University in Dorpat (now Tartu, Esthonia) in 1842. In 1844 he was sent to Armenia by the Russian authorities. For the next three decades his fieldwork with about 190 publications was concentrated on the Great and Lesser Caucasus. This was a period of Russian expansion to the South with long-lasting regional fights. But he enjoyed the support of powerful governors. He was an indefatigable and enthusiastic explorer and a precise observer and designer. His interests covered many fields: morphology, glaciology, structural geology, volcanology with Thermal Springs, mineral resources from hydrocarbons, coal, salt to ores, stratigraphy and paleontology as a base for geological maps. But he also gave advice for practical problems, and he was active in meteorology, botany and archaeology. Alltogether he became “the Father of Caucasus Geology”. The following sketch stresses only on three aspects of his activities. He was one of the first pioneers in hydrocarbon exploration, especially around the anticlines with the mud volcanoes near Baku. In many respects, however, his fundamental ideas were erronous. He explained the structure of the Great Caucasus by the traditional theories of Leopold von Buch and Elie de Beaumont. The Caucasus anticline “was elevated by forces acting from beneath”. Following them he tried to discover regularities in the strike of mountain chains. Similarily he treated volcanism like Alexander von Humboldt and Leopold von Buch with their two groups of phenomena: voluminous, mostly basaltic “elevation craters” versus isolated, mostly trachytic and relatively small cones of “true volcanoes”. In spite of the isolation of the Caucasus region he had cultivated continuously contacts with leading geologists in Europe and was honoured by many institutions. He left Russia in 1876 for Vienna planning to write there the final monograph volumes about his investigations but he died before he could complete them.
Schallreuter, Karin U.; Institute for Pigmentary Disorders in Association with EM Arndt University of Greifswald; University of Bradford
The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10{sup -3}M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. {sup 45}Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H{sub 2}O{sub 2}-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m{sup 2} surfacemore » area with its calcium gradient in the 10{sup -3}M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue.« less
Montenegro, M F; Moral-Naranjo, M T; Páez de la Cadena, M; Campoy, F J; Muñoz-Delgado, E; Vidal, C J
2008-09-25
Butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) display both esterase and aryl acylamidase (AAA) activities. Their AAA activity can be measured using o-nitroacetanilide (ONA). In human samples depleted of acetylcholinesterase, we noticed that the ratio of amidase to esterase activities varied depending on the source, despite both activities being due to BuChE. Searching for an explanation, we compared the activities of BuChE molecular forms in samples of human colon, kidney and serum, and observed that BuChE monomers (G(1)) hydrolyzed o-nitroacetanilide much faster than tetramers (G(4)). This fact suggested that association might cause differences in the AAA site between single and polymerized subunits. This and other post-translational modifications in BuChE subunits probably determine their level of AAA activity. The higher amidase activity of monomers could justify the presence of single BuChE subunits in cells as a way to preserve the AAA activity of BuChE, which could be lost by oligomerization.
Objective: To examine the role of butyrylcholinesterase (BuChE) in cholinergic signaling and neurologic conditions, such as Alzheimer’s disease (AD). The rationale for inhibiting cholinesterases in the management of AD, including clinical evidence supporting use of the dual acetylcholinesterase (AChE) and BuChE inhibitor rivastigmine, is discussed. Data Sources: PubMed searches were performed using butyrylcholinesterase as a keyword. English-language articles referenced in PubMed as of September 2011 were included. Study Selection and Data Synthesis: English-language articles related to BuChE considered to be of clinical relevance to physicians were included. English-language articles specifically related to AChE were not included, as the role of AChE in cholinergic signaling and the underlying pathology of AD is well documented. Reference lists of included publications were used to supplement the search. Results: AChE and BuChE play a role in cholinergic signaling; BuChE can hydrolyze acetylcholine and compensate for AChE when levels are depleted. In the AD brain, AChE levels decrease, while BuChE levels are reportedly increased or unchanged, with changes becoming more pronounced during the disease course. Furthermore, BuChE genotype may influence AD risk and rate of disease progression. Strategies that increase acetylcholine levels (eg, cholinesterase inhibitors) demonstrate symptomatic efficacy in AD. Rivastigmine has proven cognitive efficacy in clinical trials, and data suggest that its action is mediated, in part, by inhibition of BuChE. Retrospective analyses of clinical trials provide evidence that BuChE genotype may also influence treatment response. Conclusions: AChE-selective inhibitors and a dual AChE and BuChE inhibitor demonstrate symptomatic efficacy in AD. Mounting preclinical and clinical evidence for a role of BuChE in maintaining normal cholinergic function and the pathology of AD provides a rationale for further studies investigating use of rivastigmine in AD and the influence of BuChE genotype on observed efficacy. PMID:23930233
Background The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. Methods and Findings AD patients aged 50–85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman’s colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2%increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. Conclusion The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation. PMID:19199870
The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients. AD patients aged 50-85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman's colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by 10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2% increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively. The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation.
Montenegro, María F; María, T Moral-Naranjo; de la Cadena, María Páez; Campoy, Francisco J; Muñoz-Delgado, Encarnación; Vidal, Cecilio J
2008-04-01
Apart from its esterase activity, butyrylcholinesterase (BuChE) displays aryl acylamidase (AAA) activity able to hydrolyze o-nitroacetanilide (ONA) and its trifluoro-derivative (F-ONA). We report here that, despite amidase and esterase sites residing in the same protein, in human samples depleted of acetylcholinesterase the ratio of amidase to esterase activity varied depending on the source of BuChE. The much faster degradation of ONA and F-ONA by BuChE monomers (G1) of colon and kidney than by the tetramers (G4) suggests aggregation-driven differences in the AAA site between single and polymerized subunits. The similar ratio of F-ONAto butyrylthiocholine hydrolysis by serum G1 and G4 forms support structural differences in the amidase site according to the source of BuChE. The changing ratios of amidase to esterase activities in the human sources probably arise from post-translational modifications in BuChE subunits, the specific proportion of monomers and oligomers and the variable capacity of the tetramers for degrading ONA and F-ONA. The elevated amidase activity of BuChE monomers and the scant activity of the tetramers justify the occurrence of single BuChE subunits in cells as a means to sustain the AAA activity of BuChE which otherwise could be lost by tetramerization.
Some clinicians assess the efficacy of pralidoxime in organophosphorus (OP) poisoned patients by measuring reactivation of butyrylcholinesterase (BuChE). However, the degree of BuChE inhibition varies by OP insecticide, and it is unclear how well oximes reactivate BuChE in vivo. We aimed to assess the usefulness of BuChE activity to monitor pralidoxime treatment by studying its reactivation after pralidoxime administration to patients with laboratory-proven World Health Organization (WHO) class II OP insecticide poisoning. Patient data were derived from 2 studies, a cohort study (using a bolus treatment of 1g pralidoxime chloride) and a randomized controlled trial (RCT) (comparing 2g pralidoxime over 20min, followed by an infusion of 0.5g/h, with placebo). Two grams of pralidoxime variably reactivated BuChE in patients poisoned by 2 diethyl OP insecticides, chlorpyrifos and quinalphos; however, unlike acetylcholinesterase reactivation, this reactivation was not sustained. It did not reactivate BuChE inhibited by the dimethyl OPs dimethoate or fenthion. The 1-g dose produced no reactivation. Pralidoxime produced variable reactivation of BuChE in WHO class II OP-poisoned patients according to the pralidoxime dose administered, OP ingested, and individual patient. The use of BuChE assays for monitoring the effect of pralidoxime treatment is unlikely to be clinically useful. PMID:24052565
Nam, Dae Cheol; Ha, Yu Mi; Park, Min Kyu; Cho, Sung Kweon
2016-08-01
Organophosphorus pesticides (OPs) are a human health hazard. OPs inhibit acetylcholinesterase (AChE) at nerve endings and accumulate acetylcholine (ACh) at these sites. High levels of ACh and long exposure promote cholinergic crisis. The hydrolysis of OPs by serum paraoxonase 1 (PON1) plays a role in cholinergic crisis in humans. Human serum PON1 can break down organophosphate before binding to ChE. We investigated the effect of PON1 polymorphisms on AChE activity after OP treatment. 50 healthy volunteers were randomly recruited with informed consent. We investigated butyrylcholinesterase (BuChE) activity changes in plasma as a biomarker of AChE after OP treatment in human blood samples immediately following blood sampling. After the standardization of BuChE activity in human blood, we correlated changes in BuChE activity with changes in blood pH. We analyzed the PON1 polymorphisms (rs854560 and rs662) of 50 participants to retrospectively investigate the interindividual variability of changes in BuChE activity. Changes in BuChE activity are strongly correlated with pH changes after OP treatment (R2 = 0.913). We used changes in pH as a surrogate marker for BuChE inhibition after OP treatment. OP treatment significantly decreased BuChE activity by 56.4 ± 5.1% (p < 0.001). The degree of BuChE inhibition was significantly different in the PON1 rs662 genotype (56.10 ± 4.74% vs. 57.96 ± 5.67% vs. 52.34 ± 1.51%; GG vs. GA vs. AA, respectively). Changes in pH can be used as a surrogate marker for the detection of BuChE inhibition after OP exposure. The rs662 polymorphism of PON1 may explain the inter-individual variability in BuChE inhibition.
The role of acetylcholinesterase (AChE) in the termination of the cholinergic response through acetylcholine (ACh) hydrolysis and the involvement of plasma butyrylcholinesterase (BuChE), mainly of hepatic origin, in the metabolism of xenobiotics with ester bonds is well known. Besides, BuChE has a crucial role in ACh hydrolysis, especially when selective anticholinesterases inhibit AChE. Herein, we analyzed the gender-related differences and the circadian changes of rat plasma cholinesterases. Plasma and liver cholinesterase activities were evaluated in control or 2-30-day castrated adult male and female rats. Plasma and liver AChE activities did not differ between genders and were not influenced by sex hormone deprivation. BuChE plasma activity was 7 times greater in female, reflecting gender differences in liver enzyme expression. Castration increased liver and plasma BuChE activity in male, while reduced it in female, abolishing gender differences in enzyme activity. Interestingly, female AChE and BuChE plasma activities varied throughout the day, reaching values 27% and 42% lower, respectively, between 2 p.m. and 6 p.m. when compared to the morning peaks at 8 a.m. Castration attenuated daily female BuChE oscillation. On the other hand, male plasma enzymes remained constant throughout the day. In summary, our results show that liver and plasma BuChE, but not AChE, expression is influenced by sex hormones, leading to high levels of blood BuChE in females. The fluctuation of female plasma BuChE during the day should be taken into account to adjust the bioavailability and the therapeutic effects of cholinesterase inhibitors used in cholinergic-based conditions such Alzheimer's disease. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
Ferris, Steven; Nordberg, Agneta; Soininen, Hilkka; Darreh-Shori, Taher; Lane, Roger
2014-01-01
Objective Evaluate the influence of gender and butyrylcholinesterase (BuChE) genotype on incidence of progression to AD, rate of cognitive and functional decline, and response to rivastigmine treatment in mild cognitive impairment (MCI) subjects. Methods This retrospective exploratory analysis from a 3–4 year, randomized, placebo-controlled study of rivastigmine in MCI subjects included participants who consented to pharmacogenetic testing. Results Of 1018 total patients, 490 (253 [52%] female) were successfully genotyped for BuChE. In subjects receiving placebo, the BuChE wt/wt genotype was associated with a statistically significantly higher rate of progression to AD and functional decline in women, compared with men with the BuChE wt/wt genotype. In subjects with a BuChE-K allele receiving placebo, incidence of progression to AD and rate of functional decline were not significantly different by gender, however cognitive decline was significantly faster in men. Statistically significant benefits of rivastigmine treatment on progression to AD, functional decline, ventricular volume expansion, whole brain atrophy and white matter loss were evident in female BuChE wt/wt. Conclusion Gender appears to differentially influence the type of decline in MCI subjects according to BuChE genotype, with more rapid progression of cognitive decline in male BuChE-K, and more rapid progression to AD and functional decline in female BuChE wt/wt. Cognitive decline in male BuChE-K and functional decline and progression to AD in female BuChE wt/wt were significantly attenuated by rivastigmine. Rivastigmine treatment also significantly reduced ventricular expansion, whole brain atrophy rate and white matter loss in female BuChE wt/wt, suggesting a possible disease-modifying effect. PMID:19617863
Astronaut James F. Buchli, wearing an extravehicular mobility unit (EMU), is about to be submerged in the weightless environment training facility (WETF) to simulate a contingency extravehicular activity (EVA) for STS 61-A. In this portrait view, Buchli is wearing a communications carrier assembly (CCA).
Darvesh, Sultan; Arora, Rakesh C; Martin, Earl; Magee, David; Hopkins, David A; Armour, J Andrew
2004-08-01
Cholinesterase inhibitors used to treat the symptoms of Alzheimer's disease (AD) inhibit both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), albeit to different degrees. Because central and peripheral neurons, including intrinsic cardiac neurons located on the surface of the mammalian heart, express both BuChE and AChE, we studied spontaneously active intrinsic cardiac neurons in the pig as a model to assess the effects of inhibition of AChE compared to BuChE. Neuroanatomical experiments showed that some porcine intrinsic cardiac neurons expressed AChE and/or BuChE. Enzyme kinetic experiments with cholinesterase inhibitors, namely, donepezil, galantamine, (+/-) huperzine A, metrifonate, rivastigmine, and tetrahydroaminoacridine, demonstrated that these compounds differentially inhibited porcine AChE and BuChE. Donepezil and (+/-) huperzine A were better reversible inhibitors of AChE, and galantamine equally inhibited both the enzymes. Tetrahydroaminoacridine was a better reversible inhibitor of BuChE. Rivastigmine caused more rapid inactivation of BuChE as compared to AChE. Neurophysiological studies showed that acetylcholine and butyrylcholine increase or decrease the spontaneous activity of the intrinsic cardiac neurons. Donepezil, galantamine, (+/-) huperzine A, and tetrahydroaminoacridine changed spontaneous neuronal activity by about 30-35 impulses per minute, while rivastigmine changed it by approximately 100 impulses per minute. It is concluded that (i) inhibition of AChE and BuChE directly affects the porcine intrinsic cardiac nervous system, (ii) the intrinsic cardiac nervous system represents a suitable model for examining the effects of cholinesterase inhibitors on mammalian neurons in vivo, and (iii) the activity of intrinsic cardiac neurons may be affected by pharmacological agents that inhibit cholinesterases.
Butyrylcholinesterase (BuChE, EC 3.1.1.8) is an important pharmacological target for Alzheimer's disease (AD) treatment. However, the currently available BuChE inhibitor screening assays are expensive, labor-intensive, and compound-dependent. It is necessary to develop robust in silico methods to predict the activities of BuChE inhibitors for the lead identification. In this investigation, support vector machine (SVM) models and naive Bayesian models were built to discriminate BuChE inhibitors (BuChEIs) from the noninhibitors. Each molecule was initially represented in 1870 structural descriptors (1235 from ADRIANA.Code, 334 from MOE, and 301 from Discovery studio). Correlation analysis and stepwise variable selection method were applied to figure out activity-related descriptors for prediction models. Additionally, structural fingerprint descriptors were added to improve the predictive ability of models, which were measured by cross-validation, a test set validation with 1001 compounds and an external test set validation with 317 diverse chemicals. The best two models gave Matthews correlation coefficient of 0.9551 and 0.9550 for the test set and 0.9132 and 0.9221 for the external test set. To demonstrate the practical applicability of the models in virtual screening, we screened an in-house data set with 3601 compounds, and 30 compounds were selected for further bioactivity assay. The assay results showed that 10 out of 30 compounds exerted significant BuChE inhibitory activities with IC50 values ranging from 0.32 to 22.22 μM, at which three new scaffolds as BuChE inhibitors were identified for the first time. To our best knowledge, this is the first report on BuChE inhibitors using machine learning approaches. The models generated from SVM and naive Bayesian approaches successfully predicted BuChE inhibitors. The study proved the feasibility of a new method for predicting bioactivities of ligands and discovering novel lead compounds.
Hofmann, Jonathan N; Keifer, Matthew C; De Roos, Anneclaire J; Fenske, Richard A; Furlong, Clement E; van Belle, Gerald; Checkoway, Harvey
2010-01-01
Objective To identify potential risk factors for serum cholinesterase (BuChE) inhibition among agricultural pesticide handlers exposed to organophosphate (OP) and N-methyl-carbamate (CB) insecticides. Methods We conducted a longitudinal study among 154 agricultural pesticide handlers who participated in the Washington State cholinesterase monitoring program in 2006 and 2007. BuChE inhibition was analyzed in relation to reported exposures before and after adjustment for potential confounders using linear regression. Odds ratios estimating the risk of ‘BuChE depression’ (>20% from baseline) were also calculated for selected exposures based on unconditional logistic regression analyses. Results An overall decrease in mean BuChE activity was observed among study participants at the time of follow-up testing during the OP/CB spray season relative to pre-season baseline levels (mean decrease of 5.6%, P < 0.001). Score for estimated cumulative exposure to OP/CB insecticides in the past 30 days was a significant predictor of BuChE inhibition (β = −1.74, P < 0.001). Several specific work practices and workplace conditions were associated with greater BuChE inhibition, including mixing/loading pesticides and cleaning spray equipment. Factors that were protective against BuChE inhibition included full-face respirator use, wearing chemical-resistant boots, and storing personal protective equipment in a locker at work. Conclusions Despite existing regulations, agricultural pesticide handlers continue to be exposed to OP/CB insecticides at levels resulting in BuChE inhibition. These findings suggest that modifying certain work practices could potentially reduce BuChE inhibition. Replication from other studies will be valuable. PMID:19819864
Butyrylcholinesterase (BuChE) was examined as an in vivo exogenous scavenger for highly toxic organophosphorus (OP) poisons. Protection studies with equine BuChE were carried out in rhesus monkeys trained to perform a Serial Probe Recognition task. The pharmacokinetics of equine BuChE administered i.v. in rhesus monkeys revealed an elimination T1/2 of -620 hr. Animals given 503 nmol of BuChE i.v. and then challenged with 220 to 260 nmol of soman (two LD50; a lethal dose in untreated animals) all survived with no clinical signs of OP poisoning. Serial Probe Recognition performance was depressed after enzyme administration and at 1 hr postsoman.more » However, all monkeys performed the task at base-line levels at 8 hr after soman and throughout the remainder of the experimental period. Two different monkeys each were given two doses of sarin, 183 nmol/ dose (one LD50) after 460 nmol of BuChE. No signs were observed. A third group of monkeys given 253 or 340 nmol (three and four LD50, respectively) of soman after 460 nmol of BuChE required 1 mg/kg of atropine i.v. 1 0 min postsoman, but recovered completely within 24 hr. Our results indicate that BuChE has the required properties to function as a biological scavenger to protect against the pharmacological and behavioral toxicity of OP poisons. Exogenous scavenger, butyrylcholinesterase, nerve agent.« less
STS-48 Discovery, Orbiter Vehicle (OV) 103, Mission Specialist (MS) James F. Buchli (left) and MS Charles D. Gemar listen to instructions while on the middeck of JSC's Motion Based (MB) Shuttle Mission Simulator (SMS). Buchli and Gemar are reviewing inflight procedures during this preflight familiarization session held in the Mission Simulation and Training Facility Bldg 5.
Petzer, Anél, E-mail: 12264954@nwu.ac.za; Harvey, Brian H.; Petzer, Jacobus P.
Methylene blue (MB) is reported to possess diverse pharmacological actions and is attracting increasing attention for the treatment of neurodegenerative disorders such as Alzheimer's disease. Among the pharmacological actions of MB, is the significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These activities may, at least in part, underlie MB's beneficial effects in Alzheimer's disease. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl metabolite, is the predominant species. Azure B has been shown to be pharmacologically active and also possesses a variety of biological actions. Azure B therefore may contribute to the pharmacological profile ofmore » MB. Based on these considerations, the present study investigates the possibility that azure B may, similar to MB, act as an inhibitor of human AChE and BuChE. The results document that azure B inhibits AChE and BuChE with IC{sub 50} values of 0.486 μM and 1.99 μM, respectively. The results further show that azure B inhibits AChE and BuChE reversibly, and that the modes of inhibition are most likely competitive. Although the AChE and BuChE inhibitory activities of azure B are twofold and fivefold, respectively, less potent than those recorded for MB [IC{sub 50}(AChE) = 0.214 μM; IC{sub 50}(BuChE) = 0.389 μM] under identical conditions, azure B may be a contributor to MB's in vivo activation of the cholinergic system and beneficial effects in Alzheimer's disease. - Highlights: • Methylene blue (MB) is a known inhibitor of AChE and BuChE. • Azure B, the major metabolite of MB, also is an inhibitor of AChE and BuChE. • Azure B may be a contributor to MB's in vivo activation of the cholinergic system. • Azure B may contribute to MB's potential in Alzheimer's disease therapy.« less
Masson, Patrick; Froment, Marie-Thérèse; Gillon, Emilie; Nachon, Florian; Darvesh, Sultan; Schopfer, Lawrence M
2007-09-01
The aryl-acylamidase (AAA) activity of butyrylcholinesterase (BuChE) has been known for a long time. However, the kinetic mechanism of aryl-acylamide hydrolysis by BuChE has not been investigated. Therefore, the catalytic properties of human BuChE and its peripheral site mutant (D70G) toward neutral and charged aryl-acylamides were determined. Three neutral (o-nitroacetanilide, m-nitroacetanilide, o-nitrophenyltrifluoroacetamide) and one positively charged (3-(acetamido) N,N,N-trimethylanilinium, ATMA) acetanilides were studied. Hydrolysis of ATMA by wild-type and D70G enzymes showed a long transient phase preceding the steady state. The induction phase was characterized by a hysteretic "burst". This reflects the existence of two enzyme states in slow equilibrium with different catalytic properties. Steady-state parameters for hydrolysis of the three acetanilides were compared to catalytic parameters for hydrolysis of esters giving the same acetyl intermediate. Wild-type BuChE showed substrate activation while D70G displayed a Michaelian behavior with ATMA as with positively charged esters. Owing to the low affinity of BuChE for amide substrates, the hydrolysis kinetics of neutral amides was first order. Acylation was the rate-determining step for hydrolysis of aryl-acetylamide substrates. Slow acylation of the enzyme, relative to that by esters may, in part, be due suboptimal fit of the aryl-acylamides in the active center of BuChE. The hypothesis that AAA and esterase active sites of BuChE are non-identical was tested with mutant BuChE. It was found that mutations on the catalytic serine, S198C and S198D, led to complete loss of both activities. The silent variant (FS117) had neither esterase nor AAA activity. Mutation in the peripheral site (D70G) had the same effect on esterase and AAA activities. Echothiophate inhibited both activities identically. It was concluded that the active sites for esterase and AAA activities are identical, i.e. S198. This excludes any other residue present in the gorge for being the catalytic nucleophile pole.
STS-48 Mission Specialist (MS) James F. Buchli, wearing an extravehicular mobility unit (EMU) and communications carrier assembly (CCA), smiles as he listens to a technician's instructions prior to an underwater extravehicular activity (EMU) session in JSC's Weightless Environment Training Facility (WETF) Bldg 29. Buchli is fully suited with the exception of his helmet as he stands on the WETF platform. He will be lowered into the WETF's 25-foot deep pool and once underwater he will practice contingency EVA operations for his upcoming mission aboard Discovery, Orbiter Vehicle (OV) 103.
STS-48 Mission Specialist (MS) James F. Buchli 'catches' goldfish snack crackers as they float in the weightless environment of the earth-orbiting Discovery, Orbiter Vehicle (OV) 103. Buchli's eating activity on the middeck was documented using the Electronic Still Camera (ESC). Crewmembers were testing the ESC as part of Development Test Objective (DTO) 648, Electronic Still Photography. The digital image was stored on a removable hard disk or small optical disk, and could be converted to a format suitable for downlink transmission. The ESC is making its initial appearance on this Space Shuttle mission.
Discussion of teaching methods used with the text, "Deutsch, Erstes Buch" by Hugo Mueller, focuses on practical approaches to the problem of teaching culture through the spoken language and the use of pattern practice. While concentrating on Chapter Eight, "In der Sommerfrische," discussion is presented in subdivisions characteristic of every…
The effect of non-ionic detergents like Triton X-100, Lubrol PX, Brij 35 and Tween 80 on the esterase activity and inhibitor sensitivity of human serum butyrylcholinesterase (BuChE) were studied. The results showed that though BuChE is not a detergent dependent enzyme, the esterase activity and inhibitor sensitivity of it can be modulated by the presence of detergents. All the detergents caused a marginal activation of the esterase activity. The presence of Lubrol PX, Brij 35 or Tween 80 did not affect the 50% molar inhibition concentration (IC50) of the inhibitors tested. But in the presence of Triton X-100 the IC50 values were increased for neostigmine, eserine and tetraisopropylpyrophosphoramide (acylation site interacting inhibitors), whereas for inhibitors like ethopropazine, imipramine and procainamide (choline binding pocket specific inhibitors) the IC50 values were unaltered. In addition, in the presence of Triton X-100 the bimolecular reaction constant for phosphorylation reaction (ki) of BuChE for the acyl pocket specific tetraisopropylpyrophosphoramide was reduced. Triton X-100 partially protected BuChE against this tetraisopropylpyrophosphoramide inactivation. These results indicate that Triton X-100 by interacting with the acyl pocket hydrophobic region is able to activate the esterase activity of BuChE. Further it reduces the capacity of the enzyme to react with inhibitors that inactivate it by interacting with the serine residue of the acylation site.
A series of pyridinium salts bearing alkylphenyl groups at 1 position and hydrazone structure at 4 position of the pyridinium ring were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The cholinesterase (ChE) inhibitory activity studies were carried out by using the Ellman's colorimetric method. All compounds displayed considerable AChE and BuChE inhibitory activity and some of the compounds manifested remarkable anti-AChE activity compared to the reference compound, galantamine. Among the title compounds, the series including benzofuran aromatic ring exhibited the best inhibitory activity both on AChE and BuChE enzymes. Compound 3b, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-(3-phenylpropyl)pyridinium bromide, was the most active compound with IC50 value of 0.23 (0.24) µM against enantiomeric excess (ee)AChE (human (h)AChE) while compound 3a, 4-[2-(1-(benzofuran-2-yl)ethylidene)hydrazinyl]-1-phenethylpyridinium bromide, was the most active compound with IC50 value of 0.95 µM against BuChE. Moreover, 3a and b exhibited higher activity than the reference compound galantamine (eeAChE (hAChE) IC50 0.43 (0.52) µM; BuChE IC50 14.92 µM). Molecular docking studies were carried out on 3b having highest inhibitory activity against AChE.
recombinant human BUChE; Sf, Spodoptera frugiperda ; VX, 0-ethyl S-[2-[bis(I -methylethyl)amino]ethyl]methyl phosphonothiolate; wt, wild-type. 1 To whom...ATCC (Rockville, MD, U.S.A.). Insect cells ( Spodoptera frugiperda Sf9 cells and T. ni High 5 cells) and wild-type (wt)-AcNPV were purchased from
A new series of tertiary amine derivatives of chlorochalcone (4a∼4l) were designed, synthesized and evaluated for the effect on acetylcholinesterase (AChE) and buthylcholinesterase (BuChE). The results indicated that all compounds revealed moderate or potent inhibitory activity against AChE, and some possessed high selectivity for AChE over BuChE. The structure-activity investigation showed that the substituted position of chlorine significantly influenced the activity and selectivity. The alteration of tertiary amine group also leads to obvious change in bioactivity. Among them, IC 50 of compound 4l against AChE was 0.17 ± 0.06 µmol/L, and the selectivity was 667.2 fold for AChE over BuChE. Molecular docking and enzyme kinetic study on compound 4l suggested that it simultaneously binds to the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Further study showed that the pyrazoline derivatives synthesized from chlorochalcones had weaker activity and lower selectivity in inhibiting AChE compared to that of chlorochalcone derivatives.
optimization has received considerable attention in robotics [15], [16], [17]. However, solving a nonlinear optimization problem requires a significant...Professorship award to Jonas Buchli and by the Swiss National Centre of Competence in Research Robotics (NCCR Robotics ). Carmelo Sferrazza carmelos...student.ethz.ch, Diego Pardo depardo@ethz.ch and Jonas Buchli buchlij@ethz.ch are with the Agile Dexterous Robotics Lab at the Institute of Robotics and
The phenomenon of the rise of the Scandinavian shield during the Holocene and the concomitant fall in level of the Baltic Sea has been investigated for centuries. Already in medieval times, there were reports about the coastlines of the Gulf of Bothnia that are full of relevant observations. During the eighteenth century, scientists such as Celsius and Linnaeus collected observations such as these. The result was that the search for the possible explanations of this rise-and-fall phenomenon intensified. The generally favoured explanation was that there was an active sinking of sea level in the Baltic rather than an active rising of the land surface in Fennoscandia. This was because water was seen as mobile, in contrast to a "terra firma". The relevant discussion was often emotional, and here, we try to illustrate it using material from the Geologenarchiv Freiburg (von Hoff, von Buch and Goethe). No more than a few decades later, it became obvious by the theory of Ice Age that both the sea level and the land could be mobile (eustatic sea level changes—glacial isostasy). Additionally, of course, plate tectonics had some influence: Norway is situated at the western end of the Eurasian plate and is part of a passive continental margin. There are still open research problems, many of which can be addressed using modern methods of satellite-based geophysics and geodesy. Some other aspects as the permanent uplift trend of Scandinavia since the Cambrium or the rhythmic to and fro of magma in the upper mantle during the Pleistocene are mentioned.
Markowicz-Piasecka, Magdalena; Sikora, Joanna; Mateusiak, Łukasz; Mikiciuk-Olasik, Elżbieta; Huttunen, Kristiina M
2017-01-01
The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer's disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μ mol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC 50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC 50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC 50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.
Objectives: The brain of mammals contains two major form of cholinesterase enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The dual inhibition of these enzymes is considered as a promising strategy for the treatment of neurological disorder such as Alzheimer's disease (AD), senile dementia, ataxia, and myasthenia gravis. The present study was undertaken to explore the anticholinesterase inhibition property of allicin. Materials and Methods: An assessment of cholinesterase inhibition was carried out by Ellman's assay. Results: The present study demonstrates allicin, a major ingredient of crushed garlic (Allium sativum L.) inhibited both AChE and BuChE enzymes in a concentration-dependent manner. For allicin, the IC50 concentration was 0.01 mg/mL (61.62 μM) for AChE and 0.05 ± 0.018 mg/mL (308.12 μM) for BuChE enzymes. Conclusions: Allicin shows a potential to ameliorate the decline of cognitive function and memory loss associated with AD by inhibiting cholinesterase enzymes and upregulate the levels of acetylcholine (ACh) in the brain. It can be used as a new lead to target AChE and BuChE to upregulate the level of ACh which will be useful in alleviating the symptoms associated with AD. PMID:26288480
Ramírez-Jiménez, Rocío; Martínez-Salazar, María Fernanda; Almenares-López, Damianys; Yáñez-Estrada, Leticia; Monroy-Noyola, Antonio
2018-03-01
The enzymes butyrylcholinesterase (BuChE) and paraoxonase-1 (PON1) are the primary bioscavenging enzymes in serum and exhibit antioxidant and anti-inflammatory activities. PON1 has been associated with diseases caused by high oxidative stress, whereas BuChE appears to be involved in the pathophysiology of the metabolic syndrome and related disorders. It has been suggested that children from rural communities in Mexico may have a predisposition to develop obesity or type 2 diabetes during adolescence or adulthood. The objective of this study was to determine whether associations exist between the paraoxonase (PONase)/arylesterase (AREase) activity of PON1, its PON1-Q192R and PON1-L55M polymorphisms, and BuChE activity with the nutritional status and lipid profiles in a group of children from rural communities in Mexico. A group of 97 boys and girls from a rural community in Mexico were assessed for body mass index, the enzymatic activities of BuChE, PONase, and AREase were measured in serum, and their lipid profiles were determined. Genetic polymorphisms of PON1-L55M and PON1-Q192R were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The children were classified into four groups: thinness, normal weight, overweight, and obese. Of the children studied, 34.4% were overweight and obese. The mean age of the participants was 9.5 years (standard deviation = 1.8). The L allele of the PON1-L55M genotype was the most frequent (83.3%), and the R allele of the PON1-Q192R genotype was the most frequent (61.8%). Overweight and obese children had higher values of BuChE, total cholesterol, triglycerides (TG), and lower high-density lipoprotein (HDL-C) values than children with thinness or normal weight (P = 0.028, P = 0.019, P = 0.004, P = 0.069 and P = 0.021, respectively). The levels of AREase and PONase and the prevalence of PON1-L55M and PON1-Q192R genotypes were similar between groups (P = 0.484 and P = 0.380, respectively). This study establishes a positive association of BuChE activity with nutritional status and serum TG.
Santos, Wanderson Praxedes; da Silva Carvalho, Ana Carla; dos Santos Estevam, Charles; Santana, Antônio Euzébio Goulart; Marçal, Rosilene Moretti
2012-07-01
Erythrina velutina (EV) Willd (Fabaceae-Faboideae) is a medicinal tree that is commonly used in Brazil for the treatment of several central nervous system disorders. The anticholinesterase activity of EV is described in this work. Concentration-response curves (0-1.6 mg/mL) for EV leaf aqueous extract (AE) and alkaloid-rich extracts (AKEs) were performed in vitro. Cholinesterase inhibition was examined in mouse brains, as the cholinesterase source, and in pure acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE). Mice were treated with AE or AKE (100, 200, and 400 mg/kg, p.o.) and their brains were used for the measurement of cholinesterase activity (CA) ex vivo. CA was inhibited by AE (IC(50) = 0.57 [0.43-0.75] mg/mL) and AKE (IC(50) = 0.52 [0.39-0.70] mg/mL) in brain homogenates in a concentration-dependent manner. The ex vivo experiments indicated that AE (400 mg/kg, p < 0.05, 32.2 ± 3.9% of inhibition) and AKE (all doses: p < 0.05-p < 0.001, 29.6 ± 3.2% as the maximum inhibition) significantly inhibited CA in the central nervous system after oral administration. AE and AKE inhibited AChE and BuChE activities in a concentration-dependent manner (AE: IC(50AChE) = 0.56 [0.38-0.81] mg/mL, IC(50BuChE) = 2.95 [1.51-5.76] mg/mL, AKE: IC(50AChE) = 0.87 [0.60-12.5] mg/mL, IC(50BuChE) = 2.67 [0.87-8.11] mg/mL). These data indicated that AE and AKE crossed the blood-brain barrier to inhibit CA in the brain. AE and AKE also exhibited a dual inhibitory action on acetyl- and BuChE.
Kousba, Ahmed A.; Poet, Torka S.; Timchalk, Charles
2003-02-12
Chlorpyrifos (CPF) is a commonly used organophosphate insecticide (OP). The primary mechanism of action for CPF involves the inhibition of acetylcholinesterase (AChE) by the active metabolite, CPF-oxon, with subsequent accumulation of acetylcholine (ACh) resulting in a wide range of neutotoxicity. CPF-oxon, can likewise inhibit other non-target cholinesterases (ChE) such as butyrylcholinesterase (BuChE), which represents a detoxification mechanism and a potential biomarker of exposure/response. Biological monitoring for OPs has focused on measuring parent chemical or metabolite in blood and urine or blood ChE inhibition. Salivary biomonitoring has recently been explored as a practical method for examination of chemical exposure; however, theremore » are a limited number of studies exploring its use for OPs. To evaluate the use of salivary ChE as a biological monitor for OP exposure, the current study characterized salivary ChE activity in Sprague-Dawley rats through its comparison with brain and plasma ChE using BW284C51 and iso-OMPA as selective inhibitors of AChE and BuChE, respectively. The study also estimated the kinetic constants describing BuChE interaction with CPF-oxon. A modified Ellman assay in conjunction with pharmacodynamic (PD) modeling was used to characterize the in vitro titration of diluted rat salivary ChE enzyme with CPF-oxon. The results indicated that, more than 95% of rat salivary ChE activity was associated with BuChE activity, total BuChE active site concentration was 0.0012 0.00013 nmol/ml saliva, reactivation rate constant (Kr) was 0.068 0.008 h-1 and inhibitory (Ki) rate constant of 8.825 and 9.80 nM-1h-1 determined experimentally and using model optimization respectively. These study results would be helpful for further evaluating the potential utility of salivary ChE as a practical tool for biological monitor of OP exposures.« less
Nguyen, Tan Phat; Minh, Nhat Phan; Dat, Trong Bui; Le, Tien Dung; Tran Nguyen, Minh An; Pham, Thi Nhat Trinh; Tri, Dinh Mai
2017-10-01
For first time, the chemical constituents of the rhizomes of Luvunga scandens (Roxb.) Buch. Ham. were investigated and led to the isolation of one new limonoid named Luvunga A (1), together with seven known compounds, including one limonoid (2) and six coumarins (3-8) were isolated for the first time from the species L. scandens by various chromatography methods. Their chemical structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments and compared with literatures.
Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots. PMID:26483842
Ibrar, Aliya; Khan, Ajmal; Ali, Majid; Sarwar, Rizwana; Mehsud, Saifullah; Farooq, Umar; Halimi, Syed M. A.; Khan, Imtiaz; Al-Harrasi, Ahmed
2018-01-01
In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a–o) and coumarin-oxadiazole 11(a–h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogs were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer's disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 ± 0.09 μM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 ± 3.37 μM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 ± 0.23 μM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 ± 0.09 μM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i, and 6k) were found to interact with AChE in the active site with MOE score of −10.19, −9.97, −9.68, and −11.03 Kcal.mol−1, respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a–h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a, and 11b) provided MOE score of −9.9, −7.4, and −8.2 Kcal.mol−1, respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction. PMID:29632858
Ibrar, Aliya; Khan, Ajmal; Ali, Majid; Sarwar, Rizwana; Mehsud, Saifullah; Farooq, Umar; Halimi, Syed M. A.; Khan, Imtiaz; Al-Harrasi, Ahmed
2018-03-01
In a continuation of our previous work for the exploration of novel enzyme inhibitors, two new coumarin-thiazole 6(a–o) and coumarin-oxadiazole 11(a–h) hybrids have been designed and synthesized. All the compounds were characterized by 1H- and 13C-NMR spectroscopy and elemental analysis. New hybrid analogues were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in order to know their potential for the prevention of Alzheimer’s disease (AD). In coumarinyl thiazole series, compound 6b was found as the most active member against AChE having IC50 value of 0.87 ± 0.09 µM, while the compound 6j revealed the same efficacy against BuChE with an IC50 value of 11.01 ± 3.37 µM. In case of coumarinyl oxadiazole series, 11a was turned out to be the lead candidate against AChE with an IC50 value of 6.07 ± 0.23 µM, whereas compound 11e was found significantly active against BuChE with an IC50 value of 0.15 ± 0.09 µM. To realize the binding interaction of these compounds with AChE and BuChE, the molecular docking studies were performed. Compounds from coumarinyl thiazole series with potent AChE activity (6b, 6h, 6i and 6k) were found to interact with AChE in the active site with MOE score of ‒10.19, ‒9.97, ‒9.68, and ‒11.03 Kcal.mol‒1, respectively. The major interactions include hydrogen bonding, π-π stacking with aromatic residues, and interaction through water bridging. The docking studies of coumarinyl oxadiazole derivatives 11(a-h) suggested that the compounds with high anti-butyrylcholinesterase activity (11e, 11a and 11b) provided MOE score of ‒9.9, ‒7.4 and ‒8.2 Kcal.mol‒1 respectively, with the active site of BuChE building π-π stacking with Trp82 and water bridged interaction.
A rapid, high-sensitivity, chemiluminescence (CL) enzyme assay for the determination of organophosphate (OP) residues in milk is presented. The assay for quantification of OP residues in milk is based on the inhibition of enzyme butyrylcholinesterase (BuChE). BuChE was stabilized and preloaded in 384 well plates at 30 °C. The assay permits rapid determination of OPs in milk within 12 min including an incubation step. The enzyme assay was tested for individual and mixtures of OPs such as methyl paraoxon (MPOx), methyl parathion (MP) and malathion (MT) in milk to evaluate their synergistic effect on BuChE inhibition. Good linearity was obtained in the range 0.005–50 μg·L−1 for MPOx and 0.5–1,000 μg·L−1 for MP as well as MT in milk. Mean recovery of 93.2%–98.6% was obtained for MPOx spiked milk samples with 0.99%–1.67% reproducibility (RSD). The proposed method facilitated rapid screening of milk samples in 384 well plate formats with further miniaturization presented in 1,536 well plates. PMID:22163525
Chu, Si-Juan; Zhang, Lan; Liu, Gang; Zhou, Wen-Xia; Li, Lin
2013-05-01
The purpose of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on the activity of cholinesterases in vitro, and to investigate the mechanism of CIG's treating Alzheimer's disease (AD). The sources of cholinesterases were prepared from human blood cells, rat brain homogenate and human blood plasma, respectively. The biochemical methods were used to detect the activity of acetylcholine esterase (AChE) and butyryl cholinesterase (BuChE) to investigate the influence of CIG on cholinesterases. The results showed that CIG inhibited the activity of AChE of human blood cells and rat brain homogenate, with the 50% inhibition rate (IC50) of 1.6 g . L-1 and 3.3 g . L-1, respectively; and the inhibition of AChE of CIG is reversible. CIG also inhibited the activity of BuChE of human blood plasma, with the IC50 of 2.9 g . L-1. In conclusion, CIG can inhibit the activity of AChE and BuChE in vitro, which may be one of the mechanisms of CIG to treat AD.
The cholinesterase inhibitor, rivastigmine, ameliorates cognitive dysfunction and is approved for the treatment of Alzheimer's disease (AD). Rivastigmine is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); however, the impact of BuChE inhibition on cognitive dysfunction remains to be determined. We compared the effects of a selective BuChE inhibitor, N1-phenethylnorcymserine (PEC), rivastigmine and donepezil (an AChE-selective inhibitor) on cognitive dysfunction induced by amyloid-β peptide (Aβ1–40) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly (i.c.v.) with either Aβ1–40 or the control peptide Aβ40–1 on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0 mg/kg), rivastigmine (0.03, 0.1, 0.3 mg/kg) or PEC (1.0, 3.0 mg/kg) 20 min prior to, or immediately after the acquisition session (Day 4) ameliorated the Aβ1–40 induced memory impairment, indicating a beneficial effect on memory acquisition and consolidation. In contrast, none of the investigated drugs proved effective when administrated before the retention session (Day 5). Repeated daily administration of donepezil, rivastigmine or PEC, on Days 0–3 inclusively, ameliorated the cognitive dysfunction in Aβ1–40 challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Aβ1–40 induced tyrosine nitration of hippocampal proteins, a marker of oxidative damage. These results indicate that BuChE inhibition, as well as AChE inhibition, is a viable therapeutic strategy for cognitive dysfunction in AD. PMID:21820013
Weingand-Ziade, A; Ribes, F; Renault, F; Masson, P
2001-01-01
The inactivation process of native (N) human butyrylcholinesterase (BuChE) by pressure and/or heat was found to be multi-step. It led to irreversible formation of an active intermediate (I) state and a denatured state. This series-inactivation process was described by expanding the Lumry-Eyring [Lumry, R. and Eyring, H. (1954) J. Phys. Chem. 58, 110-120] model. The intermediate state (I) was found to have a K(m) identical with that of the native state and a turnover rate (k(cat)) twofold higher than that of the native state with butyrylthiocholine as the substrate. The increased catalytic efficiency (k(cat)/K(m)) of I can be explained by a conformational change in the active-site gorge and/or restructuring of the water-molecule network in the active-site pocket, making the catalytic steps faster. However, a pressure/heat-induced covalent modification of native BuChE, affecting the catalytic machinery, cannot be ruled out. The inactivation process of BuChE induced by the combined action of pressure and heat was found to continue after interruption of pressure/temperature treatment. This secondary inactivation process was termed 'remnant inactivation'. We hypothesized that N and I were in equilibrium with populated metastable N' and I' states. The N' and I' states can either return to the active forms, N and I, or develop into inactive forms, N(')(in) and I(')(in). Both active N' and I' intermediate states displayed different rates of remnant inactivation depending on the pressure and temperature pretreatments and on the storage temperature. A first-order deactivation model describing the kinetics of the remnant inactivation of BuChE is proposed. PMID:11368776
This study aims at evaluating perceived service quality in Zanjan University of Medical Sciences (ZUMS). This study was cross-sectional and authors surveyed educational services at ZUMS. Through stratified random sampling, 384 students were selected and an adapted SERVQUAL instrument was used for data collection. Data analysis was performed by…
Acetylcholinesterase and butyrylcholoinesterase inhibitors are well-known drugs commonly used in the treatment ofAlzheimer's disease (AD) to improve cognitive function. These enzyme inhibitors were reported to be found in manyplants. Apai-sa-le recipe was a Thai tradition used as nootropic recipe and formerly claimed to improve memory. Therefore, it is interesting to investigate cholinesterase inhibitory activity ofthe recipe and its ingredients. To determine the whole recipe ofApai-sa-le and its ingredients for inhibitory effect on acetylcholinesterase (AChE) and human butyrylcholinesterase (BuChE) activities. Thirty grams of each plant and 181 grams of the whole recipe were separately extracted by 95% ethanol, after filtered the filtrate were evaporated and vacuum-dried at 45°C. By Elman method, the inhibitory activities of both enzymes were assessed. The volatile constituents ofeach extract were determined by GCMS. The constituents in the non- volatile extract were examined by TLC and the antioxidant activity was determined. Four plants exhibited specific BuChE inhibitor were Lepidium sativum Linn. (Ls), Piper nigrum L. (Pn), Angelica dahurica Benth (Ad) andAtractylodes lancea DC. (Al), which shown the lC50 of 5.59, 24.52, 73.23, 96.25 μg/ml, respectively whereas galantamine and the whole recipe showed IC50 of 0.59 and 236 μg/ml. Only Pn extract inhibited AChE at lCso of 25.46 μg/ml. By GCMS and TLC fingerprints revealed the main constituents in LS, Ad, Al andPn as apiol, cumialdehyde, furanodiene and piperine. Moreover nine plant extracts and the whole recipe showed antioxidant activity. Lepidium sativum Linn. (Ls) extract showed the most potency on BuChE inhibitory effect. Three ingredients and the whole recipe exhibited mild activity. Only Piper nigrum L demonstrated inhibition effect on both AChE and BuChE.
De Jaco, Antonella; Kovarik, Zrinka; Comoletti, Davide; Jennings, Lori L; Gaietta, Guido; Ellisman, Mark H; Taylor, Palmer
2005-12-15
An Arg to Cys mutation in the extracellular domain of neuroligin-3 (NL3) was recently found in a twin set with autism [S. Jamain, H. Quach, C. Betancur, M. Rastam, C. Colineaux, I.C. Gillberg, H. Soderstrom, B. Giros, M. Leboyer, C. Gillberg, T. Bourgeron, Paris Autism Research International Sibpair Study, mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism, Nat. Genet. 34 (2003) 27-29]. The Cys substitution in NL3 causes altered intracellular protein trafficking, intracellular retention and diminished association with its cognate partner, beta-neurexin [D. Comoletti, A. De Jaco, L.L. Jennings, R.E. Flynn, G. Gaietta, I. Tsigelny, M.H. Ellisman, P. Taylor, The R451C-neuroligin-3 mutation associated with autism reveals a defect in protein processing, J. Neurosci. 24 (2004) 4889-4893]. NL3, butyrylcholinesterase (BuChE), and acetylcholinesterase (AChE), as members of the (/(-hydrolase fold family of proteins, share over 30% of amino acid identity in their extracellular domains. In particular, Arg451 in NL3 is conserved in the alpha/beta-hydrolase fold family being homologous to Arg386 in BuChE and Arg395 in AChE. A Cys substitution at the homologous Arg in the BuChE was found studying post-succinylcholine apnea in an Australian population [T. Yen, B.N. Nightingale, J.C. Burns, D.R. Sullivan, P.M. Stewart, Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population, Clin. Chem. 49 (2003) 1297-308]. We have made the homologous mutation in the mouse AChE and BuChE genes and showed that the Arg to Cys mutations resulted in identical alterations in the cellular phenotype for the various members of the alpha/beta-hydrolase fold family proteins.
Im Mai 1752 wurde in Marly bei Paris auf Anregung des amerikanischen Forschers und Politikers Benjamin Franklin erstmals die elektrische Natur des Blitzes nachgewiesen. Damals beschrieb Franklin auch eine technische Vorrichtung, die als Schutz von Gebäuden vor Blitzschlägen dienen sollte: den Blitzableiter. Diese aus heutiger Sicht scheinbar triviale Vorrichtung wurde aber keineswegs unmittelbar akzeptiert. Und bis heute ist die Forschung zum Schutz von Einrichtungen vor Blitzschlägen nicht abgeschlossen.
Physical inactivity is a major public health concern since it increases individuals’ risk of morbidity and mortality. A subgroup at particular risk is postmenopausal overweight women. The aim of this study was to assess the feasibility and effect of a 12-week ZumBeat dance intervention on cardiorespiratory fitness and psychosocial health. Postmenopausal women with a body mass index (BMI) >30 kg/m2 or a waist circumference >94 cm who were not regularly physically active were asked to complete a 12-week ZumBeat dance intervention with instructed and home-based self-training sessions. Before and after the intervention, peak oxygen consumption (VO2peak) was assessed on a treadmill; and body composition and several psychometric parameters (including quality of life, sports-related barriers and menopausal symptoms) were investigated. Of 17 women (median age: 54 years; median BMI: 30 kg/m2) enrolled in the study, 14 completed the study. There was no apparent change in VO2peak after the 12-week intervention period (average change score: −0.5 mL/kg/min; 95% confidence interval: −1.0, 0.1); but, quality of life had increased, and sports-related barriers and menopausal symptoms had decreased. A 12-week ZumBeat dance intervention may not suffice to increase cardiorespiratory fitness in postmenopausal overweight women, but it increases women’s quality of life. PMID:29910253
Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.
Für die Erforschung von Biomolekülen bieten Neutronen einzigartige Eigenschaften. Vor allem ihre unterschiedliche Wechselwirkung mit dem natürlichen Wasserstoff und seinem schweren Isotop Deuterium ermöglicht tiefe Einblicke in Struktur, Funktion und Dynamik von Proteinen, Nukleinsäuren und Biomembranen. Bei vielen Fragestellungen zur Strukturaufklärung gibt es kaum oder keine Alternative zum Neutron. Das Institut Laue-Langevin trägt Bahnbrechendes zum Erfolg der Neutronen-Methoden in der Biologie bei.
A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS·+), superoxide anion radical (O2·-) and nitric oxide radical (·NO) assays. We also studied d-amino acid oxidase (DAAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Almost each of newly synthesised compounds exhibited radical scavenging capabilities. Moreover, several compounds showed moderate inhibitory activities against DAAO, AChE and BuChE. Compounds with significant free-radical scavenging activity may be potential candidates for therapeutics used in oxidative-stress-related diseases.
Krenz, Jennifer E.; Hofmann, Jonathan N.; Smith, Theresa R.; Cunningham, Rad N.; Fenske, Richard A.; Simpson, Christopher D.; Keifer, Matthew
2015-01-01
Objectives: Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are used widely in agriculture to manage insect pests of economic importance. Agricultural workers are more likely to suffer exposure because of the widespread use of OP/CBs in agriculture, and pesticide-related illnesses among handlers may be more severe when compared to other farm workers. The goal of this study was to identify occupational and personal characteristics associated with butyrylcholinesterase (BuChE) inhibition in participants recruited from the Washington State Cholinesterase Monitoring Program from 2006 to 2011. Methods: We conducted a longitudinal study among agricultural pesticide handlers in Washington State during the OP/CB spray season (March–July) over a 6-year period (2006–2011). Linear mixed effects regression models were used to evaluate BuChE inhibition in relation to self-reported occupational and personal characteristics. Results: Relative to pre-season baseline levels, the mean decrease in BuChE activity during the OP/CB spray season over all years of the study period was 3.77% (P < 0.001). Greater BuChE inhibition was observed among handlers who reported using multiple OP/CBs (β = −2.70, P = 0.045), mixed or loaded OP/CBs (β = −3.97, P = 0.002), did not store personal protective equipment (PPE) in a locker at work (β = −3.4, P = 0.014), or did not wear chemical-resistant boots (β = −16.6, P < 0.001). Discussion and Conclusions: The Washington State Cholinesterase Monitoring Program has provided a valuable opportunity to evaluate potential sources of OP/CB exposure among agricultural pesticide handlers. Several previously reported associations were confirmed in the current analysis, which included a larger number of pesticide handlers enrolled over a longer time period. The use of multiple OP/CBs and mixing/loading activities were significant risk factors, and the use of chemical-resistant boots and lockers for PPE storage were protective factors. Our findings point toward logical interventions to reduce exposure such as the implementation of engineering controls for mixing/loading activities, requirements for appropriate footwear, and the regular use of lockers for PPE storage. PMID:25261454
Dem Allgemeinen steht begrifflich das Besondere gegenüber. In diesem Sinne sind allgemeine Überlegungen zum Verstehen von Mathematik zu ergänzen durch Untersuchungen hinsichtlich des Verstehens der einzelnen mathematischen Disziplinen, insbesondere der Geometrie. Hier haben viele Schülerinnen und Schüler Probleme. Diese rühren hauptsächlich daher, dass eine fertige geometrische Konstruktion in ihrer statischen Präsentation auf Papier nicht mehr die einzelnen Konstruktionsschritte erkennen lässt; zum Nachvollzug müssen sie daher ergänzend in einer Konstruktionsbeschreibung festgehalten werden.
Das beliebte Arbeitsbuch "Probleme aus der Physik" bietet nun auch zur 17. Auflage von Gerthsen Vogel "Physik" (ISBN 3-540-56638-4) mit über 1150 gelösten Aufgaben aus der Physik und ihren Anwendungen in Technik, Astrophysik, Geound Biowissenschaften eine Fülle an Material zum Üben und Weiterlernen, zur Prüfungsvorbereitung und zum Selbststudium. Neu hinzugekommen ist ein Kapitel zur nichtlinearen Dynamik. Aufgaben aller Schwierigkeitsgrade machen "Probleme aus der Physik" unentbehrlich für Studenten der Physik im Haupt- und Nebenfach; Schüler der Leistungskurse Physik finden hier eine hervorragende Ergänzung.
A series of novel tacrine derivatives and tacrine-coumarin heterodimers were designed, synthesized, and biologically evaluated for their potential inhibitory effect on both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Of these compounds, tacrine-coumarin heterodimer 7c and tacrine derivative 6b were found to be the most potent inhibitors of human AChE (hAChE), demonstrating IC50 values of 0.0154 and 0.0263 μM. Ligands 6b, 6c, and 7c exhibited the highest levels of inhibitory activity against human BuChE (hBuChE), demonstrating IC50 values that range from 0.228 to 0.328 μM. Docking studies were performed in order to predict the binding modes of compounds 6b and 7c with hAChE/hBuChE.
An antigenic glycosylated cysteine protease has been purified from the latex of Euphorbia nivulia Buch.-Ham. It exhibits remarkable protease activity in the presence of metal ions, oxidizing agents, organic solvents, and detergents. This enzyme showed potential role in leather processing industry due to its dehairing activity for animal hide without hydrolyzing fibrous proteins, producing, by this way, a better quality product. The enzyme can also be used for silver recovering from X-ray plates. In addition, the stability (temperature and surfactants) and hydrolysis of blood stain data also revealed its application in detergent industries. Agriculturally, this protease finds application in biocontrol process against the infectious management of root knot nematode, Meloidogyne incognita. Biologically, it shows noticeable wound healing, haemostatic and antibacterial activity.
An antigenic glycosylated cysteine protease has been purified from the latex of Euphorbia nivulia Buch.-Ham. It exhibits remarkable protease activity in the presence of metal ions, oxidizing agents, organic solvents, and detergents. This enzyme showed potential role in leather processing industry due to its dehairing activity for animal hide without hydrolyzing fibrous proteins, producing, by this way, a better quality product. The enzyme can also be used for silver recovering from X-ray plates. In addition, the stability (temperature and surfactants) and hydrolysis of blood stain data also revealed its application in detergent industries. Agriculturally, this protease finds application in biocontrol process against the infectious management of root knot nematode, Meloidogyne incognita. Biologically, it shows noticeable wound healing, haemostatic and antibacterial activity. PMID:24348183
Aim: To design novel bifunctional derivatives of huperzine B (HupB) based on the concept of dual binding site of acetylcholinesterase (AChE) and evaluate their pharmacological activities for seeking new drug candidates against Alzheimer's disease (AD). Methods: Novel 16-substituted bifunctional derivatives of HupB were synthesized through chemical reactions. The inhibitory activities of the derivatives toward AChE and butyrylcholinesterase (BuChE) were determined in vitro by modified Ellman's method. Cell viability was quantified by the reduction of MTT. Results: A new preparative method was developed for the generation of 16-substituted derivatives of HupB, and pharmacological trials indicated that the derivatives were multifunctional cholinesterase inhibitors targeting both AChE and BuChE. Among the derivatives tested, 9c, 9e, 9f, and 9i were 480 to 1360 times more potent as AChE inhibitors and 370 to 1560 times more potent as BuChE inhibitors than the parent HupB. Further preliminary pharmacological trials of derivatives 9c and 9i were performed, including examining the mechanism of AChE inhibition, the substrate kinetics of the enzyme inhibition, and protection against hydrogen peroxide (H2O2)-induced cytotoxicity in PC12 cells. Conclusion: Preliminary pharmacological evaluation indicated that 16-substituted derivatives of HupB, particularly 9c and 9i, would be potentially valuable new drug candidates for AD therapy, and further exploration is needed to evaluate their pharmacological and clinical efficacies. PMID:19578388
Nakayama, M; Natori, Y; Tachi, H; Yoshizawa, M; Takayama, S; Miura, H; Kanayama, M; Kamei, T
1986-01-01
Vestibular function testing was done regularly on the cases given streptomycin, kanamycin, or enviomycin and a method to detect the cases of vestibular dysfunction at an early stage was discussed, as well as the time these drugs should be discontinued. Subjects were 85 cases of tuberculosis treated with streptomycin, kanamycin, or enviomycin who were admitted to our hospital from December 1984 to May 1986. The method of equilibrium examination performed at regular intervals is as follows: standing test (Romberg test), stepping test, and Meyer zum Gottesberge's head-shaking test were done once a week for a month after starting antituberculous injections and they were re-examined once every 2 weeks for at least 3 months after beginning the injections. After the 3 months these tests were done once a month. Eight cases of vestibular damage due to streptomycin or enviomycin could be easily detected at an early stage by performing Meyer zum Gottesberge's head-shaking test, together with the standing test and the stepping test. Vestibular dysfunction is apt to occur after about 1 month or within a month from the start of daily injections especially with streptomycin. Therefore, the method of equilibrium examination, we suggest, is that the Meyer zum Gottesberge's head-shaking test, the standing test (Romberg test), and the stepping test should be performed once a week during the first month after the start of this drug. When the result of the Meyer zum Gottesberge's head-shaking test is less than 50% and swaying and/or rotation occur in the stepping test, the drugs being given should be discontinued.
Jasminum amplexicaule Buch-Ham. (Oleaceae) has been commonly used in the traditional medicine in dysentery, diarrhoea and bellyache in China. In the present work, the methanol extract of Jasminum amplexicaule (JME) was examined for pharmacology on human colonic epithelial cell line T84 by the short-circuit current technique. The results showed that pretreatment of T84 cells with JME produced a concentration-dependent (0-1000 μg/mL. EC50 = 0.055 mg/ mL) inhibition effect on adrenalin (Adr.)-induced Cl- secretion. The maximal response was observed at 200 μg/mL. It has been demonstrated that JME has a direct effect on the enterocyte. Our results also demonstrated that the JME exerted inhibitory effect on gastrointestinal Cl(-)secretion that effected by acting on basolateral β-adrenoreceptors. These results suggested that the Chinese traditional medicine of JME can be used for the treatment of acute diarrhea and bellyache.
Für eine erfolgreiche Transformation, vom reinen Energieversorger hin zum Energiedienstleister, werden innovative Business-Intelligence-Lösungen notwendig sein und eine zentrale Rolle einnehmen. Dabei ist es zunächst essenziell, die Herausforderungen zu kennen und ihnen mit geeigneten Analysen zu begegnen. Die Basis hierzu bildet eine abgestimmte und auf die strategischen Unternehmensziele ausgerichtete Architektur und Vorgehensweise. Zwei Beispiele veranschaulichen, wie ein gesamtheitlicher Ansatz, auch bei Datenvielfalt und hoher Komplexität, operative Prozesse optimiert, und fortgeschrittene Analysen zukünftig einen Beitrag zum Unternehmenserfolg liefern können.
Heutige Pkw sind zum Schutz der Insassen bei Frontalkollisionen zu etwa 90 % fahrerseitig und zu ca. 70 % auf der Beifahrerseite mit Airbags ausgestattet, während die Seiten-Airbags zum Schutz des Kopfes und des Thorax von Insassen bei Seitenkollisionen nur mit ungefähr 40 bis 50% vertreten sind [1]. Weitere Schutzmaßnahmen wie Fuß- und Fond-Airbags befinden sich im Entwicklungsstadium, ihr Einsatz in der Serie ist umstritten und wird sich, wenn überhaupt, nur in Einzelfällen durchsetzen. In Bild C3-1 sind Airbags dargestellt, die heute serienmäßig in Pkw anzutreffen sind.
Kompakte Objekte besitzen zum einen eine sehr hohe Dichte, und zum anderen sind sie durch die Tatsache charakterisiert, dass keine nuklearen Reaktionen mehr in ihrem Inneren stattfinden können. Aus diesem Grund können sie im Unterschied zu gewöhnlichen Sternen der Gravitation nicht mehr mit dem Druck des thermischen Gases widerstehen. In den Weißen Zwergen bzw. Neutronensternen wird der Gravitation der Quantendruck eines Elektronengases bzw. einer Neutronenflüssigkeit entgegengesetzt. Ein solches Gas besteht aus Elektronen bzw. Neutronen, die auf ihr niedrigstes Energieniveau zusammengepresst wurden. Durch die daraus resultierende hohe Bewegungsenergie der Fermionen wird der sogenannte Quantendruck erzeugt.
Montenegro, María F; Moral-Naranjo, María T; Muñoz-Delgado, Encarnación; Campoy, Francisco J; Vidal, Cecilio J
2009-04-01
Besides esterase activity, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) hydrolyze o-nitroacetanilides through aryl acylamidase activity. We have reported that BuChE tetramers and monomers of human blood plasma differ in o-nitroacetanilide (ONA) hydrolysis. The homology in quaternary structure and folding of subunits in the prevalent BuChE species (G4(H)) of human plasma and AChE forms of fetal bovine serum prompted us to study the esterase and amidase activities of fetal bovine serum AChE. The k(cat)/K(m) values for acetylthiocholine (ATCh), ONA and its trifluoro derivative N-(2-nitrophenyl)-trifluoroacetamide (F-ONA) were 398 x 10(6) M(-1) min(-1), 0.8 x 10(6) M(-1) min(-1), and 17.5 x 10(6) M(-1) min(-1), respectively. The lack of inhibition of amidase activity at high F-ONA concentrations makes it unlikely that there is a role for the peripheral anionic site (PAS) in F-ONA degradation, but the inhibition of ATCh, ONA and F-ONA hydrolysis by the PAS ligand fasciculin-2 points to the transit of o-nitroacetalinides near the PAS on their way to the active site. Sedimentation analysis confirmed substrate hydrolysis by tetrameric 10.9S AChE. As compared with esterase activity, amidase activity was less sensitive to guanidine hydrochloride. This reagent led to the formation of 9.3S tetramers with partially unfolded subunits. Their capacity to hydrolyze ATCh and F-ONA revealed that, despite the conformational change, the active site architecture and functionality of AChE were partially retained.
The female rhesus monkey has a menstrual cycle like the human. Additionally, several differences in enzyme levels between males and females and in the female during the menstrual cycle are present. Therefore we quantitated plasma cholinesterase (ChE/BuChE) and erythrocyte (RBC) acetylcholinesterase (AChE) activity before and after exposure to sarin (GB)(1 5 ug/kg, iv; a 0.75 LD50), in male and female rhesus (Macaca mulatta) monkeys. Twenty-eight-day preexposure baseline plasma ChE and RBC AChE values for six male and six female rhesus monkeys were compared for intra-animal, within sex and between sex differences. After these baseline values were obtained, the organophosphorus (OP)more » compound/Isopropyl methylphosphono-fluoridate (GB) was administered to atropinized monkeys to determine if there was a significant in vivo difference between the sexes in their response to this intoxication in regard to the rate of BuChE /AChE inhibition, pyridine-2-aldoxime methyl chloride (2-PAM) reactivation of the phosphonylated BuChE and the rate of aging of the phosphonylated:BuChE/AChE. In the pre-exposure portion of the protocol; the intra-animal and intra-group BuChE/AChE variations were found to be minimal; but there were significant differences between the male and female monkeys in both plasma BuChE and RBC AChE levels; although probably clinically insignificant in respect to an OP intoxication. No significant cyclic fluctuations were seen during the 28-day study in either sex.« less
Reinen, Jelle; Nematollahi, Leyla; Fidder, Alex; Vermeulen, Nico P E; Noort, Daan; Commandeur, Jan N M
2015-04-20
Tri-ortho-cresyl phosphate (ToCP) is a multipurpose organophosphorus compound that is neurotoxic and suspected to be involved in aerotoxic syndrome in humans. It has been reported that not ToCP itself but a metabolite of ToCP, namely, 2-(ortho-cresyl)-4H-1,2,3-benzodioxaphosphoran-2-one (CBDP), may be responsible for this effect as it can irreversibly bind to human butyrylcholinesterase (BuChE) and human acetylcholinesterase (AChE). The bioactivation of ToCP into CBDP involves Cytochrome P450s (P450s). However, the individual human P450s responsible for this bioactivation have not been identified yet. In the present study, we aimed to investigate the metabolism of ToCP by different P450s and to determine the inhibitory effect of the in vitro generated ToCP-metabolites on human BuChE and AChE. Human liver microsomes, rat liver microsomes, and recombinant human P450s were used for that purpose. The recombinant P450s 2B6, 2C18, 2D6, 3A4 and 3A5 showed highest activity of ToCP-bioactivation to BuChE-inhibitory metabolites. Inhibition experiments using pooled human liver microsomes indicated that P450 3A4 and 3A5 were mainly involved in human hepatic bioactivation of ToCP. In addition, these experiments indicated a minor role for P450 1A2. Formation of CBDP by in-house expressed recombinant human P450s 1A2 and 3A4 was proven by both LC-MS and GC-MS analysis. When ToCP was incubated with P450 1A2 and 3A4 in the presence of human BuChE, CBDP-BuChE-adducts were detected by LC-MS/MS which were not present in the corresponding control incubations. These results confirmed the role of human P450s 1A2 and 3A4 in ToCP metabolism and demonstrated that CBDP is the metabolite responsible for the BuChE inactivation. Interindividual differences at the level of P450 1A2 and 3A4 might play an important role in the susceptibility of humans in developing neurotoxic effects, such as aerotoxic syndrome, after exposure to ToCP.
Kandiah, Nagaendran; Pai, Ming-Chyi; Senanarong, Vorapun; Looi, Irene; Ampil, Encarnita; Park, Kyung Won; Karanam, Ananda Krishna; Christopher, Stephen
2017-01-01
Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE−BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations. PMID:28458525
Loss of cognition is one of the age related mental problems and a characteristic symptom of neurodegenerative disorders like Alzheimer’s. Crataeva nurvala Buch-Ham, a well explored traditional Indian medicinal plant of Westernghats, is routinely used as folkloric medicine to treat various ailments in particular urolithiasis and neurological disorders associated with cognitive dysfunction. The objective of the study was to evaluate the nootropic activity of Crataeva nurvala Buch-Ham stem bark in different learning and memory paradigm viz. Elevated plus maze and Y-maze against scopolamine induced cognitive impairment. Moreover, to elucidate possible mechanism, we studied the influence of Crataeva nurvala ethanolic extract on central cholinergic activity via estimating the whole brain acetyl cholinesterase enzyme. Ethanolic extracts of Crataeva nurvala (100, 200 and 400 mg/kg body weight) were administered to adult Wistar rats for successive seven days and the acquisition, retention and retrieval of spatial recognition memory was determined against scopolamine (1 mg/kg, i.p.) induced amnesia through exteroceptive behavioral models viz. Elevated plus maze and Y-maze models. Further, whole brain acetyl cholinesterase enzyme was estimated through Ellman’s method. Pretreatment with Crataeva nurvala ethanolic extract significantly improved spatial learning and memory against scopolamine induced amnesia. Moreover, Crataeva nurvala extract decreased rat brain acetyl cholinesterase activity in a dose dependent manner and comparable to the standard drug Piracetam. The results indicate that ethanolic extract of Crataeva nurvala might be a useful as nootropic agent to delay the onset and reduce the severity of symptoms associated with dementia and Alzheimer’s disease. The underlying mechanism of action of its nootropic potentiality might be attributed to its anticholinesterase property. PMID:27065767
Kandiah, Nagaendran; Pai, Ming-Chyi; Senanarong, Vorapun; Looi, Irene; Ampil, Encarnita; Park, Kyung Won; Karanam, Ananda Krishna; Christopher, Stephen
2017-01-01
Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7), rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual AChE-BuChE inhibitory activity of rivastigmine as a therapeutic strategy in the treatment of neurological disorders, with a focus on the role of rivastigmine in subcortical dementias such as vascular dementia (VaD) and PDD. Toward this objective, we performed a literature search in PubMed and Ovid with limits to articles published in the English language before June 2016. The available evidence from the literature suggests that the dual inhibition of AChE and BuChE may afford additional therapeutic potential of rivastigmine in subcortical dementias (subcortical VaD and PDD) with benefits on cognition and behavioral symptoms. Rivastigmine was found to specifically benefit executive dysfunction frequently observed in subcortical dementias; however, large randomized clinical studies are warranted to support these observations.
An in vitro screening method for selective acetylcholinesterase (AChE) inhibitors was established. Inhibitory activity of AChE and butyrylcholinesterase (BuChE) was measured and the culture broths of microorganisms that showed selective inhibition against AChE were characterized. By using this method, a strain producing the novel and selective inhibitors of AChE, arisugacins A and B, was picked out among over seven thousand microorganisms tested. Arisugacins were obtained as white powders from the culture broth together with three known compounds, territrems B and C and cyclopenin that also showed selective inhibition against AChE. Arisugacins and territrems are members of the meroterpenoid compounds. They showed potent inhibitory activities against AChE with IC50 values in range of 1.0 approximately 25.8 nM. Furthermore, they showed greater than 2,000-fold more potent inhibition against AChE than BuChE.
Jasminum amplexicaule Buch-Ham. (Oleaceae) has been commonly used in the traditional medicine in dysentery, diarrhoea and bellyache in China. In the present work, the methanol extract of Jasminum amplexicaule (JME) was examined for pharmacology on human colonic epithelial cell line T84 by the short-circuit current technique. The results showed that pretreatment of T84 cells with JME produced a concentration-dependent (0-1000 μg/mL. EC50 = 0.055 mg/ mL) inhibition effect on adrenalin (Adr.)–induced Cl- secretion. The maximal response was observed at 200 μg/mL. It has been demonstrated that JME has a direct effect on the enterocyte. Our results also demonstrated that the JME exerted inhibitory effect on gastrointestinal Cl-secretion that effected by acting on basolateral β-adrenoreceptors. These results suggested that the Chinese traditional medicine of JME can be used for the treatment of acute diarrhea and bellyache. PMID:25276197
Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by the deficits in the cholinergic system and deposition of beta amyloid (Aβ) in the form of neurofibrillary tangles and amyloid plaques. Since the cholinergic system plays an important role in the regulation of learning and memory processes, it has been targetted for the design of anti-Alzheimer's drugs. Cholinesterase inhibitors enhance cholinergic transmission directly by inhibiting the enzyme acetylcholinesterase (AChE) which hydrolyses acetylcholine. Furthermore, it has been also demonstrated that both acetylcholinesterase and butrylcholinesterase (BuChE) play an important role in Aβ-aggregation during the early stages of senile plaque formation. Therefore, AChE and BuChE inhibition have been documented as critical targets for the effective management of AD by an increase in the availability of acetylcholine in the brain regions and decrease in the Aβ deposition. This review discusses the different classes of cholinesterase inhibitors including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para-aminobenzoic acid, coumarin, flavonoid, and pyrrolo-isoxazole analogues developed for the treatment of AD.
Aqueous extracts of aerial flowering parts of five Agrimonia species (Rosaceae): Agrimonia coreana Nakai, Agrimonia japonica (Miq.) Koidz, Agrimonia procera Wallr., Agrimonia eupatoria L. and Agrimonia leucantha Kunze were investigated on their antioxidant activity, measured using five different methods; the best was the extract from A. procera with IC50 values from 6 to 29 μg/mL. All the extracts displayed inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) at the tested concentration of 100 μg/mL. We found the highest inhibition of cholinesterase in the extract of A. japonica with inhibition 70.4% for AChE and 79.8% for BuChE. These findings are statistically significant in comparison with those of other extracts (p < 0.001). The phytochemical analyses showed that the antioxidant activity of Agrimonia extracts can be affected especially by hexahydroxydiphenoyl (HHDP)-glucose and quercetin glycosides, and inhibition of cholinesterases by apigenin, luteolin and quercetin glycosides.
Delmonte Corrado, M U; Politi, H; Trielli, F; Angelini, C; Falugi, C
1999-01-01
By histochemical and immunohistochemical methods, the presence of cholinergic-like molecules has previously been demonstrated in Paramecium primaurelia, and their functional role in mating-cell pairing was suggested. In this work, both true acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities were electrophoretically investigated, and the presence of molecules immunologically related to BuChE was checked by immunoblotting. The AChE activity, shown in the membrane protein fraction of mating-competent cells and in the cytoplasmic fraction of immature cells, is due to a 260-kDa molecular form, similar to the membrane-bound tetrameric form present in human erythrocytes. This AChE activity does not appear in either the cytoplasmic fraction of mating-competent cells or in the membrane protein fraction of immature cells. No evidence was found for the presence or the activity of BuChE-like molecules. The role of AChE in P. primaurelia developmental cycle is discussed.
Perea Saavedra, Héctor; Methe, Heiko; Wintermantel, Erich
Gegenwärtig sind kardiovaskuläre Erkrankungen, allen voran die Arteriosklerose koronarer und zerebraler Gefäße, Ursache für 38% aller Todesfälle in Nordamerika und häufigste Todesursache europäischer Männer < 65 Jahre und zweithäufigste Todesursache bei Frauen [4]. Es wird prognostiziert, dass innerhalb der nächsten 10-15 Jahre kardiovaskuläre Erkrankungen und deren Komplikationen weltweit die häufigste Todesursache stellen werden. Dies ist zum einen Folge der ansteigenden Prävalenz kardiovaskulärer Erkrankungen in Osteuropa und zunehmend auch in den Entwicklungsländern, zum anderen Folge der kontinuierlich ansteigenden Inzidenz von Übergewicht und Diabetes mellitus in den westlichen Ländern.
Extensive epidemiological and clinical studies revealed that Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (T2D) are most likely to appear simultaneously in aged people as T2D is a major risk factor for AD. Therefore, development of potential multifunctional agents for dual therapy of AD and T2D has received much attention. Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis have been used extensively in popular medicine. The present study was aimed at phytochemical profiling and evaluating multifunctional ability of titled plants in the AD and T2D dual therapy. Methanolic extracts and their derived fractions were evaluated for their inhibitory capacities against acetylcholinesterase (AChE) & butyrylcholinesterase (BuChE), and α- & β-glucosidase besides kinetic analysis of inhibition using methods of Elmann and Shibano, respectively. Antioxidant potency of active fractions was assessed by their DPPH and ABTS radical scavenging activities. Active fractions were tested by the MTT assay to verify cytotoxicity and neuroprotective ability in human nueroblastoma cell lines. Phytochemical screening was done with the aid of spectrophotometric methods. All the methanolic extracts of test plants (BAM, HIM, RMM) showed concentration dependent inhibitory activities against AChE, BuChE, α- and β-glucosidase enzymes. Subsequent fractionation and evaluation revealed that chloroform fractions BAC, HIC and RMC with IC 50 values of 12.29±2.14, 9.94±2.14, 16.65±1.99 and 27.38±1.24; 28.14±0.9, 5.16±0.22, 11.03±0.5 and 87.64±15.41; 41.35±1.6, 15.86±7.3, 26.04±0.37 and 25.33±0.3 were most prominent with regard to inhibition potential against AChE, BuChE, α- and β-glucosidase, respectively. Kinetic analysis of these active fractions proved that they disclosed mixed-type inhibition against AChE, BuChE, α- and β-glucosidase enzymes. In the MTT assay, active fractions BAC, HIC, RMC showed significant cell viability at high concentrations (400 μg). Moreover, in MTT assay, the active fractions displayed excellent neuroprotective effects against oxidative stress induced cell death and significant cell viability in SK N SH cells at all concentrations. The strong anticholinesterase, antiglucosidase, antioxidant and neuroprotective activities of methanolic extracts and their derived chloroform fractions indicate the potential of Buchanania axillaris, Hemidesmus indicus and Rhus mysorensis as multifunctional therapeutic remedies for the dual therapy of T2D and AD.
In this paper, the effectiveness of a "CyberBuch," a multimedia program for reading authentic German texts, is assessed in three areas. First, based on user evaluation of the visual interface design, the usability of the program is assessed with particular regard to user reaction to the multimedia components of the program. Second,…
In Drosophila, a simple network of nutrient-sensing neuroendocrine cells, analogs of pancreatic islet alpha and beta cells, regulates carbohydrate metabolism. Work presented in this issue of Cell Metabolism (Buch et al., 2008) shows that signals from these cells control expression of a glycogen-specific glucosidase in response to dietary protein and carbohydrate.
This teacher's guide to cultural instruction in a level-1 German course is designed to be used with the text "Deutsch, Erstes Buch, Erster Teil." Instructional observations pertain to the first eight lessons of the text and comprise the major portion of this text including: (1) die Post, (2) Munchen, (3) Sport in Deutschland, (4) die deutschen…
Jia, Qiang; Su, Weiwei; Peng, Wei; Li, Peibo; Wang, Yonggang
2008-09-26
Jasminum amplexicaule Buch.-Ham. (Oleaceae) has been commonly used in the traditional medicine in dysentery, diarrhoea and bellyache in China. In the present work, the methanol extract of Jasminum amplexicaule and different fractions of this extract were studied for anti-diarrhoea and analgesic activities. The anti-diarrhoea activities were investigated using castor oil-induced, magnesium sulphate-induced diarrhoea models, antienteropooling assay and gastrointestinal motility models in mice. The analgesic activities were studied using hot-plate, writhing and formalin models in mice. At the doses of 100, 200 and 400mg/kg, the methanol extract (ME) showed significant and dose-dependent anti-diarrhoea and analgesic activity in these models. The chloroform fraction (CHF), ethyl acetate fraction (EAF) and the residual methanol fraction (RMF) exhibited similar activity using a dose of 200mg/kg in these models. The pharmacological activities of the n-butanol fraction (BUF) were lesser than the ME extract and other fractions. These results may support the fact that this plant is traditionally used to cure diarrhoea and pain.
Unter Starterkulturen versteht man Mikroorganismen (Bakterien, Hefen, Pilze), die pflanzlichen bzw. tierischen Rohstoffen zur gezielten Veränderung ihrer chemischen Zusammensetzung zugesetzt werden. Sie dienen im Wesentlichen der Aromabildung, der Strukturveränderung und der Konservierung der Lebensmittel und werden aufgrund spezieller, funktioneller Eigenschaften selektiert. Die Zugabe von Starterkulturen erfolgt in der Regel in relativ hohen Keimzahlen in Form von Rein- oder Mischkulturen. Die zum Einsatz kommenden Mikroorganismen sind ebenso zahlreich wie die daraus resultierenden Produkte und reichen von der Fermentation von Milchprodukten, Fleisch und Gemüse durch Milchsäurebakterien über die Essigsäureherstellung bis hin zum Einsatz von Hefen in der Brau- und Weinindustrie. Hieraus ergibt sich auch eine zunehmende Bedeutung schneller und zuverlässiger Methoden zur taxonomischen Identifizierung, aber auch zur Charakterisierung des genetischen Potenzials der jeweiligen Starterkulturen.
The STS-48 mission launched aboard the Space Shuttle Discovery on September 12, 1991 at 7:11:04 pm. Five astronauts composed the crew including: John O. Creighton, commander; Kenneth S. Reightler, pilot; and Mark N. Brown, Charles D. (Sam) Gemar, and James F. Buchli, all mission specialists. The primary payload of the mission was the Upper Atmosphere Research Satellite (UARS).
This teacher's guide to cultural instruction in a level-2 German course is designed to be used with the text "Deutsch, Erstes Buch, Erster Teil." Instructional observations pertain to the seventh through the 12th lessons and comprise the major portion of this text including: )1) die Eisenbahn, (2) Reisen und Essen in Deutschland, (3) die Familie,…
Mit der zunehmenden Verfügbarkeit immer größerer Querschnitts- und Längschnittsdatensätze für Personen, Haushalte und Betriebe sowie deren Verknüpfungen hat sich die mikroökonometrische Forschung in den vergangenen Jahren rasant weiterentwickelt. Dies gilt sowohl aus methodischer als auch aus empirischer, anwendungsorientierter Sicht. Mikrodaten und mikroökonometrische Ansätze dienen dazu, aktuelle, politikrelevante Fragen aufzugreifen, sie zu analysieren und fundierte politische Empfehlungen zu geben, beispielsweise im Rahmen der Arbeitsmarkt- und Sozialpolitik, der Finanzanalyse und der Marketingforschung. Die Deutsche Statistische Gesellschaft (DStatG) und deren Mitglieder haben sich in den Ausschüssen und in Hauptversammlungen kontinuierlich mit den Weiterentwicklungen der mikroökonometrischen Methodik und den empirischen Anwendungen befasst. Zahlreiche Publikationen von Mitgliedern der DStatG haben entscheidend zum kritischen Diskurs und zum wissenschaftlichen Fortschritt in diesem Bereich beigetragen.
Hai Ren; Hongfang Lu; Weijun Shen; Charlie Huang; Qinfeng Guo; Zhi' an Li; Shuguang Jian
2010-01-01
By the end of 1990s when China initiated a 10-year mangrove reforestation project, the mangrove forest area had decreased from250,000 to 15,000 ha. Over 80% of current Chinese mangroves are degraded secondary forests or plantations. As an initial restoration and reforestation effort, Sonneratia apetala, a native of...
... or bruxism (say: BRUK-sih-zum), which is grinding your teeth while you sleep. Grinding stretches the muscles and joints in your mouth ... closing completely at night, which keeps you from grinding your teeth. Getting Fitted for and Wearing a ...
Während mittlerweile rund 950 Planeten außerhalb des Sonnensystems gefunden wurden, steht der Nachweis von extrasolaren Monden noch aus. Aktuelle Studien zeigen, dass dies mit der heutigen Technologie zum ersten Mal möglich ist.
To examine the natural colonisation of native mangrove species into remediated exotic mangrove stands in Leizhou Bay, South China, we compared soil physicalâchemical properties, community structure and recruitments of barren mangrove areas, native mangrove species plantations, and exotic mangrove speciesâSonneratia apetala Buch.Hamâbetween plantations and natural...
Ellison, Corie A., E-mail: cellison@buffalo.edu; Crane, Alice L., E-mail: alcrane@buffalo.edu; Bonner, Matthew R., E-mail: mrbonner@buffalo.edu
Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n = 120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase)more » and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P ≤ 0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P ≤ 0.05) and PON1 192 (P ≤ 0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal. -- Highlights: ► CPF exposure resulted in an increase in TCPy and decreases in BuChE and AChE. ► CPOase activity decreased in subjects with the PON1 55LM and PON1 55 MM genotypes. ► Neither PON1 genotype nor CPOase activity had an effect on BuChE or AChE inhibition.« less
Paraoxonase (PON1) plays an important role in mechanism of organophosphorus compound (OP) toxicity, as seen both in vitro and in vivo studies. Polymorphisms of PON1 gene at coding and promoter regions have also been to affect on the hydrolytic activity and PON1 level. The objectives of this study were to determine PON1 polymorphism and activity in an OP-exposed population and the effects on inhibition of cholinesterase activity. The studied population consisted of control (n=30) and exposed groups (n=90). All enzyme activities (AChE, BuChE, paraoxonase, arylesterase and diazonase) were measured once for control group and two periods of exposure for exposed group. Three polymorphisms of PON1 (Q192R, L55M and T-108C) were identified only in the exposed subjects. The results demonstrated that AChE activity in both high (345.5 microkat/gHb) and low exposure periods (496.9 microkat/gHb) of the exposed group were significantly different from control group (649.7 microkat/gHb, p<0.01). For BuChE activity, the exposed group also showed the statistically lower level in both periods (high exposure period: 62.17 microkat/L and low exposure period: 81.84 microkat/L) than those in the control group (93.35 microkat/L). Serum paraoxonase activity was significantly different among individual genotypes, RR>QR>RR, LL>LM and -108CC>-108CT>-108TT, but this was not found for those of arylesterase and diazonase activities. Q192R and L55M as well as Q192R and T-108C also presented substantial linkage disequilibrium. Further analysis was performed with haplotypes and various enzyme activities. AChE activity was not affected by haplotypes. Individuals with "211" haplotype showed significantly higher paraoxonase activity and BuChE activity than other haplotypes but not in diazonase activity. In conclusion, PON1 gene exhibited a wide variation in enzyme activities both within and between genotypes which implied insights of a potentially difference in sensitivity to OP toxicity.
STS048-S-002 (August 1991) --- These five astronauts have been assigned to NASA's mission, scheduled for September. Astronaut John O. Creighton, center, is mission commander. Astronaut Kenneth S. Reightler Jr. (right front) will be pilot for the flight aboard the Space Shuttle Discovery. Mission specialists are Mark N. Brown (left, front row) and (left to right, back row) Charles D. (Sam) Gemar and James F. Buchli.
STS048-S-170 (12 Sept 1991) ---- With five astronauts and the Upper Atmosphere Research Satellite (UARS) onboard, the Space Shuttle Discovery heads toward a six day mission in Earth orbit. Onboard are astronauts John O. Creighton, Kenneth S. Reightler, Charles D. (Sam) Gemar, James F. Buchli and Mark N. Brown. Liftoff occurred at 7:11:04 p.m. (EDT), September 12, 1991.
STS048-S-171 (12 Sept 1991) --- With five astronauts and the Upper Atmosphere Research Satellite (UARS) onboard, the Space Shuttle Discovery heads toward a six day mission in Earth orbit. Onboard are astronauts John O. Creighton, Kenneth S. Reightler, Charles D. (Sam) Gemar, James F. Buchli and Mark N. Brown. Liftoff occurred at 7:11:04 p.m. (EDT), September 12, 1991.
Widmer, Markus; von Felten-Rösler, Ursula; Wintermantel, Erich
Die Hüftgelenk-Endoprothese wird im vorliegenden Buch als herausragendes Beispiel eines lasttragenden orthopädischen Implantates aufgeführt. Lasttragende Implantate werden in dieser Monographie den metabolisch induktiven Implantaten gegenübergestellt, bei denen Kräfte eine untergeordnete Rolle sowohl in der Werkstoffentwicklung als auch beim späteren Einsatz im Empfängerorganismus darstellen. Zu den metabolisch induktiven Implantaten werden beispielsweise Zellträger und “drug-release”-Systeme gerechnet.
S89-26240 (20 Jan 1989) --- Four of the five STS-29 crewmembers inspect the content of their emergency medical and medication kits during the recent bench review of middeck locker equipment avaialable for their scheduled March 1989 flight. From left to right are Astronauts James H. Buchli, John E. Blaha, James P. Bagian and Michael L. Coats. Not pictured is Robert C. Springer.
This workbook is intended as a text for the learner of German as a foreign language. The workbook is complete with exercises that require students to provide information about themselves. Students provide information by reading questions and filling in the blanks. Questions are asked about families, friends, likes and dislikes, hobbies, and even…
The objectives of this study are to investigate the sensitivity of different classes of esterases in various aquatic species to environmental contaminants and the possible use of these enzymes as biomarkers for monitoring the effects of pollutants. Acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and the non-specific carboxylesterases (CaE) were analyzed in three fish species, Ictiobus bubalus (small mouth buffalo), Ictiobus cyprinellus (big mouth buffalo) and Lepisosteus oculatus (spotted gar) and the green tree frog, Hyla cinerea. These samples were collected from the Devil`s Swamp Site (DSS), an industrial site known to be highly contaminated at the Mississippi River Basin, and Lake Tunica,more » a nonindustrial site. ACHE and BuChE activities in the subcellular fractions of liver and brain were significantly lower in fishes and frogs obtained from DSS when compared to the same species obtained from Tunica swamp site. The greatest decrease was observed with ACHE activity in the liver and brain of Ictiobus bubalus from DSS. CaE activity analyzed with p-nitrophenyl acetate was found to be significantly lower in the liver of all three fish species collected from DSS when compared to the same fish species obtained from the Tunica swamp site.« less
Onor, Maria Luisa; Trevisiol, Marianna; Aguglia, Eugenio
2007-01-01
Alzheimer’s disease is the most common form of dementia in industrialized countries. In the European Union, about 54% of dementia cases are believed to be due to Alzheimer’s disease. The condition is an age-related neurodegenerative disorder characterized by multiple cognitive deficiencies, including loss of memory, judgment, and comprehension. These manifestations are accompanied by behavioral and mood disturbances. Although no cure has yet been discovered for Alzheimer’s disease, symptomatic therapies are now widely available and offer significant relief to patients and benefits to caregivers in terms of reduced care burden. At the start of the 21st century, health technology assessments recommended three agents for the symptomatic treatment of mild to moderate Alzheimer disease: rivastigmine, donepezil, and galantamine. Rivastigmine (Exelon®, Novartis Basel—Switzerland) is a slowly reversible inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), while donepezil (Aricept®, Pfizer, New York, USA) and galantamine (Reminyl®, Janssen, New Jersey,USA) show no functional inhibition of BuChE, and are considered AChE-selective, rapidly-reversible inhibitors. The efficacy of all three agents has been evaluated in large, double-blind, placebo-controlled clinical trials of up to 6 months’ duration. Rivastigmine treatment in mild to moderate Alzheimer’s disease improves cognition, activities of daily living, and global function. PMID:18044073
The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of a series of pyrano[2,3-b]quinolines (2, 3), [1,8]naphthyridines (5, 6), 4-amino-2,3-diaryl-5,6,7,8-tetrahydrofuro[2,3-b]quinolines (11-13)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]furo[2,3-b]pyridine (14), 4-amino-5,6,7,8-tetrahydro-2,3-diphenylthieno[2,3-b]quinoline (15)/ 4-amino-6,7,8,9-tetrahydro-2,3-diphenyl-5H-cyclohepta[e]thieno[2,3-b]pyridine (16) are described. These compounds are tacrine analogues that have been prepared from readily available polyfunctionalized ethyl [6-amino-5-cyano-4H-pyran]-3-carboxylates (9, 10), ethyl [6-amino-5-cyanopyridine]-3-carboxylates (7, 8), 2-amino-3-cyano-4,5-diarylfurans (17-19) and 2-amino-3-cyano-4,5-diphenylthiophene (20) via Friedländer condensation with selected ketones. These compounds are competitive and, in a few cases, non-competitive inhibitors for AChE, the most potent being compound (14), though three-fold less active than tacrine. The BuChE inhibitory activity is only significant in compounds 11 and 14, ten-fold less active than tacrine. Furthermore, the products 12 and 13 are selective and moderate AChE inhibitors.
Uplifts caused by magma intrusion have been observed and mapped since the pioneering work of von Buch two hundred years ago. Von Buch's "Craters of elevation theory", developed in the Auvergne and Canaries, was, unfortunately, discredited and mostly forgotten until recent work has shown that the forced folds mapped in seismic sections in sedimentary basins are the same type of feature. Also, these magmatic bulges are being found on an increasing number of volcanoes. The Danakil region of Ethiopia contains a superb range of forced folds with craters of elevation, which we have mapped using Google Earth and other satellite imagery, and some ground truthing. This preliminary work provides a geological map that is inspired from the 1970 Barberi and Vallet map, and which sets out in detail the structure and lava flow units of this area. We describe the main structures of each uplift, and suggest a preliminary general structural evolutionary pattern that provides a model for future research. This work has been untertaken by a group from multiple universities sharing interpretations and data in an open format. We aim to continue this work to study these superb geological features. Their superb nature and preservation is such that we would also press for them to be made a geoheritage reserve of global importance: Either a Geopark or a World Heritage site.
Normung ist aus dem täglichen Leben nicht wegzudenken. In allen Bereichen des Lebens begegnet man Normen, die Aktivitäten reichen von Festlegungen für Kindersitze im Auto über Implantate zum Gelenkersatz bis zu Schraubengrößen oder Verfahren zur Optimierung von Unternehmen.
Val, Jose Cajide; Philipp, Rita Radl; Castro, Ana Porto
1998-01-01
Investigates the teaching, research, and management entailed in four new degree programs--physics, agricultural engineering, agricultural food-processing technology, and pharmacy courses--at Spain's University of Santiago de Compostela. Reports students' opinions of reforms in these courses, revealing dissatisfaction with facilities for practical…
"Dies ist kein Lehrbuch der theoretischen Physik, auch kein Kompendium der Physikgeschichte ... , vielmehr eine recht anspruchsvolle Sammlung historischer Miniaturen zur Vergangenheit der theoretischen Physik - ihrer "Sternstunden", wenn man so will. Frei vom Zwang, etwas Erschöpfendes vorlegen zu müssen, gelingt dem Autor etwas Seltenes: einen "lebendigen" Zugang zum Ideengebäude der modernen Physik freizulegen, ... zu zeigen, wie Physik in praxi entsteht... Als Vehikel seiner Absichten dienen dem Autor geschichtliche Fallstudien, insgesamt sieben an der Zahl. Aus ihnen extrahiert er das seiner Meinung nach Lehrhafte, dabei bestrebt, mathematische Anachronismen womöglich zu vermeiden... Als Student hätte ich mir diese gescheiten Essays zum Werden unserer heutigen physikalischen Weltsicht gewünscht. Sie sind originell, didaktisch klug und genieren sich auch nicht, von der Faszination zu sprechen, die ... von der Physik ausgeht. Unnötig darauf hinzuweisen, das sie ein gründliches "konventionelles" Studium weder ersetzen wollen noch können, sie vermögen aber, dazu zu ermuntern." #Astronomische Nachrichten (zur englischen Ausgabe)#1
Die Energiewende wird ohne eine umfassende Digitalisierung der Energiewirtschaft Stückwerk bleiben. Die historisch gewachsene, aus hunderten fossilen Großkraftwerken getriebene Energieversorgung hat sich durch den Zubau von mehr als einer Millionen dezentraler Erzeugungseinheiten innerhalb der vergangenen 15 Jahren radikal verändert. Zum Ausgleich von Last und Erzeugung, aber auch zum Aufbau neuer Geschäftsfelder ist die digitale Technik unverzichtbar. Ihre Möglichkeiten scheinen nahezu unbegrenzt, ihre Rolle wird in einer zukünftig nahezu vollständig elektrifizierten Gesellschaft zunehmend wichtiger werden. Neue Anbieter drängen auf den Markt und setzen die traditionelle Energiewirtschaft unter Druck. Energieversorger, die sich dem Wandel nicht stellen, drohen den Anschluss zu verpassen. Noch werden Verbundunternehmen und Stadtwerke von weitreichenden regulatorischen Vorgaben geschützt. Beispiele aus anderen Branchen zeigen aber, dass die Digitalisierung im Stande ist, regulatorische Mechanismen außer Kraft zu setzen. Zugleich verhindert die enge Regulierung und ein falsch verstandener Datenschutzbegriff in Deutschland die Entwicklung neuer Geschäftsmodelle, die energie- und volkswirtschaftlich sinnvoll wären.
The crew assigned to the STS-51C mission included (kneeling in front left to right) Loren J. Schriver, pilot; and Thomas K. Mattingly, II, commander. Standing, left to right, are Gary E. Payton, payload specialist; and mission specialists James F. Buchli, and Ellison L. Onzuka. Launched aboard the Space Shuttle Discovery on January 24, 1985 at 2:50:00 pm (EST), the STS-51C was the first mission dedicated to the Department of Defense (DOD).
above and cholinesterase activity was measured in the supernatants after 0, 15, 30 and 60 min= exposure to PB (100 nM). Drugs and biological...a quaternary carbamate that does not cross the blood brain barrier (BBB) appreciably and inhibits reversibly AChE and BuChE with similar potencies... activity could be maintained by ACh released from cholinergic neurons in our culture. In the continuous presence of atropine, exposure of the neurons to
The STS-48 crew portrait includes (front row left to right): Mark N. Brown, mission specialist; John O. Creighton, commander; and Kenneth S. Reightler, pilot. Pictured on the back row (left to right) are mission specialists Charles D. (Sam) Gemar, and James F. Buchli. The crew of five launched aboard the Space Shuttle Discovery on September 12, 1991 at 7:11:04 pm (EDT). The primary payload of the mission was the Upper Atmosphere Research Satellite (UARS).
STS029-S-063 (18 March 1989) --- Discovery's main landing gear touches down on Runway 22 at Edwards Air Force Base in California following a successful five-day mission in Earth orbit. Onboard the spacecraft were Astronauts Michael L. Coats, John E. Blaha, James F. Buchli, Robert C. Springer and James P. Bagian. Wheels came to a stop at 6:36:40 a.m. (PST), March 18, 1989.
Tripathi, Rati K P; M Sasi, Vishnu; Gupta, Sukesh K; Krishnamurthy, Sairam; Ayyannan, Senthil R
2018-12-01
A series of 2-amino-5-nitrothiazole derived semicarbazones were designed, synthesised and investigated for MAO and ChE inhibition properties. Most of the compounds showed preferential inhibition towards MAO-B. Compound 4, (1-(1-(4-Bromophenyl)ethylidene)-4-(5-nitrothiazol-2-yl)semicarbazide) emerged as lead candidate (IC 50 = 0.212 µM, SI = 331.04) against MAO-B; whereas compounds 21 1-(5-Bromo-2-oxoindolin-3-ylidene)-4-(5-nitrothiazol-2-yl)semicarbazide (IC 50 = 0.264 µM) and 17 1-((4-Chlorophenyl) (phenyl)methylene)-4-(5-nitrothiazol-2-yl)semicarbazide (IC 50 = 0.024 µM) emerged as lead AChE and BuChE inhibitors respectively; with activity of compound 21 almost equivalent to tacrine. Kinetic studies indicated that compound 4 exhibited competitive and reversible MAO-B inhibition while compounds 21 and 17 showed mixed-type of AChE and BuChE inhibition respectively. Docking studies revealed that these compounds were well-accommodated within MAO-B and ChE active sites through stable hydrogen bonding and/or hydrophobic interactions. This study revealed the requirement of small heteroaryl ring at amino terminal of semicarbazone template for preferential inhibition and selectivity towards MAO-B. Our results suggest that 5-nitrothiazole derived semicarbazones could be further exploited for its multi-targeted role in development of anti-neurodegenerative agents. [Formula: see text] A library of 2-amino-5-nitrothiazole derived semicarbazones (4-21) was designed, synthesised and evaluated for in vitro MAO and ChE inhibitory activity. Compounds 4, 21 and 17 (shown) have emerged as lead MAO-B (IC 50 :0.212 µM, competitive and reversible), AChE (IC 50 :0.264 µM, mixed and reversible) and BuChE (IC 50 :0.024 µM, mixed and reversible) inhibitor respectively. SAR studies disclosed several structural aspects significant for potency and selectivity and indicated the role of size of aryl binding site in potency and selectivity towards MAO-B. Antioxidant activity and neurotoxicity screening results further suggested their multifunctional potential for the therapy of neurodegenerative diseases.
progress to self-sustained seizures ( status epilepticus , SE) and result in extensive neuropathology as seen in rats (de Araujo Furtado et al., 2009, 2010...physostigmineOP organophosphorus BuChE butyrylcholinesterase ChE cholinesterase SE status epilepticus ATR atropine sulfate 2-PAM 2-pralidoxime NMDA N...L.C., Lichtenstein, S., Yourick, D.L., 2010. Spontaneous recurrent seizures after status epilepticus induced by soman in Sprague-Dawley rats
The increasing interest in the Mediterranean diet is based on the protective effects against several diseases, including neurodegenerative disorders. Polyphenol-rich functional foods have been proposed to be unique supplementary and nutraceutical treatments for these disorders. Extra-virgin olive oils (EVOOs) obtained from 'Brava' and 'Mansa', varieties recently identified from Galicia (northwestern Spain), were selected for in vitro screening to evaluate their capacity to inhibit key enzymes involved in Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (5-LOX)), major depressive disorder (MDD) and Parkinson's disease (PD) (monoamine oxidases: h MAO-A and h MAO-B respectively). 'Brava' oil exhibited the best inhibitory activity against all enzymes, when they are compared to 'Mansa' oil: BuChE (IC 50 = 245 ± 5 and 591 ± 23 mg·mL -1 ), 5-LOX (IC 50 = 45 ± 7 and 106 ± 14 mg·mL -1 ), h MAO-A (IC 50 = 30 ± 1 and 72 ± 10 mg·mL -1 ) and h MAO-B (IC 50 = 191 ± 8 and 208 ± 14 mg·mL -1 ), respectively. The inhibitory capacity of the phenolic extracts could be associated with the content of secoiridoids, lignans and phenolic acids.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline associated with a deficit in cholinergic function. Inhibitors of acetylcholinesterase (AChE) and/or butyrylcholinesterase (BuChE), such as donepezil, galantamine or rivastigmine, are widely prescribed as symptomatic treatments for AD. These agents exhibit a wide variation in their pharmacological properties. Here we review clinical data from 1998 to 2009 investigating the effect of different cholinesterase inhibitor treatments on the levels and activities of cholinesterases in the cerebrospinal fluid (CSF) of AD patients. These studies suggest that treatment with rapidly-reversible cholinesterase inhibitors (e.g. donepezil, galantamine, tacrine) are associated with marked and significant upregulation of AChE activities and protein levels in the CSF of AD patients. In contrast, pseudo-irreversible cholinesterase inhibition (e.g. rivastigmine) is associated with a significant decrease in both CSF AChE and BuChE activities, with no upregulation of CSF protein levels. Additionally, donepezil is associated with a decrease in the level of the AChE-R isoform relative to the synaptic AChE-S isoform, whereas rivastigmine seems to increase this ratio. These findings suggest that these agents exert different effects on CSF cholinesterases. The clinical effects of these pharmacological differences are yet to be fully established.
Es wird ein statistisches Modell zum Einfluß der thermischen Bewegung auf die NMR-Linienform vorgestellt, das die Verschmälerung von Festkörper-Spektren bei wachsender Temperatur beschreibt. Das Modell geht von der Annahme aus, daß nach einer Ortsveränderung eines Kerns infolge thermischer Bewegung jede beliebige Kernresonanzfrequenz mit der durch das Festkörperspektrum vorgegebenen Wahrscheinlichkeit angenommen werden kann. Am Beispiel der Festkörper-Gaußlinie wird der Unterschied zu dem bekannten Modell von ANDERSON und WEISS verdeutlicht.Translated AbstractA Statistical Model for the Influence of Thermal Motion on N. M. R. Spectra in SolidsA theory is proposed which allows to describe the narrowing of n. m. r.-line width in the presence of thermal motions of the spins. The model is based on the assumption, that the local resonance frequency of a given spin immediately after the jump is distributed according to the n. m. r.-line shape of the rigid lattice. The difference to the well-known ANDERSON-WEISS-model of spectral narrowing is demonstrated for a gaussian line shape.
STS048-21-04 (15 Sept 1991) --- The five astronauts pose on the Space Shuttle Discovery's middeck for the traditional in-flight crew portrait. Astronaut John O. Creighton, mission commander, is at center. Others are (front row, left to right) Kenneth S. Reightler, pilot; and James F. Buchli, mission specialist; and (rear row, left to right) astronauts Mark N. Brown and Charles D. (Sam) Gemar, both mission specialists. The image was photographed with a pre-set 35mm camera.
STS29-02-033 (3-18 March 1989) --- In what appears to be a juggling act in the microgravity of space, James P. Bagian, a physician, is actually attempting to organize audio cassettes. Other frames taken during the flight document Bagian's medical testing of his fellow crewmembers. This photographic frame was among NASA's third STS-29 photo release. Monday, March 20, 1989. Crewmembers were Astronauts Michael L. Coats, John E. Blaha, James F. Buchli, Robert C. Springer and James P. Bagian.
Auf dem Höhepunkt der Verbreitung und astronomischen Anwendung von Schmidt-Teleskopen legen S. Marx und W. Pfau einen reich illustrierten Bildband zu diesem Fernrohrtyp vor. Der thematische Bogen reicht von der Teleskoptechnik und ihrer Geschichte über das Leben von Berhard Schmidt bis zu den schönsten, hier in hervorragender Qualität wiedergegebenen Himmelsaufnahmen und ihrer wissenschaftlichen Interpretation. Praktische Hinweise zu eigener fotografischer Tätigkeit und ein Glossar machen das Buch nützlich für jeden Liebhaber der Himmelskunde.
STS029-04-029 (13-18 March 1989) --- Astronaut Michael L. Coats appears to like the status of the STS-29 flight as he offers a big smile from the commander's station on the flight deck. He takes a momentary break from updating the crew activity plan (CAP) to pose for the photo. This photographic frame was among NASA's third STS-29 photo release. Monday, March 20, 1989. Crew members were astronauts Michael L. Coats, John E. Blaha, James F. Buchli, Robert C. Springer and James P. Bagian. Photo credit: NASA
STS-48 crewmembers eat preflight breakfast at Kennedy Space Center (KSC) Operations and Checkout (O and C) Building before boarding Discovery, Orbiter Vehicle (OV) 103. Sitting around the table (left to right) are Mission Specialist (MS) James F. Buchli, Pilot Kenneth S. Reightler, Jr, Commander John O. Creighton, MS Charles D. Gemar, and MS Mark N. Brown. Cake decorated with the STS-48 mission insignia and a small teddy bear are in the center of the table.
STS-29 crewmembers, wearing suit coats (blazers) and ties, eat preflight breakfast at Kennedy Space Center (KSC) Operations and Checkout (O and C) Building before boarding Discovery, Orbiter Vehicle (OV) 103. Sitting around table (left to right) are Mission Specialist (MS) Robert C. Springer, MS James F. Buchli, Commander Michael L. Coats, Pilot John E. Blaha, and MS James P. Bagian. A cake decorated with the STS-29 mission insignia is in the center of the table.
STS029-S-064 (18 Mar 1989) --- A rear view photographed from the ground just after Discovery's main landing gear touches down on Runway 22 at Edwards Air Force Base in California following a successful five-day mission in Earth orbit. Onboard the spacecraft were Astronauts Michael L. Coats, John E. Blaha, James F. Buchli, Robert C. Springer and James P. Bagian. Wheels came to a stop at 6:36:40 a.m. (PST), March 18, 1989.
Eine topologische Oberflächenmodifikation von metallischen Implantaten kann aus verschiedenen Gründen sinnvoll sein. Im Allgemeinen lassen sich zwei Hauptziele unterscheiden. Zum einen dienen Oberflächen dazu, bestimmte Zellreaktionen zu forcieren. Die Anwendungsbeispiele reichen hier von sehr rauen Oberflächen in Fällen wo eine gute Integration eines Permanentimplantates in das Gewebe erwünscht ist bis hin zu glatt polierten Oberflächen. Letztere werden in erster Linie dort eingesetzt, wo das Implantat in direktem Kontakt mit Blut ist. Ein Beispiel für die Erforderlichkeit einer hohen Rauheit (Rz > 100 μm) sind meist aus Titan gefertigte Schäfte von Gelenksimplantaten [1,2]. Die Autoren machten den Vorschlag, die Aufrauung von Titan- und Edelstahl-Stents analog der Aufrauung bei Hüftprothesenschäften zu versuchen, um eine noch bessere Biokompatibilität zu erreichen. [7, 8 ,9]. Sehr glatte Oberflächen, in der Regel mit Rz Werten von unter 0,1 μm, sind z. B. bei Herzklappenprothesen und der Innenseite von Gefäßstützen gefordert. Mittlere Rauheiten werden oft bei temporären Implantaten eingesetzt, in die in reguliertem Maße Gewebe einwachsen, allerdings keine unlösbare Verbindung bilden sollen. Sehr genau eingestellt werden müssen auch die Oberflächentopographien bei Implantaten in sehr empfindlichen Gebieten wie z. B. der Gehirnregion. Hierbei muss eine gute Verankerung im Gewebe vorhanden sein, um ein Verrutschen des Implantates zu verhindern. Zum anderen darf keine überschüssige Zellproliferation entstehen, um ein Einwachsen in sensible Regionen zu verhindern. Zum anderen werden Oberflächenmikrostrukturen genutzt, um Wirkstoffe in Implantate einzubringen, die lokal über einen bestimmten Zeitraum freigesetzt werden sollen. Als wichtigste Wirkstoffe sind hier Antibiotika und entzündungshemmende Mittel sowie im kardiovaskulären Bereich Proliferationshemmer zu nennen.
Discussion of two basic conceptions: Wilhelm von Humboldt's idea of language as energeia'' existing within and without man, and Noam Chomsky's idea of language generated by the speaker according to an innate apparatus. Revised version of lectures presented at the University of Bonn, West Germany in August 1971. (RS)
Describes work at a Goethe Institute branch with two groups of foreign students learning German, in which radio news, after preparatory work by the teacher, was used to induce question-and-answer dialogue. Many types of teaching aids and exercises used are described, including three-way conversation. (Text is in German.) (IFS/WGA)
Ball lightning phenomena and properties gleaned from a collection of observations are examined. The observations of a diffusion combustion of minute gas admixtures in air are thoroughly examined because they display the greatest resemblance to natural ball lightning. A comparison of properties with the qualities of the luminous clouds during diffusion combustion shows very good agreement. (W.D.M.)
Bautista-Aguilera, Oscar M; Esteban, Gerard; Chioua, Mourad; Nikolic, Katarina; Agbaba, Danica; Moraleda, Ignacio; Iriepa, Isabel; Soriano, Elena; Samadi, Abdelouahid; Unzeta, Mercedes; Marco-Contelles, José
2014-01-01
The design, synthesis, and biochemical evaluation of donepezil-pyridyl hybrids (DPHs) as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential treatment of Alzheimer's disease (AD) is reported. The 3D-quantitative structure-activity relationship study was used to define 3D-pharmacophores for inhibition of MAO A/B, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) enzymes and to design DPHs as novel multi-target drug candidates with potential impact in the therapy of AD. DPH14 (Electrophorus electricus AChE [EeAChE]: half maximal inhibitory concentration [IC50] =1.1±0.3 nM; equine butyrylcholinesterase [eqBuChE]: IC50 =600±80 nM) was 318-fold more potent for the inhibition of AChE, and 1.3-fold less potent for the inhibition of BuChE than the reference compound ASS234. DPH14 is a potent human recombinant BuChE (hBuChE) inhibitor, in the same range as DPH12 or DPH16, but 13.1-fold less potent than DPH15 for the inhibition of human recombinant AChE (hAChE). Compared with donepezil, DPH14 is almost equipotent for the inhibition of hAChE, and 8.8-fold more potent for hBuChE. Concerning human monoamine oxidase (hMAO) A inhibition, only DPH9 and 5 proved active, compound DPH9 being the most potent (IC50 [MAO A] =5,700±2,100 nM). For hMAO B, only DPHs 13 and 14 were moderate inhibitors, and compound DPH14 was the most potent (IC50 [MAO B] =3,950±940 nM). Molecular modeling of inhibitor DPH14 within EeAChE showed a binding mode with an extended conformation, interacting simultaneously with both catalytic and peripheral sites of EeAChE thanks to a linker of appropriate length. Absortion, distribution, metabolism, excretion and toxicity analysis showed that structures lacking phenyl-substituent show better druglikeness profiles; in particular, DPHs13-15 showed the most suitable absortion, distribution, metabolism, excretion and toxicity properties. Novel donepezil-pyridyl hybrid DPH14 is a potent, moderately selective hAChE and selective irreversible hMAO B inhibitor which might be considered as a promising compound for further development for the treatment of AD.
As technology has advanced, the scientific study of auroral phenomena has increased by leaps and bounds. A look back at the earliest descriptions of aurorae offers an interesting look into how medieval scholars viewed the subjects that we study.Although there are earlier fragmentary references in the literature, the first accurate description of the aurora borealis appears to be that published by the German Catholic scholar Konrad von Megenberg (1309-1374) in his book Das Buch der Natur (The Book of Nature). The book was written between 1349 and 1350.
S91-43614 (25 July 1991) --- The astronaut crewmembers for NASA's STS 48 mission, attired in orange partial pressure garments used for Shuttle launch and entry, prepare to participate in an emergency egress training session at the Johnson Space Center. The crewmembers are, left to right, astronauts Mark N. Brown, James F. Buchli and Charles D. (Sam) Gemar, all mission specialists, and John O. Creighton, Mission commander, and Kenneth S. Reightler, pilot. STS 48 is currently scheduled for mid-September of this year.
61A-39-052 (30 Oct-6 Nov 1985) --- This Earth view shows Quinhuangdao, China. The Great Wall of China can be seen in this photograph. The center coordinates are 40.0 north latitude and 120.0 east longitude. This photograph was taken from an altitude of 180 miles, on the 24th orbit of the Space Shuttle Challenger. The crew consists of astronauts Henry W. Hartsfield, Jr., commander; Steven R. Nagel, pilot; mission specialists James F. Buchli, Guion S. Bluford, Jr., Bonnie J. Dunbar; payload specialists Reinhard Furrer (DFVLR), Ernst Messerschmid (DFVLR), and Wubbo J. Ockels (ESA).
Gertrud Soeken (1897-1978), paediatrician as well as psychiatrist and neurologist, was involved in National Socialist medicine through her practical and scientific work. She supported both National Socialist health care and ideology. This article confronts her activities in science and health care politics with the strategy of her denazification proceedings, which ended with her suspension as chief physician in Berlin-Buch. The relevance of the professional network on which she was able to rely is particularly discussed.
STS-29 Discovery, Orbiter Vehicle (OV) 103, crewmembers are trained in procedures to follow in the event of a fire. Here, the crew is briefed on the correct handling of the fire extinguisher by Robert Fife (far left) of NASA's fire / security staff. Pictured, left to right are Pilot John E. Blaha, Commander Michael L. Coats, Mission Specialist (MS) Robert C. Springer, MS James F. Buchli, and MS James P. Bagian. The in fire fighting training took place at JSC's fire training pit across from the Gilruth Center Bldg 207.
S88-54948 (6 Dec 1988) --- The STS-29 crewmembers are trained in procedures to follow in the event of a fire with their spacecraft. Here, the crew is briefed on correct handling of the fire extinguisher by Robert Fife (far left) of NASA's fire and security staff. Pictured, left to right, are Astronauts John E. Blaha, pilot; Michael L. Coats, mission commander; Robert C. Springer, James F. Buchli and James P. Bagian, mission specialists. The training exercise took place on the northern end of the 1625-acre JSC facility.
perturbation pressure isobars. There is a ridge in (a) and a trough in (b) at the equator and to the east of the forcing region. Note that the pressure...Climatology course project team), CDR Eric Buch (C6F Oceanographer), Mr. Samson Brand (NRL Monterey), VADM Paul Gaffney (ret.), Prof. Russell Elsberry, LT...pressure isobars. There is a ridge in (a) and a trough in (b) at the equator and to the east of the forcing region. Note that the pressure to the west
Um Sprache und Musik über größere Entfernungen zu übertragen, wird der Hörschall mit einem Mikrofon in ein proportionales elektrisches Signal umgewandelt und auf drahtlosem Wege (Beispiel Rundfunkübertragung) oder drahtgebunden (Beispiel Telefon, Kabelrundfunk, oft in Kombination mit dem drahtlosen Weg) zum Empfänger übermittelt. Am Empfangsort setzt z. B. ein Lautsprecher das elektrische Signal wieder in ein akustisches Signal um.
In keinem anderen Land der Erde ist der Anteil ausländischer Studenten im Fach Physik größer als in den USA. Nach den Terroranschlägen vom 11. September werden jedoch zunehmend ausländische Studenten, insbesondere aus China und dem mittleren Osten, abgewiesen - zum Leidwesen der Studenten und der Universitäten.http://www.aip.org/statistics
products and for occupational safety and health protection, into a majority rule, the elaboration and adoption of directives was additionally speeded up...they contain. Safety standards serve to protect life, health and material goods and so, for the field of technology, express the requirements laid...p. 19, 13.02.1996 Press release 05-97: Entscheidung zum Arbeitsschutzmanagement (Decision on industrial safety management ) http://www.din.de
In seinem Kommentar schließt Traugott Scheytt die faunistische Bioindikation über die Nutzung von Grundwassermessstellen aus methodischen Gründen aus. Er postuliert auch, dass die faunistische Indikation hydrogeologischer Zusammenhänge wegen der eingeschränkten Ausbreitungsfähigkeit der Tiere in Porengrundwasserleitern nicht möglich sei und stellt grundsätzlich die Befunde unserer Untersuchungen am Kaiserstuhl in Frage. Dabei überträgt Herr Scheytt seine Erfahrungen aus der unbelebten Hydrogeologie direkt auf den Lebensraum Grundwasser. Seine Argumentation berücksichtigt dabei weder die Prinzipien der Ökologie noch den aktuellen Stand der grundwasserökologischen Forschung. Wir gehen davon aus, dass für die Untersuchungen am Kaiserstuhl sowohl unsere Arbeitshypothese wie auch die angewandten Methoden und die Interpretation der Ergebnisse der Fragestellung angemessen sind und internationalem, wissenschaftlichem Standard entsprechen. Aus den oben benannten Gründen bleiben wir dabei: Biondikation im Grundwasser funktioniert und sie bietet hervorragende Möglichkeiten, gerade auch für die Hydrogeologie.
Hoffman, D.J.; Henny, C.J.; Hill, E.F.; Keith, J.A.; Grove, R.A.
2000-01-01
High concentrations of mercury from past mining activities have accumulated in the food chain of fish-eating birds nesting along the mid to lower Carson River. Activities of nine plasma and tissue enzymes, and concentrations of other plasma and tissue constituents were measured for black-crowned night-heron, Nycticorax nycticorax, (BCNH) and snowy egret, Egretta thula, (SE) nestlings from two high mercury sites and one low mercury site. Geometric mean blood Hg concentrations for BCNHs at the high mercury sites were 2.6 and 2.8 ppm (ww) and 0.6 ppm at the low mercury site. Blood concentrations for SEs were 3.6 and 1.9 ppm at the high mercury sites and 0.7 ppm at the low mercury site. In BCNHs plasma glutathione peroxidase (GSH peroxidase) activity was lower in both high mercury sites relative to the low mercury site. Butyryl cholinesterase (BuChe), ALT, glutathione reductase (GSSG-reductase) and LDH-L activities were lower in one high mercury site. In SEs significant differences were lower BuChe and LDH-L, but elevated GGT activities. Evidence of renal stress in both species at high mercury sites included increased plasma uric acid, blood urea nitrogen, and creatinine concentrations as well as oxidative stress in the kidney tissue itself where oxidized glutathione increased. A number of the mercury site-related effects, including decreased plasma GSH-peroxidase and hepatic G-6-PDH activities, higher GSSG-reductase activity, and lower hepatic concentrations of reduced thiols have been reported in methylmercury feeding studies with great egrets and mallards. These findings suggest the utility of herons and egrets for monitoring mercury sites.
New placement procedure at Humboldt University includes interviews and placement tests. Interviews reveal response ability, tempo, pronunciation, comprehension, etc. The 60-minute test that follows is described and results discussed, as well as difficulty level and grading. Results: better grouping of students, less shifting, better work. (Text is…
Anmerkungen zum Balassa - Samuelson -Effekt, Nr. 3/2002, erschienen in: Stefan Reitz (Hg.): Theoretische und wirtschaftspolitische Aspekte der internatio- nalen...However, the argument is slightly more complex. Using a simple model with differentiated networks, Buehler and Haucap (2004) show that the incumbent’s...Elasticities The above arguments suggest that it is more difficult to gain market share in the presence of switching costs, as undercutting needs to be
Wolf, EU-Erweiterung: Anmerkungen zum Balassa - Samuelson -Effekt, Nr. 3/2002, erschienen in: Stefan Reitz (Hg.): Theoretische und wirtschafispolitische...the individualistic norm. Their main argument is that the contradiction between collective coercion and individual freedom cannot be dissolved at the... arguments against this way of reasoning for there usually will be holes in that veil, so that it may be possible to draw conclusions from the past with
This article talks about the subjunctive of indirect speech, in which its important functions and meanings are depicted. An analysis of the instructional materials used in the first and second years of language study, followed by practical curriculum recommendations, demonstrates how this grammatical phenomenon can be established in an advanced…
The questionnaire dealt with: earmarks of weaker students, parents' attitude, the teachers' training and working conditions, problems of individual instruction, time-frame, existence of professional associations, evaluation of professional conferences, and the use of media. Some evaluations are appended. (IFS/WGA)
61A-40-38 (30 Oct-6 Nov 1985) --- The coral reef forming the atoll of Midway sits atop a volcanic seamount that has descended more than 3,000 feet (1000 meters) below the sea surface in this ancient region of the Hawaiian volcanic chain. This view was taken by the crew members onboard the Earth-orbiting Space Shuttle Challenger. The crew consisted of astronauts Henry W. Hartsfield, Jr., commander; Steven R. Nagel, pilot; James F. Buchli, Guion S. Bluford, Jr., and Bonnie J. Dunbar, all mission specialists; Reinhard Furrer, Ernst Messerschmid, and Wubbo J. Ockels, all payload specialists. Ockels represents the European Space Agency (ESA).
STS029-01-001 (16 Marach 1989) --- Astronaut John E. Blaha, STS-29 pilot, checks an incubator on the mid deck of Earth-orbiting Discovery during Flight Day 4 activity. The incubator is part of a student involvement program experiment titled, "Chicken Embryo Development in Space." The student experimenter is John C. Vellinger. The experiment's sponsor is Kentucky Fried Chicken. This photographic frame was among NASA's third STS-29 photo release. Monday, March 20, 1989. Crewmembers were Astronauts Michael L. Coats, John E. Blaha, James F. Buchli, Robert C. Springer and James P. Bagian.
STS-29 Discovery, Orbiter Vehicle (OV) 103, crewmembers receive briefing on Student Experiment (SE) 83-9 Chicken Embryo Development in Space or 'Chix in Space' from student experimenter John C. Vellinger and sponsor Mark S. Deusser. Vellinger (right) explains operation of an incubator used in his experiment to crewmembers, seated around table, and other support personnel in audience. Clockwise from Mission Specialist (MS) Robert C. Springer (hands together at left) are MS James F. Buchli (glasses), Commander Michael L. Coats, Pilot John E. Blaha, MS James P. Bagian, Vellinger, and Deusser. The student's sponsor is Kentucky Fried Chicken (KFC).
Argues that the thesis of discrimination against girls in coeducation schools has been replaced by a belief that, during certain phases or in specific subjects, abandonment of coeducation would promote equal opportunities. Questions whether classic or recent surveys provide empirical evidence for this moderate skeptical attitude towards…
Wir bemühen uns, insbesondere bei Kindern, den Lernprozess auch im Mathematikunterricht durch den Einsatz von Materialien zu unterstützen. Die Arbeitsschritte dienen dabei oft der Vorbereitung oder Herleitung von Verfahren - in der Hoffnung, dass durch die Veranschaulichung Zusammenhänge besser verstanden werden. Worin dann das Verstehen besteht, wenn im Ergebnis ein Verfahren von den Kindern erfolgreich abgearbeitet wird, ist nicht unmittelbar zu sehen.
The typical traits of a ready-made system as well as those of an individualized system are constituent characteristics of distance education. Within the framework set by these qualities and the extent to which they differ from one another, one seeks to achieve the fundamental educational aim of distance students' autonomy. The way institutions see…
Michael, Social Capital and Regional Mobility, Nr. 4/2002. "* Schdfer, Wolf, EU-Erweiterung: Anmerkungen zum Balassa - Samuelson -Effekt, Nr. 3/2002...variations, while the argument of both the present paper and most of the previous literature on inequality and growth refers to long-run growth effects of...Diskussionsbeitriige zur Finanzwissenschaft " Josten, Stefan, Crime, Inequality, and Economic Growth. A Classical Argument for Distributional Equality
Nearly all German textbooks currently used in the USA either entirely fail to mention Austria, or else portray it by means of myths, cliches (Apfelstrudel, Sachertorte, Gemuetlichkeit), and often with outright untruths. The American student gets a picture of Austria as an "underdeveloped Disneyland of Europe". (WGA)
Reports on the introduction of video recorders at various branches of the Goethe Institute. The characteristics of video are compared with those of films, tapes and printed matter. Video's advantage is that through it authentic, unprepared material can be presented, and it provides strong motivation. (Text is in German.) (IFS/WGA)
The phonetic symbols in the "Advanced Learners Dictionary" (Oxford University Press, London) are discussed critically in articles by L. Alfes, H. Arndt, E. Bauch, G. Dahlmann-Resing, W. Friedrich, E. Germer, B. Haycraft, H. P. Kelz. Reference is made to an earlier article "Neue Zeichen", by H. G. Hoffmann. (Text is in German.)…
The ten papers in this document were developed for a meeting prepared for the Third International Congress on Mathematical Education. Each paper is concerned with research from 1970-1975 related to the mathematical learning process. The first paper describes projects conducted in England on both content and process learning. The second paper…
Störungen der embryonalen Entwicklung in der frühen Phase der Schwangerschaft können zu Fehlbildungen am Herz- und Gefäßsystem führen. Die Häufigkeit liegt bei 0.8-1 % aller lebend geborenen Kinder. In Deutschland werden jedes Jahr etwa 6.000 Kinder mit einem Herzfehler geboren (Quelle: http://www.kompetenznetzahf.de). Das Spektrum reicht von einfachen Fehlern, die das Herz-Kreislauf-System wenig beeinträchtigen, bis zu sehr schweren Herzerkrankungen, die unbehandelt zum Tode führen. Fortschritte der Kinderkardiologie, Herzchirurgie und Anästhesie ermöglichen heute ein Überleben bei über 90 % der Patienten. Auch die spezialisierte Pränataldiagnostik (vorgeburtliche Diagnostik) ermöglicht schon die frühe Weichenstellung für mögliche Therapieoptionen. Bei der chirurgischen Therapie ist jedoch festzuhalten, dass ein Herzfehler entweder korrigierend behandelt wird oder nur "palliiert“ werden kann. Bei letzterer Therapie wird bei einem Patienten eine medizinische Maßnahme durchgeführt, die nicht die Herstellung normaler Körperfunktionen zum Ziel hat, sondern in Anpassung an die physiologischen Besonderheiten des Patienten dessen Zustand lediglich stabilisiert und optimiert. Dies kann beispielsweise bei einer nicht korrigierbaren angeborenen Fehlbildung notwendig sein, bei der lediglich eine funktionelle Herzkammer vorhanden ist (z. B. hypoplastisches Linksherz). Hierbei muss eine prothetische Verbindung zur Lungenstrombahn in der Folgezeit entfernt werden.
Time course of /sup 3/H-physostigmine (Phy) concentration and cholinesterase (ChE) activity in plasma and tissues was studied in rats pretreated with Phy and then soman. Rats were dosed with Phy (100 ..mu..g/kg, i.v.), 5 or 15 min prior to soman (105 ..mu..g/kg, 1.5 LD/sub 50/, s.c.) treatment and were sacrificed at various times; Phys conc. and ChE activity were determined. BuChE activity in plasma was 5% of control from 7-30 min after Phy i.v. pretreatment and soman or soman alone treatment. Plasma Phy conc. steadily declined (32.6 ng/ml at 7 min) to 15 ng/ml at 30 min. ChE activity inmore » muscle was 60-50% of control for Phy pretreated but soman alone gave 85-72% activity from 2-30 min. Brain ChE activity was about 5% of control within 2 min after soman treatment; however, with Phy pretreatment, the activity was about 52% at 7 min, 40% at 22 min, which recovered to 45% of control at 35 min, indicating that Phy protected brain ChE. Brain Phy conc. steadily declined (58.6 ng/g at 7 min) to 11.7 ng/g at 30 min. However, pretreatment of rat with a higher dose of Phy and then soman showed BuChE in plasma and ChE in brain and muscle to be about 25, 35 and 51%, in comparison to about 5% in plasma and brain with soman alone treatment, indicating higher protection of ChE enzyme with higher conc. of Phy in plasma and brain.« less
da Silva Benetti, Carla; Silveira, Patrícia Pelufo; Wyse, Angela T S; Scherer, Emilene B S; Ferreira, Andréa G K; Dalmaz, Carla; Goldani, Marcelo Zubaran
2014-04-01
Previous studies have demonstrated that early environmental interventions influence the consumption of palatable food and the abdominal fat deposition in female rats chronically exposed to a highly caloric diet in adulthood. In this study, we verified the metabolic effects of chronic exposure to a highly palatable diet, and determine the response to its withdrawal in adult neonatally handled and non-handled rats. Consumption of foods (standard lab chow and chocolate), body weight gain, abdominal fat deposition, plasma triglycerides, and leptin, as well as serum butyrylcholinesterase (BuChE), and cerebral acetylcholinesterase (AChE) activities were measured during chronic chocolate exposure and after deprivation of this palatable food in female rats exposed or not to neonatal handling (10 minutes/day, 10 first days of life). Handled rats increased rebound chocolate consumption in comparison to non-handled animals after 1 week of chocolate withdrawal; these animals also decreased body weight in the first 24 hours but this effect disappeared after 7 days of withdrawal. Chocolate increased abdominal fat in non-handled females, and this effect remained after 30 days of withdrawal; no differences in plasma leptin were seen after 7 days of withdrawal. Chocolate also increased serum BuChE activity in non-handled females, this effect was still evident after 7 days of withdrawal, but it disappeared after 30 days of withdrawal. Chocolate deprivation decreased cerebral AChE activity in both handled and non-handled animals. These findings suggest that neonatal handling modulates the preference for palatable food and induces a specific metabolic response that may be more adaptive in comparison to non-handled rats.
Following the successful completion of the 3rd biomedical confidence building exercise (February 2013 – March 2013), which included the analysis of plasma and urine samples spiked at low ppb levels as part of the exercise scenario, another confidence building exercise was targeted to be conducted in 2014. In this 4th exercise, it was desired to focus specifically on the analysis of plasma samples. The scenario was designed as an investigation of an alleged use of chemical weapons where plasma samples were collected, as plasma has been reported to contain CWA adducts which remain present in the human body for severalmore » weeks (Solano et al. 2008). In the 3rd exercise most participants used the fluoride regeneration method to analyze for the presence of nerve agents in plasma samples. For the 4th biomedical exercise it was decided to evaluate the analysis of human plasma samples for the presence/absence of the VX adducts and aged adducts to blood proteins (e.g., VX-butyrylcholinesterase (BuChE) and aged BuChE adducts using a pepsin digest technique to yield nonapeptides; or equivalent). As the aging of VX-BuChE adducts is relatively slow (t1/2 = 77 hr at 37 °C [Aurbek et al. 2009]), soman (GD), which ages much more quickly (t1/2 = 9 min at 37 °C [Masson et al. 2010]), was used to simulate an aged VX sample. Additional objectives of this exercise included having laboratories assess novel OP-adducted plasma sample preparation techniques and analytical instrumentation methodologies, as well as refining/designating the reporting formats for these new techniques.« less
Grasing, Kenneth; Mathur, Deepan; DeSouza, Cherilyn; Newton, Thomas F.; Moody, David E.; Sturgill, Marc
2016-01-01
Background In rodents, cholinesterase inhibitors can cause sustained decreases in the reinforcing effects of cocaine. Nonetheless, cocaine is metabolized by butyrylcholinesterase (BuChE), raising concerns that cholinesterase inhibition could increase its peripheral concentrations, perhaps augmenting toxicity. Although donepezil is approved for use in patients and selective for inhibiting acetylcholinesterase over BuChE, no studies have reported cocaine bioavailability in human subjects receiving donepezil. Methods Twelve cocaine-dependent veterans received three days of treatment with either oral placebo or 5 mg daily of donepezil, followed by cross-over to the opposite treatment. During both oral treatments, double-blind intravenous cocaine was administered at 0.0, 0.18, 0.36 mg/kg in a laboratory setting, followed by determinations of heart rate, blood pressure, and plasma concentrations of cocaine and major metabolites. Results Intravenous cocaine produced dose-related increases in systolic blood pressure that were most pronounced over the initial 30 minutes after treatment. Oral donepezil attenuated drug-induced elevations of systolic blood pressure following low-dose cocaine (0.18 mg/kg). No significant difference in blood pressure following treatment with placebo or donepezil after high-dose cocaine (0.36 mg/kg). Peak values of blood pressure and heart rate were unaffected by donepezil. Plasma concentrations of cocaine and metabolites did not differ in donepezil- and placebo- treated participants. Conclusions and Scientific Significance We conclude that donepezil can attenuate drug-induced increases in systolic blood pressure following low-dose cocaine, but does not otherwise modify the cardiovascular effects of intravenous cocaine. Clinically significant changes in cocaine bioavailability and cardiovascular effects do not occur following this dose of donepezil. PMID:27392137
The responses of various xenobiotic metabolizing enzymes in fish models are rapidly evolving as important biomarkers for monitoring unacceptable levels of environmental contaminants. Ethoxyresorufin O-deethylase, a specific cytochrome P450-dependent monooxygenase, is often used as an indicator of polycyclic aromatic hydrocarbon pollution. Another class of enzymes which are potential biomarkers are the B-type esterases. These enzymes are sensitive to inhibition by organophosphates, and include the cholinesterases (ChE) and carboxylesterases. ChEs are further subdivided into acetylcholinesterase and butyryl cholinesterase. Among fish, AChE is predominantly localized in the brain and muscle, whereas, BuChE activity is found mainly in liver and plasma. The precisemore » physiological role of BuChE is unknown, although it has been regarded as a marker enzyme for glial or supportive cells or other non-neuronal elements. Inhibition of ChE activity has often been associated with exposure to organophosphate and carbamate insecticides and other neurotoxic xenobiotics. Chemicals other than carbarnates and organophosphates that are environmental contaminants can also affect the activity of ChEs. Carboxylesterases represent a heterogenous group of isozymes that can catalyze the hydrolysis of a wide range of xenobiotic esters, amides and thioesters. For most CaE, their natural substrates are unknown, therefore, their physiological functions remain to be elucidated. These enzymes (CaE) occur widely in most tissues and are generally found in high levels in the liver. The purpose of this research was to evaluate the liver and brain esterases in the spotted gar fish as biomarkers of effect to multiple contaminants in the lower Mississippi River basin. 15 refs., 3 figs., 2 tabs.« less
Martínez-Perafán, Fabián; Santoli, María Fernanda; López-Nigro, Marcela; Carballo, Marta Ana
2018-02-01
In some rural areas in Argentina, adolescents may be considered as a group indirectly exposed to agrochemicals because their parents plant small crops near their homes. This could become a health risk to children and adolescents who may be more sensitive to exposure to chemicals than adults. The objective of this study was to evaluate the health status of two different groups of Argentinian adolescents using biochemical parameters, dietary information, and cytogenetic biomarkers of genotoxicity and cytotoxicity. The study groups included 32 adolescents from Montecarlo, who were indirectly exposed to agrochemicals, and 30 unexposed adolescents from Exaltación de la Cruz. The values of total cholesterol, LDL cholesterol, triglycerides, gamma glutamyltransferase, and butyrylcholinesterase (BuChE) were higher (p < 0.05) in males from Exaltación de la Cruz compared with those from Montecarlo. The BuChE activity was also higher (p < 0.05) in females from this region. Furthermore, the consumption of citrus, vegetable-like fruits, tubers, and red meat was more frequent (p < 0.05) in Montecarlo. On the other hand, differences in frequency of biomarkers of genetic damage in lymphocytes were not found (p > 0.05). However, the cytome assay in buccal cells showed that karyorrhectic and pyknotic cells were more frequent (p < 0.05) in the Montecarlo group; whereas, the frequencies of cells with nuclear buds, condensed chromatin and karyolysis were higher (p < 0.05) in the Exaltación de la Cruz group. Despite the differences between the parameters and biomarkers evaluated, the adolescents of Montecarlo did not present health impairment probably due to the type and level of exposure to agrochemicals.
Since 2001 we minimized access (2.9-4.7 cm) for universally applicable endoscopic hybrid carinatum technique with two transsternal Willital bars in 173 endoscopic hybrid (EH) patients with very satisfactory results. In 2008-2009, endoscopic Nuss bar compression with endoscopic repair of costal flaring applied a new eight-hole stabilizer, which allows the use in pectus carinatum (PC) beyond adolescence including redos and combined deformities. This prospective study of 35 "endoscopic Berlin-Buch reversed Nuss" repairs intends to establish indications for this improved technique. In February 2008 to February 2010, we used endoscopic Nuss bar compression by applying a bilateral new eight-hole stabilizer fixed to the bar without screws or wires, which allows unprecedented versatility and the use in pectus carinatum beyond adolescence. Thirty-five patients aged 17.05 ± 10.2 years (range: 11.3-33.1 years) were recorded prospectively and followed at 3 monthly intervals. We implanted a standard Nuss bar (11-14') into an endoscopically dissected submuscular presternal pocket correcting PC by sternal pressure. The bars were put under tension by traction via bilateral eight-hole stabilizers and three pericostal wire sutures on each side. Bars were removed after 2 years. All 35 "reversed Nuss" pectus carinatum repairs, including 2 redos after Ravitch, were successful, with no conversion. So far there was no local or general complication and no seroma or bar dislocation. Thirty-one patients judged their result as excellent and 4 as good. Although this is a very early experience, "reversed Nuss" is safe and effective and new technical improvements have expanded the range of applicability to older patients and suitable redos.
This bibliography lists publications concerned with bilingual education and immersion programs and how they are used in and outside of Canada. In the beginning, an overview is provided of publications from related disciplines that have brought crucial recognition to the fields of bilingual and immersion education. These include: second and foreign…
Bock JM et al. Evaluation of the natural history of patients who aspirate. Laryngoscope 2017; 127: S1–S10 DIE KLINISCHE PROGRESSION DER ASPIRATION BIS ZU EVENTUELLEN PULMONALEN STöRUNGEN IST NICHT VOLLSTäNDIG VERSTANDEN. EMPFEHLUNGEN ZUR ERNäHRUNGSUMSTELLUNG, SCHWERE VON PENETRATION UND ASPIRATION GEMäß PAS SOWIE DIE ÄTIOLOGIE DER DYSPHAGIE BEEINFLUSSEN MöGLICHERWEISE DIE ZEITSPANNE BIS ZUM AUFTRETEN DES ERSTEN PULMONALEN EREIGNISSES SOWIE DAS GESAMTüBERLEBEN VON PATIENTEN MIT VFS-DOKUMENTIERTER, ASYMPTOMATISCHER PENETRATION UND ASPIRATION.
STS029-24-004 (18 March 1989) --- STS-29 crewmembers, wearing launch and entry suits (LESs) and launch and entry helmets (LEHs), review checklists on Discovery, Orbiter Vehicle (OV) 103, flight deck. Commander Michael L. Coats is seated at the forward flight deck commanders station with Mission Specialist (MS) James F. Buchli on aft flight deck strapped in mission specialist seat. OV-103 makes its return after five days in space. Note color in forward windows W1, W2, W3 caused by friction of entry through the Earth's atmosphere. Personal Egress Air Pack (PEAP) is visible on pilots seat back.
STS029-S-024 (13 March 1989) --- The flight crew for NASA's STS-29 mission leave the operations and checkout building en route to the van that will transport them to Launch Pad 39B, where Discovery awaits the astronauts for its second post-Challenge flight. Leading the way is astronaut Michael L. Coats, mission commander. He is followed by astronauts John E. Blaha, pilot; and James F. Buchli, James P. Bagian and Robert C. Springer, all mission specialists. In the background are astronaut Daniel C. Brandenstein, chief of the astronaut office, and Donald R. Puddy, director of flight crew operations.
Using Richard Wright's novel "Black Boy" as a model to work on, the author illustrates a 4-dimensional approach to the teaching of foreign literature: (1) scientific definition of the goals, (2) making a teaching plan, (3) defining methods, and (4) actual use on a teaching model. (Text is in German.) (IFS/WGA)
Ebert, Karl-Herbert; Ammer, Daniel; Hoffstetter, Marc; Wintermantel, Erich
Bei der Betrachtung von aktuellen Produktentwicklungen lässt sich durch alle Branchen hinweg ein deutlicher Trend zur Miniaturisierung und Funktionsintegration auf kleinstem Raum erkennen. Der Einsatz technischer Kunststoffe, die überwiegend im Thermoplast-Spritzgießverfahren verarbeitet werden, leistet dabei einen wichtigen Beitrag um diese Produktentwicklungen in marktfähige Artikel umsetzen zu können. Hierbei sind im Vergleich zum Standardspritzgießen einige Besonderheiten hinsichtlich des Formenbaus, der Anlagen- sowie Prozesstechnik und der Qualitätssicherung zu beachten.
environ- mental conditions, the growth of Hydri a and Myriophylwn is relatively poor on low density, highly organic sediments and on high density sands. Whi...A1jriophyZum 5.08 1 0.33 0.93 K HydritZa 27.8 t 0.8 0,98 M-plroph,,Uum 20.4 t 0.6 0.98 Na Hydri Z 0.42 ± 0.03 0.93 MyxiophyTZum 8.03 t 0.43 0.95 H9
Reports on an 18-hour teaching project with students at a teachers' college. Four Baldwin texts were used. Questions considered included whether Baldwin's treatment of the race problem reveals any changes or shifts of emphasis. Suggestions are made for adaptation to teaching in grades 11-13. (Text is in German.) (IFS/WGA)
Die Balanced Scorecard (BSC) ist ein Ansatz zum strategischen Management, der neben der Ausrichtung des Unternehmens auf finanzielle Zielwerte ebenso großes Gewicht auf so genannte weiche Faktoren legt, die den wirtschaftlichen Erfolg eines Unternehmens erst ermöglichen. Das entscheidende Merkmal der Balanced Scorecard ist dabei, dass sie ein ausgewogenes System strategischer Ziele herstellt, welches das Unternehmen hinsichtlich der vier Perspektiven Finanzen, Kunden, interne Prozesse und Mitarbeiter und Potenziale strategisch ausrichtet (Kaplan u. Norton 1997).
sums of exponentials of quadratics, he reduced such ýzums to exponentials of linears (geometric sums!) by simplg multiplying by their conjugates...n, the same algebraic manipulations as before lead to rn V`-~ v ie ? --8-- el4V’ .fk ts with = a+(2r+l)t, A = a+(2r+2m+l)t. To estimate the right...coefficients. These random polynomials represent the deviation in frequency response of a linear , equispaced antenna array cauised by coefficient
Die Transformation des Energiesystems von einer zentral geprägten, unidirektional orientierten und in unterschiedliche Sektoren separierten Struktur hin zu einer umfassenden, multimodalen, dezentralen und flexiblen Erzeuger- und Verbraucherlandschaft findet auf verschiedenen Ebenen statt. Randbedingung bei dieser Umwälzung ist immer die Einhaltung der Teilziele Versorgungssicherheit, Wirtschaftlichkeit und Effizienz. Im Einzelnen schlägt sich diese Transformation in einer Diversifizierung der Akteurslandschaft durch die Mechanismen des Unbundling nieder. Weiterhin finden eine Dezentralisierung der Erzeugerlandschaft und damit eine Substitution von mehrheitlich fossil betriebener Großkraftwerkstechnologie durch eine Vielzahl dezentraler Erzeuger mit zumeist regenerativem Charakter statt. Dieser Wandel hat im Wesentlichen zwei Hauptkonsequenzen. Zum einen ergeben sich durch dezentrale, flächige Verteilung der Erzeuger neue Anforderungen an den Energieaustausch, bspw. aus der Erweiterung der Stromnetze für einen bidirektionalen Energieaustausch, zum anderen werden Abstimmungsmechanismen erforderlich, welche die fluktuierende Einspeisung derart mit dem Verbrauch in Waage hält, dass sowohl elektrische Netzrestriktionen, die Qualität der Versorgung und Aspekte der Energieeffizienz und damit der Wirtschaftlichkeit berücksichtigt werden. Mögliche Antworten auf die mit dieser Betrachtung einhergehenden Fragen liegen in der Konzeption eines multimodalen Energiesystems, also in der Gesamtbetrachtung der Sektoren Strom, Wärme und Verkehr. Dieses Kapitel soll Mechanismen darlegen und Wege aufzeigen, wie eine solche Konzeption gestaltet werden kann und wie solche komplexen Systeme in der Praxis betrieben werden können.
Local actors, such as municipal authorities, can promote and shape the settlement of foreign companies in a particular manner. In many instances, actions of economic promotion can lead to several conflicts; firstly between foreign investors and their national representatives, and secondly with (supra)regional industries or business circles. Here, flexible and long-term settlement projects, the permission of migrant infrastructure, and moreover, their high-profile marketing may attract foreign companies and long-term investors.
Regional Mobility, Nr. 4/2002. "* Schafer, Wolf, EU-Erweiterung: Anmerkungen zum Balassa - Samuelson -Effekt, Nr. 3/2002, erschienen in: Stefan Reitz (Hg...generations with high long-term external costs as it is the case in the dry tomb technology. Besides the efficiency aspect an argument of justice is... argument of time- consistency according to Strotz does not play any role because the assumed "rational" way of planning cannot be realized due to the non
Umfassende Einführung in die Grundlagen der Bewegtbild-Übertragung von den Anfängen bis zum heutigen Stand des digitalen Fernsehens mit einer aus der Praxis entstandenen systemtheoretischen Analyse. Die kompakte und anschaulich bebilderte Darstellung mit elementaren mathematischen Beschreibungen macht es dem Leser leicht, sich in die Bildübertragungstechnik einzuarbeiten. Thematische Einheiten erweitern den Wissensstoff - u.a. zu den Themen visuelle Wahrnehmung, mehrdimensionale Signaldarstellung, Farbmetrik, Digitalisierung, Elektronenoptik - und zeigen deren Anwendung auf die elektronische Bildübertragung.
cross - Bruttoquerschni tt section Zahl der Flugstunden = number of flight hours Fig 2.8 Fatigue strength of ...Relationship between residual strength, strain increase and development of damage as a function of the number of cycles (Ref 732) 118 / 0 /+45 / 90 /- CFK ... cross -section) only the nett cross -section. Number of 900 where intralaminar cracks ha! increased further. cracks had occurred 4. Delaminations
Describes work at an American college with students who are receiving an introduction to colloquial German. Role-playing and picture stories prove useful in learning, in both productive and receptive aspects. Describing a picture on three levels--factual, psychological and contemplative--is shown to be very useful. (IFS/WGA)
Ashok, B K; Bhat, Savitha D; Shukla, V J; Ravishankar, B
2011-07-01
The present study was undertaken to evaluate diuretic activity of Euphorbia fusiformis root powder in Wistar strain albino rats. Randomly selected animals were divided into three groups of six animals each. The root powder was suspended in distilled water and administered orally at a dose of 90 mg/kg therapeutically equivalent dose (TED) and 180 mg/kg (TED × 02) to overnight fasted rats. The diuretic activity was evaluated by determination of urine volume and urinary electrolyte concentrations. Test drug showed significant increase in urine volume and urinary electrolyte excretion in a dose-dependant manner. Thus, from this study, it can be concluded that roots of E. fusiformis possess diuretic activity.
The potent antimalarial drug artemisinin has a high cost, since its only viable source to date is Artemisia annua (0.01-0.8% DW). There is therefore an urgent need to design new strategies to increase its production or to find alternative sources. In the current study, Artemisia carvifolia Buch was selected with the aim of detecting artemisinin and then enhancing the production of the target compound and its derivatives. These metabolites were determined by LC-MS in the shoots of A. carvifolia wild type plants at the following concentrations: artemisinin (8μg/g), artesunate (2.24μg/g), dihydroartemisinin (13.6μg/g) and artemether (12.8μg/g). Genetic transformation of A. carvifolia was carried out with Agrobacterium tumefaciens GV3101 harboring the rol B and rol C genes. Artemisinin content increased 3-7-fold in transgenics bearing the rol B gene, and 2.3-6-fold in those with the rol C gene. A similar pattern was observed for artemisinin analogues. The dynamics of artemisinin content in transgenics and wild type A.carvifolia was also correlated with the expression of genes involved in its biosynthesis. Real time qPCR analysis revealed the differential expression of genes involved in artemisinin biosynthesis, i.e. those encoding amorpha-4, 11 diene synthase (ADS), cytochrome P450 (CYP71AV1), and aldehyde dehydrogenase 1 (ALDH1), with a relatively higher transcript level found in transgenics than in the wild type plant. Also, the gene related to trichome development and sesquiterpenoid biosynthesis (TFAR1) showed an altered expression in the transgenics compared to wild type A.carvifolia, which was in accordance with the trichome density of the respective plants. The trichome index was significantly higher in the rol B and rol C gene-expressing transgenics with an increased production of artemisinin, thereby demonstrating that the rol genes are effective inducers of plant secondary metabolism.
Alzheimer's disease (AD) is characterized by deposition of amyloid-beta peptide (Aβ) plaque, disrupted Aβ-precursor protein (APP) metabolism, hyperphosphorylation of Tau leading to neurofibrillary tangles and associated neurotoxicity. Moreover, there is synaptic loss in AD, which occurs early and precedes frank amyloidosis. The central cholinergic system is especially vulnerable to the toxic events associated with AD, and reduced acetylcholine (ACh) levels in specific brain regions is thought to be the central to memory deficits in AD. First-generation cholinesterase inhibitors (ChEIs) have provided only symptomatic relief to patients with AD by prolonging the action of remaining ACh with little or no change in the course of the disease. Some second-generation cholinesterase inhibitors are multi-functional drugs that may provide more than purely palliative results. To evaluate the effects of the dual AChE and butyrylcholinesterase (BuChE) inhibitor rivastigmine on key aspects of AD, embryonic day 16 rat primary cortical cultures were treated with rivastigmine under time and media conditions observed to induce neurodegeneration. Samples were subjected to Western blotting and immunocytochemistry techniques to determine what influence this drug may have on synaptic proteins and neuronal morphology. There was a strong increase in relative cell viability as a result of rivastigmine treatment. Significant dose-dependent increases were observed in the levels of synaptic markers SNAP-25 and synaptophysin, as well as the neuron specific form of enolase. Together with an observed enhancement of neuronal morphology, our results suggest a rivastigmine-mediated novel neuroprotective and/or neurorestorative effects involving the synapse. Our observations may explain the potential for rivastigmine to alter the course of AD, and warrant further investigations into using BuChE inhibition as a therapeutic strategy for AD, especially with regard to restoration of synaptic function. PMID:19912467
Mamczarz, Jacek; Pescrille, Joseph D.; Gavrushenko, Lisa; Burke, Richard D.; Fawcett, William P.; DeTolla, Louis J.; Chen, Hegang; Pereira, Edna F.R.; Albuquerque, Edson X.
2017-01-01
Exposure of the developing brain to chlorpyrifos (CPF), an organophosphorus (OP) pesticide used extensively in agriculture worldwide, has been associated with increased prevalence of cognitive deficits in children, particularly boys. The present study was designed to test the hypothesis that cognitive deficits induced by prenatal exposure to sub-acute doses of CPF can be reproduced in precocial small species. To address this hypothesis, pregnant guinea pigs were injected daily with CPF (25 mg/kg, s.c.) or vehicle (peanut oil) for 10 days starting on presumed gestation day (GD) 53–55. Offspring were born around GD 65, weaned on postnatal day (PND) 20, and subjected to behavioral tests starting around PND 30. On the day of birth, butyrylcholinesterase (BuChE), an OP bioscavenger used as a biomarker of OP exposures, and acetylcholinesterase (AChE), a major molecular target of OP compounds, were significantly inhibited in the blood of CPF-exposed offspring. In their brains, BuChE, but not AChE, was significantly inhibited. Prenatal CPF exposure had no significant effect on locomotor activity or on locomotor habituation, a form of non-associative memory assessed in open fields. Spatial navigation in the Morris water maze (MWM) was found to be sexually dimorphic among guinea pigs, with males outperforming females. Prenatal CPF exposure impaired spatial learning more significantly among male than female guinea pigs and, consequently, reduced the sexual dimorphism of the task. The results presented here, which strongly support the test hypothesis, reveal that the guinea pig is a valuable animal model for preclinical assessment of the developmental neurotoxicity of OP pesticides. These findings are far reaching as they lay the groundwork for future studies aimed at identifying therapeutic interventions to treat and/or prevent the neurotoxic effects of CPF in the developing brain. PMID:27296654
In diesem Beitrag stellen wir neue, automatisierte Verfahren zur Visualisierung der Koronararterien einerseits und für eine direkte Vergleichbarkeit mit konventionellen Angiogrammen andererseits vor. Unser Ansatz umfasst Methoden für die automatische Extraktion des Herzens aus kontrastverstärkten CT-Daten, sowie für die Maskierung grosser kontrastmittelgefüllter Kavitäten des Herzens, um die Sichtbarkeit der Koronararterien bei der Darstellung mittels Volumenrendering zu verbessern. Zum direkten Vergleich mit konventionellen Angiographien wurde ein Verfahren zur automatischen Generierung von Projektionsansichten aus den CT-Daten entwickelt.
Die Erwähnungen und Zitierungen von Einsteins Arbeiten dokumentieren lediglich den quantifizierbaren Anteil von Einsteins Beitrag zur Physik. Gleichwohl belegen sie die außergewöhnliche Resonanz und Langzeitwirkung seiner Arbeiten. Die Häufigkeit der Zitierungen entspricht nicht der allgemeinen Einschätzung ihrer Bedeutung. Insbesondere die Pionierarbeiten werden inzwischen als bekannt vorausgesetzt und nicht mehr explizit zitiert. Interessanterweise ist seine nach 1945 meist zitierte Arbeit nicht eine der Pionierarbeiten zur Quantenphysik oder Relativitätstheorie, sondern jene aus dem Jahr 1935 zum berühmten Einstein-Podolsky-Rosen-Paradoxon.
„Ich habe doch nur mit dem Finger gedroht“, sagte der Angeklagte, und unterließ es unfairerweise darauf hinzuweisen, dass dieser am Abzug einer Pistole gelegen hatte. Der Bezug dieses Bonmots zum Gesundheitswesen soll im Folgenden weniger auf die konkreten gesundheitlichen Risiken durch Schusswaffen gelegt werden, sondern vielmehr auf die nicht weniger bedeutsame Rolle des Kontextes für Gesundheit, Krankheit und Wohlbefinden. Dass der „Kontext“, verstanden als System- und Sinnzusammenhang, sowohl das objektive Auftreten von Krankheiten in ihrer Häufigkeit und Schwere als auch das subjektive Erleben von Gesundheitszuständen beeinflusst, ist hinreichend bekannt.
Die energiewirtschaftliche Digitalisierung führt zu einem disruptiven Marktwandel. Der smarte, vernetzte Energiemarkt von morgen umfasst neue Player, neue Kommunikationsanforderungen, geändertes Kundenverhalten und mehr Daten. Etablierte Marktteilnehmer sind gezwungen, ihre bisherigen Geschäftsmodelle zu überdenken. IT wird dabei mehr und mehr zum Wettbewerbsfaktor. Ein erfolgreiches Managen der technologischen Veränderungsprozesse ist zwingende Voraussetzung für die nachhaltige Bewältigung der energiewirtschaftlichen Digitalisierung. In diesem Zusammenhang erweisen sich die daten- und entwicklungsspezifischen Synergieeffekte plattformbasierter Dienste als zentraler Mehrwert einer innovationsgetriebenen strategischen Marktpositionierung und damit als technologische Notwendigkeit.
The kinetics of lead oxidation during curing was studied by chemical analysis of the free lead content as well as by the gas volumetry of oxygen. The difference in the results in this research lies in the evolution of hydrogen as a curing reaction. This agrees with the results of curing the paste The optimal water content of the paste for lead oxidation was determined. A model for the electrolyte film during curing has been developed, which allows the results to be interpreted satisfactorily.
Hans von Gerssdorff and Hieronymus Brunschwig, who flourished in Germany in the latter half of the fifteenth century, have both left early printed treatises on Surgery which give excellent woodcuts showing pictures of instruments, operations, and costumes, at the end of the medieval period. Hieronymus Brunschwig or Hieronymus Brunschwygk (ca. 1450 - ca. 1512), was a German surgeon (wundartzot), alchemist and botanist. He was notable for his methods of treatment of gunshot wounds. His most influential book was the Buch der Cirurgia. Gersdorff(1455-1529) was a military surgeon who gained wide experience during 40 years of campaigning and was an expert in the treatment of battlefield injuries. His work covers anatomy, surgery, leprosy, and glossaries of anatomical terms, diseases, and medications.
S88-44661 (13 Aug 1988) --- Tom Kestler, with Orthopaedic Hospital, USC, one of the sponsor representatives for student experimenter Andrew Fras explains components of Fras' experiment. It will be carried onboard theDiscovery for NASA's STS-29 mission next year. His primary audience is made up of members of the STS-29 crew who will monitor in-space operation of the experiment, titled "Effects of Weightlessness on Bone Healing." Crewmembers, clockwise around the table from the left, are Astronauts Robert C. Springer, James F. Buchli, Michael L. Coats, John E. Blaha and James P. Bagian. Seated in far right background is Dr. June Marshall of the University of Southern California School of Medicine, the student's sponsoring organization.
The STS-29 Space Shuttle Discovery mission approaches for a landing at NASA's then Ames-Dryden Flight Research Facility, Edwards AFB, California, early Saturday morning, 18 March 1989. Touchdown was at 6:35:49 a.m. PST and wheel stop was at 6:36:40 a.m. on runway 22. Controllers chose the concrete runway for the landing in order to make tests of braking and nosewheel steering. The STS-29 mission was very successful, completing the launch a Tracking and Data Relay communications satellite, as well as a range of scientific experiments. Discovery's five man crew was led by Commander Michael L. Coats, and included pilot John E. Blaha and mission specialists James P. Bagian, Robert C. Springer, and James F. Buchli.
STS 61-A crew during emergency egress training. Henry W. Hartsfield Jr., STS 61-A mission commander, uses a Sky-Genie to practice emergency egress from a Shuttle vehicle. This training was held in the Shuttle mockup and integration laboratory (41244); Ernst Messerschmid, German payload specialist, goes through a rehearsal of procedures involved in preparing for launch and landing aboard the Shuttle. Briefing Messerschmid is Alan N. Rochford (41245); Descending from a simulated Shuttle orbiter, using a Sky-Genie device, is Astronaut Henry M. Hartsfield, Jr. Watching in blue flight garments are other members of the crew. They are, left to right, Ernst Messerschmid, German payload specialist; James F. Buchli, mission specialist; Bonnie J. Dunbar, mission specialist; Wubbo J. Ockels, Dutch payload specialist.
Santos, Kamilla Monteiro dos; Gonçalves, Priscila Sant'Ana; Paiva, Maria José Nunes de; Lacerda, Guilherme Araújo
2011-01-01
A treatment to the Alzheimer's disease consists inhibition of the acetylcholinesterase, which is responsible for the acetylcholine control in the synapses. We have investigated the potential of inhibition of the acetylcholinesterase produced by hexane extracts of leaves, branches, and flowers from three Bauhinia specimens, which is based on the technique of thin layer chromatography and on identifying the organ of the plant that possesses larger concentration of inhibitors. Retention factor analysis shows values of 0.31aA, 0.31aA, and 0.46aB for flowers B. variegata, B. var. candida, and B. ungulata, respectively. The flower extract of B. ungulata is the most suitable for further studies on this inhibition.
Zimmermann, Hanngörg; Heinlein, Markus; Guldner, Norbert W.
Titan gilt seit Jahrzehnten als einer der wichtigsten Implantatwerkstoffe in der Medizin. Neben den guten mechanischen Eigenschaften (Leichtigkeit, hohe Festigkeit etc.), besitzen Titanimplantate vor allem eine hervorragende Körperverträglichkeit, so dass die Implantate optimal in den humanen Organismus integriert werden [1]. Ist jedoch aufgrund der Anforderungen an das Implantat eine hohe Flexibilität und/ oder Elastizität gefragt, so scheidet der Werkstoff Titan aufgrund seiner spröden und unflexiblen Materialeigenschaften aus. Die Folge ist der Einsatz von Implantatmaterialien, sowohl künstlichen als auch biologischen Ursprungs, welche nicht selten eine unzureichende Biokompatibilität aufweisen und somit zu Fremdköper- und immunologischen Reaktionen und Einkapselung des Implantates führen können. Die Erhöhung der Körperverträglichkeit, eine Adaption an das biologische Umfeld und eine hohe Biokompatibilität sind demzufolge die wichtigsten Eigenschaften bei der bedarfsgerechten Herstellung von Implantaten und Implantatoberflächen. Zur Gestaltung von innovativen, biokompatiblen Oberflächen stehen unterschiedliche technische Lösungsansätze zur Verfügung. Zum einen besteht die Möglichkeit, geeignete Oberflächeneigenschaften aus dem Grundmaterial selbst zu optimieren. Dies geschieht unter anderem durch Modifikation der Werkstoffoberflächen in Form von Texturierungen und Oberflächenrauhigkeiten. Zum anderen können die Oberflächeneigenschaften unabhängig von denen des Trägermaterials gestaltet werden. Durch Funktionalisierung der Oberflächen mit geeigneten Beschichtungen oder der Zugabe von Medikamenten (Drug Eluting) werden die Kunststoffimplantate dahingehend verändert, dass eine Steigerung der Körperakzeptanz erreicht wird. Die Titanbeschichtung von Implantatoberflächen kombiniert die positiven Materialeigenschaften von Titan und Polymer.
Kohlenstoff-Nanoröhren sind einzelne oder mehrfach ineinander gesteckte molekulare Hohlzylinder. In ihnen bilden Kohlenstoffatome ein Graphit ähnliches Kristallgitter. Diese Fullerene zeichnen sich durch eine außerordentlich hohe Elastizität und Zugfestigkeit aus. In ihren elektronischen Eigenschaften verhalten sie sich entweder wie Halbleiter oder wie metallische Leiter. Aus halbleitenden Nanoröhren konnten bereits winzige Feldeffekttransistoren hergestellt werden, ein erster Schritt hin zu einer molekularen Elektronik. Die Grundlagenforscher interessiert vor allem das Verhalten metallischer Nanoröhren bei tiefen Temperaturen. An ihren elektronischen Systemen lassen sich zum Beispiel Quanteninterferenzphänomene oder Elektron-Elektron-Wechselwirkungen untersuchen.
Künstliche organische Materialien werden in Zukunft vermehrt in der Elektronik eingesetzt werden. Obwohl sie gute Isolatoren sind, kann ein ausreichend großes elektrisches Feld in ihnen einen elektrischen Strom fließen lassen. Dazu injizieren Metallelektroden freie Ladungsträger wie Elektronen oder Löcher in das organische Material. Diese Ladungsträgerinjektion kann die elektrischen Eigenschaften geeigneter organischer Materialien vom Isolator bis zum Leiter steuern. Eine zukünftige Domäne solcher Kunststoffe werden einfache, billige Chips sein. Bei den Displays könnten sie bald die konventionellen Flüssigkristallanzeigen technisch überflügeln.
Auf einer außerörtlichen Bundesstraße geriet ein mit vier Personen besetzter Pkw Toyota Corolla aus letztlich nicht vollständig geklärten Gründen ins Schleudern. Nachdem sich das Fahrzeug beträchtlich entgegen dem Uhrzeigersinn ausgedreht hatte, prallte ein entgegenkommender Kleintransporter VW T4 frontal an die rechte Flanke des Toyota. Der Transporter wurde gedreht, ausgehoben und durch einen Pkw Ford Escort unterfahren. Alle Fahrzeuge kamen in Kollisionsortnähe zum Endstand. Die vier Toyota-Insassen wurden getötet. Aus den anderen Fahrzeugen wurden sechs Personen überwiegend schwer verletzt. Unbeteiligte Zeugen waren nicht vorhanden.
Concerning following Books: (I) Transmitting knowledge - words, images, and instruments in early modern Europe. Kusukawa and Maclean (eds.), OUP, Oxford, 2006; (II) Widmung, Welterklärung und Wissenschaftslegitimierung: Titelbilder und ihre Funktionen in der wissenschaftlichen Revolution. Remmert, Harrassowitz, Wiesbaden, 2005; (III) The power of images in early modern science. Lefevre, Renn and Schoepflin (eds.), Birkhäuser, Basel, 2003; (IV) Immagini per conoscere - dal Rinascimento alla rivoluzione scientifica. Meroi and Pogliano (eds.), Olschki, Florenz, 2001; (V) Erkenntnis Erfindung Konstruktion - Studien zur Bildgeschichte von Naturwissenschaften und Technik vom 16. bis zum 19. Jahrhundert. Holländer (ed.), Mann, Berlin, 2000.
Acetylcholine (ACh), the classical neurotransmitter, also affects a variety of nonexcitable cells, such as endothelia, microglia, astrocytes and lymphocytes in both the nervous system and secondary lymphoid organs. Most of these cells are very distant from cholinergic synapses. The action of ACh on these distant cells is unlikely to occur through diffusion, given that ACh is very short-lived in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), two extremely efficient ACh-degrading enzymes abundantly present in extracellular fluids. In this study, we show compelling evidence for presence of a high concentration and activity of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT) in human cerebrospinal fluid (CSF) and plasma. We show that ChAT levels are physiologically balanced to the levels of its counteracting enzymes, AChE and BuChE in the human plasma and CSF. Equilibrium analyses show that soluble ChAT maintains a steady-state ACh level in the presence of physiological levels of fully active ACh-degrading enzymes. We show that ChAT is secreted by cultured human-brain astrocytes, and that activated spleen lymphocytes release ChAT itself rather than ACh. We further report differential CSF levels of ChAT in relation to Alzheimer’s disease risk genotypes, as well as in patients with multiple sclerosis, a chronic neuroinflammatory disease, compared to controls. Interestingly, soluble CSF ChAT levels show strong correlation with soluble complement factor levels, supporting a role in inflammatory regulation. This study provides a plausible explanation for the long-distance action of ACh through continuous renewal of ACh in extracellular fluids by the soluble ChAT and thereby maintenance of steady-state equilibrium between hydrolysis and synthesis of this ubiquitous cholinergic signal substance in the brain and peripheral compartments. These findings may have important implications for the role of cholinergic signaling in states of inflammation in general and in neurodegenerative disease, such as Alzheimer’s disease and multiple sclerosis in particular. PMID:23840379
Scheler, Fabian; Mitzlaff, Martin; Schröder-Preikschat, Wolfgang
Die Entscheidung, einen zeit- bzw. ereignisgesteuerten Ansatz für ein Echtzeitsystem zu verwenden, ist schwierig und sehr weitreichend. Weitreichend vor allem deshalb, weil diese beiden Ansätze mit äußerst unterschiedlichen Kontrollflussabstraktionen verknüpft sind, die eine spätere Migration zum anderen Paradigma sehr schwer oder gar unmöglich machen. Wir schlagen daher die Verwendung einer Zwischendarstellung vor, die unabhängig von der jeweils verwendeten Kontrollflussabstraktion ist. Für diesen Zweck verwenden wir auf Basisblöcken basierende Atomic Basic Blocks (ABB) und bauen darauf ein Werkzeug, den Real-Time Systems Compiler (RTSC) auf, der die Migration zwischen zeit- und ereignisgesteuerten Systemen unterstützt.
In diesem Beitrag werden Active Appearance Models (AAMs) zur Segmentierung der äußeren Kontur von Aortenaneurysmen eingesetzt. Diese Aufgabe ist wegen des geringen Kontrastes zum umliegenden Gewebe und des Aufbaus der teils thrombotisierten oder kalzifizierten Gefäßwände im Bereich eines Aneurysmas so komplex, dass sie aufgrund der Vielgestalt der Kontur in CT-Angiographie-Bildern die Verwendung eines statistischen Modells für Form und eingeschlossene Textur rechtfertigt. Für die Evaluation des Verfahrens wurden verschiedene statistische Modelle aus Schichten von neun CTA-Datensätzen trainiert und die Segmentierung anhand von Leave-One-Out-Tests überprüft.
Dem nuklearen Patt zwischen Ostblock und westlichem Staatenbündnis ist es nach weitgehend übereinstimmender Auffassung von Politik und Wissenschaft zu danken, dass der "Kalte Krieg" in der zweiten Hälfte des 20. Jahrhunderts nicht zum weltumfassenden Flächenbrand eskalierte. An der raschen Herstellung dieses Patts waren zwei Dresdner Physiker maßgeblich beteiligt, deren einer im Manhattan-Projekt in den USA gearbeitet hatte und später in England der Spionage für die Sowjetunion und des Verrats des Know-how der Atombombe überführt wurde.
CAPE CANAVERAL, Fla. -- A group from the first graduating class of astronauts after the Apollo program gathers at the Banana River viewing site at NASA's Kennedy Space Center before the launch of space shuttle Discovery on its STS-124 mission. In 1978 a new group of 35 astronauts was selected after nine years without new astronauts. The pilots were Daniel Brandenstein, Michael Coats, Richard Covey, John Creighton, Robert Gibson, Frederick D. Gregory, Frederick Hauck, Jon McBride, Francis "Dick" Scobee, Brewster Shaw, Loren Shriver, David Walker and Donald Williams. The mission specialists were Guion Bluford, James Buchli, John Fabian, Anna Fisher, Dale Gardner, S. David Griggs, Terry Hart, Steven Hawley, Jeffrey Hoffman, Shannon Lucid, Ronald McNair, Richard Mullane, Steven Nagel, George Nelson, Ellison Onizuka, Judith Resnik, Sally Ride, Rhea Seddon, Robert Stewart, Kathryn D. Sullivan, Norman Thagard and James van Hoften. Since then, a new group has been selected roughly every two years. Photo credit: NASA/Jim Grossmann
Bisher haben wir die Zustandsgrößen ν (Zahl der Mole) und N (Zahl der Teilchen im System) als konstant betrachtet. In diesem Kapitel wollen wir untersuchen, wie sich Veränderungen von ν bzw. von N beschreiben lassen. Dazu werden wir eine neue thermodynamische Größe einführen, das chemische Potential μ. Als Beispiele für die Veränderung von Teilchenzahlen werden wir diffusive Prozesse und chemische Reaktionen betrachten. Am Ende des Kapitels werden wir die quantenmechanische Gasentartung diskutieren, bei der das chemische Potential ebenfalls eine Rolle spielt. Wir werden feststellen, dass es nicht schwierig ist, einige Eigenschaften dieses interessanten Materiezustands zu verstehen. Wir behandeln das Thema bereits hier und nicht erst in der Quantenphysik am Ende des Buches, weil es in die Wärmelehre gehört und weil auf dieser Grundlage die elektrischen Eigenschaften von Metallen in Bd. III/9 leicht diskutiert werden können.
León, Rafael; de los Ríos, Cristóbal; Marco-Contelles, José; Huertas, Oscar; Barril, Xavier; Luque, F Javier; López, Manuela G; García, Antonio G; Villarroya, Mercedes
2008-08-15
In this communication, we describe the synthesis and biological evaluation of tacripyrimedones 1-5, a series of new tacrine-1,4-dihydropyridine hybrids bearing the general structure of 11-amino-12-aryl-3,3-dimethyl-3,4,5,7,8,9,10,12-octahydrodibenzo[b,g][1,8]naphthyridine-1(2H)-one. These multifunctional compounds are moderately potent and selective AChEIs, with no activity toward BuChE. Kinetic analysis and molecular modeling studies point out that the new compounds preferentially bind the peripheral anionic site of AChE. In addition, compounds 1-5 show an excellent neuroprotective profile, and a moderate blocking effect of L-type voltage-dependent calcium channels due to the mitigation of [Ca(2+)] elevation elicited by K(+) depolarization. Therefore, they represent a new family of molecules with potential therapeutic application for the treatment of Alzheimer's disease.
S78-26481 (January 1978) --- This is a montage of the individual portraits of the 35-member 1978 class of astronaut candidates. From left to right are Guion S. Bluford, Daniel C. Brandenstein, James F. Buchli, Michael L. Coats, Richard O. Covey, John O. Creighton, John M. Fabian, Anna L. Fisher, Dale A. Gardner, Robert L. Gibson, Frederick D. Gregory, S. David Griggs, Terry J. Hart, Frederick H. (Rick) Hauck, Steven A. Hawley, Jeffrey A. Hoffman, Shannon W. Lucid, Jon A. McBride, Ronald E. McNair, Richard M. (Mike) Mullane, Steven R. Nagel, George D. Nelson, Ellison S. Onizuka, Judith A. Resnik, Sally K. Ride, Francis R. (Dick) Scobee, Rhea Seddon, Brewster H. Shaw Jr., Loren J. Shriver, Robert L. Stewart, Kathryn D. Sullivan, Norman E. Thagard, James D. Van Hoften, David M. Walker and Donald E. Williams. Photo credit: NASA or National Aeronautics and Space Administration
The first animal disease act of Switzerland was released in 1872. Its revision in 1886 brought the basis for establishing a border veterinary inspection service. This service was first reporting to the federal Ministry of Agriculture; after 1914, the newly created Federal Veterinary Office became responsible for it. The border checks were first limited to live biungulate animals and horses; later on they were extended to meat and meat products and finally to venison and fishery products. At the beginning, part-time veterinarians with own practice were engaged. As the traffic increased, full time border veterinary inspectors joined the team; these were mainly active at the most important border posts (like Basel, St. Margrethen, Buchs, Chiasso, Geneva, more recently the international airports). The border veterinary inspection service, including the relevant instruction of the personnel, was (and is) financed with weight depending fees which included until 1966 a fee intended for financing the efforts to control livestocks epidemics.
Mit der Wahl von Wolfgang Wetzel zum Vorsitzenden der Deutschen Statistischen Gesellschaft im Jahre 1972 begann eine 32jährige Ära, in der die praktische und die theoretische Statistik in einem ausgewogenen Verhältnis gepflegt wurden. Ein regelmäßiger vierjähriger Wechsel im Vorsitz stärkte die Gemeinschaft und die praktische wie die wissenschaftliche Arbeit gleichermaßen. Die jährlichen Hauptversammlungen behandelten gesellschaftlich aktuelle wie zukunftsorientierte Themen, und die Ausschüsse sowie weitere Veranstaltungen gaben Gelegenheit zur Förderung und Pflege einer Vielzahl von Arbeitsgebieten der Statistik. Darüber wird nicht nur in diesem Kapitel, sondern auch in den Teilen II und III des Bandes berichtet.
Die moderne Evolutionsbiologie hat ihren Ursprung in den Arbeiten von Charles Darwin und Alfred Wallace (Darwin 1963). Der gemeinsame Ausgangspunkt des Evolutionsgedanken ist dabei die Beobachtung, dass die biologische Welt nicht konstant ist. Biologische Systeme und alle darin lebenden Organismen unterliegen über längere Zeiträume hinweg einer stetigen Veränderung. Diese grundlegende Eigenschaft biologischer Systeme macht die Biologie zu einer historischen Wissenschaft und stellt einen wichtigen Gegensatz zu großen Teilen der Physik dar. Obwohl die Aussage von der Veränderlichkeit der Arten heute trivial klingt, war sie im 19. Jahrhundert eine Revolution, da die Konstanz der Arten und der Welt eine vorherrschende Stellung im damaligen Weltbild hatte (Amundson 2005).
Viele Aufgaben in Politik, Wirtschaft und Gesellschaft erfordern nicht nur globale, sondern auch regionale Lösungen. Die Regionalstatistik ist deshalb unentbehrlich für viele Planungs- und Entscheidungsprozesse. Ihren Ausbau und ihre Nutzung zu fördern, hat sich der Ausschuss für Regionalstatistik der Deutschen Statistischen Gesellschaft zum Ziel gesetzt. Dieses Kapitel stellt zunächst einige Grundlagen der Regionalstatistik und die Aufgaben des Ausschusses dar. Es folgen das umfangreiche regionalstatistische Datenangebot der Statistischen Ämter des Bundes und der Länder und seine Nutzung. Ein ergänzender Abschnitt ist der Arbeit des Instituts für Bau-, Stadt- und Raumforschung gewidmet. Das Kapitel schließt mit einem Ausblick auf die Weiterentwicklung des regionalstatistischen Datenangebotes aus Sicht der amtlichen Statistik.
The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and helpmore » in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.« less
Ramalho, Teodorico C.; DeCastro, Alexandre A.; Silva, Daniela R.
The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and helpmore » in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.« less
Samadi, Abdelouahid; Marco-Contelles, José; Soriano, Elena; Alvarez-Pérez, Mónica; Chioua, Mourad; Romero, Alejandro; González-Lafuente, Laura; Gandía, Luis; Roda, José M; López, Manuela G; Villarroya, Mercedes; García, Antonio G; Ríos, Cristóbal de Los
2010-08-15
The synthesis, molecular modeling, and pharmacological analysis of new multipotent simple, and readily available 2-aminopyridine-3,5-dicarbonitriles (3-20), and 2-chloropyridine-3,5-dicarbonitriles (21-28), prepared from 2-amino-6-chloropyridine-3,5-dicarbonitrile (1) and 2-amino-6-chloro-4-phenylpyridine-3,5-dicarbonitrile (2) is described. The biological evaluation showed that some of these molecules were modest inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), in the micromolar range. The 2-amino (3, 4), and 2-chloro derivatives 21-23, 25, 26 were AChE selective inhibitors, whereas 2-amino derivatives 5, 14 proved to be selective for BuChE. Only inhibitor 24 was equipotent for both cholinesterases. Kinetic studies on compound 23 showed that this compound is a mixed-type inhibitor of AChE showing a K(i) of 6.33 microM. No clear SAR can be obtained form these data, but apparently, compounds bearing small groups such as the N,N'-dimethylamino or the pyrrolidino, regardless of the presence of a 2-amino, or 6-chloro substituent in the pyridine ring, preferentially inhibit AChE. Molecular modeling on inhibitors 4, 5, 22, and 23 has been carried out to give a better insight into the binding mode on the catalytic active site (CAS), and peripheral anionic site (PAS) of AChE. The most important differences in the observed binding relay on the modifications of the group at C2, as the amino group forms two hydrogen bonds that direct the binding mode, while in the case of compounds with a chlorine atom, this is not possible. The neuroprotective profile of these molecules has been investigated. In the LDH test, only compounds 26, 3, 22, and 24 showed neuroprotection with values in the range 37.8-31.6% in SH-SY5Y neuroblastoma cells stressed with a mixture of oligomycin-A/rotenone, but in the MTT test only compound 17 (32.9%) showed a similar profile. Consequently, these compounds can be considered as attractive multipotent therapeutic molecules on two key pharmacological receptors playing key roles in the progress of Alzheimer, that is, cholinergic dysfunction and oxidative stress, and neuronal vascular diseases. Copyright 2010 Elsevier Ltd. All rights reserved.
One of the aims of management priorities in medical universities is the evaluation of learning in educational departments in order to prevent educational retardation and to improve the quality of education. The aim of this study was to evaluate the interns' learning in the obstetrics and gynecology (O&G) department at Zahedan University of Medical Sciences (ZUMS). The study was performed in ZUMS, Iran, in 2002-2003 on all interns at the O&G department, including 30 men and 40 women. For data collection, a questionnaire was used and included some questions regarding the common emergencies and diseases in O&G, together with different learning indicators such as reading, observation, hearing, management, and the capability of management. The data were analyzed using descriptive statistics, tables, t test, and chi-square test using the SPSS software. The mean percentages of learning indicators of observation, bedside teaching, supervised management, and personal management in the common emergencies and diseases of O&G in male interns were significantly lower than those in female interns. Also, the mean percentages of managing capabilities were 12% and 70.5% in common emergencies and 14.2% and 59.3% in common diseases for male and female interns, respectively. The chi-square test showed a significant difference between the mean percentages of the managing capabilities in male and female interns for the majority of the common emergencies and diseases. Also, the chi-square test revealed a significant relationship between the learning indicators and the interns' managing capabilities for common emergencies and diseases. Some learning indicators in the male interns were very low. This needs urgent improvement of the learning quality in the O&G department, especially for the male interns, particularly those who are supposed to work in the deprived areas of the country after graduation in the public service.
Universal gebildete und interessierte Menschen sind selten geworden in unserer Zeit. Victor F. Weisskopf war einer von ihnen. Sein geistiger Horizont umfasste nicht nur sein eigentliches Fachgebiet, die Physik, wo er sich durch fundamentale Arbeiten in den Bereichen der Quantenfeldtheorie, der Kern- und Elementarteilchenphysik hervortat. Daneben bildeten Kunst und Musik sowie ein außergewöhnliches Engagement in sozialen und politischen Angelegenheiten die Eckpunkte seines Lebens. Der Einsatz für die Verständigung zwischen den Machtblöcken während des Kalten Krieges war für ihn ebenso selbstverständlich wie das Bedürfnis, die neuen Ideen der Physik einem breiten Publikum nahe zu bringen. Die Wissenschaft erschien ihm als das geeignete Mittel, um zum Wohle der Menschheit zu wirken.
"Wege entstehen dadurch, dass man sie geht." (Franz Kafka) Die Welt der Digitalisierung ist voll von Wegen, die jemand gegangen ist, bevor dort ein Weg war. Manche dieser Wege stellten sich als Sackgasse heraus, manche als Abkürzung und aus anderen wurden ganze Wegenetze und Städte. Die Energiewelt wird durch den digitalen Wandel nicht verschont bleiben. Durch die intelligenten Messsysteme und die zugehörigen, neuen Strukturen werden energiefremden Wettbewerbern Chancen zum Markteintritt eröffnet. EVUs müssen sich darauf einstellen, dass der permanente Wandel nicht mehr enden wird. Doch auch den EVUs eröffnen sich Optionen. Um erfolgreich zu sein, müssen sie lernen loszugehen, ohne das genaue Ziel zu kennen.
Die Digitalisierung erfasst sämtliche Bereiche des Lebens und Wirtschaftens. Auch die Kommunalwirtschaft - insbesondere die kommunale Energiewirtschaft - sieht sich perspektivisch disruptiven Entwicklungen gegenüber. Stadtwerke haben bereits viele Herausforderungen erfolgreich gemeistert und stehen auch der Digitalisierung positiv gegenüber. Vielerorts gestalten kommunale Unternehmen den digitalen Wandel bereits aktiv mit. Dieser Artikel arbeitet die Assets kommunaler Unternehmen heraus und zeigt Strategien und Handlungsoptionen zum Umgang mit der digitalen Transformation für kommunale Energieversorgungsunternehmen auf. Dabei zeigt sich, dass das politische und regulatorische Umfeld für das positive Gelingen der Digitalisierung entscheidend sind. Kommunale Unternehmen benötigen die gleichen Marktzugangsbedingungen wie andere Akteure. Ferner profitieren kommunale Unternehmen von einigen Wettbewerbsvorteilen, etwa hohen Vertrauenswerten ihrer Kunden und umfangreiches Know-how im Datenmanagement.
In der Statistischen Physik befassen wir uns mit Systemen aus sehr vielen Teilchen. Beispiele hierfür sind die Atome eines Gases oder einer Flüssigkeit, die Phononen eines Festkörpers oder die Photonen in einem Plasma. Die Gesetze für die Bewegung einzelner Teilchen sind durch die Mechanik oder die Quantenmechanik gegeben. Aufgrund der großen Zahl der Teilchen (zum Beispiel N = 6 • 1023 für ein Mol eines Gases) sind die Bewegungsgleichungen jedoch nicht auswertbar. Das Ergebnis einer solchen Auswertung, also etwa die Bahnen von 6•1023 Teilchen, wäre auch uninteressant und irrelevant. Die Behandlung dieser Systeme erfolgt daher statistisch, das heißt auf der Grundlage von Annahmen über dieWahrscheinlichkeit verschiedener Bahnen oder Zustände.
S48-E-007 (12 Sept 1991) --- Astronaut James F. Buchli, mission specialist, catches snack crackers as they float in the weightless environment of the earth-orbiting Discovery. This image was transmitted by the Electronic Still Camera, Development Test Objective (DTO) 648. The ESC is making its initial appearance on a Space Shuttle flight. Electronic still photography is a new technology that enables a camera to electronically capture and digitize an image with resolution approaching film quality. The digital image is stored on removable hard disks or small optical disks, and can be converted to a format suitable for downlink transmission or enhanced using image processing software. The Electronic Still Camera (ESC) was developed by the Man- Systems Division at the Johnson Space Center and is the first model in a planned evolutionary development leading to a family of high-resolution digital imaging devices. H. Don Yeates, JSC's Man-Systems Division, is program manager for the ESC. THIS IS A SECOND GENERATION PRINT MADE FROM AN ELECTRONICALLY PRODUCED NEGATIVE
In this first part of a two part video mission-highlights set, the flight of the STS-48 Space Shuttle Orbiter Discovery is reviewed. The flight crew consisted of: J. O. Creighton (Commander); Ken Reightler (Pilot); Charles 'Sam' Gemar (Mission Specialist); James 'Jim' Buchli (MS); and Mark Brown (MS). Step-by-step pre-launch and sunset launch sequences are shown with accompanying shots inside the Mission Control Center. The primary goal of this mission was the deployment of Upper Atmosphere Research Satellite (UARS). Other (secondary) payloads included: the MidDeck Zero Gravity Experiment (MODE); the Sam/Cream device; the Shuttle Activation Monitor/Cosmic Ray Effects and Activation Monitor Experiment; and the Physiology and Anatomical Rodent Experiment (PARE). Crew activities were shown, along with Earth views (Aurora Borealis (B/W), light from the Kuwait oil fires, lightning over Italy and other areas, polar regions and ice caps, and the United States at night (B/W)). This was the thirteenth flight of the Space Shuttle Discovery. A night landing is shown.
A lot of medicinal plants, traditionally used for thousands of years, are present in a group of herbal preparations of the Indian traditional health care system (Ayurveda) named Rasayana proposed for their interesting antioxidant activities. Among the medicinal plants used in ayurvedic Rasayana for their therapeutic action, some of these have been throughly investigated. In the present paper seven plants (Emblica officinalis L., Curcuma longa L., Mangifera indica L., Momordica charantia L., Santalum album L., Swertia chirata Buch-Ham, Withania somnifera (L.) Dunal) are viewed for their historical, etymological, morphological, phytochemical and pharmacological aspects. The plants described contain antioxidant principles, that can explain and justify their use in traditional medicine in the past as well as the present. In order to identify the plants with antioxidant activity in Ayurveda, a formulation of some rasayanas with well defined antioxidant properties has been examinated. For this purpose, we have considered Sharma's work on the preparation MAK4, MAK5, MA631, MA 471, MA Raja's Cup, MA Student Rasayana, MA Ladies Rasayana.
CAPE CANAVERAL, Fla. -- All eyes look skyward as space shuttle Discovery launches on its STS-124 mission. The group gathered here at the Banana River viewing site at NASA's Kennedy Space Center are members of the first graduating class of astronauts after the Apollo program. In 1978 a new group of 35 astronauts was selected after nine years without new astronauts. The pilots were Daniel Brandenstein, Michael Coats, Richard Covey, John Creighton, Robert Gibson, Frederick D. Gregory, Frederick Hauck, Jon McBride, Francis "Dick" Scobee, Brewster Shaw, Loren Shriver, David Walker and Donald Williams. The mission specialists were Guion Bluford, James Buchli, John Fabian, Anna Fisher, Dale Gardner, S. David Griggs, Terry Hart, Steven Hawley, Jeffrey Hoffman, Shannon Lucid, Ronald McNair, Richard Mullane, Steven Nagel, George Nelson, Ellison Onizuka, Judith Resnik, Sally Ride, Rhea Seddon, Robert Stewart, Kathryn D. Sullivan, Norman Thagard and James van Hoften. Since then, a new group has been selected roughly every two years. Photo credit: NASA/Jim Grossmann
In order to study the structure-activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a-8d) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro. The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound 6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 μmol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound 6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE.
Die Sternbilder, die seit alters her die Menschen in ihren Bann gezogen haben, und die damit verbundenen Mythen werden in zweifacher Weise vorgestellt. Erstens ist es die Absicht, dem Leser zu helfen, sich am Sternenhimmel zurechtzufinden, und zweitens will es ihm die Vielfalt der Bilder vermitteln, die damit verbunden sind. Am Anfang des Buches stehen die prächtigen Erzählungen aus Ovids Metamorphosen. Dann ist vom Sternenhimmel im Jahreskreis die Rede, um den Leser anzuregen, diesen fast unendlichen Bilderreichtum sich selbst durch eigene Beobachtungen zu erschließen. Ein umfangreicher Abschnitt behandelt die einzelnen Sternbilder und das hierzu überlieferte Wissen. Sternkarten und alte Kupferstiche aus dem Bestand der Österreichischen Nationalbibliothek zeigen, wie man sich in früheren Jahrhunderten den Sternenhimmel vorgestellt hat. Sternsagen und Mythen werden erzählt und auch das ptolemäische und das kopernikanische Weltsystem werden einander gegenübergestellt. Ausführliche Sachverzeichnisse mit über 3000 Suchbegriffen erleichtern den Zugang zu Stern- und Sternbildnamen und zur Mythologie.
S78-26569 (31 Jan. 1978) --- The 35 new astronaut candidates, presented Jan. 31, 1978, in the Building 2 auditorium at NASA's Johnson Space Center, pose for photographers. They are arranged in alphabetical order with top left as beginning point and bottom right as stopping point. They are Guion S. Bluford, Daniel C. Brandenstein, James F. Buchli, Michael L. Coats, Richard O. Covey, John O. Creighton, John M. Fabian, Anna L. Fisher, Dale A. Gardner, Robert L. Gibson, Frederick D. Gregory, S. David Griggs, Terry J. Hart, Frederick H. (Rick) Hauck, Steven A. Hawley, Jeffrey A. Hoffman, Shannon W. Lucid, Jon A. McBride, Ronald E. McNair, Richard M. (Mike) Mullane, Steven R. Nagel, George D. Nelson, Ellison S. Onizuka, Judith A. Resnik, Sally K. Ride, Francis R. (Dick) Scobee, Rhea Seddon, Brewster H. Shaw Jr., Loren J. Shriver, Robert L. Stewart, Kathryn D. Sullivan, Norman E. Thagard, James D. van Hoften, David M. Walker and Donald E. Williams. Photo credit: NASA or National Aeronautics and Space Administration
Das Kapitel "Verbrennungsmotoren" gibt eine Einführung in das wichte und große Gebiet der Verbrennungsmotoren. Leserinnen und Lesern, die noch nie etwas über Verbrennungsmotoren gehört haben, wird empfohlen, zunächst den Abschnitt 1 zu lesen. Dieser ist bewusst einfach und anschaulich geschrieben, um den Zugang zum Thema zu erleichtern. Danach können gezielt weitergehende Informationen in den Abschnitten 2 bis 9 studiert werden. Diese Abschnitte wurden so verfasst, dass man sie nicht nacheinander lesen muss. Grundlage ist jeweils nur der Abschnitt 1. Dieser selbst ist so verfasst, dass das Wichtigste ganz am Anfang steht. Je weiter hinten man in diesem Abschnitt ankommt, umso spezieller werden die Themen. Bei nur begrenztem Interesse an dem Thema Verbrennungsmotoren kann man das Lesen des Abschnitts 1 jederzeit abbrechen und hat trotzdem das bis dahin Wichtigste erfahren.
Bildgebende Verfahren haben sich in den letzten Jahren einen festen Platz in der Medizin erobert und die medizinische Forschung und Diagnostik revolutioniert. Sie ermöglichen Ärzten und Forschern einen Einblick in lebendes Gewebe. Mit der fortschreitenden technischen Entwicklung liefern die Verfahren immer höhere Auflösungen, schärfere Bilder und mehr Details. Bildgebende Verfahren sind ohne Mathematik undenkbar, von der Bildrekonstruktion aus den gemessenen Signalen, bis hin zur Auswertung der Bildinformation. Für die Analyse der großen Menge an Bilddatenpunkten (Voxel, volume element, im Gegensatz zum zweidimensionalen Pixel, picture element) werden häufig insbesondere Methoden der mathematischen Statistik benötigt. Zufällige Fehler in der Messung äußern sich als Bildrauschen, die Bilder wirken unscharf und gestört. Dadurch werden diagnostische Entscheidungen erschwert.
Im Jahr 1859 veröffentlichte Charles Darwin "On the Origin of Species“. Seine Evolutionstheorie ist das wohl spektakulärste Beispiel einer naturwissenschaftlichen Theorie großer gesellschaftlicher Relevanz. Ihre verschiedenen Facetten wurden in der Öffentlichkeit kontrovers diskutiert, unter anderem auch ihre Anwendung zur Erklärung von Zuständen und Prozessen menschlicher Gesellschaften. Zum Teil wurde die Seiensweise der Natur - scheinbar unabhängig von gesellschaftlichen Interessen - für die Erklärung und Legitimation gesellschaftlicher Zustände oder die Legitimation von politischen Ideologien herangezogen (Sozialdarwinismus). Denn Gesellschaft funktioniere ja so, wie Darwin die Natur erklärt habe: es herrsche z. B. Konkurrenzkampf, Auslese und Arbeitsteilung, Erfolg hätten diejenigen, die sich an die Bedingungen am Besten anpassten.
Geffroy, Claude; Buch, Arnaud; David, Marc; Aissat, Lyes; El Mufleh, Amel; Papot, S.; Sternberg, Robert
Many organic molecules are present in interstellar clouds and might be carried to the early Earth by comets and meteorites during the heavy bombardment phase in the first few hundred million years of the solar system. It has been suggested that extraterrestrial organic material may well represent an important part of the organic material available for the origin of life. Until samples, brought by future space missions, are available on Earth, in situ measurements are one of the way to get unaltered and non-contaminated samples for analysis. The analytical technique has to be robust, sensitive and non-specific due to the large scope of targets molecules. The only currently flight qualified technique of analysis of organic molecules in space is gas chromatography (Viking, Cassini-Huygens, SAM-MSL, COSAC-Rosetta). The main objective of this work is to present a new approach with multi step analysis using derivatisation and thermochemolysis reagents for a one pot in situ analysis of volatile and refractory organics in surface or sub-surface samples (Mars, comets).Indeed, no single technology enables to identify all organic compounds because naturally occurring molecules have different polarities, molecular weights, being extractible or recalcitrant, bonded trapped or adsorbed on minerals. Thus, we propose to wider the scope of chemical reagent already validated for in situ wet chemistry such as MTBSTFA (Rodier et al. 2001, 2002), DMF-DMA (Rodier et al. 2002), or TMAH (Rodier et al, 2005, Geffroy-Rodier et al; 2009) to analyze enantiomers of amino acids, carbohydrates and lipids in a one pot several steps sub system using a multi reagent and multi step approach. Thus using a new derivatizing agent, we successfully identified twenty one amino acids including twelve of the twenty proteinic amino acids without inhibiting following multi step thermochemolysis. *Geffroy-Rodier C, Grasset L, Sternberg R. Buch A. Amblès A. (2009) Thermochemolysis in search for organics in extraterrestrial environments, Journal of Applied Pyrolysis 85: 454-459. *Rodier C, Sternberg R, Raulin F, Vidal-Madjar C (2001). In situ detection of organic molecules in extraterrestrial environment by gas chromatography / mass spectrometry. Journal of Chromatography A 915: 199-207. *Rodier C, Laurent C, Szopa C. Sternberg R, Raulin F (2002) Chirality and the origin of life: in situ enantiomeric separation for future space missions, Chirality 14: 527-532. *Rodier C. Sternberg R, Szopa C, Buch A, Cabane M and Raulin F (2005) Search for organics in extraterrestrial environments by in situ gas chromatography analysis. Advances in Space Research 36: 195-200. This work has been funded by CNES
Aim: To examine the protective effects of scutellarin (Scu) on rats with learning and memory deficit induced by β-amyloid peptide (Aβ). Methods: Fifty male Wistar rats were randomly divided into 5 groups: control, sham operation, Aβ, Aβ+Scu, and Aβ+piracetam groups. Aβ25–35 was injected into the lateral ventricle (10 μg each side). Scu (10 mg/2 mL) or piracetam (10 mg/2 mL was intragastrically administered per day for 20 consecutive days following Aβ treatment. Learning and memory was assessed with Morris water maze test. The protein and mRNA levels of nicotinic acetylcholine receptor (nAChR) α4, α7, and β2 subunits in the brain were examined using Western blotting and real-time PCR, respectively. The activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain and plasma were measured using Ellman's colorimetric method. Results: In Aβ group, the escape latency period and first platform cross was significantly increased, and the total number of platform crossings was significantly decreased, as compared with the control and the sham operation groups. Both Scu and piracetam treatment significantly reduced the escape latency period and time to cross platform, and increased the number of platform crosses, but there were no significant differences between Aβ+Scu and Aβ+piracetam groups. In Aβ group, the protein levels of nAChR α4 and α7 subunits in the cerebral cortex were significantly decreased by 42%–47% and 58%–61%, respectively, as compared to the control and the sham operation groups. Scu treatment caused upregulation of α4 and α7 subunit proteins by around 24% and 30%, respectively, as compared to Aβ group, but there were no significant differences between Aβ+Scu and Aβ+piracetam groups. The protein level of nAChR β2 subunit had no significant difference among different groups. The mRNA levels of nAChR α4, α7, and β2 subunits were not significantly changed. In Aβ group, the activities of AChE and BuChE in the brain were significantly increased, but were significantly decreased in the plasma, as compared to the control and the sham operation groups. Scu or piracetam treatment restored the activities in brain and plasma nearly to the levels in the control group. Conclusion: The results suggest that Scu may rescue some of the deleterious effects of Aβ, possibly by stimulating nAChR protein translation and regulating cholinesterase activity. PMID:21986571
Werner Heisenberg war eine der prägendsten Gestalten der Physik des 20. Jahrhunderts. Zu seinen wichtigsten Verdiensten gehören die Grundlegung der Quantenmechanik, die Formulierung der Unschärferelationen sowie die Beteiligung an der Ausarbeitung der Kopenhagener Deutung der Quantenmechanik. Darüber hinaus lieferte er Arbeiten von fundamentalem Charakter zur Theorie des Atomkerns, zur kosmischen Strahlung und zur Quantenfeldtheorie. Während des Krieges war er an den Arbeiten des Uranvereins beteiligt, der die Möglichkeit einer Entwicklung von Kernwaffen untersuchte, jedoch über Vorarbeiten zur Reaktorphysik nicht hinauskam. Wegen dieser Tätigkeit wurde er bei Kriegsende für einige Monate in England interniert. Nach seiner Rückkehr widmete er sich vor allem dem Aufbau der Physik in Deutschland, die während der NS-Zeit nahezu ihrer gesamten Substanz beraubt worden war.
Dauerhafter Unternehmenserfolg ist nur mit einer fortschrittlichen Instandhaltung zu erzielen. Durch den enormen Kostendruck infolge der Globalisierung und die Innovationssprünge auf der technischen Seite wird auch die Frage nach der modernen Organisationsform für die Instandhaltung gestellt. Eine Möglichkeit der Kostenoptimierung ist das Outsourcing von Instandhaltungsleistungen. Hierbei ist es unerlässlich, dass sich die Mitarbeiter zum Dienstleister entwickeln. In diesem Beitrag wird die Entwicklung der InfraServ Knapsack von einer internen Instandhaltungsabteilung hin zu einem Industriellen Dienstleister beschrieben und Aspekte der Zusammenarbeit mit externen Kunden aus der Sicht des outgesourcten Instandhalters geschildert. Es werden die wichtigen Entwicklungsschritte zur Dienstleistungsorientierung der früheren Eigeninstandhaltung aufgezeigt. Dieser Beitrag ist nicht als "Königsweg“ zu verstehen, er soll vielmehr anhand der Erfahrungen einer outgesourcten Eigeninstandhaltung Anregungen für die Entwicklung der eigenen Instandhaltungsorganisation liefern.
Das in der Medizin mit am häufigsten verwendete Implantat weltweit ist die Intraokulare Linse (IOL). Die Gründe hierfür sind vielschichtig: einmal haben die Operationstechniken in den letzten 30 Jahren eine wesentliche Steigerung an Gleichmäßigkeit, Erfolg und Effizienz erfahren, zum anderen verursachen die gestiegenen Anforderungen des Alltags in den Industrienationen und im Berufsleben den höheren Anspruch an das Sehvermögen. Ist die menschliche Linse Ursache für schlechtes Sehvermögen, besteht meist eine Trübung des Linsenproteins. Diese Trübung nennt wird Volksmund Grauer Star genannt, wissenschaftlich die Katarakt (cataracta). Es gibt unterschiedliche Formen wie angeborene (congenita) oder erworbene, traumatische, krankheitsoder altersbedingte Formen [45]. Wird die eingetrübte Linse nun mittels moderner Operationsverfahren entfernt, muss für Ersatz dieses lichtbrechenden Mediums gesorgt werden [2].
Since the successful reactivation of the schönbuch railway between Böblingen and Dettenhausen the number of passengers has increased continuously. Due to this high demand of over 8000 people per day and the increase of popularity the current expansion projects include the electrification of the 17 km long track and the installation of double-track sections for providing a 15-minute-service between Böblingen and Holzgerlingen. To realize the new operational concept, Zweckverband Schönbuchbahn (ZVS), the public transport authority, has ordered nine light rail-styled vehicles (with costs around 51,3 mio. euro for developing and construction). In this way the schönbuch railway is an important factor to guarantee a sustainable and forward-looking mobility in the metropolitan area of Stuttgart and for restricting car traffic.
Elektrotechnik und Mechanik verknüpfen sich zunehmend, z. B. bei der Konstruktion von Maschinen. Als Beispiel sei ein Roboter genannt, dessen Bewegungsabläufe elektrisch gespeichert sind und über elektrische Antriebe ausgeführt werden. Bei der Bewegung eines massebehafteten Roboterarmes kommen u. a. Begriffe wie Geschwindigkeit, Beschleunigung, Bewegung im Koordinatensystem und Energie bewegter Massen zum Tragen. Dieses Kapitel erfasst die grundlegenden Gesetze der Mechanik. Behandelt werden folgende Themen: Kinematik des Massenpunktes (Geschwindigkeit, Beschleunigung, Freier Fall, Senkrechter Wurf); Zusammengesetzte Bewegungen (Schiefer Wurf, Kreisbewegung); Dynamik; Newtonsche Axiome; Kraft; Zerlegung und Zusammensetzung von Kräften; Impuls; Impulserhaltungssatz; Arbeit; Leistung; Wirkungsgrad; Energie; Stoß (elastisch und unelastisch); Rotation (Drehmoment, Schwerpunkt, Drehimpuls, Trägheitsmoment, Rotationsenergie); Gravitation; Elastische Verformung fester Körper; Mechanik der ruhenden Flüssigkeiten und Gase (Druck, Kompressibilität); Hydrostatischer Druck; Schweredruck in Gasen (Auftrieb); Hydrodynamik (Kontinuitätsgleichung, Bernoulli-Gleichung).
Das Gesetz zur Digitalisierung der Energiewende ist verabschiedet. Ab 2017 sind moderne Messeinrichtungen (mME) und intelligente Messsysteme (iMSys) zu verbauen und zu betreiben. Der "deutsche Weg" für die Einführung von Smart Metern sieht einen stufenweisen Rollout sowie ein Höchstmaß an Informations- und Datensicherheit vor. Dabei spielen iMSys und mME eine wichtige Rolle bei der Neugestaltung der intelligenten Netze (Smart Grids) und des neuen Marktmodells (Smart Market). Dieser Beitrag beschäftigt sich mit den neuen Gesetzen, den Marktrollen und ihren Aufgaben, Datenschutz und Datensicherheit, dem iMSys als sichere Lösung, dem sicheren Betrieb von Smart Meter Gateways, Smart Grid - Smart Market, dem Zusammenspiel zwischen reguliertem Bereich und Markt, den Einsatzbereichen der iMSys sowie den Auswirkungen auf Prozesse und Systeme und gibt Handlungsempfehlungen.
CAPE CANAVERAL, Fla. -- Brewster Shaw is a former astronaut from the first graduating class of astronauts after the Apollo program. He and others from the class were guests at NASA's Kennedy Space Center for the launch of space shuttle Discovery on its STS-124 mission. Shaw is Vice President and General Manager, Space Exploration, for Integrated Defense Systems, The Boeing Company. In 1978 a new group of 35 astronauts was selected after nine years without new astronauts. The pilots were Daniel Brandenstein, Michael Coats, Richard Covey, John Creighton, Robert Gibson, Frederick D. Gregory, Frederick Hauck, Jon McBride, Francis "Dick" Scobee, Brewster Shaw, Loren Shriver, David Walker and Donald Williams. The mission specialists were Guion Bluford, James Buchli, John Fabian, Anna Fisher, Dale Gardner, S. David Griggs, Terry Hart, Steven Hawley, Jeffrey Hoffman, Shannon Lucid, Ronald McNair, Richard Mullane, Steven Nagel, George Nelson, Ellison Onizuka, Judith Resnik, Sally Ride, Rhea Seddon, Robert Stewart, Kathryn D. Sullivan, Norman Thagard and James van Hoften. Since then, a new group has been selected roughly every two years. Photo credit: NASA/Jim Grossmann
The "Garden of Health" (Gart der Gesundheit) is the first illustrated book of herbs in German language. Its author, Johann Wonnecke from Kaub on the Rhine, was born in 1430 and worked as a city doctor in Frankfurt/Main until his death in 1503 or 1504. In his book, he refers to "proven Greek, Latin and Arabic masters of medicine" (bewerte meister in der artzeney), whose writings he was instructed to collect by Bernard von Breidenbach in 1480. Wonnecke carried out he task in a special way, deceiving five generations of historians of science, who proceeded from the false assumption, that the Gart der Gesundheit was compiled and translated from Latin sources. Wonnecke established the desired authors skilfully in his report, but under a more detailed investigation they reveal themselves as not taken from Latin sources but copied off from native language scriptures, e.g. Alterer deutscher Macer and Buch der Natur by Konrad von Megenberg. To these hitherto known sources used by him now the Speyrer Kräuterbuch is added, which supplied the medical knowledge of Hildegard von Bingen to the "Gart".
Ramalho, Teodorico C; de Castro, Alexandre A; Silva, Daniela R; Silva, Maria Cristina; Franca, Tanos C C; Bennion, Brian J; Kuca, Kamil
2016-01-01
The re-emergence of chemical weapons as a global threat in hands of terrorist groups, together with an increasing number of pesticides intoxications and environmental contaminations worldwide, has called the attention of the scientific community for the need of improvement in the technologies for detoxification of organophosphorus (OP) compounds. A compelling strategy is the use of bioremediation by enzymes that are able to hydrolyze these molecules to harmless chemical species. Several enzymes have been studied and engineered for this purpose. However, their mechanisms of action are not well understood. Theoretical investigations may help elucidate important aspects of these mechanisms and help in the development of more efficient bio-remediators. In this review, we point out the major contributions of computational methodologies applied to enzyme based detoxification of OPs. Furthermore, we highlight the use of PTE, PON, DFP, and BuChE as enzymes used in OP detoxification process and how computational tools such as molecular docking, molecular dynamics simulations and combined quantum mechanical/molecular mechanics have and will continue to contribute to this very important area of research.
Marco-Contelles, José; León, Rafael; de los Ríos, Cristóbal; García, Antonio G; López, Manuela G; Villarroya, Mercedes
2006-12-15
The synthesis and the biological evaluation (neuroprotection, voltage dependent calcium channel blockade, AChE/BuChE inhibitory activity and propidium binding) of new multipotent tetracyclic tacrine analogues (5-13) are described. Compounds 7, 8 and 11 showed a significant neuroprotective effect on neuroblastoma cells subjected to Ca(2+) overload or free radical induced toxicity. These compounds are modest AChE inhibitors [the best inhibitor (11) is 50-fold less potent than tacrine], but proved to be very selective, as for most of them no BuChE inhibition was observed. In addition, the propidium displacement experiments showed that these compounds bind AChE to the peripheral anionic site (PAS) of AChE and, consequently, are potential agents that can prevent the aggregation of beta-amyloid. Overall, compound 8 is a modest and selective AChE inhibitor, but an efficient neuroprotective agent against 70mM K(+) and 60microM H(2)O(2). Based on these results, some of these molecules can be considered as lead candidates for the further development of anti-Alzheimer drugs.
Die Evolution hat viele spektakuläre Phänomene hervorgebracht - von der Eleganz des Vogelflugs über die gigantischen Körper der Dinosaurier und die farbenprächtige Vielfalt der Korallenriffe bis hin zu ihrem jüngsten Geniestreich - der menschlichen Kunst. Die schönen Künste - Malerei, Bildhauerei und Architektur, Theater, Tanz, Oper und Filmkunst, Musik und Literatur - Produkte der Evolution? Diese Vorstellung mutet vielen Menschen fremd an, aber wie könnte es anders sein? Denn wenn Charles Darwin recht hat, dann sind nicht nur die körperlichen Merkmale der Menschen als Antworten auf die Erfordernisse des Lebens entstanden, sondern auch ihre geistigen Fähigkeiten und Verhaltensweisen. Im Jahr 1859 hatte er auf den letzten Seiten seines berühmten Buches über die Entstehung der Arten eine kühne Prophezeiung gemacht: Durch die Evolutionstheorie werde es "zu einer bemerkenswerten Revolution in der Naturwissenschaft kommen […]. Die Psychologie wird auf die neue Grundlage gestellt, dass jede geistige Kraft und Fähigkeit notwendigerweise durch graduelle Übergänge erworben wird“ (Darwin 1859, S. 484, 488; Junker 2008).
The essential oil extracted from fruit of Micromelum integrrimum were evaluated through gas chromatography and gas chromatography-mass spectroscopy. 52 compounds were identified from the fruit oil representing 99.98% of the oil. The major components of the total fruit oil are monoterpene hydrocarbons (72.23%), oxygenated monoterpenes (14.78%) and sesquiterpene (11.54%) which were predominated by terpinolene (32.21%), α-pinene (17.24%), β-pinene (17.24%), and camphene (4.05%). Moreover, other components that present in 1.45% were aromatic compounds, fatty acid, etc. The essential oil exhibited broad spectrum antimicrobial activity which is concentration dependent and 100 μL of the fruit oil showed the inhibition zones ranging from 7-16 mm. Fruit oil exhibited strong inhibition activity compared to standard anti-bacterial drug neomycin B (22 mm) against Bacillus subtilis MTCC 441 and Bacillus spizizenii ATCC 6633. This is the first hand report on the chemical profiles and promising anti-microbial activity of Micromelum integrrimum fruit essential oil towards Basillus Sp.
Schulz, Malte; von Arx, Thomas; Altermatt, Hans Jörg; Bosshardt, Dieter
2009-05-01
The aim of this was to evaluate the histology of periapical lesions in teeth treated with periapical surgery. After root-end resection, the root tip was removed together with the periapical pathological tissue. Histologic sectioning was performed on calcified specimens embedded in methylmethacrylate (MMA) and on demineralized specimens embedded in LR White (Fluka, Buchs, Switzerland). The samples were evaluated with light and transmission electron microscopy (TEM). The histologic findings were classified into periapical abscesses, granulomas, or cystic lesions (true or pocket cysts). The final material comprised 70% granulomas, 23% cysts and 5% abscesses, 1% scar tissues, and 1% keratocysts. Six of 125 samples could not be used. The cystic lesions could not be subdivided into pocket or true cysts. All cysts had an epithelium-lined cavity, two of them with cilia-lined epithelium. These results show the high incidence of periapical granulomas among periapical lesions obtained during apical surgery. Periapical abscesses were a rare occasion. The histologic findings from samples obtained during apical surgery may differ from findings obtained by teeth extractions. A determination between pocket and true apical cysts is hardly possible when collecting samples by apical surgery.
Solowey, Douglas P; Mane, Manoj V; Kurogi, Takashi; Carroll, Patrick J; Manor, Brian C; Baik, Mu-Hyun; Mindiola, Daniel J
2017-11-01
Selectively converting linear alkanes to α-olefins under mild conditions is a highly desirable transformation given the abundance of alkanes as well as the use of olefins as building blocks in the chemical community. Until now, this reaction has been primarily the remit of noble-metal catalysts, despite extensive work showing that base-metal alkylidenes can mediate the reaction in a stoichiometric fashion. Here, we show how the presence of a hydrogen acceptor, such as the phosphorus ylide, when combined with the alkylidene complex (PNP)Ti=CH t Bu(CH 3 ) (PNP=N[2-P(CHMe 2 ) 2 -4-methylphenyl] 2 - ), catalyses the dehydrogenation of cycloalkanes to cyclic alkenes, and linear alkanes with chain lengths of C 4 to C 8 to terminal olefins under mild conditions. This Article represents the first example of a homogeneous and selective alkane dehydrogenation reaction using a base-metal titanium catalyst. We also propose a unique mechanism for the transfer dehydrogenation of hydrocarbons to olefins and discuss a complete cycle based on a combined experimental and computational study.
Periwinkles, as typical inhabitants of sea-shores, are subjected to extreme changes of environmental conditions, which affect their excretion. In Littorina littorea uric acid, urea and ammonium were detected particularly in the kidney, but the only metabolite excreted was ammonium. Only the concentration of uric acid was dependent on the availability of water; decreasing periods of submersion during low tide and raised salinities caused a higher concentration of uric acid, while increasing periods of submersion and lowered salinities effected the opposite. Transfer of periwinkles within their intertidal habitat and laboratory experiments to test the effect of salinity showed that the concentration of uric acid in the kidney is adaptable. The dependence of uric acid concentration in the kidney on environmental conditions and the ammoniotelic excretion of L. littorea are discussed with regard to its particular living conditions. It is suggested that uric acid serves as nitrogen depot and has a particular function in osmoregulation.
Energie wird zum Gebrauchsgegenstand, zur Commodity und rückt doch in den Blickpunkt der Aufmerksamkeit. Volkswirtschaftliche, politische, gesellschaftliche und betriebswirtschaftliche Ansprüche lassen Services rund um die Energieversorgung (Energy-related Services) entstehen. Convenience Services, die den Ansprüchen der Konsumenten gerecht werden, wie Visualisierung von (dezentraler) Energieerzeugung und -verbrauch auf Basis digitaler Smart Meter, die den analogen Ferraris-Zähler ersetzen, sowie optimierter Energieeinsatz halten in Haushalten als digitalisierten Standorten (Smart Sites) Einzug. Energieoptimierung auf Basis des Paradigmas "Verbrauch folgt Erzeugung" stellt Nachfrageflexibilität industrieller Prozesse (Demand Response) als Energie-Effizienz-Faktor in den Vordergrund und lässt Services wie ihre Vermarktung als Regelenergie zur Stabilisierung der Netzfrequenz entstehen. Ein Innovation Action Plan liefert einen Ausblick, wohin die Integration neuer Technologien, die Steigerung der Kundennähe und die Entwicklung neuer Geschäftsmodelle die Energiewirtschaft führen kann. Mit Eco-Home und Power-Pool werden zwei konkrete Beispiele für Energy as a Service vorgestellt.
Until now, Philipp Feselius has been perceived only indirectly as Kepler's antagonist. Not much is known about his life besides his work as Baden private physician and his book against astrology which was cited intensely in Kepler's «Tertius Interveniens». This paper traces the stations of his career as a physician, about his presumable provenance and education in Strasbourg, his academic career in Tübingen, Strasbourg, Rostock and Padua, the doctorate in Basel in 1592, up to his employment, in 1599, as a court physician in Sulzburg and later in Durlach. Further hand-written and printed traces of Feselius are presented, and his social environment is investigated so that his personality becomes clearer, and relations can be established between his education and his writing against astrology.
Kaum eine Branche hat in den letzten zehn Jahren einen tiefgreifenderen Wandel erfahren als die Energiewirtschaft. Einstmals geprägt durch Großkonzerne, die flächendeckend alle Formen von Energiedienstleistungen erbracht haben, stellt sich heute eine gänzlich veränderte Landschaft dar. Nicht nur das es heute eine Vielzahl von Erzeugern gibt, die zunehmend dezentral aufgestellt sind, auch die klassischen Marktrollen wechseln: Erzeuger werden zu Händlern, Verbraucher werden zu Erzeugern. Darüber hinaus drängen heute neue, vormals branchenfremde, Marktteilnehmer in die Energiewirtschaft. Leicht nachzuvollziehen, dass es eine neue Art der Kommunikation braucht. Ziel ist alle Akteure zu vernetzen, um so neuartige Geschäftsmodelle zu ermöglichen. Das Internet of Things (IoT) und die Serviceplattformen bieten hierzu die geeignete Grundlage und Lösungen für neue und zukünftige Prozesse in der Energiebranche. Hierbei stehen auch Themen, wie Big Data, Datenformate, Datennutzung und -sicherheit im Fokus.
Representatives of the family Myxococcaceae, Myxococcus fulvus and M. virescens as well as Archangium gephyra could be isolated from marine sediments (depth range 5 58 m), collected near the island of Helgoland (North Sea); dunes and rudiments of salt marshes additionally yielded M. coralloides and the rare species Melittangium licenicola and M. boletus (Cystobacteriaceae). In soil samples from the island, M. fulvus, M. virescens, M. coralloides, A. gephyra, Cystobacter fuscus and Stigmatella erecta were found. These results were confirmed by data, obtained from the coastal zone of the island of Amrum and marine sediments from various regions. On the other hand samples from shallow fresh water (depth range 0.3 1 m) proved to be richer in species. It is assumed that the myxobacteria found in marine sediments occur as resting cells.
Neue Treiber der Digitalisierung bestimmen die Geschicke der etablierten Unternehmen im Energiebereich, dabei haben diese in vielen Fällen noch nicht einmal adäquat auf die altbekannten Treiber der Energiewende reagiert. Eine ganze Branche ist im Umbruch, alte Erlösmodelle brechen ein und Einigkeit scheint bei den Verantwortlichen nur in der Frage zu herrschen, wie in Zukunft noch Geld verdient werden kann. Dieser Beitrag erklärt die prägenden Treiber der Veränderung, analysiert die Ausgangslage und nennt Herausforderungen der Branche. Darüber hinaus legt er den Fokus auf die Betrachtung der neuen digitalen Wertschöpfung. Dazu wird ein Modell eingeführt, welches von der klassischen Wertschöpfungskette über datenbasierte Geschäftsmodelle im Energiesystem bis hin zum Internet of Smart Services reicht. Mit dem Modell geben die Autoren gleichsam Einblick in das geplante Energiewendeprojekt enera.
Zusammenfassung In der Arbeit wird über die Ergebnisse einer numerischen Studie, betreffend die stationäre Konvektionsströmung und den stationären Wärmeübergang in einer rechteckigen, mit einem porösen, phasenveränderlichen Medium (PCM) verfüllten Kavität, berichtet. Den zwei vertikalen Berandungen der Kavität sind zwei, den Schmelzpunkt des PCM einschließende Temperaturen aufgeprägt, während die beiden horizontalen Berandungen adiabat gehalten werden. Das poröse Medium ist durch einen anisotropen Permeabilitätstensor charakterisiert, dessen Hauptachsen bezüglich des Gravitationsvektors beliebig orientiert sein können. Das Problem ist durch das Seitenverhältnis A, die Rayleigh-Zahl Ra, das Anisotropienverhältnis R und den Orientierungswinkel Θ des Permeabilitätstensor bestimmt. Hauptaugenmerk gilt dem Einfluß der anisotropen Permeabilität auf das Strömungsverhalten und den Wärme-übergang beim Phasenwechselprozeß flüssig/fest. Die Lösungsmethode basiert auf dem Kontrollvolumenprinzip in Verbindung mit der Landau-Transformation über welche das irreguläre Strömungsgebiet in ein rechteckiges abgebildet wird. Ergebnisse bezüglich Strömungsfeld, Temperaturverteilung, Phasengrenzenort und Wärmeübergang werden fürA=2,5Ra=40 0<=Θ<=π 0,25<=R<=4 mitgeteilt. Es zeigte sich, daß der Gleichgewichtszustand des Phasenwechselsprozesses fest/flüssig sowohl durch das Anisotropieverhältnis R als auch durch den Orientierungswinkel Θ des Permeabilitätstensors wesentlich beeinflußt werden kann. Zum einen existiert bei festgehaltenen ParameternA, Ra undR eine optimale Orientierung Θmax, bei der die Stromstärke, das Flüssigkeitsvolumen und der Wärmestrom Maximalwerte erreichen, während für Θmin=Θmax+π/2 Minimalwerte resultieren. Ist das anisotrope Medium entlang der Optimalrichtung Θmax orientiert, so ergibt sich zum anderen, daß eine Vergrößerung der in diese Richtung fallenden Permeabilitätskomponente die Stromstärke und den Wärmestrom in gleichem Maße erhöht, während eine Vergrößerung der anderen Permeabilitätskomponente nur vernachlässigbaren Einfluß hat. In den untersuchten Parameterbereichen lag die Optimalrichtung zwischen dem Gravitationsvektor und der Hauptstromrichtung.
Jets are highly collimated flows of matter. They are present in a large variety of astrophysical sources: young stars, stellar mass black holes (microquasars), galaxies with an active nucleus (AGN) and presumably also intense flashes of gamma-rays. In particular, the jets of microquasars, powered by accretion disks, are probably small-scale versions of the outflows from AGN. Beside observations of astrophysical jet sources, also theoretical considerations have shown that magnetic fields play an important role in jet formation, acceleration and collimation. Collimated jets seem to be systematically associated with the presence of an accretion disk around a star or a collapsed object. If the central object is a black hole, the surrounding accretion disk is the only possible location for a magnetic field generation. We are interested in the formation process of highly relativistic jets as observed from microquasars and AGN. We theoretically investigate the jet collimation region, whose physical dimensions are extremely tiny even compared to radio telescopes spatial resolution. Thus, for most of the jet sources, global theoretical models are, at the moment, the only possibility to gain information about the physical processes in the innermost jet region. For the first time, we determine the global two-dimensional field structure of stationary, axisymmetric, relativistic, strongly magnetized (force-free) jets collimating into an asymptotically cylindrical jet (taken as boundary condition) and anchored into a differentially rotating accretion disk. This approach allows for a direct connection between the accretion disk and the asymptotic collimated jet. Therefore, assuming that the foot points of the field lines are rotating with Keplerian speed, we are able to achieve a direct scaling of the jet magnetosphere in terms of the size of the central object. We find a close compatibility between the results of our model and radio observations of the M87 galaxy innermost jet. We also calculate the X-ray emission in the energy range 0.2--10.1,keV from a microquasar relativistic jet close to its source of 5 solar masses. In order to do it, we apply the jet flow parameters (densities, velocities, temperatures of each volume element along the collimating jet) derived in the literature from the relativistic magnetohydrodynamic equations. We obtain theoretical thermal X-ray spectra of the innermost jet as composition of the spectral contributions of the single volume elements along the jet. Since relativistic effects as Doppler shift and Doppler boosting due to the motion of jets toward us might be important, we investigate how the spectra are affected by them considering different inclinations of the line of sight to the jet axis. Emission lines of highly ionized iron are clearly visible in our spectra, probably also observed in the Galactic microquasars GRS 1915+105 and XTE J1748-288. The Doppler shift of the emission lines is always evident. Due to the chosen geometry of the magnetohydrodynamic jet, the inner X-ray emitting part is not yet collimated. Ergo, depending on the viewing angle, the Doppler boosting does not play a major role in the total spectra. This is the first time that X-ray spectra have been calculated from the numerical solution of a magnetohydrodynamic jet. Astrophysikalische Jets sind stark kollimierte Materieströmungen hoher Geschwindigkeit. Sie stehen im Zusammenhang mit einer Fülle verschiedener astrophysikalischer Objekte wie jungen Sternen, stellaren schwarzen Löchern ('Mikro-Quasare'), Galaxien mit aktivem Kern (AGN) und wahrscheinlich auch mit dem beobachteten intensiven Aufblitzen von Gamma-Strahlung (Gamma Ray Bursts). Insbesondere hat sich gezeigt, dass die Jets der Mikro-Quasare wahrscheinlich als kleinskalige Version der Jets der AGN anzusehen sind. Neben den Beobachtungen haben vor allem auch theoretische Überlegungen gezeigt, dass Magnetfelder bei der Jetentstehung, -beschleunigung und -kollimation eine wichtige Rolle spielen. Weiterhin scheinen Jets systematisch verknüpft zu sein mit dem Vorhandensein einer Akkretionsscheibe um das zentrale Objekt. Insbesondere wenn ein schwarzes Loch den Zentralkörper darstellt, ist die umgebende Akkretionsscheibe der einzig mögliche Ort um Magnetfeld erzeugen zu können. Wir sind speziell interessiert am Entstehungsprozess hoch relativistischer Jets wie sie bei Mikro-Quasaren und AGN beobachtet werden. Insbesondere untersuchen wir die Region, in der der Jet kollimiert, eine Region, deren räumliche Ausdehnung extrem klein ist selbst im Vergleich zur Auflösung der Radioteleskope. Dies ist ein Grund, wieso zum heutigen Zeitpunkt für die meisten Quellen die theoretische Modellierung die einzige Möglichkeit darstellt, um Information über die physikalischen Prozesse in der innersten Region der Jetentstehung zu erhalten. Uns ist es zum ersten Mal gelungen, die globale zwei-dimensionale Magnetfeldstruktur stationärer, axialsymmetrischer, relativistischer und stark magnetisierter (kräfte-freier) Jets zu berechnen, die zum einen asymptotisch in einen zylindrischen Jet kollimieren, zum anderen aber in einer differential rotierenden Akkretionsscheibe verankert sind. Damit erlaubt dieser Ansatz eine physikalische Verkn¨upfung zwischen Akkretionsscheibe und dem asymptotischen Jet. Nimmt man also an, dass die Fupunkte der Magnetfeldlinien mit Keplergeschwindigkeit rotieren, so kann man eine direkte Skalierung der Jetmagnetosphere mit der Gröe des Zentralobjektes erhalten. Unsere Resultate zeigen eine gute Übereinstimmung zwischen unserem Modell und Beobachtungen des Jets von M87. Für das Beispiel eines relativistischen Mikroquasarjets haben wir die Röntgenemission im Bereich von 0.2-10.1 keV berechnet. Dafür haben wir in der Literatur aus den relativistischen magnetohydrodynamischen Gleichungen berechnete Jetgröen (Dichte-, Geschwindigkeits-, und Temperaturprofil) verwendet und das Spektrum für jeden Punkt entlang der Jetströmung abgeleitet. Das theoretische thermische Röntgenspektrum des innersten, heien Teils des Jets erhalten wir zusammengesetzt aus den spektralen Anteilen der einzelnen Volumenelemente entlang des Jets. Um relativistische Effekte wie Dopplerverschiebung und -verstärkung (boosting) aufgrund der Jetbewegung zu untersuchen, haben wir für verschiedene Inklinationswinkel des Jets zur Sichtlinie berechnet, wie die erhaltenen Spektren davon beeinflusst werden. Unsere Spektren zeigen deutlich die hochionisierten Eisen-Emissionslinien, die in den galaktischen Mikroquasaren GRS 1915+105 und XTE J1748-288 andeutungsweise beobachtet wurden. Eine Dopplerverschiebung dieser Linien ist in unseren Spektren deutlichzu sehen. Da die innerste, Röntgenstrahlung emittierende Region des magnetohydrodynamischen Jets allerdings noch unkollimiert ist, spielt Dopplerboosting in unseren Spektren, abhängig vom Sichtwinkel, keine groe Rolle. Mit unseren Resultaten konnte zum ersten Mal ein Röntgenspektrum gewonnen werden, das auf der numerischen Lösung eines magnetohydrodynamischen Jets beruht.
Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr5) showed significant neuroprotective activity, followed by 100% part (Fr6). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect.
Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr5) showed significant neuroprotective activity, followed by 100% part (Fr6). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect. PMID:28304399
Lepidium meyenii (Maca), originated from Peru, has been cultivated widely in China as a popular health care food. However, the chemical and effective studies of Maca were less in-depth, which restricted its application seriously. To ensure the quality of Maca, a feasible and accurate strategy was established. One hundred and sixty compounds including 30 reference standards were identified in 6 fractions of methanol extract of Maca by UHPLC-ESI-Orbitrap MS. Among them, 15 representative active compounds were simultaneously determined in 17 samples by UHPLC-ESI-QqQ MS. The results suggested that Maca from Yunnan province was the potential substitute for the one from Peru. Meanwhile, the neuroprotective effects of Maca were investigated. Three fractions and two pure compounds showed strong activities in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced zebrafish model. Among them, 80% methanol elution fraction (Fr 5 ) showed significant neuroprotective activity, followed by 100% part (Fr 6 ). The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) was a possible mechanism of its neuroprotective effect.
The cascade of events that occurs in Alzheimer's disease involving oxidative stress and the reduction in cholinergic transmission can be better addressed by multifunctional drugs than cholinesterase inhibitors alone. For this purpose, we prepared a large number of derivatives of indoline-3-propionic acids and esters. They showed scavenging activity against different radicals in solution and significant protection against cytotoxicity in cardiomyocytes and primary cultures of neuronal cells exposed to H2O2 species and serum deprivation at concentrations ranging from 1 nM to 10 μM depending on the compound. For most of the indoline-3-propionic acid derivatives, introduction of N-methyl-N-ethyl or N-methyl-N-(4-methoxyphenyl) carbamate moieties at positions 4, 6, or 7 conferred both acetyl (AChE) and butyryl (BuChE) cholinesterase inhibitory activities at similar concentrations to those that showed antioxidant activity. The most potent AChE inhibitors were 120 (3-(2-aminoethyl) indolin-4-yl ethyl(methyl)carbamate dihydrochloride) and 94 (3-(3-methoxy-3-oxopropyl)-4-(((4-methoxyphenyl)(methyl) carbamoyl)oxy)indolin-1-ium hydrochloride) with IC50s of 0.4 and 1.2 μM, respectively.
A novel family of cinnamic acid derivatives has been developed to be multifunctional cholinesterase inhibitors against AD by fusing N-benzyl pyridinium moiety and different substituted cinnamic acids. In vitro studies showed that most compounds were endowed with a noteworthy ability to inhibit cholinesterase, self-induced Aβ (1-42) aggregation, and to chelate metal ions. Especially, compound 5l showed potent cholinesterase inhibitory activity (IC 50 , 12.1 nM for eeAChE, 8.6 nM for hAChE, 2.6 μM for eqBuChE and 4.4 μM for hBuChE) and the highest selectivity toward AChE over BuChE. It also showed good inhibition of Aβ (1-42) aggregation (64.7% at 20 μM) and good neuroprotection on PC12 cells against amyloid-induced cell toxicity. Finally, compound 5l could penetrate the BBB, as forecasted by the PAMPA-BBB assay and proved in OF1 mice by ex vivo experiments. Overall, compound 5l seems to be a promising lead compound for the treatment of Alzheimer's diseases.
The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC 50 ) = 37.02 nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC 50 = 101.40 nM). Besides, it inhibited amyloid β-protein self-aggregation by 65.49% at 25 μM. In subsequent in vivo scopolamine-induced AD models, compound 10g obviously ameliorated the cognition impairment and showed preliminary safety in hepatotoxicity evaluation. These data suggest compound 10g as a promising multifunctional agent in the drug discovery process against AD.
Objective(s): To investigate the efficiency of a novel series of coumarin derivatives bearing benzoheterocycle moiety as novel cholinesterase inhibitors. Materials and Methods: Different 7-hydroxycoumarin derivatives were synthesized via Pechmann or Knoevenagel condensation and conjugated to different benzoheterocycle (8-hydroxyquinoline, 2-mercaptobenzoxazole or 2-mercaptobenzimidazole) using dibromoalkanes 3a-m: Final compounds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by Ellman’s method. Kinetic study of AChE inhibition and ligand-protein docking simulation were also carried out for the most potent compound 3b. Results: Some of the compounds revealed potent and selective activity against AChE. Compound 3b containing the quinoline group showed the best activity with an IC50 value of 8.80 μM against AChE. Kinetic study of AChE inhibition revealed the mixed-type inhibition of the enzyme by compound 3b. Ligand-protein docking simulation also showed that the flexibility of the hydrophobic five carbons linker allows the quinoline ring to form π-π interaction with Trp279 in the PAS. Conclusion: We suggest these synthesized compounds could become potential leads for AChE inhibition and prevention of AD symptoms. PMID:28868119
Di Bari, Maria; Reale, Marcella; Di Nicola, Marta; Orlando, Viviana; Galizia, Sabrina; Porfilio, Italo; Costantini, Erica; D'Angelo, Chiara; Ruggieri, Serena; Biagioni, Stefano; Gasperini, Claudio; Tata, Ada Maria
2016-11-30
Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis.
Mangrove plants are specialized woody plants growing in the swamps of tidal-coastal areas and river deltas of tropical and subtropical parts of the world. They have been utilized for medicinal and other purposes by the coastal people over the years. Heritiera fomes Buch. Ham. (family: Sterculiaceae) commonly known as Sundari (Bengali) is a preeminent mangrove plant occurring in the Sundarbans forest located in the southern part of Bangladesh and adjoining West Bengal province of India. The plant has applications in traditional folk medicine as evidenced by its extensive use for treating diabetes, hepatic disorders, gastrointestinal disorders, goiter, and skin diseases by the local people and traditional health practitioners. A number of investigations indicated that the plant possesses significant antioxidant, antinociceptive, antihyperglycemic, antimicrobial, and anticancer activities. Phytochemical analyses have revealed the presence of important chemical constituents like saponins, alkaloids, glycosides, tannins, steroids, flavonoids, gums, phytosterols, and reducing sugars. The present study is aimed at compiling information on phytochemical, biological, pharmacological, and ethnobotanical properties of this important medicinal plant, with a view to critically assess the legitimacy of the use of this plant in the aforementioned disorders as well as providing directions for further research. PMID:27382611
Di Bari, Maria; Reale, Marcella; Di Nicola, Marta; Orlando, Viviana; Galizia, Sabrina; Porfilio, Italo; Costantini, Erica; D’Angelo, Chiara; Ruggieri, Serena; Biagioni, Stefano; Gasperini, Claudio; Tata, Ada Maria
2016-01-01
Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis. PMID:27916909
Inestrosa, N C; Labarca, R; Perelman, A; Campos, E O; Araneda, R; González, M; Brandan, E; Sánchez, J P; González-Plaza, R
1990-10-01
The biology of planktotrophic larvae of Concholepas concholepas is the main bottleneck towards developing biotechnologies to rear this muricid. Data concerning planktonic larvae development, diets and environmental signals triggering larval settlement and recruitment is scarce. We have begun the study of the molecular and cell biology of embryos, larvae and recruits having as a final goal, the development of appropriate biotechnologies to rear this gastropod. First, an inverse ratio between BuChE and AChE enzyme activities was established. This ratio may be a precise developmental marker for this species. Second, for the first time a phosphoinositide related regulatory pathway is reported in a muricid, opening a new approach to the biotechnological management of larvae. Third, the relation between sulfate in sea water and larval motility was studied. Concentrations below 125 microM sulfate decreases larval motility. The sulfate is incorporated in proteoglycans which participate in different developmental phenomena. Lastly, a genomic Concholepas concholepas DNA sequence, similar to that of a human growth hormone probe was detected. This is very interesting since growth factors are key molecules during development, growth and are involved in food conversion rates in fish and also, in a variety of marine invertebrates.
María De la Rosa, José; Sánchez-Martín, Águeda; Villaverde-Capellán, Jaime; Madrid, Fernando; Paneque, Marina; Knicker, Heike
2017-04-01
Biochar may act as a soil conditioner, enhancing plant growth by supplying and retaining nutrients and by providing other services such as improving soil physical, chemical and biological properties. Feedstock properties and production conditions drive the nature of produced biochars [1]. Special attention have to be paid to their content of polycyclic aromatic hydrocarbons (PAHs), which are persistent organic pollutants formed during biochar production due to incomplete combustion (pyrolysis step) [2]. These PAHs may enter the environment when the biochar is applied as soil conditioner. Therefore, the intention of this study was to test a potential hazardous impact of biochar amendment due to the presence of PAHs. In order to find a relationship between pyrolysis conditions, feedstock and abundance of PAHs, four biochars produced from different feedstock were analyzed. Three biochars were produced by technical pyrolysis (500-600 °C; 20 min) from wood, paper sludge and sewage sludge respectively (samples B1, B2 and B3). The fourth biochar sample derived from old grapevine wood by using the traditional carbonization method in kilns (kiln-stack wood biochar; B4). A detailed characterization of physical and chemical properties of these samples can be found in De la Rosa et al, [3]. Two different PAHs extraction techniques were applied to evaluate the total and available PAHs content of the biochars. They consisted in an extraction with toluene using a Soxhlet extractor and a non-exhaustive extraction with Cyclodextrins (CDs). Chromatographic and mass spectrometric conditions applied are described in [1]. Total PAHs yielded between 3 ppm (B3) and 7 (B4) ppm. The production of biochar by using traditional kilns instead of controlled pyrolysis, increased significantly the total PAHs levels. No direct relationship was found between the total PAHs and the PAHs extracted by CDs, which can be considered as the bioavailable fraction. This parameter should replace the total PAHs to determine the real hazardous impact of the use of biochar as soil amendment. [1] J.M. De la Rosa, M. Paneque, I. Hilber, F. Blum, H. Knicker, T. Bucheli, J. Soils and Sediments 16 (2016) 557-565. [2] T. Bucheli, I Hilber, H. Schmidt. In Lehmann J, Joseph S (eds) Biochar for Environmental Management (2nd ed.), Earthscan, London, UKA. (2015). [3] J.M. De la Rosa, M. Paneque, A.Z. Miller, H. Knicker, Science of the Total Environment 499 (2014) 175-184. Acknowledgements: J.M. de la Rosa thanks The Spanish Ministry of Economy and Competitiveness (MINECO) for his "Ramón y Cajal" post-doctoral contract. MINECO, the European Regional Development Fund and the Marie Curie Integration Grants of 7th European Community Framework Programme are thanked for the financial support to this study (projects CGL2015-64811-P and PCIG12-GA-2012-333784).
While establishing new norms for the questionnaire Aussagen-Liste zum Selbstwertgefühl für Kinder und Jugendliche (ALS; Schauder, 1991, 1996, 2011) data from the year 1989 were compared to the new data from 2009. The expected differences in the areas school, leisure and family and a certain trend during puberty towards a decrease of self-esteem between the agegroups 10/11 and 12/13 could be shown for both times of examination. The difference in experiencing their self-esteem for boys and girls is not relevant anymore in 2009. Girls show higher scores today and express an equally high self-esteem as boys. Changes in the self-esteem over the period of times can be seen as follows: overall the tested children in 2009 express a higher self-esteem than in 1989. This applies to all age groups and boys and girls for all tested areas and is partly statistically very significant. Girls show the most obvious improvement in self-esteem.
Der vorliegende Beitrag diskutiert an einem konkreten Forschungsprojekt, wie aus den Überwachungsdaten von Photovoltaikanlagen Algorithmen entwickelt wurden, die zukünftig die automatisierte Fehlererkennung und damit eine verbesserte Betriebsführung ermöglichen können. Um von Daten zum optimierten Prozess zu gelangen, sind vier Stufen notwendig. Nach der Datenintegration folgen die Qualitätssicherung, dann die Analyse und schließlich die Umsetzung in eine betrieblich nutzbare Anwendung. Für die Entwicklung valider, praxisrelevanter Modelle stellte es sich als unumgänglich heraus, dass bereits frühzeitig die datengenerierenden Prozesse und damit auch die physikalischen Grundlagen der Anlagen nicht nur von den Prozessexperten, sondern genauso von den Data Scientists verstanden wurden: Es genügt eben nicht, Daten zu konsolidieren und in ein Analysetool zu stecken, sondern die Wertschöpfung aus Daten gelingt nur, wenn eine domänen- und kompetenzübergreifend interdisziplinäre Zusammenarbeit erfolgt, in der beide Seiten bereit sind, kontinuierlich voneinander zu lernen.
Gilfedder, Benjamin; Peiffer, Stefan; Pöschke, Franziska; Spirkaneder, Andrea
2018-06-01
Groundwater can play an important role in lake water and chemical budgets. The aim of this study was to map and quantify groundwater discharge to Lake Steißlingen, a small lake in south-west Germany, using Rn as a natural groundwater tracer. 222Rn, nutrients, temperature and oxygen concentration were measured in depth profiles and in sediment-near water samples during April and June 2016. The spatial distribution of Rn activities (max. 944 Bq m-3) showed that groundwater discharges into the middle of the lake and along the northeastern shore from springs in the hypolimnion (11-14 m depth). Based on a Rn mass-balance groundwater accounts for 70% of the total water input (GWflux = 11 l s-1) to the lake. There were significant positive correlations between methane and nitrite with Rn activity, suggesting the groundwater as a common source. Overall the inflow of groundwater causes a deterioration in lake water quality.
Es wird eine Untersuchung vorgestellt, in der Wissen und Überzeugungen von Lehramtsstudierenden aller Fächer zum Thema Evolution an zwei Universitäten in Deutschland und der Türkei erhoben worden sind. Die Befragung wurde in Dortmund und in Ankara durchgeführt. Es stellte sich heraus, dass ausgeprägte Defizite im Verständnis der Evolutionsmechanismen herrschen. Viele Studierende, insbesondere aus der Türkei, sind nicht von der Faktizität der Evolution überzeugt. Dies gilt sowohl für Studierende mit Fach Biologie als auch für Studierende mit anderen Fächern. Näher untersucht worden sind die Faktoren, die die Überzeugungen zur Evolution beeinflussen können, was ja in Anbetracht der hohen Ablehnungsrate der Evolution von besonderem Interesse ist. Das Vertrauen in die Wissenschaft spielt hierbei eine besondere Rolle: Wer der Wissenschaft vertraut, ist auch eher von der Evolution überzeugt, als diejenigen, die skeptisch gegenüber der Wissenschaft sind.
In den vergangenen zwei Jahrzehnten wandelte sich das Internet von einer Spielwiese für technikbegeisterte Computerspezialisten zu einem vielseitig einsetzbaren weltweiten Netzwerk für Privatpersonen und Unternehmen. Maßgeblichen Anteil daran besaß die rasante Entwicklung des World Wide Web (WWW), das, durch die Möglichkeit multimediale Inhalte zu vermitteln, für einen großen Teil der Bevölkerung industrialisierter Länder zu einem wesentlichen Bestandteil des täglichen Lebens wurde. Dass diese Entwicklung noch lange nicht abgeschlossen ist, zeigt die derzeitige Diskussion zum Thema Web 2.0 bzw. 3.0. Waren es in den letzten Jahren die hohen Umsatzzuwächse im E-Commerce und multimedial gestaltete Webseiten in Kombination mit aufwändigen Applikationen, die für ständig steigende Nutzerzahlen im World Wide Web sorgten, so wird dieser Innovationsschub nunmehr durch eine Vielzahl von Anwendungen fortgesetzt, die sich durch die zunehmende Vernetzung der Nutzer untereinander auszeichnen.
Marco, José L; de los Ríos, Cristóbal; García, Antonio G; Villarroya, Mercedes; Carreiras, M Carmo; Martins, Carla; Eleutério, Ana; Morreale, Antonio; Orozco, M; Luque, F Javier
2004-05-01
The synthesis and the biological activity of compounds 5-40 as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as modulators of voltage-dependent Ca(2+) channels and nicotinic receptors, are described. These molecules are tacrine analogues, which have been prepared from polyfunctionalized 6-amino-5-cyano-4H-pyrans, 6-amino-5-cyano-pyridines and 5-amino-2-aryl-3-cyano-1,3-oxazoles via Friedländer reaction with selected cycloalkanones. These compounds are moderate acetylcholinesterase and butyrylcholinesterase inhibitors, the BuChE/AChE selectivity of the most active molecules ranges from 10.0 (compound 29) to 76.9 (compound 16). Interestingly, the 'oxazolo-tacrine' derivatives are devoid of any activity. All compounds showed an important inhibitory effect on the nicotinic acetylcholine receptor. Most of them also blocked L-type Ca(2+) channels, and three of them, 64, 19 and 67, the non-L type of Ca(2+) channels. Molecular modelling studies suggest that these compounds might bind at the peripheral binding site of AChE, which opens the possibility to design inhibitors able to bind at both, the catalytic and peripheral binding sites of the enzyme.
Marco, José L; De Los Ríos, Cristóbal; Carreiras, María C; Baños, Josep E; Badia, Albert; Vivas, Nuria M
2002-07-01
The acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition activities of a series of 4-amino-2, 3-diaryl-5, 6, 7, 8-tetrahydrofuro[2, 3-b]quinolines (10-12)/4-amino-5, 6, 7, 8-tetrahydro-2, 3-diphenylthieno[2, 3-b]quinoline (14) and 4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-diphenylcyclohepta[e]furo[2, 3-b]pyridine (13)/4-amino-5, 6, 7, 8, 9-pentahydro-2, 3-phenylcyclohepta[e]thieno[2, 3-b]pyridine (15) are described. These compounds are tacrine (THA) analogues which have been prepared either from readily available 2-amino-3-cyano-4, 5-diarylfurans (16-18) or from 2-amino-3-cyano-4, 5-diphenylthiophene (19), via Friedländer condensation with cyclohexanone or cycloheptanone. These compounds are competitive inhibitors for acetylcholinesterase, the more potent being compound (13) which is three-fold less active than tacrine. The butyrylcholinesterase inhibition activity is significant only in compounds 10 and133, which are ten-fold less active than tacrine. It is found that the products 11 and 12 strongly inhibit acetylcholinesterase, and show excellent selectivity regarding butyrylcholinesterase.
To examine the natural colonisation of native mangrove species into remediated exotic mangrove stands in Leizhou Bay, South China, we compared soil physical-chemical properties, community structure and recruitments of barren mangrove areas, native mangrove species plantations, and exotic mangrove species-Sonneratia apetala Buch.Ham-between plantations and natural forest. We found that severely degraded mangrove stands could not regenerate naturally without human intervention due to severely altered local environments, whereas some native species had been recruited into the 4-10 year S. apetala plantations. In the first 10 years, the exotic species S. apetala grew better than native species such as Rhizophora stylosa Griff and Kandelia candel (Linn.) Druce. The mangrove plantation gradually affected soil physical and chemical properties during its recovery. The exotic S. apetala was more competitive than native species and its plantation was able to restore soil organic matter in about 14 years. Thus, S. apetala can be considered as a pioneer species to improve degraded habitats to facilitate recolonisation by native mangrove species. However, removal to control proliferation may be needed at late stages to facilitate growth of native species. To ensure sustainability of mangroves in South China, the existing mangrove wetlands must be managed as an ecosystem, with long-term scientific monitoring program in place. ?? 2007 The Ecological Society of Japan.
Solano, Maria I; Thomas, Jerry D; Taylor, James T; McGuire, Jeffrey M; Jakubowski, Edward M; Thomson, Sandra A; Maggio, Vincent L; Holland, Kerry E; Smith, J Richard; Capacio, Benedict; Woolfitt, Adrian R; Ashley, David L; Barr, John R
2008-01-01
The lack of data in the open literature on human exposure to the nerve agent O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) gives a special relevance to the data presented in this study in which we report the quantification of VX-butyrylcholinesterase adduct from a relatively low-level accidental human exposure. The samples were analyzed by gas chromatography-high resolution mass spectrometry using the fluoride ion regeneration method for the quantification of multiple nerve agents including VX. Six human plasma samples from the same individual were collected after the patient had been treated once with oxime immediately after exhibiting signs of exposure. Detection limits of approximately 5.5 pg/mL plasma were achieved for the G-analogue of VX (G-VX). Levels of the G-VX ranged from 81.4 pg/mL on the first day after the exposure to 6.9 pg/mL in the sample taken 27 days after the exposure. Based on the reported concentration of human butyrylcholinesterase in plasma of approximately 80 nM, it can be calculated that inhibition levels of >or= 0.05% of BuChE can be accurately quantified. These data further indicate that the fluoride ion regeneration method is a potentially powerful tool that can be used to assess low-level exposure to VX.
Nach anfänglichen Schwierigkeiten durch den 1. Weltkrieg erlangte die Deutsche Statistische Gesellschaft (DStatG) unter dem renommierten Statistiker und Vorsitzenden der DStatG, Friedrich Zahn, durch eine Vielzahl von Aktivitäten hohes Ansehen. Es gab Bestrebungen, Statistiker aus allen Arbeitsfeldern der Statistik in die DStatG zu integrieren, wobei die "Mathematische Statistik" nur zögerlich akzeptiert wurde (Konjunkturforschung, Zeitreihenanalyse). Nach der Machtübernahme 1933 durch Adolf Hitler geriet die DStatG in das Fahrwasser nationalsozialistischer Ideologie und Politik (Führerprinzip, Gleichschaltung des Vereinswesens). Damit war eine personelle Umstrukturierung in der DStatG verbunden. Politisch Missliebige und rassisch Verfolgte mussten die DStatG verlassen (Bernstein, Freudenberg, Gumbel u.a.). Unter den Statistikern gab es alle Abstufungen im Verhalten zum Regime von Ablehnung und zwangsweiser Anpassung über bereitwilliges Mitläufertum bis zu bewusster Täterschaft. Besonders die Bevölkerungsstatistik wurde durch die NS- Rassenpolitik auf lange Sicht diskreditiert. Im Rahmen von Wirtschaftsplanung und Aufrüstung wurden neue zukunftsträchtige statistische Modelle (Grünig, Bramstedt, Leisse) entwickelt.
Dieses Zitat des britischen Mathematikers G. H. Hardy bringt pointiert die unter praktizierenden Mathematikern, aber auch unter Philosophen der Mathematik weithin akzeptierte Ansicht zum Ausdruck, dass mathematische Schönheit eine nicht zu vernachlässigende Rolle in der mathematischen Forschungspraxis spielt und sowohl interessante ästhetiktheoretische, epistemische als auch ontologische Aspekte aufweist. Danach beeinflusst also das Verständnis dessen, was mathematische Schönheit ist, auch das Verständnis dessen, was Mathematik ist: "Was sind die Träger mathematischer Schönheit?" ist die Frage nach der Art der Gegenstände, für deren Schönheit Mathematiker sich begeistern und nach der sie streben. "Was sind die Kriterien für mathematische Schönheit?" ist die Frage nach den Kategorien, unter denen Mathematiker ihre Arbeit bewerten. Egal, ob sich das Phänomen mathematischer Schönheit als Ausnahmemerkmal oder als ständiger Begleiter mathematischen Tuns erweist - ein adäquates allgemeines Mathematikverständnis sollte dieses Phänomen berücksichtigen und bestenfalls auch erklären können.
Die kontinuierlich fortschreitende Miniaturisierung in integrierten Schaltungen führt zu einem Anstieg des intrinsischen Rauschens. Um den Einfluss von intrinsischem Rauschen auf die Zuverlässigkeit zukünftiger digitaler Schaltungen analysieren zu können, werden Methoden benötigt, die auf CAD-Verfahren wie Analogsimulation statt auf abschätzenden Berechnungen beruhen. Dieser Beitrag stellt eine neue Methode vor, die den Einfluss von intrinsischem Rauschen in digitalen Schaltungen für eine gegebene Prozesstechnologie analysieren kann. Die Amplituden von thermischen, 1/f und Schrotrauschen werden mit Hilfe eines SPICE Simulators bestimmt. Anschließend wird der Einfluss des Rauschens auf die Schaltungszuverlässigkeit durch Simulation analysiert. Zusätzlich zur Analyse werden Möglichkeiten aufgezeigt, wie die durch Rauschen hervorgerufenen Effekte im Schaltungsentwurf mit berücksichtigt werden können. Im Gegensatz zum Stand der Technik kann die vorgestellte Methode auf beliebige Logikimplementierungen und Prozesstechnologien angewendet werden. Zusätzlich wird gezeigt, dass bisherige Ansätze den Einfluss von Rauschen bis um das Vierfache überschätzen.
Medical end-of-life decisions that potentially shorten life (Sterbehilfe) are normally divided into four categories: Passive Sterbehilfe refers to withholding or withdrawing life-prolonging measures, indirect Sterbehilfe refers to the use of agents such as opioids or sedatives to alleviate symptoms of a terminally ill patient, assisted suicide (Suizidbeihilfe or Beihilfe zum Suizid) refers to prescribing and/or supplying a lethal drug in order to help someone to end his own life, and active euthanasia - which is illegal in any circumstances - means a doctor actively ending a patients life. In passive and indirect euthanasia, the will of a competent patient, or the presumed will of an incompetent patient respectively, is crucial. Assisted suicide is not illegal according to the Swiss Penal Code as long as there are no motives of self-interest of the individual assisting, and the individual assisted has decisional capacity. However, for doctors participating in assisted suicide, specific requirements of medical due care have to be met. What this means in the context of assisted suicide has recently been elaborated by the Swiss Federal Court of Justice.
Evolutionistische Argumentationen außerhalb der Biologie sind weit verbreitet. Wenn sie vertreten werden, heißt das mitnichten, dass sie notwendigerweise von darwinischen Argumenten geprägt sind. Wenn man Evolution und Kultur aus explizit darwinischer Perspektive zusammen bringt, bedeutet das noch lange nicht unbedingt Soziobiologie. Und es bedeutet sicherlich nicht Sozialdarwinismus. Dieser Beitrag soll einen Überblick der so genannten evolutionären Ansätze bzw. evolutionistischen Ansätze zu menschlichen Gesellschaften bzw. Kulturen geben. Es soll gezeigt werden, was in den Ansätzen analytisch zu trennen ist und was synthetisch zusammen gehört. Mein Beitrag ist nicht wissenschaftsgeschichtlich angelegt, sondern systematisch ausgerichtet und hat zwei Schwerpunkte (Antweiler 2008; Antweiler 2009b). Zum einen geht es um kausale Zusammenhänge von organischer Evolution und gesellschaftlichem Wandel. Auf der anderen Seite werden Analogien zwischen biotischer und kultureller Evolution erläutert, die als spezifische Ähnlichkeiten dieser beiden als grundsätzlich verschieden gesehenen Prozesse aufgefasst werden. Dadurch wird die Frage aufgeworfen, ob die Evolution von Organismen einerseits und die Transformation von Gesellschaften bzw. Kulturen andererseits, spezielle Fälle eines allgemeinen Modells von Evolution darstellen.
Mit Daten aus eigenen Erhebungen können das einkaufsbezogene Informations- und Einkaufsverhalten im Zusammenhang mit den verkehrlichen Aspekten (Distanzen, Verkehrsmittel, Wegekopplungen) dargestellt werden. Die Differenzierung in die drei Produktkategorien des täglichen, mittelfristigen und des langfristigen Bedarfs berücksichtigt in erster Linie die Wertigkeit eines Gutes, die seine Erwerbshäufigkeit unmittelbar bestimmt. Der Einsatz moderner IKT wie das Internet eröffnet dem Endverbraucher neue Möglichkeiten bei Information und Einkauf. Die verkehrliche Relevanz von Online-Shopping wird deutlich, wenn man berücksichtigt, dass im Mittel rund 17% aller Online-Einkäufe, die die Probanden durchgeführt haben, Einkäufe in Ladengeschäften ersetzen. Dies gilt in verstärktem Maße für Online-Informationen: etwa die Hälfte hätte alternativ im stationären Einzelhandel stattgefunden. Da der Erwerb von Gütern des täglichen Bedarfs häufig nahräumlich und in relevantem Anteil nicht-motorisiert erfolgen kann, sind in diesem Segment - im Gegensatz zum mittel- und langfristigen Bedarf - nur geringe Substitutionseffekte zu beobachten.
Die Energiewirtschaft benötigt neue, digitale Geschäftsmodelle. Gegenwärtig folgt auf Liberalisierung und Energiewende die nächste Stufe einer weitreichenden Bereinigung des Versorgungsmarktes. Digitalisierung und Dezentralisierung sind heute in aller Munde und verlangen nach neuen Produkten und Dienstleistungen. Dabei wirken die immensen Herausforderungen einer digitalen Energiewelt wie Beschleuniger für die Transformation im Versorgungssektor und tragen damit zur breiten Etablierung von Utilities 4.0 bei. Dieser Entwicklungsprozess vollzieht sich mithilfe unterschiedlicher Methoden zur Realisierung neuer Geschäftsideen. Allerdings greifen die gängigen Konzepte zur Entwicklung von Geschäftsmodellen gerade im Hinblick auf die Berücksichtigung komplexer, unbeständiger Rahmenbedingungen und spezifischer Anforderungen der digitalen Energiewelt mitunter zu kurz. Vor diesem Hintergrund wird das auf dem ganzheitlichen St. Galler Management-Konzept beruhende Integrierte Geschäftsmodell iOcTen als geeignetes Instrumentarium zur Geschäftsmodellentwicklung vorgestellt. Neben der Modellbeschreibung unterstützt ein intuitiv verständlicher Leitfaden den Praktiker bei der Transformation vom klassischen Versorgungsunternehmen zum digitalen Energiedienstleistungsunternehmen.
Poisoning by nerve agents via the percutaneous (p.c.) route is an issue because the slow absorption of agent could result in poisoning which outlasts the protection provided by conventional pharmacological therapy. The bioscavenger approach is based on the concept of binding nerve agent in the bloodstream, thus preventing nerve agent from reaching the target tissues and inhibiting acetylcholinesterase activity. One bioscavenger that has been extensively studied is human butyrylcholinesterase (huBuChE). Protexia® is a pegylated form of recombinant huBuChE. We used a guinea-pig model of p.c. nerve agent poisoning, using an implanted telemetry system to collect physiological data. Guinea-pigs were poisoned with the nerve agent VX (0.74 mg/kg) (~2.5×LD50). Two hours following VX exposure, Protexia (72 mg/kg) or saline control was administered intramuscularly. All guinea-pigs treated with Protexia (n=8) survived, compared to no survivors in a saline-treated control group (n=8). Survival following VX and Protexia treatment was associated with minimal incapacitation and observable signs of poisoning, and the mitigation or prevention of the detrimental physiological changes (e.g. seizure, bradycardia and hypothermia) observed in control animals. The opportunity for post-exposure treatment may have utility in both civilian and military scenarios, and this is a promising indication for the use of a bioscavenger. PMID:21620937
Keifer, M.C.; Checkoway, H.; De Roos, A.J.; Farin, F.M.; Fenske, R.A.; Richter, R.J.; van Belle, G.; Furlong, C.E.
2011-01-01
Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are widely used in agriculture in the US and abroad. These compounds – which inhibit acetylcholinesterase (AChE) enzyme activity – continue to be responsible for a high proportion of pesticide poisonings among US agricultural workers. It is possible that some individuals may be especially susceptible to health effects related to OP/CB exposure. The paraoxonase (PON1) enzyme metabolizes the highly toxic oxon forms of some OPs, and an individual's PON1 status may be an important determinant of his or her sensitivity to these chemicals. This chapter discusses methods used to characterize individual PON1 status and reviews previous epidemiologic studies that have evaluated PON1-related sensitivity to OPs in relation to various health endpoints. It also describes an ongoing longitudinal study among OP-exposed agricultural pesticide handlers who are participating in a recently implemented cholinesterase monitoring program in Washington State. This study will evaluate handlers' PON1 status as a hypothesized determinant of butyrylcholinesterase (BuChE) inhibition. Such studies will be useful to determine how regulatory risk assessments might account for differences in PON1-related OP sensitivity when characterizing inter-individual variability in risk related to OP exposure. Recent work assessing newer and more sensitive biomarkers of OP exposure is also discussed briefly in this chapter. PMID:20221867
Arafath, Md. Azharul; Adam, Farook; Al-Suede, Fouad Saleih R.; Razali, Mohd R.; Ahamed, Mohamed B. Khadeer; Abdul Majid, Amin Malik Shah; Hassan, Mohd Zaheen; Osman, Hasnah; Abubakar, Saifullah
2017-12-01
Four heterocyclic embedded Schiff base derivatives (1-4) were synthesized and characterized by melting point, elemental analysis, FTIR, 1H, 13C NMR, UV-Visible spectral data. The structures of compounds 1, 2 and 4 were successfully established through single crystal X-ray diffraction analysis. In vitro cholinesterase inhibition assays showed that the cyclized derivative 1 displayed higher BuChE enzyme inhibitory activity with IC50 value of 1.45 ± 0.09 μM. The anti-proliferative efficacies of the compounds were also evaluated using human colorectal HCT 116 and breast MCF-7 adenocarcinoma cell lines. In addition, a human normal endothelial cell line (Ea.hy926) was also tested to assess the safety and selectivity of the compounds towards normal and cancer cells, respectively. Among the compounds tested, compound 2 displayed potent cytotoxic effect (IC50 = 34 μM) against HCT 116 cells with highest selectivity index of 3.1 with respect to the normal endothelial cells. Whereas, compound 4 exhibited significant anti-proliferative effect (IC50 = 21.1 μM) against MCF-7 cells with highest selectivity index of 3.3 with respect to the normal endothelial cells. The docking result of these compounds against hAChE showed potent activities with different binding modes. These compounds could be a promising pharmacological agent to treat cancer and Alzheimer's disease.
Bouremel, Yann; Yianneskis, Michael; Ducci, Andrea
2009-11-01
Simultaneous PIV-PLIF measurements were carried out to investigate the mixing occurring in a laminar vortex ring flow during the formation stage (Re=357-1072). In the first part of the work a control volume analysis was used to determine the variation in time of the scalar concentration mean, variance, and probability density function. In the second part the advection-diffusion differential equations of the scalar, ξ, and of its energy, 0.5 2̂, were studied in depth to gain insight into the effect of the strain rate tensor, S, on the local scalar concentration for increasing Re. The measurements were obtained with a high spatial resolution (12 μm for the PLIF) in order to resolve the scalar dissipative scales. Reliable estimates of the scalar dissipation rate (∇ξ.∇ξ), and of the symmetric contraction term (∇ξ.S .∇ξ), shown in equation 1, were obtained. ∇ξ.S .∇ξ accounts for the reduction of scalar dissipation due to the straining component directed as the local scalar gradient (see Southerland et al.footnotetextSoutherland K B., Porter III J. R., Dahm, W. J. A., Buch K. A., An experimental study of the molecular mixing process in an axisymmetric laminar vortex ring, Phys. Fluids A 3 (5), May 1991) Equation 1: ( t+u.∇+1ReSc∇^2 )12( ∇ξ.∇ξ )=-( ∇ξ.S.∇ξ )-1ReSc∇(∇ξ):∇(∇ξ)
Chronic overexposure to cobalt (Co) may result in neurotoxic effects, but the mechanism of Co-induced neurotoxicity is not yet well established. Our study was conducted to determine whether Co is associated to the induction of central nervous system damage in pregnant rats and their progeny. Twelve pregnant female rats were randomly divided into 2 groups: group I served as controls and group II received Co (350 mg/L, orally). Treatments started from the 14th day of pregnancy until day 14 after delivery. Co concentration in plasma was higher in the treated groups than in the controls. Exposure to Co also increased the levels of MDA, PCO, H2O2, and AOPP, while Na(+)K(+)-ATPase and Mg(2+)-ATPase, AChE, and BuChE activities decreased in the cerebrum and cerebellum of suckling pups. A smear without ladder formation on agarose gel was also shown in the cerebrum and cerebellum, indicating random DNA degradation. A reduction in GPx, SOD, CAT, GSH, NPSH, and vitamin C values was observed. The changes were confirmed by histological results. In conclusion, these data showed that the exposure of pregnant and lactating rats to Co resulted in the development of oxidative stress and the impairment of defense systems in the cerebrum and cerebellum of their suckling pups.
The cytoprotective agent amifostine (AMI) is capable to protect healthy cells (contrary to tumor cells) due to higher activity of alkaline phosphatase at the membrane site of normal cells. In seven clinical trials the influence of AMI on the pharmacokinetics of different cytostatics was investigated. Preadministration of AMI increased Cmax of doxorubicin (+ 44 %, p < 0.06), epirubicin (+ 31 %, P < 0.08), mitomycin C (+ 41 %, p < 0.01) and docetaxel (+ 31 % and + 17 %, not significant). In contrary, the peak concentration of pirarubicin , the tetrahydropyranyl-prodrug of doxorubicin was decreased (- 50 %, P < 0.03), leading to an equal higher concentrationof doxorubicin in the blood . In accordance to the peak concentrations, the AUC'ast was increased by chemoprotection: doxorubicin + 53 % (p < 0.01) and epirubicin + 23 % (not significant), docetaxel + 25 % and + 31 % (not significant). AUC'ast of mitomycin C and paclitaxel seemed to be unaffected by preadministered AMI. A particular inhibition of the protein binding by AMI has been identified as one reason for higher serum concentrations of anthracycline drugs. After cytoprotection, a possible increase of the cytostatic's Serum concentrations should be taken into account for optimal dosage schedules.
Der Aufbau des menschlichen Körpers ist derart komplex, dass die vollständige funktionelle Substitution seiner Strukturen mit künstlichen Werkstoffen und Bauteilen unwahrscheinlich ist. Die meisten heute klinisch eingesetzten Implantate ersetzen in der Regel einfache mechanische oder andere physikalische Funktionen des menschlichen Körpers, die aufgrund eines singulären Defektes im Gewebe oder als Ergebnis einer chronischen Erkrankung substituiert werden müssen. Gelenkprothesen beispielsweise übertragen Lasten, eine künstliche intraokulare Linse ermöglicht Lichttransmission und eine künstliche Arterie sorgt für die Aufrechterhaltung der Blutversorgung. Neben der Funktionserfüllung müssen die medizinisch eingesetzten Werkstoffe zusätzlich den Anforderungen der Körperverträglichkeit genügen, die die vollständige und dauerhafte Aufnahme des Implantates im Körper zum Ziel hat. Die Erkenntnisse der Werkstoffwissenschaft und deren Umsetzung in neue Produkte hat die Entwicklung und Fortschritte in der Medizin und in der Chirurgie entscheidend geprägt. Werkstoffe stehen in ihrem klinischen Einsatz als Temporärimplantate (z. B. Kathetersysteme) sowie als Langzeitimplantate (z. B. Hüftgelenksimplantate oder Herzschrittmacher) in direktem Kontakt mit den Geweben des Körpers und müssen deshalb biokompatibel sein.
Die Behandlung der Knochentumoren unterlag in den letzten 20 Jahren einem raschen und stetigen Wandel, was zum einen auf die verbesserten Therapieerfolge durch den Einsatz von neoadjuvanten Therapieformen zurückzuführen ist, und andererseits von medizintechnischen Entwicklungen bezüglich moderner Schnittbilddiagnostik, neuer 3D Operationsplanungsverfahren wie das Rapid Prototyping und adaptiv modularer Tumorendoprothesensystemen u. a. begleitet wurde. Gerade die technischen Entwicklungen haben dazu geführt, daß im Bereich der Extremitäten und der Wirbelsäule radikalere Eingriffe durchgeführt werden können, was die lokale Tumorkontrolle wesentlich verbessert hat. In zunehmenden Maße werden deshalb nicht nur Kurzzeiterfolge sondern auch mittel- und langfristige Fortschritte bei der Behandlung der malignen Knochentumoren einschließlich der Metastasenbehandlung erreicht. Grundlage der Therapie ist dabei immer primär die Sicherung der Diagnose mittels Biopsie und die bildgebende sowie histologische Stadieneinteilung des malignen Tumors. Nach der Tumorresektion kann die Rekonstruktion biologisch oder mit Endoprothesensystemen erfolgen. Gerade die weiterentwickelten modularen Systeme führen zu guten funktionellen Ergebnissen mit langen Standzeiten und einer reduzierten Komplikationsrate. Individuell angefertigte Implantate sind vor allem im Bereich der Rekonstruktion komplexer Beckentumoren von großer klinischer Bedeutung.
In early-twentieth-century Berlin, agents of speed and industrialisation, such as the railway, contributed to the seemingly unbridled velocity of urban life. Doctors and cultural critics took an ambivalent stance toward the impact of speed and technology on the human body. Critics argued that these factors, in conjunction with sexual excess and prostitution, accelerated the sexual maturation of young men, thereby endangering ‘healthy’ male sexuality. This comparison of Hans Ostwald's socio-literary study Dunkle Winkel in Berlin (1904) with Georg Buschan's sexual education primer Vom Jüngling zum Mann (1911) queries the extent to which speed shaped the understanding of ‘the masculine’ in pre-World-War-I Germany. The essay thus examines Ostwald's and Buschan's arguments and postulates that speed in the city (Berlin) can be seen as a feminised, sexualised force that determined sex in the city. According to this reading, the homosexual urban dandy resisted the accelerated modernist urban tempo, whereas the heterosexual man and hegemonic, heteronormative masculinity yielded to speed. ‘“Das Verhältnis”’ became a fleeting, momentary alternative to stable marital relationships, which in turn contributed to the general ‘crisis’ of – and in– masculinity in early-twentieth-century Berlin.
Nondo, Ramadhani S O; Erasto, Paul; Moshi, Mainen J; Zacharia, Abdallah; Masimba, Pax J; Kidukuli, Abdul W
2016-01-01
Plants used in traditional medicine have been the source of a number of currently used antimalarial medicines and continue to be a promising resource for the discovery of new classes of antimalarial compounds. The aim of this study was to evaluate in vivo antimalarial activity of four plants; Erythrina schliebenii Harms, Holarrhena pubescens Buch-Ham, Phyllanthus nummulariifolius Poir, and Caesalpinia bonducella (L.) Flem used for treatment of malaria in Tanzania. In vivo antimalarial activity was assessed using the 4-day suppressive antimalarial assay. Mice were infected by injection via tail vein with 2 × 10(7) erythrocytes infected with Plasmodium berghei ANKA. Extracts were administered orally, once daily, for a total of four daily doses from the day of infection. Chloroquine (10 mg/kg/day) and solvent (5 mL/kg/day) were used as positive and negative controls, respectively. The extracts of C. bonducella, E. schliebenii, H. pubescens, and P. nummulariifolius exhibited dose-dependent suppression of parasite growth in vivo in mice, with the highest suppression being by C. bonducella extract. While each of the plant extracts has potential to yield useful antimalarial compounds, the dichloromethane root extract of C. bonducella seems to be the most promising for isolation of active antimalarial compound(s). In vivo antimalarial activity presented in this study supports traditional uses of C. bonducella roots, E. schliebenii stem barks, H. pubescens roots, and P. nummulariifolius for treatment of malaria.
Nurunnabi, Tauhidur Rahman; Nahar, Lutfun; Al-Majmaie, Shaymaa; Rahman, S M Mahbubur; Sohrab, Md Hossain; Billah, Md Morsaline; Ismail, Fyaz M D; Rahman, M Mukhlesur; Sharples, George P; Sarker, Satyajit D
Whitney, Heather M; Michaelson, Louise V; Sayanova, Olga; Pickett, John A; Napier, Johnathan A
2003-10-01
The Ranunculaceae are known to accumulate a wide range of unusual fatty acids in their seed lipids, and this variability has been advocated as a taxonomic marker. The Anemone species, Anemone leveillei L. and Anemone rivularis Buch.-Ham., have previously been reported to accumulate Delta5-desaturated fatty acids in their seed tissue [K. Aitzetmüller (1995) Plant Syst Evol 9:229-240]. Two cDNAs, AL1 and AL2, with similarity to plant cytochrome b5-fusion "front-end" desaturases were isolated from developing seeds of A. leveillei and their function identified by expression in Saccharomyces cerevisiae. AL2 was characterised as a sphingolipid long-chain-base Delta8-desaturase, while AL1 acted as a fatty acid desaturase. However, AL1 did not produce Delta5-desaturated fatty acids as expected; instead, when expressed in transgenic S. cerevisiae or Arabidopsis thaliana this enzyme was functionally characterised as a Delta6-desaturase. Northern analysis confirmed the expression of this gene in seed tissue and leaf tissue of A. leveillei, though Delta6-desaturated fatty acids were found to accumulate only in the leaf tissue. The unexpected characterisation of a Delta6-desaturase in A. leveillei has implications for the use of fatty acids in chemotaxonomic studies. This is also the first report of a higher-plant Delta6-desaturase from a family other than the Boraginaceae.
Although plant diversity is postulated to resist invasion, studies have not provided consistent results, most of which were ascribed to the influences of other covariate environmental factors. To explore the mechanisms by which plant diversity influences community invasibility, an experiment was conducted involving grassland sites varying in their species richness (one, two, four, eight, and sixteen species). Light interception efficiency and soil resources (total N, total P, and water content) were measured. The number of species, biomass, and the number of seedlings of the invading species decreased significantly with species richness. The presence of Patrinia scabiosaefolia Fisch. ex Trev. and Mosla dianthera (Buch.-Ham. ex Roxburgh) Maxim. significantly increased the resistance of the communities to invasion. A structural equation model showed that the richness of planted species had no direct and significant effect on invasion. Light interception efficiency had a negative effect on the invasion whereas soil water content had a positive effect. In monocultures, Antenoron filiforme (Thunb.) Rob. et Vaut. showed the highest light interception efficiency and P. scabiosaefolia recorded the lowest soil water content. With increased planted-species richness, a greater percentage of pots showed light use efficiency higher than that of A. filiforme and a lower soil water content than that in P. scabiosaefolia. The results of this study suggest that plant diversity confers resistance to invasion, which is mainly ascribed to the sampling effect of particular species and the complementarity effect among species on resources use.
Stereospermum colais (Buch.-Ham. ex Dillw.) Mabberley (Bignoniaceae), which has traditional medicinal properties, is distributed all over deciduous forests. In spite of its many uses, the antidiabetic, antiperoxidative and radical scavenging activities of this species have not been assessed, and its chemical composition is scarcely known. Antidiabetic, antiperoxidation, xanthine oxidase (XO) inhibition, and radical scavenging activities of acetone and methanol extracts of Stereospermum colais roots were investigated. Protective effects of Stereospermum colais root extract in stabilizing sunflower oil was also examined. The protective effect of acetone (ASC) and methanol (MSC) extracts of Stereospermum colais root for the potential inhibition of α-glucosidase and α-amylase enzymes were studied by in vitro method. Glycation inhibitory activity was also studied to inhibit the production of glycated end products. Compared with acarbose, ASC showed a strong inhibitory activity against α-glucosidase (IC(50) 61.21 µg/mL) and a moderate inhibitory activity against α-amylase (IC(50) 681.08 µg/mL). Glycation inhibitory activity of Stereospermum colais root extracts by using an in vitro glucose-bovine serum albumin (BSA) assay was also done and compared with standard gallic acid. ASC also shows high XO inhibition potential, free radical scavenging activities, and low p-anisidine value indicates the high medicinal potency of Stereospermum colais root. These results suggest that the extract of Stereospermum colais may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia, and or as food additives due to its antiradical efficiency.
Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC 50 for AChE = 0.82 ± 0.08 μmol•L -1 , IC 50 for BuChE = 46.30 ± 3.26 μmol•L -1 ) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC 50 for AChE = 10.54 ± 0.86 μmol•L -1 , IC 50 for BuChE = 0.26 ± 0.08 μmol•L -1 ). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.
In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (ΔE ele+ΔG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.
Zusammenfassung Hintergrund Trotz großer Fortschritte in der Entwicklung der Hard- und Software von Navigationssystemen finden diese aufgrund ihrer vermeintlichen Komplexität, umständlichen Integration in klinische Arbeitsabläufe und fraglichen Vorteilen gegenüber konventionellen bildgebenden Verfahren bisher wenig Einsatz in den heutigen Operationssälen. Ziel der Arbeit Entwicklung einer „Augmented-reality“(AR)-Darstellung zur chirurgischen Navigation ohne Infrarot(„IR“)-Tracking-Marker und Vergleich zum konventioneller Röntgen in einem simulierten Eingriff. Material und Methoden Navigationssystem bestehend aus „Cone-beam-CT“(CBCT)-fähigem C-Bogen und „Red-green-blue-depth“(RGBD)-Kamera. Testung durch Kirschner(K)-Draht-Platzierung in Modellen unter Berücksichtigung der benötigten Zeit, der Strahlendosis und der Benutzerfreundlichkeit der Systeme. Ergebnisse Eine signifikante Reduktion der benötigten Zeit, der Röntgenbilder und der gesamten Strahlendosis bei der AR-Navigation gegenüber dem konventionellen Röntgen bei gleichbleibender Präzision. Schlussfolgerung Die AR-Navigation mithilfe der RGBD-Kamera bietet flexible und intuitive Darstellungsmöglichkeiten des Operations-situs für navigierte Osteosynthesen ohne Tracking-Marker. Hiermit ist es möglich, Operationen schneller, einfacher und mit geringerer Strahlenbelastung für Patient und OP-Personal durchzuführen. PMID:29500506
Hoffstetter, Marc; Pfeifer, Stefan; Schratzenstaller, Thomas; Wintermantel, Erich
In hoch entwickelten Industrieländern stehen laut Weltgesundheitsorganisation (WHO) Herz-Kreislauf-Erkrankungen und speziell die Koronare Herzkrankheit (KHK) an erster Stelle der Todesursachen. In Deutschland betrug die Zahl der erfassten, an KHK erkrankten Personen ohne Berücksichtigung der Dunkelziffer allein im Jahre 2001 über 473.000. Die KHK war im Jahre 2003 mit 92.673 erfassten Todesfällen immer noch die häufigste Todesursache, obgleich in Deutschland die Häufigkeit der Koronarinterventionen zur Behandlung der KHK zwischen 1984 und 2003 um fast das 80fache von 2.809 auf 221.867 Eingriffe pro Jahr gestiegen ist [1]. Neben der hohen Zahl an Todesfällen haben die betroffenen Personen durch chronische Schmerzen und eingeschränkte körperliche Leistungsfähigkeit zusätzlich eine starke Beeinträchtigung der Lebensqualität [2].In Folge dessen wird die erkrankte Person häufig zum Pflegefall was neben den gesundheitlichen Aspekten auch eine sozioökonomische Komponente in Form der fehlenden Arbeitskraft und den auftretenden Pflegekosten nach sich zieht. Die Kosten für die Behandlung der KHK in Deutschland beliefen sich im Jahre 2002 laut Statistischem Bundesamt auf rund 6,9 Mrd. €. Verglichen mit ähnlichen Zahlen der USA dürfte sich der entstandene Schaden für die deutsche Volkswirtschaft im zwei- bis dreistelligen Milliardenbereich bewegen [3].
Digitalisierung muss im Stadtwerk dazu führen, Kundenerwartungen, die heutzutage schon vielfach durch digitales Know-how und Erfahrungen geprägt sind, in einzigartiger Weise zu entsprechen - in Form digitaler Kundenkontaktpunkte, automatisierter Prozesse oder plattformbasierter Geschäftsmodelle. Eine große Rolle spielen dabei unternehmensweit nutzbare Informationen, die eine 360-Grad-Sicht auf den Kunden ermöglichen. Nur in dieser Kombination werden sich nachhaltig Wettbewerbsvorteile generieren lassen. Manch ein Kunde wird die Lust, einen Prozess zu Ende zu gehen, schon vor dem Abschluss verlieren, wenn er nicht unmittelbar und ohne die digitale Welt zu verlassen zum Ziel kommt. Eine nur "halb digitale Kundenerfahrung" wird weder zu Neugeschäft noch zur positiven emotionalen Bindung zwischen Kunden und Stadtwerk führen. Nicht zu unterschätzen sind zudem Erwartungen hinsichtlich zukünftiger Geschäftsmodelle, aus denen sich disruptive Bedrohungen für die herkömmlichen Strom- und Gasangebote ergeben werden. Erste innovative Ansätze finden sich bereits im Markt, die erahnen lassen, dass zurzeit viel diskutierte Technologien wie die Blockchain nicht mehr nur hypothetischer Natur sind. Die Auseinandersetzung mit der Digitalisierung erfolgt dabei sinnvollerweise in einem unternehmensweit abgestimmten Rahmen, der eine zielgerichtete und ganzheitliche Vorgehensweise ermöglicht.
Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET ; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments) . The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models t
Das Werner-Syndrom ist eine segmental progeroide Erkrankung mit Beginn in der Adoleszenz oder im frühen Erwachsenenalter. Typische Symptome, die zum vorgealterten Phänotyp beitragen, sind ein post-pubertär auftretender Kleinwuchs, Katarakte, eine vorzeitige Ergrauung/Ausdünnung des Haupthaars, sklerodermieähnliche Hautveränderungen und eine regionale Atrophie des subkutanen Fettgewebes. Darüber hinaus kommt es früh und gehäuft zu „Alterserkrankungen“ wie z. B. einem Diabetes mellitus Typ 2, einer Osteoporose, einer Atherosklerose sowie verschiedenen malignen Tumoren. Das Werner-Syndrom wird autosomal- rezessiv vererbt und ist durch Mutationen im Werner-Gen (WRN) bedingt. Es wurden bis heute mehr als 70 über das gesamte Gen verteilte Mutationen identifiziert, die typischerweise zu einem Verlust der Genfunktion führen. WRN kodiert für eine RecQ-Typ- Helikase, die u. a. an der DNA-Reparatur und der Aufrechterhaltung der DNA-Integrität beteiligt ist, was sich in einer erhöhten genetischen Instabilität in Patientenzellen wider-spiegelt. Trotz der relativen Seltenheit ist die Analyse des Werner-Syndroms von allgemeiner Bedeutung, um die Rolle der DNA-Stabilität und Integrität für das Altern sowie die Entwicklung altersassoziierter Erkrankungen besser zu verstehen. PMID:25309043
The reactions of early-transition-metal complexes with H 2 O have been investigated. An understanding of these elementary steps promotes the design of precursors for the preparation of metal oxide materials or supported heterogeneous catalysts. Density functional theory (DFT) calculations have been conducted to investigate two elementary steps of the reactions between tungsten alkylidyne complexes and H 2 O, i.e., the addition of H 2 O to the W≡C bond and ligand hydrolysis. Four tungsten alkylidyne complexes, W(≡CSiMe 3 )(CH 2 SiMe 3 ) 3 (A-1), W(≡CSiMe 3 )(CH 2 t Bu) 3 (B-1), W(≡C t Bu)(CH 2 t Bu) 3 (C-1), and W(≡C t Bu)(O t Bu) 3 (D-1), have been compared. The DFT studies provide an energy profile of the two competing pathways. An additional H 2 O molecule can serve as a proton shuttle, accelerating the H 2 O addition reaction. The effect of atoms at the α and β positions has also been examined. Because the lone-pair electrons of an O atom at the α position can interact with the orbital of the proton, the barrier of the ligand-hydrolysis reaction for D-1 is dramatically reduced. Both the electronic and steric effects of the silyl group at the β position lower the barriers of both the H 2 O addition and ligand-hydrolysis reactions. These new mechanistic findings may lead to the further development of metal complex precursors.
Siddiqui, Sabahat Zahra; Ali, Saima; Rehman, Azizur; Rubab, Kaniz; vAbbasi, Muhammad Athar; Ajaib, Muhammad; Z Rasool, Zahid Ghulam
2015-09-01
Pyrus pashia Buch. & Ham. was subjected to extraction with methanol. Methanolic extracts of fruit, bark and leaf were partitioned separately with four organic solvents in order of increasing polarity, asn-hexane, chloroform, ethyl acetate and n-butanol after dissolving in distilled water. Phytochemical screening revealed the presence of phenolics, flavonoides, alkaloids and cardiac glycosides in large amount in chloroform, ethyl acetate and n-butanol soluble fractions. The antioxidant activity of crude methanolic extracts, all the obtained fourorganic fractions and remaining aqueous fractions was evaluated by different methods such as: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, ferric reducing antioxidant power (FRAP) assay and total antioxidant activity by phosphomolybdenum complex method as well as determination of total phenolics. The results of antioxidant activity exhibited that chloroform soluble fraction of fruit showed the highest value of percent inhibition of DPPH (48.16 ± 0.21 μg/ml) at the concentration of 10 μg/ml. Ethyl acetate soluble fraction displayed the lowest antioxidant activity having IC50 value of bark as (8.64 ± 0.32 μg/ml) relative to butylated hydroxytoluene (BHT), having IC50 of 12.1 ± 0.92 μg/ml. The ethyl acetate soluble fraction of bark revealed the highest FRAPs value (174.618 ± 0.11TE µM/ml) among all the three parts. This fraction also showed the highest value of total antioxidant activity as (1.499 ± 0.90), determined by phosphomolybdenum complex method. Moreover, this fraction also conferred the highest phenolic content (393.19 ± 0.72) as compared to other studied fractions of fruit and leaf.
chelators can modulate β-amyloid accumulation, protect against tau hyperphosphorylation, and block metal-related oxidative stress, and thereby hold considerable promise as effective anti-AD drugs. At present, a growing interest is focusing on increasing the efficacy and targeting of chelators through drug design. To this end, we have developed a new class of multifunctional prochelators from three FDA- approved drugs rasagiline, rivastigmine, and donepezil or tacrine. HLA20 A was designed by merging the important pharmacophores of rasagiline, rivastigmine, and donepezil into our newly developed multifunctional chelator HLA20. M30D was constructed using the key pharmacophoric moieties from rasagiline, rivastigmine, and tacrine. Experiments showed that both compounds possess potent anti-acetylcholinesterase (AChE) activity in vitro with weak inhibition of butyrylcholinesterase (BuChE), and without significant metal-binding activity. M30D was found also to be a highly potent MAO A inhibitor with moderate inhibition of MAO B in vitro. Both HLA20 and M30D can be activated by inhibition of AChE to release active chelators HLA20 and M30, respectively. HLA20 and M30 have been shown to be able to modulate amyloid precursor protein regulation and beta-amyloid reduction, suppress oxidative stress, and passivate excess metal ions (Fe, Cu, and Zn). Compared with the activated chelator HLA20 or M30, both HLA20A and M30D exhibited lower cytotoxicity in SH-SY5Y neuroblastoma cells, substantiating the prochelator strategy for minimizing toxicity associated with poor targeted chelators.
Following the Sample Analysis at Mars (SAM) experiment onboard the Curiosity rover, the Mars Organic Molecule Analyzer (MOMA) experiment onboard the future ExoMars 2018 mission will continue to investigate the organic composition of the martian subsurface. MOMA will have the advantage of extracting the sample from as deep as 2 meters below the martian surface where the deleterious effects of radiation and oxidation on organic matter are minimized. To analyse the wide range of organic compounds (volatile and non-volatile compounds) potentially present in the martian soil, MOMA includes two operational modes: UV laser desorption / ionization ion trap mass spectrometry (LDI-ITMS) and pyrolysis gas chromatography ion trap mass spectrometry (pyr-GC-ITMS). In order to analyse refractory organic compounds and chirality, samples which undergo GC-ITMS analysis may be derivatized beforhands, consisting in the reaction of the sample components with specific chemical reagents (MTBSTFA [1], DMF-DMA [2] or TMAH [3]). To prove the feasibility of the derivatization within the MOMA conditions we have adapated our laboratory procedure for the space conditions (temperature, time, pressure and size). Goal is optimize our detection limits and increase the range of the organic compounds that MOMA will be able to detect. Results of this study, show that Thermochemolysis is one of the most promising technique onboard MOMA to detect organic material. References : [1] Buch, A. et al. (2009) J Chrom. A, 43, 143-151. [2] Freissinet, C. et al. (2013) J Chrom. A, 1306, 731-740. [3] Geffroy-Rodier, C. et al. (2009) JAAP, 85, 454-459.
The objective of this research is to generate leads for developing our ultimate poly-active molecules with utility in central nervous system (CNS) diseases. Indeed, poly-active molecules capable of mitigating brain free radical damage while enhancing acetylcholine signaling (via cholinesterase inhibition) are still being sought for combating Alzheimer's disease (AD). We differentiate "poly-active" agents from "multi-target" ones by defining them as single molecular entities designed to target only specific contributory synergistic pharmacologies in a disease. For instance, in AD, free radicals either initiate or act in synergy with other pharmacologies, leading to disease worsening. For this preliminary report, a total of 14 (i.e., 4,5-dimethoxy-2-nitrobenzohydrazide plus 1-(1-benzylpiperidin-4-yl)ethan-1-one) derivatives were synthesized and screened, in silico and in vitro, for their ability to scavenge free radicals and inhibit acetylcholinesterase (AChE)/butyrylcholinesterase (BuChE) enzymes. Overall, six derivatives ( 4a , 4d , 4e , 4f , 4g , 9b ) exhibited potent (>30%) antioxidant properties in the oxygen radical absorbance capacity (ORAC) assay. The antioxidant values were either comparable or more potent than the comparator molecules (ascorbic acid, resveratrol, and trolox). Only three compounds ( 4d , 9a , 9c ) yielded modest AChE/BuChE inhibitions (>10%). Please note that a SciFinder substance data base search confirmed that most of the compounds reported herein are new, except 9a and 9c which are also commercially available.
Medicinal plants are crucial for about 80% of the world population in developing and developed countries for their primary and basic health care needs owing to better tolerability, superior compatibility with human body and having lesser side effects. The present study was conducted on various solvent extracts of three plant samples of Indian and Nepali origin Swertia Chirayita (Roxb.) Buch-ham (Chiratia) collected from various places to establish their comparative phytochemical analysis, chromatographic profile, hepatoprotective and antioxidant activities. Nepali Swertia Chirayita was found to have finest Chromatographic profile (TLC). Phytochemical analysis revealed Alkaloids, flavonoids, saponins, ascorbic acid, glycosides, steroids and triterpenoids in all samples. Different solvent fractions of the methanolic plant extracts of Swertia chirayita were assessed for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats. The grade of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT/AST), alkaline phosphatase (ALP), serum glutamate pyruvate transaminase (SGPT/ALT) and total bilirubin. The in-vitro antioxidant activity of the extracts was also evaluated by the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. The methanolic and aqueous extracts, at a dose of 200mg/kg and 300mg/kg, produced significant (p<0.05) hepatoprotection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions. Decreased observed in the biochemical parameters suggests that the plant extracts possesses hepatoprotective as well as antioxidant activities without any significant variation amongst them. These activities reside mainly in the methanolic extract of whole plant.
As the use of wireless technology has increased around the world, Radio Frequency Interference (RFI) has become more and more of a problem for radio astronomers. Preventative measures exist to limit the presence of RFI, and programs exist to remove it from saved data, but the routine use of algorithms to detect and remove RFI as an observation is occurring is much less common. Such a method would be incredibly useful for observations in which the data must undergo several rounds of processing before being saved, as in pulsar timing studies. Strategies for real-time mitigation have been discussed and tested with simulated data (Buch et al., 2016), but ideally the results of any approach would be validated by a detailed comparison of the final data products - for pulsar timing, the variance in the pulse times of arrival (TOAs) - with and without mitigation applied. The goal of this project is to develop an RFI mitigation approach based on the previously suggested strategies and test this program on actual data from the observation of pulsar J1713+0747. We use a Median Absolute Deviation (MAD) filter to identify interference in the observation and replace the compromised data with random Gaussian noise to match a characteristic radio signal from space. In order to verify our results, we analyze the pulsar’s TOAs obtained both from the mitigated data and from the unmitigated data processed through offline RFI removal software. Comparing the two, our preliminary findings indicate that our program is able to improve the quality of timing results from the observation.
Schumacher, Jörg; Stöbel-Richter, Yve; Brähler, Elmar
2002-07-01
The present study concerns the impact of recalled parental rearing behaviour on both the intensity of the wish to have a child and on different motives to have a child. Until now there are no empirical studies as to this objective. Our study is based on a representative sample of 1509 persons aged 18 to 50 years. The statistical analyses were restricted to those subjects who lived in partnership and reported an actual wish to have a child (n = 331). The data were assessed by self-reporting scales: The Questionnaire of Recalled Parental Rearing Behaviour "Fragebogen zum erinnerten elterlichen Erziehungsverhalten, FEE", the Partnership Questionnaire "Partnerschaftsfragebogen, PFB", and the Leipzig Questionnaire of Motives to Have a Child "Leipziger Fragebogen zu Kinderwunschmotiven, LKM". A recalled parental rearing behaviour, which was characterized as having been rejective, overprotective and less emotionally warm was associated with such motives which do not promote the wish to have own children (fear of personal restrictions and a low degree of social support). Simultaneously, a negative parental rearing behaviour was correlated with a stronger desire for social recognition by an own child. The recalled maternal rearing behaviour was altogether stronger associated with motives to have a child than the paternal. On the other hand, no relevant associations could be found between the recalled parental rearing behaviour and the intensity of the wish to have a child.
Abstract Return and adjustment to school in adolescents who have survived cancer have become of increasing interest as the numbers of childhood cancers survivors have grown due to advances in treatments. Perceived parental rearing behavior is an important factor related to school adjustment. This study examined the relationships between maternal and parental rearing practices, general characteristics, and school adjustment in adolescent cancer survivors in Korea. We conducted a descriptive, exploratory study of 84 adolescents with cancer using the Korean version of the Fragebogen zum erinnerten elterlichen Erziehungsverhalten: FEE (Recalled Parental Rearing Behavior) and a school adjustment measurement. Descriptive, Pearson correlational, and multiple regression analyses were used to investigate the data. In bivariate analysis, age (r = −0.358, P < .05), mother's emotional warmth (r = 0.549, P < .01), and father's emotional warmth (r = 0.391, P < .05) were significantly associated with school adjustment. However, the results of multiple regression analysis showed that only mother's emotional warmth (β = .720, P < .05) was significantly associated with school adjustment. Adolescent cancer survivors who reported higher mother's emotional warmth exhibited better school adjustment. This finding indicates that it is important to help parents of adolescent cancer survivors enhance their parental rearing behaviors, such as emotional warmth, to help adolescents adjust to school. PMID:28796068
In the archives of the Astronomisches Rechen-Institut at Heidelberg, there is an old set of 31 documents which are related to the calendar used in Prussia and which originated in the period from 1700 to 1854. The oldest document is an original print of the 'Calendar Edict' issued on 10 May 1700. In this edict, Friedrich III., Elector of Brandenburg, gave a monopoly for issuing calendars in his country to an academy which was founded slightly later. He founded at the same time an observatory in Berlin. The main task of the employed astronomers was to edit the 'Improved Calendar' which was newly introduced in his Protestant country. The Astronomisches Rechen-Institut, which was founded in Berlin and was moved to Heidelberg in 1945, considers this Calendar Edict as his foundation document too. All the other documents are handwritten, mainly letters, but also a detailed expose 'On the Calendar Issues in the Prussian State' from 1843. Two of the scripts stem from the 18th century. The remaining documents are related to the work of the Royal Prussian Calendar Deputation and were written between 1816 and 1854. In this paper we describe, commentate, and transliterate all the documents of this 'Kalender-Konvolut'.
Somboonna, Naraporn; Wan, Raymond; Ojcius, David M.; Pettengill, Matthew A.; Joseph, Sandeep J.; Chang, Alexander; Hsu, Ray; Read, Timothy D.; Dean, Deborah
2011-01-01
ABSTRACT Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L2/434 and outbreak strain L2b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L2c, isolated from an MSM with severe hemorrhagic proctitis. L2c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L2c was a recombinant of L2 and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomatis based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation. PMID:21540364
Rhizophora mucronata Lam. (Rhizophoraceae), commonly known as Asiatic mangrove, has been used traditionally among Asian countries as folk medicine. This study investigates the cholinesterase inhibitory potential and antioxidant activities of R. mucronata. Rhizophora mucronata leaves were successively extracted using solvents of varying polarity and a dosage of 100-500 µg/ml were used for each assay. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were assessed according to the method of Ellman. In vitro antioxidant activity was assessed using free radical scavenging, reducing power, and metal-chelating activity (duration - 3 months). Total phenolic and flavonoid content were quantified spectrophotometrically. Compound characterization was done using column chromatography, NMR, FTIR, and LC-MS analysis. Methanolic leaf extract (500 µg/ml) exhibited the highest inhibitory activity against AChE (92.73 ± 0.54%) and BuChE (98.98 ± 0.17%), with an IC50 value of 59.31 ± 0.35 and 51.72 ± 0.33 µg/ml, respectively. Among the different solvent extracts, methanolic extract exhibited the highest antioxidant activity with an IC50 value of 47.39 ± 0.43, 401.45 ± 18.52, 80.23 ± 0.70, and 316.47 ± 3.56 µg/ml for DPPH, hydroxyl, nitric oxide radical, and hydrogen peroxide, respectively. Total polyphenolic and flavonoid contents in methanolic extract were observed to be 598.13 ± 1.85 µg of gallic acid equivalent and 48.85 ± 0.70 μg of rutin equivalent/mg of extract. Compound characterization illustrated (+)-catechin as the bioactive compound responsible for cholinesterase inhibitory and antioxidant activities. The presence of rich source of flavonoids, in particular catechin, might be responsible for its cholinesterase inhibitory and antioxidant activities.
Petrov, Konstantin A; Yagodina, Lilia O; Valeeva, Guzel R; Lannik, Natalya I; Nikitashina, Alexandra D; Rizvanov, Albert A; Zobov, Vladimir V; Bukharaeva, Ellya A; Reznik, Vladimir S; Nikolsky, Eugeny E; Vyskočil, František
2011-01-01
BACKGROUND AND PURPOSE The rat respiratory muscle diaphragm has markedly lower sensitivity than the locomotor muscle extensor digitorum longus (EDL) to the new acetylcholinesterase (AChE) inhibitors, alkylammonium derivatives of 6-methyluracil (ADEMS). This study evaluated several possible reasons for differing sensitivity between the diaphragm and limb muscles and between the muscles and the brain. EXPERIMENTAL APPROACH Increased amplitude and prolonged decay time of miniature endplate currents were used to assess anti-cholinesterase activity in muscles. In hippocampal slices, induction of synchronous network activity was used to follow cholinesterase inhibition. The inhibitor sensitivities of purified AChE from the EDL and brain were also estimated. KEY RESULTS The intermuscular difference in sensitivity to ADEMS is partly explained caused by a higher level of mRNA and activity of 1,3-bis[5(diethyl-o-nitrobenzylammonium)pentyl]-6-methyluracildibromide (C-547)-resistant BuChE in the diaphragm. Moreover, diaphragm AChE was more than 20 times less sensitive to C-547 than that from the EDL. Sensitivity of the EDL to C-547 dramatically decreased after treadmill exercises that increased the amount of PRiMA AChE(G4), but not ColQ AChE(A12) molecular forms. The A12 form present in muscles appeared more sensitive to C-547. The main form of AChE in brain, PRiMA AChE(G4), was apparently less sensitive because brain cholinesterase activity was almost three orders of magnitude more resistant to C-547 than that of the EDL. CONCLUSIONS AND IMPLICATIONS Our findings suggest that ADEMS compounds could be used for the selective inhibition of AChEs and as potential therapeutic tools. PMID:21232040
The treatment and diagnosis of Alzheimer's Disease (AD) are two of the most urgent goals for research around the world. The cognitive decline is generally associated with the elevated levels of extracellular senile plaques, intracellular neurofibrillary tangles (NFTs), and with a progressive shutdown of the cholinergic basal forebrain neurons transmission. Even if several key targets are under fervent investigation in the cure of AD, till now, the only approved therapeutic strategy is the treatment of symptoms by using cholinesterases inhibitors. It has been demonstrated that both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes are not only responsible of acetylcholine levels, but also play an pivotal role in Aβ-aggregation during the early stages of senile plaque formation. On the other hand the difficult management of AD is also related to effective diagnostic methods and efficient assays for the study of pathological features. In such complex a wide framework, heterocyclic molecules are essential backbone to build new and selective drugs as well as diagnostic probes. The goal of this review is to examine a selected sample of relevant applications of five- and six-membered heterocycles in AD's therapeutic approaches. Concerning the research on AD, the contribution of heterocyclic compounds is huge and here we report some representative examples. The review is organized in two main sections focused on five and six-membered heterocycles. The analyzed cases have been classified on the base of the structural features of molecules, taking into account the progressive increase in heteroatoms number. The discovery of an effective therapy or a diagnostic protocol for AD is still far, but consistent improvements are underway and contribution of heterocyclic compounds will be consistent and hopefully determinant.
Pinnick, V. T.; Buch, A.; Szopa, C.; Grand, N.; Danell, R.; Grubisic, A.; van Amerom, F. H. W.; Glavin, D. P.; Freissinet, C.; Coll, P. J.; Stalport, F.; Humeau, O.; Arevalo, R. D., Jr.; Brinckerhoff, W. B.; Steininger, H.; Goesmann, F.; Raulin, F.; Mahaffy, P. R.
2015-12-01
Following the SAM experiment aboard the Curiosity rover, the Mars Organic Molecule Analyzer (MOMA) experiment aboard the 2018 ExoMars mission will be the continuation of the search for organic matter on the Mars surface. One advancement with the ExoMars mission is that the sample will be extracted as deep as 2 meters below the Martian surface to minimize effects of radiation and oxidation on organic materials. To analyze the wide range of organic composition (volatile and non-volatile compounds) of the Martian soil, MOMA is equipped with a dual ion source ion trap mass spectrometer utilizing UV laser desorption / ionization (LDI) and pyrolysis gas chromatography (pyr-GC). In order to analyze refractory organic compounds and chiral molecules during GC-ITMS analysis, samples may be submitted to a derivatization process, consisting of the reaction of the sample components with specific reactants (MTBSTFA [1], DMF-DMA [2] or TMAH [3]). Previous experimental reports have focused on coupling campaigns between the breadboard versions of the GC, provided by the French team (LISA, LATMOS, CentraleSupelec), and the MS, provided by the US team (NASA-GSFC). This work focuses on the performance verification and optimization of the GC-ITMS experiment using the Engineering Test Unit (ETU) models which are representative of the form, fit and function of the flight instrument including a flight-like pyrolysis oven and tapping station providing by the German team (MPS). The results obtained demonstrate the current status of the end-to-end performance of the gas chromatography-mass spectrometry mode of operation. References: [1] Buch, A. et al. (2009) J Chrom. A, 43, 143-151. [2] Freissinet et al. (2011) J Chrom A, 1306, 59-71. [3] Geffroy-Rodier, C. et al. (2009) JAAP, 85, 454-459.
Chowdhury, Md. Qumruzzaman; De Ridder, Maaike; Beeckman, Hans
2016-01-01
Mangroves occur along the coastlines throughout the tropics and sub-tropics, supporting a wide variety of resources and services. In order to understand the responses of future climate change on this ecosystem, we need to know how mangrove species have responded to climate changes in the recent past. This study aims at exploring the climatic influences on the radial growth of Heritiera fomes from a local to global scale. A total of 40 stem discs were collected at breast height position from two different zones with contrasting salinity in the Sundarbans, Bangladesh. All specimens showed distinct tree rings and most of the trees (70%) could be visually and statistically crossdated. Successful crossdating enabled the development of two zone-specific chronologies. The mean radial increment was significantly higher at low salinity (eastern) zone compared to higher salinity (western) zone. The two zone-specific chronologies synchronized significantly, allowing for the construction of a regional chronology. The annual and monsoon precipitation mainly influence the tree growth of H. fomes. The growth response to local precipitation is similar in both zones except June and November in the western zone, while the significant influence is lacking. The large-scale climatic drivers such as sea surface temperature (SST) of equatorial Pacific and Indian Ocean as well as the El Niño-Southern Oscillation (ENSO) revealed no teleconnection with tree growth. The tree rings of this species are thus an indicator for monsoon precipitation variations in Bangladesh. The wider distribution of this species from the South to South East Asian coast presents an outstanding opportunity for developing a large-scale tree-ring network of mangroves. PMID:26927229
Aim of the study This study was made to investigate the antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham.) Nees & Eberm (Tejpat) oil (CTO) in streptozotocin (STZ) induced diabetes in rats along with evaluation of chemical constituents. Materials and methods The GC-MS (Gas chromatography–mass spectrometry) analysis of the oil showed 31 constituents of which cinnamaldehyde was found the major component (44.898%). CTO and cinnamaldehyde was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic models. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results CTO (100 mg/kg and 200 mg/kg), cinnamaldehyde (20 mg/kg) and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as compared to control group. The results of CTO and cinnamaldehyde were found comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO using various models showed significant antioxidant activity. In vivo antioxidant studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH). Conclusion Thus the investigation results that CTO has significant antidiabetic, antioxidant and hypolipidemic activity. PMID:22882757
Mit der vorliegenden Arbeit werden exemplarisch Chancen und Grenzen der Integration von Umwelt- und Naturschutz in Verfahren der ackerbaulichen Landnutzung aufgezeigt. Die Umsetzung von Zielen des Umwelt- und Naturschutzes in Verfahren der Landnutzung ist mit verschiedenen Schwierigkeiten verbunden. Diese liegen zum einen in der Konkretisierung der Ziele, um diese umsetzen zu können, zum anderen in vielfach unzulänglichem Wissen über den Zusammenhang zwischen unterschiedlichen Formen der Landnutzung und insbesondere den biotischen Naturschutzzielen. Zunächst wird die Problematik der Zielfestlegung und Konkretisierung erörtert. Das Umweltqualitätszielkonzept von Fürst et al. (1992) stellt einen Versuch dar, Ziele des Umwelt- und Naturschutzes zu konkretisieren. Dieses Konzept haben Heidt et al. (1997) auf einen Landschaftsausschnitt von ca. 6000 ha im Biosphärenreservat Schorfheide-Chorin im Nordosten Brandenburgs angewendet. Eine Auswahl der von Heidt et al. (1997) formulierten Umweltqualitätsziele bildet die Basis dieser Arbeit. Für die ausgewählten Umweltqualitätsziele wurden wesentliche Einflussfaktoren der Landnutzung identifiziert und ein Bewertungssystem entwickelt, mit dem die Auswirkungen von landwirtschaftlichen Anbauverfahren auf diese Umweltqualitätsziele abgebildet werden können. Die praktizierte Landnutzung von 20 Betrieben im Biosphärenreservat Schorfheide-Chorin wurde von 1994 bis 1997 hinsichtlich ihrer Auswirkungen auf die Umweltqualitätsziele analysiert. Die Analyse ergab ein sehr differenziertes Bild, das zum Teil Unterschiede in der Auswirkung auf die Umweltqualitätsziele für den Anbau einzelner Kulturen oder für bestimmte Betriebstypen zeigte. Es zeigte sich aber auch, dass es bei der Gestaltung des Anbaus einzelner Kulturarten große Unterschiede gab, die für Umweltqualitätsziele Bedeutung haben. Neben der Analyse der Landnutzung im Biosphärenreservat Schorfheide-Chorin wurde ein System entwickelt, mit dem die modellhafte Abbildung von Verfahren der Landnutzung möglich ist. Die Modellverfahren wurden in eine umfangreiche Datenbank eingebunden. Sie wurden mit Hilfe eines Fuzzy- Regelsystems hinsichtlich ihrer Auswirkungen auf die Umweltqualitätsziele bewertet. Die systematisch bewerteten Verfahren wurden in ein Betriebsmodell integriert, womit eine weitergehende Analyse der Zielbeziehungen und die Berechnung von Szenarien mit unterschiedlichen Rahmenbedingungen ermöglicht wurde. Die Analyse der Beziehung verschiedener Ziele zueinander (Zieldivergenz, Zielkonvergenz) zeigte, dass sich mit der Verfolgung vieler Umweltqualitätsziele auch positive Effekte für andere Umweltqualitätsziele ergaben. Teilweise konnte allerdings auch eine Zieldivergenz festgestellt werden, die auf mögliche Zielkonflikte hinweist. Bei der Analyse der Szenarienergebnisse zeigte sich, dass die vorgeschlagenen Veränderungen von Rahmenbedingungen vielfach eine Verschlechterung für verschiedene Umweltqualitätsziele mit sich bringen. Eine Ursache dafür liegt darin, dass bei der Definition der Szenarien die Bedeutung der Stilllegungen unterschätzt wurde. The objective of this research was to show the opportunities and limitations associated with integrating of environmental goals into agricultural land use management. For this purpose, the impact of agricultural land uses on six environmental quality goals was analysed for an approximately 16.000 ha study region within the biosphere reserve Schorfheide-Chorin in north-eastern Brandenburg (Germany). The environmental quality goals considered were protection of ground water, preservation of groundwater recharge, protection of the soil against wind and water erosion and preservation of animal species typical of the agricultural landscape, in particular partridge, amphibians and cranes. For each environmental quality goal, an evaluation framework is presented which enables an assessment of the impact of agricultural land uses on the environmental quality goals. The evaluation framework was applied to assess the impact of land uses of twenty farms in the study area from 1994 to 1997. It was demonstrated that the impact of agricultural land uses on the environmental quality of the region is very complex, and - although some crops did significantly impact certain aspects, one factor did not overwhelmingly contribute to the overall environmental quality. The evaluation framework was integrated further into a system of modelled cropping practices for optimisation calculations. For this purpose, a model framework was established based on a MS Access database. In the database, cropping practices for 17 crops are stored. Inputs and yields are adapted to the site-specific yield potential. In addition to the cropping practices, the model framework is comprised of an evaluation module and optimisation module. Hence, the impact of the cropping practices can be assessed for each site. This model framework provides the basis for optimisation calculations to forecast various land uses under different conditions. A step-wise integration of the environmental quality goals into the optimisation algorithm of a model farm allows for showing trade-offs between economic and ecological goals. The results of the trade-offs show that an improvement of ecological goal achievement is possible with little impact on the gross margin, as long as the improvement is less than 30% of the starting situation. If improvements greater than 30% are desired, very high losses of gross margin must be taken into consideration. Another result of the calculations shows that high achievements of environmental quality goals often correlate with the percentage of set-aside land within the total area.
Background Parental rearing behavior is a significant etiological factor for the vulnerability of psychopathology and has been an issue of clinical research for a long time. For this scope instruments are important who asses economically recalled parental rearing behavior in a clinical practice. Therefore, a short German instrument for the assessment of the recalled parental rearing behavior Fragebogen zum erinnerten elterlichen Erziehungsverhalten (FEE) was psychometrically evaluated [Recalled Parental Rearing Behavior]. Methods This questionnaire was evaluated in a representative population sample (N = 2.948) in Germany which included 44.2% male and 55.8% female persons with a mean age of M = 47.35 (SD = 17.10, range = 18–92). For the content evaluation of the FEE the Life Satisfaction Questionnaire (FLZ) and the Inventory of Interpersonal Problems (IIP) was filled out by the participants. Results The FEE scales yielded a good to satisfactory internal consistency and split-half reliability. Its three factors (rejection/punishment, emotional warmth, control/overprotection) correlated positively with most of the areas of life satisfaction. Furthermore, positive associations between interpersonal problems and parental rejection and control could be identified. Conclusion The FEE is a short, reliable and valid instrument that can be applied in the clinical practice. In addition, the data proved an association between recalled parental rearing behavior, life satisfaction and interpersonal problems conform to the literature. Finally, specific problems with the retrospective assessment of parental rearing behavior were addressed as well. PMID:19267894
Der Zweck dieser Studie (zwecks Überblick siehe dazu Abb. 9.1) war zu untersuchen, wie die Schüler der Sekundarstufe II ein Verständnis von der Theorie der biologischen Evolution entwickeln. Vom Ausgangspunkt "Vorurteile der Schüler“ ausgehend wurden Unterrichtssequenzen entwickelt und drei verschiedene Lernexperimente in einem zyklischen Prozess durchgeführt. Das Wissen der Schüler wurde vor, während und nach den Unterrichtssequenzen mit Hilfe von schriftlichen Tests, Interviews und Diskussionsrunden in kleinen Gruppen abgefragt. Etwa 80 % der Schüler hatten vor dem Unterricht alternative Vorstellungen von Evolution, und in dem Nachfolgetest erreichten circa 75 % ein wissenschaftliches Niveau. Die Argumentation der Schüler in den verschiedenen Tests wurde sorgfältig unter Rücksichtnahme auf Vorurteile, der konzeptionellen Struktur der Theorie der Evolution und den Zielen des Unterrichts analysiert. Daraus konnten Einsichten in solche Anforderungen an Lehren und Lernen gewonnen werden, die Herausforderungen an Schüler und Lehrer darstellen, wenn sie anfangen, evolutionäre Biologie zu lernen oder zu lehren. Ein wichtiges Ergebnis war, dass das Verständnis existierender Variation in einer Population der Schlüssel zum Verständnis von natürlicher Selektion ist. Die Ergebnisse sind in einer inhaltsorientierten Theorie zusammengefasst, welche aus drei verschiedenen Aspekten besteht: 1) den inhaltsspezifischen Aspekten, die einzigartig für jedes wissenschaftliche Feld sind; 2) den Aspekten, die die Natur der Wissenschaft betreffen; und 3) den allgemeinen Aspekten. Diese Theorie kann in neuen Experimenten getestet und weiter entwickelt werden.
Big Data, Internet der Dinge, Mobile Computing und soziale Medien - die modernen Informationstechnologien durchdringen den Alltag der meisten Menschen und lösen hierdurch eine digitale Transformation aus. Im Unternehmenskontext manifestiert sich die Digitalisierung durch eine neue Qualität der wissensbasierten Entscheidungsunterstützung und der Automatisierung bzw. Autonomisierung der Geschäftsprozesse. Für Stadtwerke gilt es nun, die Chancen der Digitalisierung zu ihren Gunsten zu nutzen. Ein Startpunkt könnte hierbei sein, wie Stadtwerke zukünftig mit ihren Kunden interagieren. Ausgelöst durch die Liberalisierung der Märkte rückt der Kunde heute stärker in den Mittelpunkt - die Energiewirtschaft steht nun vor der Herausforderung, dem Wettbewerb einen Schritt voraus zu sein und dem Kunden ein absolut positives Kundenerlebnis (Customer Experience) sowohl als Maßnahme zur Kundenbindung als auch zum Kundenaufbau zu bieten. Das vorliegende Kapitel zeigt hierfür die Erfolgskriterien für die gelungene Etablierung des Kundenfokus im eigenen Unternehmen auf. Mit dem Customer-Focus-Cycle-Modell von Fujitsu, angelehnt an den Deming-Kreislauf, wird ein allgemeingültiger Ansatz für ein mögliches Vorgehen beim Aufbau des Kundenfokus vorgestellt. Die sechs Phasen werden dabei anhand praktischer Beispiele erläutert und geben zudem Hinweise zu Methoden und Tools. Aus dem vorgestellten "Werkzeugkasten" wird ferner die Customer-Journey-Methode im Detail erläutert. Weiter soll das präsentierte Reifegradmodell Unternehmen dabei unterstützen, den eigenen Status quo festzustellen und die persönlichen Ziele auf dem Weg zur kundenzentrierten Organisation festzulegen.
Gross, Katharina M.; Schote, Andrea B.; Schneider, Katja Kerstin; Schulz, André; Meyer, Jobst
2014-01-01
Primary hyperhidrosis is defined as excessive sweating of certain body areas without physiological reasons. Hyperhidrotic individuals report a high psychological strain and an impairment of their quality of life. Thus, the aim of the study is to investigate the relation between hyperhidrosis and different psychological as well as physiological aspects of chronic stress as a co-factor for the etiology of depression. In this study, forty hyperhidrotic subjects were compared to forty age- and sex-matched healthy control subjects. The Trier Inventory of Chronic Stress (‘Trierer Inventar zum chronischen Stress’: TICS), the Beck Depression Inventory (BDI-II) and the Screening for Somatoform Disorders (SOMS-2) were used to examine the correlation between primary hyperhidrosis and stress as well as accompanying depressive and somatic symptoms. The cortisol awakening response of each subject was analyzed as a physiological stress correlate. In hyperhidrotics, we found a significant lack of social recognition as well as significantly more depressive symptoms compared to the control subjects. A subgroup of patients with axillary hyperhidrosis had the highest impact on these increased issues of chronic stress, pointing to a higher embarrassment in these subjects. Especially in social situations, hyperhidrotics showed higher stress levels, whereby a vicious circle of stress and sweating is triggered. However, the cortisol awakening response did not significantly differ between hyperhidrotics and controls. Moreover, affected persons suffer from more depressive symptoms, which may be caused by feelings of shame and a lack of self-confidence. This initial study provides an impetus for further investigation to reveal a causative relationship between hyperhidrosis and its psychological concomitants. PMID:24647796
In homeopathy ARNICA is widely used as a woundhealing medication and for the treatment of hematomas. In this pilot study the efficacy and safety of ARNICA D12 in patients following varicose vein surgery were investigated. Prospective, randomized, double-blind, placebo-controlled pilot trial according to ICH GCP guidelines. The study was conducted by a surgeon at the Angiosurgical Clinic, Berlin- Buch. After randomized allocation, 60 patients received either ARNICA D12 or placebo. Start of medication occurred the evening before operation with 5 globules. On the operation day one preoperative and hourly postoperative dosages after awakening were given. On days 2-14 of the study 5 globules 3 times a day were given. OUTCOME CRITERIA: Surface (in cm(2) and using a three-point verbal rating scale) and intensity of hematomas induced by operation, complications of wound healing, and intensity of pain (five-point verbal rating scale) as well as efficacy and safety of the study medication were assessed. Hematoma surface was reduced (from day 7 to day 14) under ARNICA by 75.5% and under placebo by 71.5% (p = 0.4726). The comparison of hematoma surface (small, medium, large) using the verbal rating scale yielded a value of p = 0.1260. Pain score decreased by 1.0 +/- 2.2 points under ARNICA and 0.3 +/- 0.8 points under placebo (p = 0.1977). Remission or improvement of pain was observed in 43.3% of patients in the ARNICA group and in 27.6% of patients in the placebo group. Tolerability was rated as very good in all cases. The results of this pilot study showed a trend towards a beneficial effect of ARNICA D12 with regard to reduction of hematoma and pain during the postoperative course. For a statistically significant proof of efficacy of ARNICA D12 in patients following varicose vein surgery a larger sample size is necessary. Copyright 2003 S. Karger GmbH, Freiburg
Buch, A.; Pinnick, V. T.; Szopa, C.; Grand, N.; Danell, R.; van Amerom, F. H. W.; Freissinet, C.; Glavin, D. P.; Stalport, F.; Arevalo, R. D., Jr.; Coll, P. J.; Steininger, H.; Raulin, F.; Goesmann, F.; Mahaffy, P. R.; Brinckerhoff, W. B.
2016-12-01
After the SAM experiment aboard the curiosity rover, the Mars Organic Molecule Analyzer (MOMA) experiment aboard the future ExoMars mission will be the continuation of the search for the organic composition of the Mars surface with the advantage that the sample will be extracted as deep as 2 meters below the martian surface to minimize effects of radiation and oxidation on organic materials. To analyse the wide range of organic composition (volatile and non volatils compounds) of the martian soil MOMA is composed with an UV laser desorption / ionization (LDI) and a pyrolysis gas chromatography ion trap mass spectrometry (pyr-GC-ITMS). In order to analyse refractory organic compounds and chirality samples which undergo GC-ITMS analysis may be submitted to a derivatization process, consisting of the reaction of the sample components with specific reactants (MTBSTFA [1], DMF-DMA [2] or TMAH [3]). To optimize and test the performance of the GC-ITMS instrument we have performed several coupling tests campaigns between the GC, providing by the French team (LISA, LATMOS, CentraleSupelec), and the MS, providing by the US team (NASA, GSFC). Last campaign has been done with the ITU models wich is similar to the flight model and wich include the oven and the taping station providing by the German team (MPS). The results obtained demonstrate the current status of the end-to-end performance of the gas chromatography-mass spectrometry mode of operation. References:[1] Buch, A. et al. (2009) J chrom. A, 43, 143-151. [2] Freissinet et al. (2011) J Chrom A, 1306, 59-71. [3] Geffroy-Rodier, C. et al. (2009) JAAP, 85, 454-459. Acknowledgements: Funding provided by the Mars Exploration Program (point of contact, George Tahu, NASA/HQ). MOMA is a collaboration between NASA and ESA (PI Goesmann, MPS). MOMA-GC team acknowledges support from the French Space Agency (CNES), French National Programme of Planetology (PNP), National French Council (CNRS), Pierre Simon Laplace Institute.
Ist Biologie das jüngste Mitglied in der Familie von Big Science? Die vermehrte Zusammenarbeit in der biologischen Forschung wurde in der Folge des Human Genome Project zwar zum Gegenstand hitziger Diskussionen, aber Debatten und Reflexionen blieben meist im Polemischen verhaftet und zeigten eine begrenzte Wertschätzung für die Vielfalt und Erklärungskraft des Konzepts von Big Science. Zur gleichen Zeit haben Wissenschafts- und Technikforscher/innen in ihren Beschreibungen des Wandels der Forschungslandschaft die Verwendung des Begriffs Big Science gemieden. Dieser interdisziplinäre Artikel kombiniert eine begriffliche Analyse des Konzepts von Big Science mit unterschiedlichen Daten und Ideen aus einer Multimethodenuntersuchung mehrerer großer Forschungsprojekte in der Biologie. Ziel ist es, ein empirisch fundiertes, nuanciertes und analytisch nützliches Verständnis von Big Biology zu entwickeln und die normativen Debatten mit ihren einfachen Dichotomien und rhetorischen Positionen hinter sich zu lassen. Zwar kann das Konzept von Big Science als eine Mode in der Wissenschaftspolitik gesehen werden – inzwischen vielleicht sogar als ein altmodisches Konzept –, doch lautet meine innovative Argumentation, dass dessen analytische Verwendung unsere Aufmerksamkeit auf die Ausweitung der Zusammenarbeit in den Biowissenschaften lenkt. Die Analyse von Big Biology zeigt Unterschiede zu Big Physics und anderen Formen von Big Science, namentlich in den Mustern der Forschungsorganisation, der verwendeten Technologien und der gesellschaftlichen Zusammenhänge, in denen sie tätig ist. So können Reflexionen über Big Science, Big Biology und ihre Beziehungen zur Wissensproduktion die jüngsten Behauptungen über grundlegende Veränderungen in der Life Science-Forschung in einen historischen Kontext stellen. PMID:27215209
Die Übertragungsnetze stellen eine zuverlässige Versorgung von Haushalt, Gewerbe und Industrie mit elektrischer Energie sicher und sind damit Grundlage einer modernen Wirtschaft und Gesellschaft. Die mittlerweile unumkehrbaren Entwicklungen der nationalen und europäischen Energiewende stellen den Übertragungsnetzbetreiber in seinen Kernaufgaben, dem Bau und Betrieb von Netzen, dem Markt- und Netzzugang und der Integration der erneuerbaren Energien vor neue und große Herausforderungen. Verbrauchsnahe dezentrale Erzeugung wie verbrauchsferne zentrale Erzeugung muss im Sinne der Gewährleistung der Systemstabilität gemanagt und in Einklang mit dem Verbrauch gebracht werden. Erneuerbare Energien müssen zudem in einem solchen System ihren Beitrag zur System- und Marktintegration leisten. All das erfordert mehr Daten, um in einem Gesamtsystem dynamische Reaktionsmöglichkeiten gewährleisten zu können. Erst die "Digitalisierung" schafft dabei die notwendigen Voraussetzungen die Komplexität zu stemmen. Die Digitalisierung stellt daher ein Kernelement dieses Wandels des Übertragungsnetzbetreibers dar, die einerseits mit zum Entstehen der neuen Herausforderungen beiträgt, andererseits aber auch hilft Werkzeuge bereitzustellen, diesen Herausforderungen zu begegnen. Im folgenden Beitrag wird aufgezeigt, wie die Digitalisierung die Aufgaben und Instrumente des Übertragungsnetzbetreibers verändern. Ausgehend von den heutigen Aufgaben eines Übertragungsnetzbetreibers und dem gültigen Rechtsrahmen werden unter dem Begriff "Notwendiges Set für morgen" smarte Elemente und Werkzeuge beschrieben, die bereits heute im Einsatz sind oder in den nächsten Jahren notwendig werden. Im Anschluss erfolgt anhand einiger Beispiele aus unterschiedlichen Bereichen eine Konkretisierung der Einsatzzwecke der Digitalisierung beim Übertragungsnetzbetreiber. Ein kurzer Ausblick mit Fokus auf den weiteren Veränderungsprozess rundet den Beitrag ab.
The prevalence of tobacco smoking in Germany is high (~27%). Monitoring of national patterns of smoking behaviour and data on the "real-world" effectiveness of cessation methods are needed to inform policies and develop campaigns aimed at reducing tobacco-related harm. In England, the Smoking Toolkit Study (STS) has been tracking such indicators since 2006, resulting in the adaptation of tobacco control policies. However, findings cannot be directly transferred into the German health policy context. The German Study on Tobacco Use (DEBRA: "Deutsche Befragung zum Rauchverhalten") aims to provide such nationally representative data. In June 2016, the study started collecting data from computer-assisted, face-to-face household interviews in people aged 14 years and older. Over a period of 3 years, a total of ~36,000 respondents will complete the survey with a new sample of ~2000 respondents every 2 months (=18 waves). This sample will report data on demographics and the use of tobacco and electronic (e-)cigarettes. Per wave, about 500-600 people are expected to be current or recent ex-smokers (<12 months since quitting). This sample will answer detailed questions about smoking behaviour, quit attempts, exposure to health professionals' advice on quitting, and use of cessation aids. Six-month follow-up data will be collected by telephone. The DEBRA study will be an important source of data for tobacco control policies, health strategies, and future research. The methodology is closely aligned to the STS, which will allow comparisons with data from England, a country with one of the lowest smoking prevalence rates in Europe (18%). This study has been registered at the German Clinical Trials Register ( DRKS00011322 ) on 25th November 2016.
Johnson, C. Annette; Kaeppeli, Michael; Brandenberger, Sandro; Ulrich, Andrea; Baumann, Werner
1999-12-01
The leachate composition of the Landfill Lostorf, Buchs, Switzerland has been examined as a function rain events and dry periods between November 1994 and November 1996. Discharge and electrical conductivity of the central drainage discharge were monitored continuously, whilst samples for chemical analysis were taken at discrete intervals. The average total concentrations of Na, Cl, K, Mg, Ca and SO 4 are 44.5, 47.1, 11.8, 0.63, 8.2 and 12.4 mM, respectively. During rain events, the leachate is diluted by the preferential flow of rainwater into the drainage discharge. Drainage discharge pH values range between 8.68 and 11.28, the latter under dry conditions. Thermodynamic calculations indicate that CaSO 4, ettringite (3CaOAl 2O 3CaSO 4·32H 2O) and Al(OH) 3 may control the concentrations of the components Ca, SO 4 and Al. Dissolved Si may be in thermodynamic equilibrium with either Ca silicate hydrate or imogolite. Cadmium, Mo, V, Mn and Zn are also diluted during rain events and concentration changes agree with those of conductivity (representing the major constituents). Average concentrations are 0.012, 5.4, 2.3, 0.085, and 0.087 μM, respectively. Components such as Al, Cu, Sb and Cr increase in concentration with increased discharge. Average concentrations are 1.6, 0.27 and 0.21 μM, respectively. For Cu, the explanation lies in its affinity for total organic carbon (TOC). Thermodynamic calculations indicate that whilst dissolution/precipitation reactions with metal hydroxides and carbonates can explain the observed concentrations of Cd, sorption and complexation reactions probably influence the concentrations of Cu, Pb (average measurable concentration 0.013 μM), Zn and Mn. For the oxyanion species such as MoO 4 and WO 4 (average concentration 0.61 μM), it is probable that Ca metallate formation plays a dominant role in determining concentration ranges. Geochemical processes appear to determine concentration ranges and the hydrological factors, the fluctuations in concentration.
Reale, Marcella; Di Nicola, Marta; Velluto, Lucia; D’Angelo, Chiara; Costantini, Erica; Lahiri, Debomoy K.; Kamal, Mohammad A.; Yu, Qian-sheng; Greig, Nigel H.
2016-01-01
Increasing evidence suggests that the early pathogenesis of Alzheimer’s disease (AD) is driven by elevated production and/or reduced clearance of amyloid-β peptide (Aβ), which is derived from the larger Aβ precursor protein (APP). Aβ aggregates to form neurotoxic soluble oligomers that trigger a cascade of events leading to neuronal dysfunction, neurodegeneration and, ultimately, clinical dementia. Inflammation, both within the brain and systemically, together with a deficiency in the brain neurotransmitter acetylcholine, which underpinned the development of anticholinesterases for the symptomatic treatment of AD, are invariable hallmarks of the disease. The inter-relation between Aβ, inflammation and cholinergic signaling is complex, with each feeding back onto the others to drive disease progression. To elucidate these interactions plasma samples and peripheral blood mononuclear cells (PBMCs) were evaluated from healthy control (HC) subjects and AD patients. Plasma levels of acetyl- (AChE) and butyrylcholinesterase (BuChE) as well as Aβ were significantly elevated in AD vs. HC subjects, and acetylcholine showed a trend towards reduced levels. Aβ challenge of the AD and HC PBMCs resulted in greater release of inflammatory cytokines interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) from AD vs. HC subjects, with IL-10 expression being similarly affected. THP-1 monocytic cells, a cell culture counterpart of PBMCs and brain microglial cells, responded similarly to Aβ as well as to phytohaemagglutinin (PHA) challenge, to allow preliminary analysis of the cellular and molecular pathways that underpin Aβ-induced changes in cytokine expression. In light of prior studies demonstrating that APP expression was regulated by specific cytokines and anticholinesterase drugs, the latter were evaluated on Aβ- and PHA-induced chemo-cytokine expression. Co-incubation with selective inhibitors, such as the acetylcholinesterase (AChE)-inhibitor (−)-phenserine and the butyrylcholinesterase (BuChE)-inhibitor (−)-cymserine analogues mitigated the rise in cytokine levels, and suggest that augmentation of the cholinergic anti-inflammatory pathway may prove valuable in AD. PMID:24359497
Buch, A.; Grand, N.; Pinnick, V. T.; Szopa, C.; Humeau, O.; Danell, R.; van Amerom, F. H. W.; Freissinet, C.; Glavin, D. P.; Belmahdi, I.; Coll, P. J.; Lustrement, B.; Brinckerhoff, W. B.; Arevalo, R. D., Jr.; Stalport, F.; Steininger, H.; Goesmann, F.; Raulin, F.; Mahaffy, P. R.
2014-12-01
The Mars Organic Molecule Analyzer (MOMA) aboard the ExoMars rover (Pasteur) will be a key analytical tool in providing chemical (molecular) information from the solid samples collected by the rover, with a particular focus on the characterization of the organic content. Samples will be extracted as deep as 2 meters below the martian surface to minimize effects of radiation and oxidation on organic materials. The core of the MOMA instrument is a dual source UV laser desorption / ionization (LDI) and pyrolysis gas chromatography (pyr-GC) ion trap mass spectrometer (ITMS) which provides the unique capability to characterize a broad range of compounds, including both of volatile and non-volatile species. Samples which undergo GC-ITMS analysis may be submitted to a derivatization process, consisting of the reaction of the sample components with specific reactants (MTBSTFA [1], DMF-DMA [2] or TMAH [3]) which increase the volatility of complex organic species. With the goal to optimize this instrumentation, and especially the GC-ITMS coupling, a series of tests is currently being carried out with prototypes of MOMA instrumentation and with the ETU models wich is similar to the flight model. The MOMA oven and tapping station are also part of these end-to-end experiments. Qualitative and quantitative tests has been done on gas, liquid and solid samples. The results obtained demonstrate the current status of the end-to-end performance of the gas chromatography-mass spectrometry mode of operation. Both prototypes individually meet the performance requirements, but this work particularly demonstrates the capabilities of the critical GC-MS interface. References: [1] Buch, A. et al. (2009) J chrom. A, 43, 143-151. [2] Freissinet et al. (2011) J Chrom A, 1306, 59-71. [3] Geffroy-Rodier, C. et al. (2009) JAAP, 85, 454-459. Acknowledgements: Funding provided by the Mars Exploration Program (point of contact, George Tahu, NASA/HQ). MOMA is a collaboration between NASA and ESA (PI Goesmann, MPS). MOMA-GC team acknowledges support from the French Space Agency (CNES), French National Programme of Planetology (PNP), National French Council (CNRS), Pierre Simon Laplace Institute.
Sample Analysis at Mars (SAM) is one of the instruments of the MSL mission. Three analytical devices are onboard SAM: the Tunable Laser Spectrometer (TLS), the Gas Chromatography (GC) and the Mass Spectrometer (MS). To adapt the nature of a sample to the analytical devices used on SAM, a sample preparation and gas processing system is implemented with (a) a pyrolysis system, (b) wet chemistry: MTBSTFA and TMAH (c) the hydrocarbon trap (silica beads, Tenax® TA and Carbosieve G) which is employed to concentrate volatiles released from the sample prior to GC-MS analysis [1].Volatile compounds and abundant chlorinated hydrocarbons have been detected with SAM when analyzing samples collected in several sites explored by Curiosity rover. Some volatile compounds (chlorinated and non-chlorinated) come from the degradation of the MTBSTFA under high temperature or by the reaction of Martian oxychlorine compounds (present in the samples) with terrestrial carbon coming from the derivatization agent (MTBSTFA) used in SAM [2,3]. But other chlorinated compounds do not follow this pathway. For example, Chlorobenzene has been detected by SAM but it cannot be formed by the reaction of MTBSTFA and perchlorates. Then, two other reaction pathways for chlorobenzene were therefore proposed: (1) reactions between the volatile thermal degradation products of perchlorates (e.g. O2, Cl2 and HCl) and Tenax® and (2) the interaction of perchlorates (T>200°C) with organic material from Mars's soil such as benzenecarboxylates. However, even if major part of the chlorobenzene detected has been identified as Martian origin [4] it is important to list all the potential byproducts able to be released from the Tenax®.Thus, this study inventory all the possible compounds which are originated from Tenax®, MTBSTFA and their interaction with perchlorate.References: [1] Buch, A. et al. (2009) J chrom. A, 43, 143-151. [2] Glavin, D., A. et al. (2013), LPSC. [3] Eigenbrode, J. et al. (2013), LPSC. [4] Freissinet, C. et al., JGR (2015)
A multidisciplinary study has been carried out to contribute to the understanding of the geologic evolution of the largest known occurrence of ultra-high-pressure (UHP) rocks on Earth, the Dabie Shan of eastern China. Geophysical data, collected along a ca. 20 km E-W trending seismic line in the eastern Dabie Shan, indicate that the crust comprises three layers. The upper crust has a homogeneously low reflectivity and exhibits roughly subhorizontal reflectors down to ca. 15 km. It is therefore interpreted to portray a crustal UHP slab thrust over non-UHP crust. An aprubt change in intensity and geometry of observed reflectors marks the boundary of a mid- to lower crustal zone which is present down to ca. 33 km. This crustal zone likely represents cratonal Yangtze crust that was unaffected by the Triassic UHP event and which has acted as the footwall during exhumation of the crustal wedge. Strong and continuous reflectors occurring at ca. 33-40 km depth most likely trace the Moho at the base of the crust. Any trace of a crustal root, that may have formed in response to collision tectonics, is therefore not preserved. A shollow tomographic velocity modell based on inversion of the first arrivals is constructed additionally. This model clearly images the distinct lithologies on both sides of the Tan Lu fault. Sediments to the east exhibit velocities of about 3.4 - 5.0 km* s^-1, whereas the gneisses have 5.2 - 6.0 km*s^-1. Geometry of velocity isolines may trace the structures present in the rocks. Thus the sediments dip shallowly towards the fault, whereas isoclinal folds are imaged to occur in the gneisses. Field data from the UHP unit of the Dabie Shan enables definition of basement-cover sequences that represent sections of the former passive margin of the Yangtze craton. One of the cover sequences, the Changpu unit, still displays a stratigraphic contact with basement gneisses, while the other, the Ganghe unit, includes no relative basement exposure. The latter unit is in tectonic contact with the basement of the former unit via a greenschist-facies blastomylonite. The Changpu unit is chiefly constituted by calc-arenitic metasediments intercalated with meta-basalts, whereas the Ganghe unit contains arenitic-volcanoclastic metasediments that are likewise associated with meta-basalts. The basement comprises a variety of felsic gneisses, ranging from preserved eclogitic- to greenschist-facies paragenesis, and locally contains mafic-ultramafic meta-plutons in addition to minor basaltic rocks. Metabasites of all lithologies are eclogite-facies or are retrogressed equivalents, which, with the exception of those from the Ganghe unit, bear coesite and thus testify to an UHP metamorphic overprint. Mineral chemistry of the analysed samples reveal large compositional variations among the main minerals, i.e. garnet and omphacite, indicating either distinct protoliths or different degrees of interaction with their host-rocks. Contents of ferric iron in low Fetot omphacites are determined by wet chemical titration and found to be rather high, i.e. 30-40 %. However, a even more conservative estimate of 50% is applied in the corresponding calculations, in order to be comparable with previous studies. Textural constraints and compositional zonation pattern are compatible with equilibrium conditions during peak metamorphism followed by a retrogressive overprint. P-T data are calculated with special focus on the application of the garnet-omphacite-phengite barometer, combined with Fe-Mg exchange thermometers. Maximum pressures range from 42-48 kbar (for the Changpu unit) to ~37 kbar (for the Ganghe unit and basement rocks). Temperatures during the eclogite metamorphism reached ca. 750 °C. Although the sample suite reveals variable peak-pressures, temperatures are in reasonable agreement. Pressure differences are interpreted to be due to strongly Ca-dominated garnet (up to 50 mol % grossular in the Changpu unit) and modification of peak-compositions during retrogressive metamorphism. The integrated geological data presented in this thesis allow it to be concluded that, i) basement and cover rocks are present in the Dabie Shan and both experienced UHP conditions ii) the Dabie Shan is the metamorphic equivalent of the former passive margin of the Yangtze craton iii) felsic gneisses undergoing UHP metamorphism are affected by volume changes due to phase transitions (qtz coe), which directly influence the tectono-metamorphic processes iv) initial differences in temperature may account for the general lack of lower crustal rocks in UHP-facies Um das Verständnis der geologischen Entwicklung des größten bekannten Vorkommens von ultra-hochdruck (UHP) Gesteinen auf der Erde, des Dabie Shan im östlichen China, zu erhöhen, wurde eine multidisziplinäre Studie durchgeführt. Geophysikalische Daten wurden entlang einer ca. 20 km langen seismischen Linie im östlichen Dabie Shan gesammelt. Diese reflektionsseismischen Daten zeigen, dass die Kruste aus drei Lagen besteht. Die Oberkruste besitzt eine durchgehend niedrige Reflektivität und meist subhorizontale Reflektoren bis in eine Tiefe von ca. 15 km. Aufgrund dieser Charakteristika wird diese Zone als UHP-bezogener krustaler Keil interpretiert, der auf nicht UHP Kruste überschoben wurde. Ein abrupter Wechsel in der Geometrie aber auch Intensität der Reflektoren markiert die Grenze zu einer mittel- bis unterkrustalen Zone, die sich bis ca. 33 km Tiefe erstreckt. Diese Zone repräsentiert wahrscheinlich kratonale Yangtze Kruste, die von der triassischen UHP-Orogenese nicht erfasst wurde, aber während der Exhumierung das Liegende relativ zum UHP Keil war. Starke und kontinuierliche Reflektoren im Tiefenintervall von 33-40 km bilden höchstwahrscheinlich die Moho an der Basis der Kruste ab. Relikte einer Krustenwurzel, die sich wahrscheinlich während der Kollisionstektonik gebildet hatte, sind nicht sichtbar. Ein flaches tomographisches Geschwindigkeitsmodell, das auf der Inversion der Ersteinsätze gründet, konnte zusätzlich erstellt werden. Dieses Modell bildet deutlich die unterschiedlichen Lithologien auf beiden Seiten der Tan Lu Störung ab. Sedimente östlich der Störung zeigen Geschwindigkeiten von 3.4 - 5.0 km* s^-1, wohingegen die Gneise im Westen 5.2 - 6.0 km*s^-1 aufweisen. Die Geometrie der Geschwindigkeits-Isolinien kann als Ausdruck der Strukturen der Gesteine angenommen werden. Somit zeigen die Sedimente ein nordwestliches Einfallen zur Störung hin, wohingegen isoklinale Falten in den Gneisen abgebildet werden. Geländedaten aus der UHP Einheit des Dabie Shan ermöglichen die Definition von Grundgebirgs- und Deckeinheiten, die Teile des ehemaligen passiven Kontinentalrandes des Yangtze Kratons repräsentieren. Eine der Deckeinheiten, die Changpu Einheit, besitzt nach wie vor einen stratigraphischen Kontakt zu den Grundgebirgs-Gneisen. Der anderen Einheit hingegen, der Ganghe Einheit, fehlt ein entsprechendes Grundgebirge. Diese Einheit steht vielmehr über einen Blasto-Mylonit in tektonischem Kontakt zum Grundgebirge der vorherigen. Die Changpu Einheit baut sich aus kalk-arenitischen Metasedimenten auf, die mit Metabasalten assoziiert sind. Die Ganghe Einheit wird von arenitisch-vulkanoklastischen Metasedimenten, die ebenfalls mit metabasaltischen Gesteinen vergesellschaftet sind, dominiert. Das Grundgebirge baut sich aus diversen felsischen Gneisen auf, die von reliktisch eklogitfaziell bis grünschieferfaziell ausgeprägt sind, und in denen, zusätzlich zu Metabasalten, sporadisch mafisch-ultramafische Meta-Plutone auftreten. Mit Ausnahme der Ganghe Einheit, führen die Metabasite Coesit und belegen somit das UHP Ereignis. Die Mineralchemie der analysierten Proben dokumentiert deutliche Variationen in der Zusammensetzung der Hauptminerale, Granat und Omphazit, was entweder unterschiedliche Protolithe oder unterschiedliche Grade von Stoffaustausch mit den Wirtsgesteinen reflektiert. Gehalte von dreiwertigem Eisen in Omphaziten mit geringen Gesamteisengehalten, wurden mittels Titration bestimmt, wobei sich Werte von 30-40 % ergaben. Dennoch wurde ein noch konservativerer Wert von 50% dreiwertigem Eisen in den entsprechenden Berechnungen angenommen, hauptsächlich, um mit anderen Arbeiten vergleichbar zu sein. Texturen und chemische Zonierungen in den Mineralen sind kompatibel mit Gleichgewichtsbedingungen während dem Höhepunkt der Metamorphose, der retrograd überprägt wird. P-T Daten wurden mit deutlicher Betonung auf das Granat-Omphazit-Phengit Barometer, das mit Fe-Mg Austausch-Thermometern kombiniert wurde, berechnet. Höchstdrucke reichen von 42-48 kbar (für die Changpu Einheit) bis ca. 37 kbar (für das Grundgebirge und die Ganghe Einheit). Während der eklogitfaziellen Metamorphose wurden Temperaturen von ca. 750 °C erreicht. Obwohl die maximalen Drucke deutlich schwanken, sind die Temperaturbestimmungen in guter Übereinstimmung. Die Druckschwankungen können zum einen durch deutlich Ca-dominierte Granate (bis zu 50 mol% Grossular in der Changpu Einheit) und/oder zum anderen durch Modifikationen der Mineralzusammensetzungen während der retrograden Metamorphose erklärt werden. Die präsentierten integrativen geologischen Daten ermöglichen die folgenden Schlussfolgerungen i) Grundgebirgs- und Deckeinheiten treten im Dabie Shan auf und wurden beide UHP metamorph überprägt ii) Der Dabie Shan ist das metamorphe Äquivalent des früheren passiven Kontinentalrandes des Yangtze Kratons iii) felsische Gneise, die eine UHP Metamorphose durchlaufen, sind von Volumenver-änderungen betroffen, die durch großräumige Phasenumwandlungen (Quarz Coesit) hervorgerufen werden, was direkt die tektono-metamorphen Prozesse beeinflusst iv) Initiale Unterschiede in der Temperatur sind möglicherweise dafür verantwortlich, dass generell Unterkrustengesteine in UHP Fazies fehlen
The nineteenth century witnessed many advances in neuroscientific concepts. Among the notable are Charles Bell's (1774-1842) and François Magendie's (1783-1855) identification of sensory and motor pathways, Thomas Henry Huxley's (1825-1895) elaboration of evolutionary theory in the context of comparative neuroanatomy, and Emile Du Bois-Reymond's (1818-1896) and Hermann von Helmholtz's (1821-1894) work in experimental neurophysiology and on the concept of nervous energy. In Germany, the idea that the nervous system consisted of two elements, one that generated nervous energy and another that conducted it throughout the body, had wide currency in mid-nineteenth century. In France, Pierre Jean Georges Cabanis (1757-1808), physician, philosopher, and one of the founders of modern psychophysiology, argued that the brain is the part of the body in which electricity is stored. In his Rapports du Physique et du Moral de l'Homme, published between 1796 and 1802 (translated into German under the title Verhältnis der Seele zum Körper (1808)), Cabanis proposed new ideas on brain function, on the brain's own sensibility, on the concept of will, and on the chemical basis of nervous activity. In the Rapports Cabanis proposed a theory of how brain and nerves relate to thought and behavior. Foreshadowing later developments in neuropsychology, he suggested that different parts of the nervous system have separate functions. Despite the fact that Cabanis had many interesting ideas about brain function, he has been largely ignored by historians of neuroscience; e. g., he is mentioned briefly in Clark and Jacyna (1989), in only two footnotes in Neuburger (1897/1981), and not at all in Finger (1994). Cabanis's far-reaching theory of how the brain works helped shape understanding of the general notion of nervous energy in nineteenth-century European neuroscience.
Vor über siebzig Jahren fand man in einer Höhle nahe Hohlenstein-Stadel, im heutigen Baden-Württemberg, eine Frau, die keiner bekannten Spezies und nicht einmal eindeutig den Hominiden zugeordnet werden konnte. Wegen ihres Aussehens wurde sie schon bald als "Löwenfrau“ bekannt (unterdessen wird sie als "Löwenmensch“ bezeichnet, da die in solchen Fragen Klarheit schaffenden Geschlechtsteile bei der Figur fehlen und in Zeiten von gender mainstreaming derartige Festlegungen gerne vermieden werden), denn sie hatte eine menschlich-aufrechte, unbehaarte Gestalt mit weiblichen Rundungen, aber zugleich eine Mähne, sowie Augen, Ohren und Schnauze eines Löwen. Eine sehr weitläufige Verwandte des Minotaurus, so schien es, und doch wesentlich älter als alle Bewohner des Olymps, denn vermutlich wurde die knapp 30 cm große Skulptur bereits in der Altsteinzeit vor etwa 32.000 Jahren aus Mammut-Elfenbein geschnitzt. Wir wissen nicht, ob sie kultischen Zwecken diente oder ein Kind mit ihr spielte, ob sie als Glücksbringer für die Jagd oder als Schamanin mit Löwenmaske verehrt und gefürchtet wurde. Aber die Löwenfrau legt nahe, dass der Mensch schon im Morgendämmern seiner Kultur über die eigene Nähe, aber auch Distanz zum Tier nachgedacht haben muss. Die Frage nach der menschlichen Selbstverortung begegnet uns in dieser Figur, und sie bestimmt viele Zeugnisse menschlichen Nachdenkens, welche uns die Altertumswissenschaften vorlegen. Mit dem Begriff "animal rationale“, wie er unter Bezug auf Aristoteles geprägt wurde, findet sie schließlich ihre klassische, für das Abendland lange Zeit maßgebliche Antwort: Der Mensch als Tier, dessen spezifisches Merkmal die Vernunftbegabtheit ist, die ihn zugleich von allen anderen Tieren abgrenzt und über sie stellt. Aber wo genau verläuft die Grenze? Und wie kann der Mensch beides zugleich sein? Die aristotelische Definition beantwortet diese Fragen nach der Doppelnatur nicht, sondern erhebt das offene Rätsel gleichsam zur Wesensbestimmung des Menschen.
USP 1995 (The United States Pharmacopeia, 23rd Edit., (1995), potassium iodide p. 1265, sodium iodide p. 1424), PH. EUR. 1997 (European Pharmacopoeia, third ed., Council of Europe, Strasbourg, (1997), potassium iodide p. 1367, sodium iodide p. 1493) and JAP 1996 (The Japanes Pharmacopoeia, 13th ed. (1996), potassium iodide p. 578, sodium iodide p. 630) determine iodide with the ICl-method (J. Am. Chem. Soc. 25 (1903) 756-761; Z. Anorg. Chem. 36 (1903) 76-83; Fresenius Z. Anal. Chem. 106 (1936) 12-23; Arzneibuch-Kommentar, Wissenschaftliche Erläuterungen zum Europäischen Arzneibuch, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, Govi-Verlag - Pharmazeutischer Verlag GmbH, Eschborn, 12th suppl. (1999), K10 p. 2), using chloroform, which is toxic and hazardous to environment. Without the application of chlorinated hydrocarbons USP 2000 (The United State Pharmacopeia, 24th ed. (2000), potassium iodide p. 1368, sodium iodide p. 1535) and Brit 1999 (British Pharmacopoeia London, (1999), Appendix VIII C, p. A162) titrate iodide with the redox indicator amaranth. A titration with potentiometric indication giving two end-points at the step of I(2) and [ICl(2)](-) is described. Due to the high concentration of hydrochloric acid required for the ICl-method, the determination with DBH (1,3-dibromo-5,5-dimethylhydantoin; 1,3-dibromo-5,5-dimethyl-2,4-imidazolidinedione) can be recommended and is performed easily. Similarly, the iodide content of gallamine triethiodide may be analyzed with DBH by application of a visual two-phase titration in water and ethyl acetate or with potentiometric indication in a mixture of 2-propanol and water. During the removal of the excess of DBH 4-bromo-triethylgallamine (2,2',2"-[1-bromo-benzene-2,3,4-triyltris(oxy)]N,N,N-triethylethanium) is formed.
Lautstarker Applaus erhob sich im Salon III/IV des Marriott-Hotels von Crystal City im amerikanischen Bundesstaat Virginia. In dem überfüllten Konferenzraum starrten alle wie gebannt auf die Leinwand, wo nicht mehr zu sehen war als ein nüchternes Diagramm aus zahlreichen Punkten und einer geschwungenen Kurve. Nureine eigenartige Personengruppe konnte sich davon zu Emotionen hinreißen lassen - Physiker auf der Jahrestagung der Astronomischen Gesellschaft, die ihren Begeisterungssturm noch minutenlang fortsetzten. Was war geschehen? Die im Diagramm aufgetragenen Daten bestätigten mit einer nie da gewesenen Genauigkeit ein fundamentales Naturgesetz zur Wärmeabstrahlung von heißen Körpern. 1900 von Max Planck entdeckt, leuchtete es nun in geradezu mathematischer Reinheit auf. Noch sensationeller war der Ursprung der Daten - Mikrowellensignale verschiedener Frequenzen, die nicht aus einem irdischen Labor stammten, sondern von einem heißen Urzustand des Universums! Ein Feuerball aus Wasserstoff und Helium, noch ohne jegliche Strukturen, die irgendwann Leben ermöglichen sollten, ließ damals seinem Licht freien Lauf. Mehr als zehn Milliarden Jahre war es bis zu den Detektoren des vom Menschen gebauten Satelliten COBE unterwegs, der wenige Tage zuvor die Daten übertragen hatte. Wenn ich das alles wie einen Film in meiner Vorstellung ablaufen lasse, bekomme ich immer eine Gänsehaut, als würde ich die inzwischen extrem abgekühlte Strahlung tatsächlich spüren. Ihre Gleichverteilung im Raum macht uns auch deutlich, dass wir uns nicht einbilden dürfen, an einem besonderen Ort im Universum zu leben - intelligente Aliens könnten sich seitdem überall entwickelt haben! Sollten sie - was nicht wahrscheinlich ist - uns wirklich von Zeit zu Zeit über die Schulter schauen, dann hätten sie an jenem Nachmittag des 13. Januar 1990, als der Vortrag stattfand, bestimmt anerkennend mit ihrem großen Kopf genickt.
Seit 1990 waren mehrere der großen Flussgebiete Mitteleuropas wiederholt von extremen Hochwassern betroffen. Da sowohl die Landoberfläche als auch die Flusssysteme weiter Teile Mitteleuropas in der Vergangenheit weitreichenden Eingriffen ausgesetzt gewesen sind, wird bei der Suche nach den Ursachen für diese Häufung von Extremereignissen auch die Frage nach der Verantwortung des Menschen hierfür diskutiert. Gewässerausbau, Flächenversiegelung, intensive landwirtschaftliche Bodenbearbeitung, Flurbereinigung und Waldschäden sind nur einige Beispiele und Folgen der anthropogenen Eingriffe in die Landschaft. Aufgrund der Vielfalt der beteiligten Prozesse und deren Wechselwirkungen gibt es allerdings bislang nur Schätzungen darüber, wie sehr sich die Hochwassersituation hierdurch verändert hat. Vorrangiges Ziel dieser Arbeit ist es, mit Hilfe eines hydrologischen Modells systematisch darzustellen, in welcher Weise, in welcher Größenordnung und unter welchen Umständen die Art der Landnutzung auf die Hochwasserentstehung Einfluss nimmt. Dies wird anhand exemplarischer Modellanwendungen in der hydrologischen Mesoskala untersucht. Zu diesem Zweck wurde das deterministische und flächendifferenzierte hydrologische Modell wasim-eth ausgewählt, das sich durch eine ausgewogene Mischung aus physikalisch begründeten und konzeptionellen Ansätzen auszeichnet. Das Modell wurde im Rahmen dieser Arbeit um verschiedene Aspekte erweitert, die für die Charakterisierung des Einflusses der Landnutzung auf die Hochwasserentstehung wichtig sind: (1) Bevorzugtes Fließen in Makroporen wird durch eine Zweiteilung des Bodens in Makroporen und Bodenmatrix dargestellt, die schnelle Infiltration und Perkolation jenseits der hydraulischen Leitfähigkeit der Bodenmatrix ermöglicht. (2) Verschlämmung äußert sich im Modell abhängig von Niederschlagsintensität und Vegetationsbedeckungsgrad als Verschlechterung der Infiltrationsbedingungen an der Bodenoberfläche. (3) Das heterogene Erscheinungsbild bebauter Flächen mit einer Mischung aus versiegelten Bereichen und Freiflächen wird berücksichtigt, indem jede Teilfläche je nach Versiegelungsgrad in einen unversiegelten Bereich und einen versiegelten Bereich mit Anschluss an die Kanalisation aufgeteilt wird. (4) Dezentraler Rückhalt von Niederschlagswasser kann sowohl für natürliche Mulden als auch für gezielt angelegte Versickerungsmulden mit definierten Infiltrationsbedingungen simuliert werden. Das erweiterte Modell wird exemplarisch auf drei mesoskalige Teileinzugsgebiete des Rheins angewandt. Diese drei Gebiete mit einer Fläche von zwischen 100 und 500 km² wurden im Hinblick darauf ausgewählt, dass jeweils eine der drei Hauptlandnutzungskategorien Bebauung, landwirtschaftliche Nutzung oder Wald dominiert. Für die drei Untersuchungsgebiete sind räumlich explizite Landnutzungs- und Landbedeckungsszenarien entworfen worden, deren Einfluss auf die Hochwasserentstehung mit Hilfe des erweiterten hydrologischen Modells simuliert wird. Im Einzelnen werden die Auswirkungen von Verstädterung, Maßnahmen zur Niederschlagsversickerung in Siedlungsgebieten, Stilllegung agrarisch genutzter Flächen, veränderter landwirtschaftlicher Bodenbearbeitung, Aufforstung sowie von Sturmschäden in Wäldern untersucht. Diese Eingriffe beeinflussen die Interzeption von Niederschlag, dessen Infiltration, die oberflächennahen unterirdischen Fließprozesse sowie, zum Beispiel im Fall der Kanalisation, auch die Abflusskonzentration. Die hydrologischen Simulationen demonstrieren, dass die Versiegelung einer Fläche den massivsten Eingriff in die natürlichen Verhältnisse darstellt und deshalb die stärksten (negativen) Veränderungen der Hochwassersituation hervorbringt. Außerdem wird deutlich, dass eine bloße Änderung des Interzeptionsvermögens zu keinen wesentlichen Veränderungen führt, da die Speicherkapazität der Pflanzenoberflächen im Verhältnis zum Volumen hochwasserauslösender Niederschläge eher klein ist. Stärkere Veränderungen ergeben sich hingegen aus einer Änderung der Infiltrationsbedingungen. Die Grenzen der entwickelten Methodik zeigen sich am deutlichsten bei der Simulation veränderter landwirtschaftlicher Bewirtschaftungsmethoden, deren mathematische Beschreibung und zahlenmäßige Charakterisierung aufgrund der Komplexität der beteiligten Prozesse mit großen Unsicherheiten behaftet ist. Die Modellierungsergebnisse belegen darüber hinaus, dass pauschale Aussagen zum Einfluss der Landnutzung auf die Hochwasserentstehung aufgrund der entscheidenden Bedeutung der klimatischen und physiographischen Randbedingungen unzulässig sind. Zu den klimatischen Randbedingungen zählen sowohl Niederschlagsintensität und -dauer als auch die Feuchtebedingungen vor einem hochwasserauslösenden Niederschlag. Die physiographischen Randbedingungen sind von der geomorphologischen und geologischen Ausstattung des Gebiets vorgegeben. Weiterhin muss der räumliche und zeitliche Maßstab, über den Aussagen getroffen werden, klar definiert sein, da sich mit steigender Einzugsgebietsgröße die relative Bedeutung sowohl der verschiedenen Niederschlagstypen als auch der physiographischen Eigenschaften verschiebt. Dies wird in der vorliegenden Arbeit im Gegensatz zu vielen anderen Untersuchungen konsequent berücksichtigt. In Abhängigkeit von Randbedingungen und räumlichen Maßstab sind aufgrund der gewonnen Erkenntnisse folgende Aussagen zum Einfluss von Landnutzungsänderungen auf die Hochwasserentstehung möglich: (1) Für intensive konvektive Niederschlagsereignisse mit tendenziell geringer Vorfeuchte ist der Einfluss der Landnutzung größer als für langanhaltende advektive Niederschläge geringer Intensität, da im ersten Fall veränderte Infiltrationsbedingungen stärker zum Tragen kommen als bei kleinen Niederschlagsintensitäten. (2) In kleinen Einzugsgebieten, wo kleinräumige Konvektivzellen zu Hochwassern führen können, ist der Einfluss der Landnutzung dementsprechend größer als in großen Flussgebieten wie dem Rheingebiet, wo vor allem langanhaltende advektive Ereignisse (unter Umständen verbunden mit Schneeschmelze) relevant sind. (3) In Gebieten mit guten Speichereigenschaften wie mächtigen, gut durchlässigen Böden und gut durchlässigem Gesteinsuntergrund ist der Einfluss der Landnutzung größer als in Gebieten mit geringmächtigen Böden und geringdurchlässigem Festgestein. Dies ist darin begründet, dass in Gebieten mit guten Speichereigenschaften bei einer Verschlechterung der Infiltrationsbedingungen mehr Speicherraum für Niederschlag verloren geht als in anderen Gebieten. Since 1990, several of the large European river basins were affected repeatedly by extreme floods. As both the landscape and the river systems in large parts of Central Europe have undergone major changes in the past, during the search for the causes of this accumulation of extreme events also the impact of human activities on flooding has been discussed. River training, surface sealing, intensive agricultural land-use, consolidation of farmland, and damages to forests are only some examples and consequences of the anthropogenic interferences with the landscape. But due to the diversity of the processes and factors involved, by now it can only be estimated how far the flood situation has changed by these interferences. Therefore, the main target of this thesis is to describe systematically in which way, to what extent and under which circumstances the land-use exerts an influence on storm-runoff generation and subsequently the discharge of rivers. This is investigated by means of exemplary model applications at the hydrological meso-scale. For this task, the deterministic and distributed hydrological model wasim-eth was chosen due to its well-balanced mixture of physically-based and conceptual approaches. In the framework of this thesis, the model has been extended in order to cope with several phenomena which are important when aiming at a characterization of the influence of land-use on flood generation: (1) Preferential flow in macropores is treated by a division of the soil into macropores and a soil matrix. This so-called double-porosity approach allows for fast infiltration and percolation beyond the hydraulic conductivity of the soil matrix. (2) Siltation expresses itself within the model as a deterioration of infiltration conditions at the soil surface, depending on precipitation intensity and the degree of vegetation covering. (3) The heterogeneous appearance of built-up areas, consisting of both sealed areas and pervious areas, is taken into account by dividing each partial area into an unsealed part and a sealed part which is connected to the sewer system. (4) Decentralized storage can be simulated for natural depressions as well as for specific infiltration measures with defined infiltration conditions. The extended model is exemplarily applied to three meso-scale tributaries of the Rhine river. These three catchments with an area of between 100 and 500 km² were chosen with regard to their prevailing land-use, one of them being heavily urbanized, one dominated by agricultural use, and one being mainly forested. For these three catchments, spatially explicit land-use and land-cover scenarios were developed. The impact of these scenarios on storm-runoff generation is being simulated using the extended hydrological model. In this context, namely urbanization, infiltration measures in settlement areas, conversion of farmland to set-aside areas, altered agricultural management practices, affor estation and storm damages in forests are taken into account. These changes influence the interception of rainfall, its infiltration into the soil, the subsurface flow processes next to the soil surface as well as, for example in the case of sewer systems, also runoff concentration. The hydrological simulations demonstrate that sealing of the soil surface is the most intensive intervention in the natural conditions among the ones which are mentioned above. Therefore it results in the strongest (negative) changes of the flooding situation in a catchment. In addition to that, the simulations show that a simple alteration in the interception capacity does not yield significant changes in catchment response, because the storage capacity of vegetation surfaces is rather low compared to the volume of storm events which normally lead to significant floods. More pronounced changes arise from modifications in the infiltration conditions. The limits of the methodology which was chosen for this thesis become obvious when simulating altered agricultural management practices. Due the complexity of the processes involved, mathematical description and parameterization is difficult and therefore afflicted with high uncertainty. In addition to that, the modelling results prove that global statements on the influence of land-use on flood generation are illegitimate because of the paramount importance of the climatic and physiographic boundary conditions. Climatic boundary conditions are precipitation intensity and duration as well as the moisture conditions before a storm event. The physiographic boundary counditions are given by the geomorphological and geological catchment properties. Furthermore, with increasing scale there is a shift in the relative importance of the different types of rainfall as well as the different geophysical catchment properties. Therefore, the spatial and temporal scale for which the results are valid have to be clearly defined. This is taken into account consequently within this thesis - in contrast to many other studies on this topic. Depending on boundary conditions and spatial scale, the findings allow the following statements regarding the influence of land-use changes on storm-runoff generation: (1) For intensive convective storm events with generally low antecedent soil moisture, the influence of land-use is greater than for long-lasting advective storm events with low rainfall intensities, because in the first case changes in the infiltration conditions are more important than during times of low precipitation intensities. (2) In small catchments, where small-scale convective cells can lead to a flood, the influence of land-use is accordingly greater than in large river basins like the Rhine basin, where long-lasting advective rainfalls (possibly in combination with snowmelt) are relevant. (3) In areas with good storage conditions like thick, permeable soils and pervious rock underneath, the influence of land-use is greater than in areas with thin soils and only slightly permeable bedrock. This is due to the fact that in case of deteriorating infiltration conditions, more storage space for precipitation is lost in areas with good storage conditions than in other areas. siehe auch: http://opus.kobv.de/ubp/volltexte/2005/398/
Chung, Tae-Wook; Lee, Jung Hee; Choi, Hee-Jung; Park, Mi-Ju; Kim, Eun-Yeong; Han, Jung Ho; Jang, Se Bok; Lee, Syng-Ook; Lee, Sang Woo; Hang, Jin; Yi, Li Wan; Ha, Ki-Tae
Mitchell, Emily H.; Raut, Ujjwal; Baragiola, Raul A.
2015-11-01
Crystalline ice has been identified on the cold surfaces of most icy satellites and TNOs [1]. This is surprising since accretion of water vapor at temperatures (T < 100 K) should result in the amorphous phase [2]. There are several possible explanations for the unexpected presence of crystalline ice on cold bodies, including cryovolcanism [3] and pulsed heating by micrometeoritic impacts [4].A salient feature of ice films condensed at low T is microporosity, known to increase with deposition angle [5]. Here we investigate the dependence of the crystallization rate on the ice porosity, which could contribute to the observed variation in crystallization time τc reported in the literature [2]. Such dependence is noted in other porous materials such as zeolites and titania [6, 7].Amorphous ice films were deposited on a CsI substrate from a collimated water vapor source at 10 K at incidences varying from 0 to 70°, as well as from an omnidirectional water vapor source. The films were heated to temperatures between 130 and 140 K following deposition. The isothermal transition from amorphous to fully crystalline phase was characterized by analyzing the time-dependent evolution of the OH-stretch absorption band using transmission infrared spectroscopy. Our initial results show that τc decreases with increasing porosity; for instance, a film deposited at 45° was observed to crystallize ~6 times faster than a film deposited at 0°. The preliminary estimate of the porosity of the 45° film is ~50% higher than that of the film deposited at normal incidence. Our findings can explain the reported variation in temperature-dependent τc [2] and contribute to the understanding of crystalline ice on cold bodies in the Outer Solar System.1. Mastrapa, R.M.E. et al. In: Gudipati, M.S. & Castillo-Rogez, J., Eds, The Science of Solar System Ices, Springer, New York, 2013.2. Baragiola, R.A. In: Devlin & Buch, Eds, Water in Confining Geometries, Springer-Verlag, 2003.3. Jewitt, D.C. & Luu, J., Nature 432, 731, 2004.4. Porter, S.B. et al. Icarus 208, 492, 2010.5. Stevenson, K.P., et al. Science 283, 1505, 1999.6. Francis, R.J. & O’Hare, D., J. Chem. Soc., Dalton Trans., 3133, 1998.7. Kirsch, B.L. et al., J. Phys. Chem. B., 108, 12698, 2004.
Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A.; Rusyn, Ivan; Tropsha, Alexander
2009-01-01
Background Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Objective A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. Methods and results A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD50 values from chemical descriptors. All models were extensively validated using special protocols. Conclusions The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity. PMID:19672406
Objective Epididymo-orchitis (EO) potentially results in reduced fertility in up to 60% of affected patients. The anti-inflammatory effects of Korean red ginseng (KRG) and its ability to act as an immunoenhancer in parallel with the beneficial effects of this ancient herbal medicine on the reproductive systems of animals and humans led us to evaluate its protective effects against acute EO. Materials and Methods This animal experimental study was conducted in the Department of Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran during 2013-2015. We divided 50 Wistar rats into five following groups (n=10 per group): i. Control-intact animals, ii. Vehicle-phosphate buffered saline (PBS) injection into the vas deferens, iii. KRG-an intraperitoneal (IP) injection of KRG, iv. EO-an injection of uropathogenic Escherichia coli (UPEC) strain M39 into the vas defer- ens, and v. EO/ KRG-injections of both UPEC strain M39 and KRG. The treatment lasted seven days. We then evaluated sperm parameters, number of germ cell layers, Johnson’s criteria, germ cell apoptosis, body weight and relative sex organs weight. Results Acute EO increased the relative weight of prostate and seminal vesicles (P≤0.05). It also reduced sperm quality such as total motility, sperm concentration (P≤0.01), and the percentage of normal sperm (P≤0.001). Moreover, acute EO decreased Miller’s (P≤0.05) and Johnsen’s scores and increased apoptotic indexes of spermatogenic cells (P≤0.001). KRG treatment decreased prostate weight gain (P≤0.05) and improved the percentage of sperm with normal morphology, total motility (P≤0.01), and progressive motility (P≤0.05). The apoptotic indexes of spermatogenic cells reduced (P≤0.001), whereas both Johnsen’s (P≤0.01) and Miller’s criteria increased in the KRG-treated EO testis (P≤0.05). Conclusion Consequently, KRG ameliorated the devastating effects of EO on the sperm retrieved from either epididymis or testicle in rats. PMID:27602327
Zhu, Hao; Ye, Lin; Richard, Ann; Golbraikh, Alexander; Wright, Fred A; Rusyn, Ivan; Tropsha, Alexander
2009-08-01
Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC(50)) and in vivo rodent median lethal dose (LD(50)) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure-activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD(50) values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC(50) and LD(50). However, a linear IC(50) versus LD(50) correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC(50) and LD(50) values: One group comprises compounds with linear IC(50) versus LD(50) relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD(50) values from chemical descriptors. All models were extensively validated using special protocols. The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity.
Botulism is one of the most important bird diseases world-wide and is caused by the intoxication with Botulinum-Neurotoxin-C1 (BoNt-C1), which is produced by toxigenic clostridia under appropriate conditions. Avian botulism leads regularly to large losses among the migrating bird populations breeding and resting at the saltwater pools of the Austrian national park Neusiedler See-Seewinkel. Despite of its ethical dubiousness and its high technical expense the mouse-bioassay is still used as the routine standard method for the detection of BoNt-C1. According to the 3R-concept, in vitro alternative methods for the qualitative detection of BoNt-C1 (immunostick-ELISA) and a corresponding BoNt-C1 gene fragment (nested-PCR) were established. In order to estimate the BoNt-C1 production potential the methods were tested with sediment samples from different saltwater pools subjected to cultivation conditions appropriate for in vitro BoNt-C1-production. With the mouse-bioassay, 52 out of 77 samples were found to have a positive toxin production potential. The immunostick-ELISA showed a similar sensitivity as the mouse-bioassay and exhibited a highly significant positive correlation (r=0.94; p<0.001) with the mouse-bioassay in detecting BoNt-C1. The nested-PCR approach revealed higher numbers of positive BoNt-C1 gene fragment detections as compared to the direct toxin analysis approaches. A weak correlation (r=0.21; p=0.07) with the mouse-bioassay was discernible, no correlation was found with the immunostick-ELISA (r=0.09; p=0.46). Obviously, the PCR approach detected the BoNt-C1 gene fragment in some of the samples where no toxin expression has occurred. Thus it is suggested that the qualitative immunostick-ELISA represents a potential in vitro alternative to the mouse-bioassay for assessing the BoNt-C1 production potential in environmental samples. In contrast, qualitative BoNt-C1 gene fragment detection via PCR led to an overestimation of the actual toxin production potential.
With the aim of separating and detecting organic compounds from Martian soil onboard the Mars Organic Molecule Analyzer (MOMA) experiment of the ExoMars 2018 upcoming joint ESA/NASA mission, we have developed three different space compatible sample preparation techniques compatible with space missions, able to extract and analyze by GC-MS a wide range of volatile and refractory compounds, including chirality analysis. Then, a sample processing utilizing three derivatization/extraction reactions has been carried out. The first reaction is based on a silyl reagent N-Methyl-N- (Tert-Butyldimethylsilyl)trifluoroacetamide (MTBSTFA) [1], the second one, N,N-Dimethylformamide Dimethylacetal (DMF-DMA) [2,3] is dedicated to the chirality detection and the third one is a thermochemolysis based on the use of tetramethylammoniumhydroxide (TMAH). The sample processing system is performed in an oven, dedicated to the MOMA experiment containing the solid sample (50-100mg). The internal temperature of the oven ranges from 20 to 900 °C. The extraction step is achieved by using thermodesorption in the range of 100 to 300°C for 5 to 20 min. Then, the chemical derivatization of the extracted compounds is performed directly on the soil sample by using a derivatyization capsule which contains a mixture of MTBSTFA-DMF or DMF-DMA solution when enantiomeric separation is required. By decreasing the polarity of the targeted molecules, this step allows their volatilization at a temperature below 250°C without any thermal degradation. Once derivatized, the volatile target molecules are trapped in a chemical trap and promptly desorbed into the gas chromatograph coupled to a mass spectrometer. Thermochemolysis is directly performed in the oven at 400°C during 5 min with a 25% (w/w) methanol solution of tetramethylammonium hydroxide (TMAH). Then, pyrolysis in the presence of TMAH allows both an efficient cleavage of polar bonds and the subsequent methylation of COOH, OH and NH2 groups, hence the release of less polar, GC-amenable compounds. By using thermochemolysis several families of biological molecules were detected such as fatty acids, n-alkenes and n-alkanols [4]. [1] A. Buch et al., Development of a gas chromatography compatible Sample Processing System (SPS) for the in-situ analysis of refractory organic matter in martian soil: preliminary result. Advances in Space Research 43, 143-151, 2009. [2] C. Freissinet et al., Journal of Chromatography A.1217 (5), 731-740, 2010. [3] U. Meierhenrich et al., Journal of Analytical and Applied Pyrolysis 60, 13-26, 2001. [4] C. Geffroy-Rodier et al., Journal of Analytical and Applied Pyrolysis, 85, 2009.
Vorwort. Teil I: Rißbreiten (Gert König) 1 Ein mechanisches Modell zur Erhöhung der Vorhersagegenauigkeit über die Rißbreiten unter Betriebsbedingungen (Gert König und Michael Fischer). 1.1 Einleitung und Zielsetzung. 1.2 Versuchsprogramm. 1.3 Meßtechnik. 1.4 Belastung und Versuchsdurchführung. 1.5 Literatur. 2 Rißbreiten und Verformungszunahme vorgespannter Bauteile unter wiederholter Last - und Zwangbeanspruchung (Gert König und Michael Fischer). 2.1 Einleitung und Zielsetzung. 2.2 Versuchsprogramm. 2.3 Auswertung. 2.4 Ausblick. 2.5 Literatur. 3 Rißverhalten von Beton bei plötzlicher Abkühlung (Viktor Mechtcherine und Harald S. Müller). 3.1 Einleitung. 3.2 Experimentelle Untersuchungen. 3.3 Formulierung eines Stoffgesetzes für thermisch beanspruchten Beton. 3.4 Riß entwicklung in einer Betonplatte unter Temperaturschock. 3.5 Zusammenfassung. 3.6 Literatur. 4 Stahlfaserbeton unter Betriebsbedingungen bei Dauerbeanspruchung (Bo Soon Kang, Bernd Schnütgen und Friedhelm Stangenberg). 4.1 Einleitung. 4.2 Wirkung von Stahlfasern im Beton. 4.3 Versuchsprogramm. 4.4 Untersuchungen zum Verbundverhalten. 4.5 Untersuchungen zum Verhalten unter Biegebeanspruchung. 4.6 Theoretische Untersuchungen. 4.7 Literatur. 5 Experimentelle Untersuchungen an Stahlbeton-Zugkörpern unter wiederholter Belastung zur Ermittlung des versteifenden Einflusses der Mitwirkung des Betons zwischen den Rissen (Petra Seibel und Gerhard Mehlhorn). 5.1 Einleitung. 5.2 Ansatz zur Bestimmung der Mitwirkung des Betons zwischen den Rissen nach Eurocode 2, Model Code 90 und Günther. 5.3 Experimentelle Untersuchungen. 5.4 Ergebnisse. 5.5 Zusammenfassung. 5.6 Literatur. 6 Riß- und Verformungsverhalten von vorgefertigten Spannbetonträgern unter Betriebsbedingungen bei besonderer Berücksichtigung des Betonalters (Monika Maske, Heinz Meichsner und Lothar Schubert). 6.1 Einleitung. 6.2 Beschreibung der Fertigteilträger. 6.3 Belastungsversuche. 6.4 Ergebnisse. 6.5 Zusammenfassung. 6.6 Literatur. Teil II: Verbundfragen (Rolf Eligehausen). 1 Ein mechanisches Modell zur Beschreibung des Verbundverhaltens zwischen Stahl und Beton (Gert König, Nguyen V. Tue und Wolfgang Kurz). 1.1 Einleitung. 1.2 Beschreibung der Kraftübertragung zwischen Stahl und Beton. 1.3 Vorstellung des Modells. 1.4 Materialgesetze für die Berechnung der Verformung des Fachwerks. 1.5 Vergleich zwischen Versuch und Modell. 1.6 Zusammenfassung und Ausblick. 1.7 Literatur. 2 Verbund unter nicht ruhender Beanspruchung (Rainer Koch und György L. Balázs). 2.1 Übersicht über die durchgeführten Versuche. 2.2 Versuchkörper und Materialien. 2.3 Versuchseinrichtungen. 2.4 Versuche und Ergebnisse. 2.5 Zusammenfassung und Ausblick. 2.6 Literatur. 3 Trag- und Verformungsverhalten von Stahlbetontragwerken unter Betriebsbelastung (Thomas M. Sippel und Rolf Eligehausen). 3.1 Einleitung. 3.2 Allgemeines. 3.3 Rechenmodell und Materialmodelle. 3.4 Vergleich zwischen Versuchen und Rechnung. 3.5 Parameterstudien. 3.6 Vereinfachtes Rechenmodell. 3.7 Zusammenfassung. 3.8 Literatur. 4 Verbundverhalten von Spanngliedern mit nachträglichem Verbund unter Betriebsbedingungen (Josef Hegger, Norbert Will und Heiner Cordes). 4.1 Einführung. 4.2 Verbundverhalten von Spanngliedern. 4.3 Zeitabhängige Effekte des Verbunds. 4.4 Versuche unter statischer Langzeitbeanspruchung. 4.5 Versuche unter dynamischer Langzeitbeanspruchung. 4.6 Bemessungsvorschlag für Verbundkennwerte. 4.7 Zusammenfassung. 4.8 Literatur. 5 Spannungsumlagerungen in gemischt bewehrten Querschnitten (Josef Hegger, Heiner Cordes und Matthias Rudlof). 5.1 Problemstellung und Zielsetzung. 5.2 Spannungsumlagerungen bei gemischter Bewehrung. 5.3 Versuche an zentrischen Zugkörpern. 5.4 Versuchsergebnisse. 5.5 Ermittlung und Vergleich von Verbundkennwerten. 5.6 Zusammenfassung. 5.7 Literatur. Teil III: Bauteile (Karl Kordina). 1 Einfluß von Längsbeanspruchungen auf den Neigungswinkel der Schubrisse (Marek Los und Ulrich Quast). 1.1 Einleitung. 1.2 Ungerissener Zustand. 1.3 Gerissener Zustand. 1.4 FEM-Berechnungen. 1.5 Zusammenfassung. 1.6 Literatur. 2 Auswirkungen des unterschiedlichen Verformungsverhaltens bei Beund Entlastung auf die Beanspruchungen im Gebrauchszustand (Jochen Keysberg). 2.1 Einleitung und Zielsetzung. 2.2 Modelle für die Momenten-Verkrümmungs-Beziehung. 2.3 Programm zur nichtlinearen Berechnung. 2.4 Einfluß von Lastwechseln auf nichtlineare Berechnungen. 2.5 Zusammenfassung. 2.6 Literatur. 3 3D-Analyse von Balken-Stützen-Verbindungen aus normal- und hochfestem Beton unter zyklischer Beanspruchung (Josko Ozbolt, Yijun Li und Rolf Eligehausen). 3.1 Einleitung. 3.2 Materialmodell und FE-Diskretisierung. 3.3 Numerische Analyse. 3.4 Schlußfolgerungen. 3.5 Zusammenfassung. 3.6 Literatur. 4 Der Einfluß von freien Schwingungen infolge dynamischer Belastung auf die Deterioration eines Bauwerks (Manfred Specht und Michael Kramp). 4.1 Veranlassung des Forschungsvorhabens. 4.2 Forschungsziele. 4.3 Versuchsträger, Versuchsdurchführung und Versuchsergebnisse. 4.4 Auswertung. 4.5 Ergebnisse für die Systemidentifikation von Stahlbetonkonstruktionen. 4.6 Literatur. 5 Lokale Schwind- und Temperaturgradienten in bewehrten, oberflächennahen Zonen von Betonkonstruktionen (Josef Eibl und Stephan Kranz). 5.1 Problemstellung. 5.2 Temperatur- und Feuchtefeldberechnung. 5.3 Numerisches Berechnungsmodell zur Spannungsanalyse im Beton. 5.4 Durchgeführte Versuche. 5.5 Rechnerische Untersuchungen. 5.6 Zusammenfassung. 5.7 Literatur. 6 Wassereindringverhalten von Flüssigkeiten beim Biegeriß (Gert König und Christian Brunsch). 6.1 Problemstellung. 6.2 Experimentelle Untersuchungen. 6.3 Entwicklung eines Modells zur rechnerischen Abschätzung des zeitlichen Eindringens einer Wassermenge in Biegerisse von Stahlbetonbauteilen. 6.4 Zusammenfassung und Diskussion der Versuchsreihe. 6.5 Literatur. 7 Dauerhaftigkeitsprobleme von offenen Becken (György Iványi, Wilhelm Buschmeyer und Udo Paas). 7.1 Einleitung. 7.2 Bestandsaufnahme. 7.3 Felduntersuchungen. 7.4 Laboruntersuchungen. 7.5 Berechnungen. 7.6 Entwurfs- und Ausführungskriterien. 7.7 Literatur. Teil IV: Korrosion und Ermüdung (Peter Schießl). 1 Ermüdungskorrosion von Spannstahl (Herbert Kupfer und Hans H. Müller). 1.1 Forschungsziel. 1.2 Korrosionsversuche an Spannstählen. 1.3 Methoden zur Erkennung von Anrissen. 2 Korrosionsermüdung von Stahl in Betonbauteilen (J. W. Weber, Peter Schießl und Jörg Moersch). 2.1 Allgemeines. 2.2 Wesentliche Einflüsse bei der Schwingungsrißkorrosion. 2.3 Ziel der Untersuchungen. 2.4 Prüfkörper und Betone. 2.5 Chloridbeaufschlagung. 2.6 Ergebnisse. 2.7 Zusammenfassung. 2.8 Literatur. 3 Untersuchungen zum Rißkorrosionsverhalten von Spannstählen unter Betriebsbedingungen (Jörg Moersch und Peter Schießl). 3.1 Einführung und Ziel. 3.2 Untersuchungsprogramm. 3.3 Ergebnisse. 3.4 Zusammenfassung der Ergebnisse. 3.5 Literatur. 4 Schwingfestigkeit von Stahlbeton bei Beanspruchung mit Meerwasser (Ulf Nürnberger und Willibald Beul). 4.1 Einführung. 4.2 Mechanismus. 4.3 Schwingfestigkeitsuntersuchungen. 4.4 Folgerungen. 4.5 Literatur. 5 Wasserstoffinduzierte Spannungsrißkorrosion von zugschwellbeanspruchten Spannstählen (Ulf Nürnberger und Willibald Beul). 5.1 Einführung. 5.2 Untersuchungen. 5.3 Folgerung. 5.4 Literatur. 6 Selbstheilung und Bewehrungskorrosion bei von schwach sauren Wässern durchströmten Trennrissen in bewehrtem Beton (Wieland Ramm und Michaela Biscoping). 6.1 Übersicht. 6.2 Einleitung. 6.3 Versuchsprogramm. 6.4 Versuchsergebnisse. 6.5 Zusammenfassung. 6.6 Literatur. 7 Untersuchungen zur Reibermüdung bei teilweise vorgespannten Bauteilen (Heiner Cordes, Josef Hegger und Jens U. Neuser). 7.1 Einleitung. 7.2 Stand der Forschung. 7.3 Versuchsaufbau und Versuchsdurchführung. 7.4 Versuchsergebnisse. 7.5 Zusammenfassung und Ausblick. 7.6 Literatur. Teil V: Junger Beton (Ferdinand S. Rostásy). 1 Ermittlung und Berechnung des Nullspannungstemperaturgradienten im jungen Beton (Rupert Springenschmid und Jean-Louis Bostvironnois). 1.1 Einleitung. 1.2 Der Nullspannungstemperaturgradient. 1.3 Ergebnisse und Schußfolgerungen. 1.4 Literatur. 2 Experimentelle Ermittlung der Verformungskennwerte von jungem Beton und der Zwangspannungen in situ (Markus Plannerer und Rupert Springenschmid). 2.1 Einleitung. 2.2 Versuche zur Ermittlung der Verformungskennwerte und der Zwangspannungen. 2.3 Laborergebnisse. 2.4 In-situ-Ergebnisse. 2.5 Zusammenfassung. 2.6 Literatur. 3 Werkstoffeigenschaften jungen Betons--Experimente und Modellierung (Ferdinand S. Rostásy und Alex-W. Gutsch). 3.1 Einleitung. 3.2 Versuche und Modellbildung. 3.3 Zusammenfassung. 3.4 Literatur.
Unzeta, Mercedes; Esteban, Gerard; Bolea, Irene; Fogel, Wieslawa A.; Ramsay, Rona R.; Youdim, Moussa B. H.; Tipton, Keith F.; Marco-Contelles, José
2016-01-01
HIGHLIGHTS ASS234 is a MTDL compound containing a moiety from Donepezil and the propargyl group from the PF 9601N, a potent and selective MAO B inhibitor. This compound is the most advanced anti-Alzheimer agent for preclinical studies identified in our laboratory.Derived from ASS234 both multipotent donepezil-indolyl (MTDL-1) and donepezil-pyridyl hybrids (MTDL-2) were designed and evaluated as inhibitors of AChE/BuChE and both MAO isoforms. MTDL-2 showed more high affinity toward the four enzymes than MTDL-1.MTDL-3 and MTDL-4, were designed containing the N-benzylpiperidinium moiety from Donepezil, a metal- chelating 8-hydroxyquinoline group and linked to a N-propargyl core and they were pharmacologically evaluated.The presence of the cyano group in MTDL-3, enhanced binding to AChE, BuChE and MAO A. It showed antioxidant behavior and it was able to strongly complex Cu(II), Zn(II) and Fe(III).MTDL-4 showed higher affinity toward AChE, BuChE.MTDL-3 exhibited good brain penetration capacity (ADMET) and less toxicity than Donepezil. Memory deficits in scopolamine-lesioned animals were restored by MTDL-3.MTDL-3 particularly emerged as a ligand showing remarkable potential benefits for its use in AD therapy. Alzheimer's disease (AD), the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills, and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, β-amyloid deposits, τ-protein phosphorylation, oxidative stress, and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept®) but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands (MTDL) based on the “one molecule, multiple targets” paradigm. Thus, in this context, different series of novel multifunctional molecules with antioxidant, anti-amyloid, anti-inflammatory, and metal-chelating properties able to interact with multiple enzymes of therapeutic interest in AD pathology including acetylcholinesterase, butyrylcholinesterase, and monoamine oxidases A and B have been designed and assessed biologically. This review describes the multiple targets, the design rationale and an in-house MTDL library, bearing the N-benzylpiperidine motif present in donepezil, linked to different heterocyclic ring systems (indole, pyridine, or 8-hydroxyquinoline) with special emphasis on compound ASS234, an N-propargylindole derivative. The description of the in vitro biological properties of the compounds and discussion of the corresponding structure-activity-relationships allows us to highlight new issues for the identification of more efficient MTDL for use in AD therapy. PMID:27252617
In the last decades, integrated water resources management studies produced integrated models that focus mainly on the assessment of water resources and water stress in the future. In some cases, socioeconomic development results to cause more impacts on the evolution of water systems than climate (Reynard et al., 2014). There is thus a need to develop demand-side approaches in the observation and modeling of human-influenced hydrological systems (Grouillet et al., 2015). We define the notion of water use cycle to differentiate water volumes that are withdrawn from the hydrological system and that circulate through anthropic hydro-systems along various steps: withdrawals, distribution, demands, consumption, restitution (Calianno et al., submitted). To address the spatial distribution and the temporal dynamics of the water use cycle, we define the concepts of water use basins and water use regimes (Calianno et al., submitted). The assessment of the temporal variability of water demands is important at thin time steps in touristic areas, where water resource regimes and water demands are highly variable. This is the case for are alpine ski resorts, where the high touristic season (winter) takes place during the low flow period in nival and glacio-nival basins. In this work, a monitoring of drinking water demands was undergone, at high temporal resolution, on different types of buildings in the ski resort of Megève (France). A dataset was created, from which a typology of water demand regimes was extracted. The analysis of these temporal signatures highlighted the factors influencing the volumes and the dynamics of drinking water demand. The main factors are the type of habitat (single family, collective, house, apartment blocks), the presence of a garden or an infrastructure linked to high standing chalets (pool, spa), the proportion of permanent and temporary habitat, the presence of snow in the ski resort. Also, temporalities linked to weekends and weekly tourism are observed. This typology of water demand regimes is at tool that can be developed to reproduce the temporal dynamics of water demands, when knowing the characteristics of habitat in a given region. References: Calianno M, Reynard E, Milano M (in prep). Water use cycle in tourist mountain territories: water demand basins and regimes. To be submitted to Water Resources Management. Calianno M, Reynard E, Milano M, Buchs A (submitted). Quantifier les usages de l'eau : concepts, terminologie et confusions. Submitted to VertigO. Grouillet B, Fabre J, Ruelland D, Dezetter A (2015) Historical reconstruction and 2050 projections of water demand under anthropogenic and climate changes in two contrasted mediterranean catchments. J Hydrol 522:684-696. Reynard E, Bonriposi M, Graefe O, Homewood C, Huss M, Kauzlaric M, Liniger H, Rey E, Rist S, Schädler B, Schneider F, Weingartner R (2014) Interdisciplinary assessment of complex regional water systems and their future evolution: how socioeconomic drivers can matter more than climate. WIREs Water 1(4):413-426.
Von den Anfängen der Quantenmechanik bis heute gibt es Versuche, sie als statistische Theorie über Ensembles individueller klassischer Systeme zu interpretieren. Die Bedingungen, unter denen Theorien verborgener Parameter zu deterministischen Beschreibungen dieser individuellen Systeme als klassisch angesehen werden können, wurden von Einstein, Podolsky und Rosen 1935 formuliert: 1. Physikalische Systeme sind im Prinzip separierbar. 2. Zu jeder physikalischen Größe, deren Wert man ohne Störung des betrachteten Systems mit Sicherheit voraussagen kann, existiert ein ihr entsprechendes Element der physikalischen Realität.Zusammen sind sie, wie Bell 1964 gezeigt hat, prinzipiell unverträglich mit der Quantenmechanik und unhaltbar angesichts neuerer Experimente. Diese erweisen einmal mehr die Quantenmechanik als richtige Theorie. Um ihre Ergebnisse zu verstehen, müssen wir entweder die in der klassischen Physik als selbstverständlich angesehene Annahme der Separierbarkeit physikalischer Systeme aufgeben oder unseren Begriff der physikalischen Realität revidieren. Eine Untersuchung des Begriffs der Separabilität und einige Überlegungen zum Problem der Messung von Observablen zeigen, daß eine Änderung des Begriffs der physikalischen Realität unumgänglich ist. Der revidierte Realitätsbegriff sollte mit klassischer Physik und Quantenmechanik verträglich sein, um ein einheitliches Weltbild zu ermöglichen.Translated AbstractDo Quantum Mechanics Force us to Drastically Change our View of the World? Thoughts and Experiments after Einstein, Podolsky and RosenSince the advent of quantum mechanics there have been attempts of its interpretation in terms of statistical theory concerning individual classical systems. The very conditions necessary to consider hidden variable theories describing these individual systems as classical had been pointed out by Einstein, Podolsky and Rosen in 1935: 1. Physical systems are in principle separable. 2. If it is possible to predict with certainty the value of a physical quantity without disturbing the system under consideration, then there exists an element of physical reality corresponding to this physical quantity.
Together they are, as was shown by Bell in 1964, incompatible in principle with quantum mechanics and no more tenable in view of recent experiments. These experiments once more corroborate quantum theory. In order to understand their results we are forced either to drop the assumption of separability of physical systems (taken for self-evident in classical physics) or to change our concept of physical reality. After investigating the notion of separability and connecting the EPR-correlations to the measurement problem we, conclude that a change of the concept of physical reality is indispensable. The revised concept should be compatible with both classical and quantum physics in order to allow a uniform view of the physical world.
Humus balances are simple mathematical tools used by farmers for assessing the overall performance of their management in terms of soil organic matter changes. They are based on humus reproduction factors which themselves mainly depend on crop rotation, residue management, and amount and type of organic fertilization. Dynamic models, on the other hand, are typically complex and need more detailed input data and are designed to calculate the time course of soil carbon content. In both cases, thorough validation is needed to utilize their potential for estimating carbon stock changes. We compared the results of three humus balance methods SALCA-SQ (Neyroud 1997), VDLUFA method (VDLUFA 2004), Humod (Brock et al. 2008) and the RothC model with measured soil carbon stocks in a long-term experiment in Switzerland for the period 1977-2005 (Fliessbach et al 2007). The field trial comprises various minerally and organically fertilized treatments, the latter differing in the amount and composition of organics applied. All methods were able to distinguish systematic management effects on soil organic carbon (SOC). However, only those SOC trajectories calculated with the dynamic model RothC matched measured stocks quantitatively. For both, humus balances and dynamic modelling the result strongly depended on parameterization of organic fertilizers, i.e. its stability and organic matter content. Therefore, incomplete information on the amount and composition of organic fertilizer and lack of knowledge about its potential for humus reproduction is regarded an uncertainty in both dynamic modelling and humus balance calculation, and seems to be a major drawback for the reliable application of these approaches at the regional scale. Our results stress the need for more detailed and harmonized data bases of organic fertilizer composition and application rates. References Brock C., Hoyer U., Leithold G., Hülsbergen K.-J., 2008. Entwicklung einer praxisanwendbaren Methode der Humusbilanzierung im ökologischen Landbau. Abschlussbericht zum Projekt 03OE084, http://forschung.oekolandbau.de unter der BÖL-Bericht-ID 16447,184 pp. Fliessbach A, Oberholzer H.-R., Gunst L., Mäder P., 2007. Soil organic matter and biological soil quality indicators after 21 years of organic and conventional farming. Agriculture, Ecosystems and Environment 118, 273-284. Leifeld J., Reiser R., Oberholzer H.-R., 2009. Consequences of conventional vs. organic farming on soil carbon: Results from a 27-year field experiment. Agronomy Journal 101, 1204-1218. Neyroud J.-A., 1997. La part du sol dans la production intégrée 1. Gestion de la matière organique et bilan humique. Revue suisse d'agriculture, 29, 45-51. VDLUFA, 2004. VDLUFA-Standpunkt: Humusbilanzierung - Methode zur Beurteilung und Bemessung der Humusversorgung von Ackerland. Verband Deutscher Landwirtschaftlicher Untersuchungs- und Forschungsanstalten, Selbstverlag.
In Austria an index of 3 μg/kg of Ochratoxin A for coffee, 0,3 μg/kg for fruit juices and 0,2 μg/kg for beer is discussed. The laboratory of the food inspection authority of the state of Vorarlberg investigated the contribution of selected foodstuffs to the daily OTA intake and compared it with the recommendation of the scientific food committee of the EC. The focal point of this study was on beverages (coffee, coffee substitutes, beer and fruit juices) and their ingredients.ZUSAMMENFASSUNG: Die Untersuchungsergebnisse von Bier, Fruchtsaft und Kaffee [Diagramm 1] zeigen, dass die Mehrzahl der Proben nur sehr schwach bis gar nicht belastet waren. Die OTA-Belastung lag bei der Mehrzahl der Proben unter der Nachweisgrenze von 0,3 μg/kg bzw. 0,01μg/1. Einzelne Proben waren aber erheblich belastet, sodass bei starkem Konsum (Fruchtsaft im Sommer) eine überschreitung der vom SCF vorgeschlagenen Höchstmenge nicht auszuschließen ist. Die Ergebnisse der Kaffeemitteluntersuchung [Diagramm 2] belegen eine höhere OTA-Belastung bei mehr als der Hälfte der Proben. Wenn die vom SCF vorgeschlagene Höchstaufnahme von 5 ng pro Tag und kg Körpergewicht zu Grunde gelegt wird, resultiert für eine 60 kg schwere Person ein Wert von 0,3 μg/Tag. Das bedeutet bei einem mit 100 μg/kg OTA kontaminierten Kaffeeersatz und dem Konsum nur einer Tasse (5 - 7 g Pulver), dass alleine aus dieser Quelle diese Höchstaufnahme deutlich überschritten wird. Der Eintrag über die restliche Nahrung wie Cerealien, die für etwa die Hälfte der OTA-Aufnahme verantwortlich sind, bleibt hier unberücksichtigt. Die Untersuchungen belegen, dass die Einhaltung der in österreich vorgeschlagenen Richtwerte bei Bier, Fruchtsäften und Kaffee keine Schwierigkeiten bereitet. Für Kaffeemittel und andere Trockenfrüchte als Weintrauben [3] wurde allerdings noch kein Richtwert vorgeschlagen. Die Ergebnisse belegen aber, dass gerade für Kaffemittel und verschiedene Trockenfrüchte vor dem Hintergrund fehlender Höchstwerte ein Richtwert in der Größenordnung von 3 μg/kg bzw. 10 μg/kg hilfreich wäre, bis die Festlegung der gemeinschaftsrechtlicher Höchstgehalte erfolgt. Mit Hinblick auf die in der Einleitung beschriebene toxische Wirkung von OTA ist es im Sinne eines vorbeugenden Verbraucherschutzes wichtig, diese hochbelasteten Chargen zu erkennen und aus dem Verkehr zu nehmen. Ursache für die OTA-Kontamination ist vor allem eine mangelhafte Produktionshygiene in den Erzeugerländern. Dort liegt auch das größte Potential für eine Verringerung der OTA-Belastung. Die überprüfung der Lebensmittel auf Ochratoxin A durch die amtliche Lebensmittelkontrolle ist ein notwendiger Beitrag zum Schutz der öffentlichen Gesundheit und zur weiteren Reduktion der Aufnahme.
Lenz, David E; Yeung, David; Smith, J Richard; Sweeney, Richard E; Lumley, Lucille A; Cerasoli, Douglas M
2007-04-20
Currently fielded treatments for nerve agent intoxication promote survival, but do not afford complete protection against either nerve agent-induced motor and cognitive deficits or neuronal pathology. The use of human plasma-derived butyrylcholinesterase (HuBuChE) to neutralize the toxic effects of nerve agents in vivo has been shown to both aid survival and protect against decreased cognitive function after nerve agent exposure. Recently, a commercially produced recombinant form of human butyrylcholinesterase (r-HuBuChE; PharmAthene Inc.) expressed in the milk of transgenic goats has become available. This material is biochemically similar to plasma-derived HuBuChE in in vitro assays. The pharmacokinetic characteristics of a polyethylene glycol coated (pegylated) form of r-HuBuChE were determined in guinea pigs; the enzyme was rapidly bioavailable with a half-life (t(1/2)) and pharmacokinetic profile that resembled that of plasma-derived huBuChE. Guinea pigs were injected with 140mg/kg (i.m.) of pegylated r-HuBuChE 18h prior to exposure (sc) to 5.5xLD(50) VX or soman. VX and soman were administered in a series of three injections of 1.5xLD(50), 2.0xLD(50), and 2.0xLD(50), respectively, with injections separated by 2h. Pretreatment with pegylated r-HuBuChE provided 100% survival against multiple lethal doses of VX and soman. Guinea pigs displayed no signs of nerve agent toxicity following exposure. Assessments of motor activity, coordination, and acquisition of spatial memory were performed for 2 weeks following nerve agent exposure. There were no measurable decreases in motor or cognitive function during this period. In contrast, animals receiving 1.5xLD(50) challenges of soman or VX and treated with standard atropine, 2-PAM, and diazepam therapy showed 50 and 100% survival, respectively, but exhibited marked decrements in motor function and, in the case of GD, impaired spatial memory acquisition. The advances in this field have resulted in the decision to select both the plasma-derived and the recombinant form of BuChE for advanced development and transition to clinical trials. Efforts have now been expanded to identify a catalytic protein capable of not only binding, but also rapidly hydrolyzing the standard threat nerve agents. Recent work has focused on paraoxonase-1 (PON1), a naturally occurring human serum enzyme with the capacity to catalyze the hydrolysis of nerve agents, albeit too slowly to afford dramatic protection. Using rational design, several amino acids involved in substrate binding have been identified and site-directed mutations have revealed that residue H115 plays an important role in binding. In addition, the stereospecificity of PON1 for the catalytic hydrolysis of soman has been examined. The enzyme exhibits a slight stereospecificity for the C+P+ isomer of soman, which is due more to preferential binding than to selective hydrolysis of this isomer. The results suggest that it may be possible to engineer a mutant form of PON1 with enhanced activity and stereospecificity for the most toxic nerve agent isoforms.
A critical re-examination of the history of the concepts of space (including spacetime of general relativity and relativistic quantum field theory) reveals a basic ontological elusiveness of spatial extension, while, at the same time, highlighting the fact that its epistemic primacy seems to be unavoidably imposed on us (as stated by A.Einstein "giving up the extensional continuum … is like to breathe in airless space"). On the other hand, Planck's discovery of the atomization of action leads to the fundamental recognition of an ontology of non-spatial, abstract entities (Quine) for the quantum level of reality (QT), as distinguished from the necessarily spatio-temporal, experimental revelations ( measurements). The elementary quantum act (measured by Planck's constant) has neither duration nor extension, and any genuinely quantum process literally does not belong in the Raum and time of our experience. As Heisenberg stresses: "Während also die klassische Physik ein objectives Geschehen in Raum and Zeit zum Gegenstand hat, für dessen Existenz seine Beobachtung völlig irrelevant war, behandelt die Quantentheorie Vorgänge, die sozusagen nur in den Momenten der Beobachtung als raumzeitliche Phänomene aufleuchten, und über die in der zwischenzeit anschaulische physikalische Aussagen sinloss sind". An admittedly speculative, hazardous conjecture is then advanced concerning the relation of such quantum ontology with the role of the pre-phenomenal continuum (Husserl) in the perception of macroscopically distinguishable objects in the Raum and time of our experience. Although rather venturesome, it brings together important philosophical issues. Coherently with recent general results in works on the foundations of QT, it is assumed that the linearity of quantum dynamical evolution does not apply to the central nervous system of living beings at a certain level of the evolutionary ramification and at the pre-conscious stage of subjectivity. Accordingly, corresponding to the onset of a non-linear dynamic evolution, a `primary spatial' reduction is `continually' taking place, thereby constituting the neural precondition for the experience of distinguishable macroscopic objects in the continuous spatial extension. While preventing the theoretically possible quantum superpositions of macroscopic objects from being perceivable by living beings, the `primary reduction' has no effect on the standard processes concerning quantum level entities involved in laboratory man-made experiments. In this connection, an experimental check which might falsify the conjecture is briefly discussed. The approach suggested here, if sound, leads to a naturalization of that part of Kant's Transcendental Aesthetics than can survive the Euclidean catastrophe. According to such naturalized transcendentalism, "space can well be transcendental without the axioms being so", in agreement with a well-known statement by Boltzman. Finally, as far as QT is concerned, the conjecture entails that a scheme for quantum measurement of the von Neumann type cannot even `leave the ground', vindicating Bohr's viewpoint. A quantum theory of measurement, in a proper sense, turns out to be unnecessary and in fact impossible.
Development of miniaturized separation and detection media represents one of the major challenges in the field of modern analytical chemistry dedicated to space exploration. To date, gas chromatography-mass spectrometry has been selected as the method of choice for exobiology flight experiments for seeking for organic molecules and especially potential chemical indicators of life. [1] Liquid phase separation methods have also been developed with for instance, the so-called Mars Organic Analyzer (MOA) capillary electrophoresis (CE) microchip.[2] Although CE offers the advantages of easy miniaturization and high separation efficiency it suffers from a lack of selectivity towards a broad range of analytes with varied chemical nature. In this respect, we propose the use of capillary columns filled with monolithic stationary phases for the electrochromatographic separation of organic molecules of exobiology interest. Polymer monoliths have attracted a great deal of interest in analytical science over the last years as (electro)chromatographic stationary phases [3], immunosensors [4]. Beyond the intrinsic properties of monolithic polymers, i.e. fast mass transport between the monolithic support and the surrounding fluid and high permeability, other major advantages are their easy in situ preparation and tuning of surface functionality. Indeed, monoliths can be simply prepared through free radical copolymerization of a homogeneous mixture made of monomers, cross-linkers, porogenic solvents and initiator. UV-initiation process has been exploited to the synthesis of a discrete section of monolith as a flow-through active element within the confines of micro channels [5,6] while two-step strategies have been reported for the design of varied adsorbent starting with a generic monolith [7,8]. Although a nearly limitless range of monolithic supports can be prepared by this traditional method, the resulting monoliths exhibit unique function. In this contribution, we describe an elegant strategy for preparing multifunctional monoliths through spatially controlled surface functionalization.[9] Photochemical initiation affords spatial control over the reaction site, i.e. site-specific immobilization of ligands on the pore surface of the monolith. Hydrophobic and hydrophilic molecular entities were successfully grafted and the obtained monoliths were applied to electrochromatographic separation application under reversed-phase and hydrophilic interaction electrochromatography modes, respectively. The panel of successfully analyzed analytes ranges from hydrophobic polycyclic aromatic hydrocarbons to life markers such as amino acids and peptides. Our approach was extended to the local design of chelating interface for the site-specific immobilisation of gold nanoparticles. Taking advantage of the unique properties of supported nano-gold, it was possible to perform surface enhanced Raman spectroscopy (SERS) sensing of organic molecules at the sub-nanomolar level. This work is funded by the French Space Agency (CNES) References [1] M.C. Pietrogrande, M.G. Zampolli, F. Dondi, C. Szopa, R. Sternberg, A. Buch, J.F. Raulin, J. Chromatogr. A 1071 (2005) 255. [2] A. M. Stockton, T.M. Chiesl, J.M. Scherer, R. A. Mathies, Anal. Chem. 81 (2009) 790 [3] B. Carbonnier, M. Guerrouache, R. Denoyel, M. C. Millot, J. Sep. Sci. 30 (2007) 3000. [4] J.k. Liu, C.F. Chen, C.W. Chang, D.L. DeVoe, Biosensors Bioelectron. 26 (2010) 182. [5] J. Krenkova, F. Svec, J. Sep. Sci. 32 (2009) 706. [6] F. Svec, J. Chromatogr. B 841 (2004) 52 [7] M. Guerrouache, M. C. Millot, B. Carbonnier, Macromol. Rapid. Commun, 30 (2009) 109. [8] M. Guerrouache, B. Carbonnier, C. Vidal-Madjar, M.C. Millot, J. Chromatogr A, 1149 (2007) 368. [9] M. Guerrouache, S. Mahouche Chergui, M.M. Chehimi, B. Carbonnier. Chem. Commun. 48 (2012) 7486.
Im Rahmen dieser Arbeit gelang es, katalytische Antikörper zur Hydrolyse von Benzylphenylcarbamaten sowie zahlreiche monoklonale Antikörper gegen Haptene herzustellen. Es wurden verschiedene Hapten-Protein-Konjugate unter Verwendung unterschiedlicher Kopplungsmethoden hergestellt und charakterisiert. Zur Generierung der hydrolytisch aktiven Antikörper wurden Inzuchtmäuse mit KLH-Konjugaten von 4 Übergangszustandsanaloga (ÜZA) immunisiert. Mit Hilfe der Hybridomtechnik wurden verschiedene monoklonale Antikörper gegen diese ÜZA gewonnen. Dabei wurden sowohl verschiedene Immunisierungsschemata als auch verschiedene Inzuchtmausstämme und Fusionstechniken verwendet. Insgesamt wurden 32 monoklonale Antikörper gegen die verwendeten ÜZA selektiert. Diese Antikörper wurden in groen Mengen hergestellt und gereinigt. Zum Nachweis der Antikörper-vermittelten Katalyse wurden verschiedene Methoden entwickelt und eingesetzt, darunter immunologische Nachweismethoden mit Anti-Substrat- und Anti-Produkt-Antikörpern und eine photometrische Methode mit Dimethylaminozimtaldehyd. Der Nachweis der hydrolytischen Aktivität gelang mit Hilfe eines Enzymsensors, basierend auf immobilisierter Tyrosinase. Die Antikörper N1-BC1-D11, N1-FA7-C4, N1-FA7-D12 und R3-LG2-F9 hydrolysierten die Benzylphenylcarbamate POCc18, POCc19 und Substanz 27. Der Nachweis der hydrolytischen Aktivität dieser Antikörper gelang auch mit Hilfe der HPLC. Der katalytische Antikörper N1-BC1-D11 wurde kinetisch und thermodynamisch untersucht. Es wurde eine Michaelis-Menten-Kinetik mit Km von 210 µM, vmax von 3 mM/min und kcat von 222 min-1 beobachtet. Diese Werte korrelieren mit den Werten der wenigen bekannten Diphenylcarbamat-spaltenden Abzyme. Die Beschleunigungsrate des Antikörpers N1-BC1-D11 betrug 10. Das ÜZA Hei3 hemmte die hydrolytische Aktivität. Dies beweist, dass die Hydrolyse in der Antigenbindungsstelle stattfindet. Weiter wurde zwischen der Antikörperkonzentration und der Umsatzgeschwindigkeit eine lineare Abhängigkeit festgestellt. Die thermodynamische Gleichtgewichtsdissoziationskonstante KD des Abzyms von 2,6 nM zeugt von einer sehr guten Affinität zum ÜZA. Hydrolytisch aktiv waren nur Antikörper, die gegen das Übergangszustandsanalogon Hei3 hergestellt worden waren. Es wird vermutet, dass die Hydrolyse der Benzylphenylcarbamate über einen Additions-Eliminierungsmechanismus unter Ausbildung eines tetraedrischen Übergangszustandes verläuft, dessen analoge Verbindung Hei3 ist. Im Rahmen der Generierung von Nachweisantikörpern zur Detektion der Substratabnahme bei der Hydrolyse wurden Anti-Diuron-Antikörper hergestellt. Einer der Antikörper (B91-CG5) ist spezifisch für das Herbizid Diuron und hat einen IC50-Wert von 0,19 µg/l und eine untere Nachweisgrenze von 0,04 µg/l. Ein anderer Antikörper (B91-KF5) reagiert kreuz mit einer Palette ähnlicher Herbizide. Mit diesen Antikörpern wurde ein empfindlicher Labortest, der ein Monitoring von Diuron auf Grundlage des durch die Trinkwasserverordnung festgeschriebenen Wertes für Pflanzenschutzmittel von 0,1 µg/l erlaubt, aufgebaut. Der Effekt der Anti-Diuron-Antikörper auf die Diuron-inhibierte Photosynthese wurde in vitro und in vivo untersucht. Es wurde nachgewiesen, dass sowohl in isolierten Thylakoiden, als auch in intakten Algen eine Vorinkubation der Anti-Diuron-Antikörper mit Diuron zur Inaktivierung seiner Photosynthese-hemmenden Wirkung führt. Wurde der Elektronentransport in den isolierten Thylakoiden oder in Algen durch Diuron unterbrochen, so führte die Zugabe der Anti-Diuron-Antikörper zur Reaktivierung der Elektronenübertragung. Attempts to produce catalytic antibodies for hydrolysis of arylcarbamates and arylureas: The aim of the investigations was to produce antibodies which are able to cleave herbicides resistant to naturally occuring enzymes. Structurally similar carbamate and urea derivatives were chosen for the experiments. Phosphonate derivatives were synthesized that mimick possible transition state analogues in structure and charge. Mice were immunized with 4 different derivatives after conjugating them to carrier proteins. 32 hybridomas were established that produce monoclonal antibodies binding to these derivatives. The possible cleavage of substrates was determined by immunoassays with monoclonal antibodies against the substrate and the products and with a photometric method based on dimethylaminocinammonaldehyde. The measuring of cleavage products was succeeded by an amperometric method. The enzyme sensor was based on immobilized tyrosinase which oxidizes p-chlorophenol and phenol. The antibodies N1-BC1-D11, N1-FA7-C4, N1-FA7-D12 und R3-LG2-F9 hydrolysed the benzylphenylcarbamates POCc18, POCc19 und Substance 27. The hydrolytic activity of these antibodies was also succeeded with HPLC. The catalytic antibody N1-BC1-D11 was investigated kinetically and thermodynamically. A Michaelis-Menten-Kinetic was observed (at pH 8.0 exhibited a Km 210 µM, a vmax 3 mM/min and a kcat 222 min-1). These values are in the range of the values obtained for the antibody-catalysed hydrolysis of diphenylcarbamates. The rate enhancement of N1-BC1 was 10. The reaction was completely inhibited by stoichiometric quantities of the transition state analogue Hei3. This is consistent with the affinity of the abzyme to Hei3 of 2.6 nM, determined by BIAcore assay. Only antibodies generated against Hei3 showed hydrolytic activity. The hydrolysis of benzylphenylcarbamates presumably occurs via an addition-elimination-Mechanism involving a tetrahedral intermediate. In summary, this work presents the first example of antibody-catalysed hydrolysis of benzylphenylcarbamates. Monoclonal anti-diuron antibodies were generated that bind to the herbicide diuron with an extremely low equilibrium dissociation constant. A sensitive immunoassay with a low detection limit of 0.2 nM for diuron was established. This is the most sensitive immunological method for detection of diuron known so far. These antibodies were also used in vitro and in vivo to prevent diuron-dependent inhibition of photosynthesis or to restore photosynthesis after inhibition. In isolated thylakoids prepared from spinach leaves (Spinacia oleracea L.) the diuron-inhibited Hill reaction was reconstituted immediately following the addition of the monoclonal antibodies. In an in vivo approach the photosynthetic oxygen evolution of the cell wall deficient mutant (cw 15) of the green alga Chlamydomonas reinhardtii Dangeard was monitored. The antibodies prevented the diuron-dependent inhibition of photosynthesis and restored photosynthesis after inhibition. Transgenic plants that synthesize and accumulate these antibodies or antibody fragments and are therefore diuron-resistant can be created.
In many cases, composition and characteristics of hillslope sediments are of particular importance related to landslide research in low mountain areas. The interaction of geologic, geomorphologic, and hydrologic factors determines the susceptibility for mass movements, which is affected by human impact as well. The present study aims to investigate factors that control mass movements and natural and anthropogenic impacts. On March 8th 2009, a landslide of 30.000 to 50.000 m³ occurred that destroyed a large part of a sports ground in the village of Hintersdorf, municipality of St. Andrä-Wördern (Lower Austria). As a result of extensive water supply ground liquefaction was initiated and the slide mass moved in form of a mud flow about 200 m down slope. As a consequence a small forest area and a fishpond were destroyed and an adjacent road was damaged. Closely to the event, first studies started and showed that the Hintersdorf landslide was triggered by extensive water saturation combined with hydrostatic pressure inside the slide mass. Heavy and long-lasting rainfalls and the start of snowmelt caused strong seepage and soil water saturation. Furthermore, insufficient ground drainage and overflow of a small retention pond intensified the unfavourable impact on soil-mechanical stability. Further studies included archive data analyse, field survey, as well as laboratory analyse and showed that high landslide susceptibility at the Hintersdorf landslide site was caused by a bundle of factors that control the process: The sports ground was built nearby the head of a trough valley that collects interflow and surface run-off from the surrounding slopes. The Flysch bedrock is covered extensively by clayey slope deposits. Furthermore, in the area of the valley head a waste deposit was operated up to the 1980's that resulted in a thick waste filling there. The Hintersdorf sports ground was constructed in 1984 on top of the waste body. Preliminary results show that hillslope sediments and soils in the landslide area are almost impermeable due to their high amount of clay. On the one hand, they are able to seal the floor and to prevent the penetration of polluted water. On the other hand they provide a slide plane for mass movements. In contrast, the comparably low consolidated waste body forms a water reservoir. Due to technical operation, for example the deposition and mechanical compaction of soil material in context with the construction of the Hintersdorf sports ground, the waste body was partly sealed. To outline the result it can be stated that the unfavourable meteorological conditions during the first days of March 2009 caused an increased water pressure in the waste body, which triggered the landslide with damages to forest and infrastructure in Hintersdorf. References Damm, B., Terhorst, B., 2009. A model of slope formation related to landslide activity in the Eastern Prealps, Austria. Geomorphology, doi:10.1016/j.geomorph.2009.11.001. Damm, B., Terhorst, B., Köttritsch, E., Ottner, F., Mayrhofer, M., 2008. Zum Einfluss bodenphysikalischer und bodenmechanischer Parameter in quartären Deckschichten auf Massenbewegungen im Wienerwald. Abh. Geol. B.-A. 62: 33-37. Terhorst, B., Damm, B., Peticzka, R., Köttritsch, E., 2009. Reconstruction of Quaternary landscape formation as a tool to understand present geomorphological processes in the Eastern Prealps (Austria). Quaternary International, 209: 66-78.
In Germany more than 99 % of fens have lost their carbon and nutrient sink function due to heavy drainage and agricultural land use especially during the last decades and thus resulted in compression and heavy peat loss (CHARMAN 2002; JOOSTEN & CLARKE 2002; SUCCOW & JOOSTEN 2001; AUGUSTIN et al. 1996; KUNTZE 1993). Therefore fen peatlands play an important part (4-5 %) in the national anthropogenic trace gas budget. But only a small part of drained and agricultural used fens in NE Germany can be restored. Knowledge of the influence of land use to trace gas exchange is important for mitigation of the climate impact of the anthropogenic peatland use. We study carbon exchanges between soil and atmosphere on several fen peatland use areas at different sites in NE-Germany. Our research covers peatlands of supposed strongly climate forcing land use (cornfield and intensive pasture) and of probably less forcing, alternative types (meadow and extensive pasture) as well as rewetted (formerly drained) areas and near-natural sites like a low-degraded fen and a wetted alder woodland. We measured trace gas fluxes with manual and automatic chambers in periodic routines since spring 2007. The used chamber technique bases on DROESLER (2005). In total we now do research at 22 sites situated in 5 different locations covering agricultural, varying states of rewetted and near-natural treatments. We present results of at least 2 years of measurements on our site of varying types of agricultural land use. There we found significant differences in the annual carbon balances depending on the genesis of the observed sites and the seasonal dynamics. Annual balances were constructed by applying single respiration and photosynthesis CO2 models for each measurement campaign. These models were based on LLOYD-TAYLOR (1994) and Michaelis-Menten-Kinetics respectively. Crosswise comparison of different site treatments combined with the seasonal environmental observations give good hints for the identification of main flux driving parameters. Based on this procedure we developed a specific methane efflux model, mainly driven by the observed groundwater fluctuation and soil temperature. Depending on the observed timescale initial starting points of the model showed up to be remarkably different. We also will present suggestions for an advanced CO2 modelling as the present approaches are both based on single parameters. Generally our experiences from our field studies show that mono-parameterized models often fail in reproducing measured flux values. References: Augustin, J., Merbach, W., Käding, H., Schnidt, W. & Schalitz, G. 1996. Lachgas- und Methanemissionen aus degradierten Niedermoorstandorten Nordostdeutschlands unter dem Einfluß unterschiedlicher Bewirtschaftung. Alfed-Wegener-Stiftung (ed.): Von den Ressourcen zum Recycling: Geoanalytik-Geomanagement-Geoinformatik. Ernst & Sohn Verlag. Berlin Charman, D. 2002: Peatland and environmental change. John Wiley & Sons, LTD, Chichester Droesler, M. 2005. Trace Gas Exchange and climatic relevance of bog ecosystems, Southern Germany, phD-thesis, TU München, München Joosten, H. & Clarke, D. 2002: Wise use of mires and peatlands-background and principles including a framework for decision-making. International Mire Conservation Group and International Peat Society (eds.), Finland Kuntze 1993: Moore als Senken und Quellen für C und N, Mitt. Deutsche Bodenkundliche Gesellschaft 69, 277-280 Lloyd, J., Taylor, J. A. 1994. On the Temperature Dependence of Soil Respiration, Functional Ecology, Vol. 8, No. 3, pp. 315-323 Succow, M. & Joosten, H. 2001: Landschaftsökologische Moorkunde, 2nd edition, Schweizerbart'sche Verlagsbuchhandlung, Stuttgart
The STS-29 Space Shuttle Discovery mission lands at NASA's then Ames-Dryden Flight Research Facility, Edwards AFB, California, early Saturday morning, 18 March 1989. Touchdown was at 6:35:49 a.m. PST and wheel stop was at 6:36:40 a.m. on runway 22. Controllers chose the concrete runway for the landing in order to make tests of braking and nosewheel steering. The STS-29 mission was very successful, completing the launch of a Tracking and Data Relay communications satellite, as well as a range of scientific experiments. Discovery's five-man crew was led by Commander Michael L. Coats, and included pilot John E. Blaha and mission specialists James P. Bagian, Robert C. Springer, and James F. Buchli. Space Shuttles are the main element of America's Space Transportation System and are used for space research and other space applications. The shuttles are the first vehicles capable of being launched into space and returning to Earth on a routine basis. Space Shuttles are used as orbiting laboratories in which scientists and mission specialists conduct a wide variety of scientific experiments. Crews aboard shuttles place satellites in orbit, rendezvous with satellites to carry out repair missions and return them to space, and retrieve satellites and return them to Earth for refurbishment and reuse. Space Shuttles are true aerospace vehicles. They leave Earth and its atmosphere under rocket power provided by three liquid-propellant main engines with two solid-propellant boosters attached plus an external liquid-fuel tank. After their orbital missions, they streak back through the atmosphere and land like airplanes. The returning shuttles, however, land like gliders, without power and on runways. Other rockets can place heavy payloads into orbit, but, they can only be used once. Space Shuttles are designed to be continually reused. When Space Shuttles are used to transport complete scientific laboratories into space, the laboratories remain inside the payload bay throughout the mission. They are then removed after the Space Shuttle returns to Earth and can be reused on future flights. Some of these orbital laboratories, like the Spacelab, provide facilities for several specialists to conduct experiments in such fields as medicine, astronomy, and materials manufacturing. Some types of satellites deployed by Space Shuttles include those involved in environmental and resources protection, astronomy, weather forecasting, navigation, oceanographic studies, and other scientific fields. The Space Shuttles can also launch spacecraft into orbits higher than the Shuttle's altitude limit through the use of Inertial Upper Stage (IUS) propulsion units. After release from the Space Shuttle payload bay, the IUS is ignited to carry the spacecraft into deep space. The Space Shuttles are also being used to carry elements of the International Space Station into space where they are assembled in orbit. The Space Shuttles were built by Rockwell International's Space Transportation Systems Division, Downey, California. Rockwell's Rocketdyne Division (now part of Boeing) builds the three main engines, and Thiokol, Brigham City, Utah, makes the solid rocket booster motors. Martin Marietta Corporation (now Lockheed Martin), New Orleans, Louisiana, makes the external tanks. Each orbiter (Space Shuttle) is 121 feet long, has a wingspan of 78 feet, and a height of 57 feet. The Space Shuttle is approximately the size of a DC-9 commercial airliner and can carry a payload of 65,000 pounds into orbit. The payload bay is 60 feet long and 15 feet in diameter. Each main engine is capable of producing a sea level thrust of 375,000 pounds and a vacuum (orbital) thrust of 470,000 pounds. The engines burn a mixture of liquid oxygen and liquid hydrogen. In orbit, the Space Shuttles circle the earth at a speed of 17,500 miles per hour with each orbit taking about 90 minutes. A Space Shuttle crew sees a sunrise or sunset every 45 minutes. When Space Shuttle flights began in April 1981, Dryden Flight Research Center, Edwards, California, was the primary landing site for the Shuttles. Now Kennedy Space Center, Florida, is the primary landing site with Dryden remaining as the principal alternate landing site.
The STS-29 Space Shuttle Discovery mission approaches for a landing at NASA's then Ames-Dryden Flight Research Facility, Edwards AFB, California, early Saturday morning, 18 March 1989. Touchdown was at 6:35:49 a.m. PST and wheel stop was at 6:36:40 a.m. on runway 22. Controllers chose the concrete runway for the landing in order to make tests of braking and nosewheel steering. The STS-29 mission was very successful, completing the launch a Tracking and Data Relay communications satellite, as well as a range of scientific experiments. Discovery's five man crew was led by Commander Michael L. Coats, and included pilot John E. Blaha and mission specialists James P. Bagian, Robert C. Springer, and James F. Buchli. Space Shuttles are the main element of America's Space Transportation System and are used for space research and other space applications. The shuttles are the first vehicles capable of being launched into space and returning to Earth on a routine basis. Space Shuttles are used as orbiting laboratories in which scientists and mission specialists conduct a wide variety of scientific experiments. Crews aboard shuttles place satellites in orbit, rendezvous with satellites to carry out repair missions and return them to space, and retrieve satellites and return them to Earth for refurbishment and reuse. Space Shuttles are true aerospace vehicles. They leave Earth and its atmosphere under rocket power provided by three liquid-propellant main engines with two solid-propellant boosters attached plus an external liquid-fuel tank. After their orbital missions, they streak back through the atmosphere and land like airplanes. The returning shuttles, however, land like gliders, without power and on runways. Other rockets can place heavy payloads into orbit, but, they can only be used once. Space Shuttles are designed to be continually reused. When Space Shuttles are used to transport complete scientific laboratories into space, the laboratories remain inside the payload bay throughout the mission. They are then removed after the Space Shuttle returns to Earth and can be reused on future flights. Some of these orbital laboratories, like the Spacelab, provide facilities for several specialists to conduct experiments in such fields as medicine, astronomy, and materials manufacturing. Some types of satellites deployed by Space Shuttles include those involved in environmental and resources protection, astronomy, weather forecasting, navigation, oceanographic studies, and other scientific fields. The Space Shuttles can also launch spacecraft into orbits higher than the Shuttle's altitude limit through the use of Inertial Upper Stage (IUS) propulsion units. After release from the Space Shuttle payload bay, the IUS is ignited to carry the spacecraft into deep space. The Space Shuttles are also being used to carry elements of the International Space Station into space where they are assembled in orbit. The Space Shuttles were built by Rockwell International's Space Transportation Systems Division, Downey, California. Rockwell's Rocketdyne Division (now part of Boeing) builds the three main engines, and Thiokol, Brigham City, Utah, makes the solid rocket booster motors. Martin Marietta Corporation (now Lockheed Martin), New Orleans, Louisiana, makes the external tanks. Each orbiter (Space Shuttle) is 121 feet long, has a wingspan of 78 feet, and a height of 57 feet. The Space Shuttle is approximately the size of a DC-9 commercial airliner and can carry a payload of 65,000 pounds into orbit. The payload bay is 60 feet long and 15 feet in diameter. Each main engine is capable of producing a sea level thrust of 375,000 pounds and a vacuum (orbital) thrust of 470,000 pounds. The engines burn a mixture of liquid oxygen and liquid hydrogen. In orbit, the Space Shuttles circle the earth at a speed of 17,500 miles per hour with each orbit taking about 90 minutes. A Space Shuttle crew sees a sunrise or sunset every 45 minutes. When Space Shuttle flights began in April 1981, Dryden Flight Research Center, Edwards, California, was the primary landing site for the Shuttles. Now Kennedy Space Center, Florida, is the primary landing site with Dryden remaining as the principal alternate landing site.
Near the village of Ófalu, in the Geresd Hills, South Hungary, within the "Mecsekalja tectonic belt", low and intermediate grade paleozoic metamorphic complex (phyllite, gneiss) contains vein-like hematitic carbonate beds, up to 30 cm in thickness. The carbonate mineral is calcite. These hematitic carbonate beds cross-cut the foliation of the phyllite, and show no signs of any metamorphic alteration. In the studied section the red carbonate beds are associated with a vein system filled with multiple generations of vein carbonates(Dabi et al., 2011). The red carbonate beds contain a vaste number of twisted stalks of the iron oxidizing taxon of Gallionella. Rarely in some siliceous parts, Leptothrix-like microbial fossils can be found and these beds also contain numerous unidentifiable, hematitic foraminifers. According to ICP-AES measurements, the hematitic carbonate beds contains 8 % Fe, 0.86 % Mn and 0.12 % Ba. XRD and Raman measurements proved that the iron phase is hematite. The SEM observations revealed that the bacterial microfossils and foraminifers are built up of micron-submicron sized pseudohexagonal platy hematite. The bacterial microfossils of the Gallionella iron oxidizer are very well preserved and reaches about 80 µm length and about 2-3 µm width. The above observations raise the following issues: 1. how did these non metamorphic hematitic-carbonatic beds get inside into the metamorphic complex?, 2. what is the age of the formation of these beds?, and 3. what was the source of the iron? If we consider that the hematitic beds contain foraminifers and iron oxidizing bacteria, and no signs of metamorphic alteration nor foliations can be observed in these beds, the only answer for the first question is that the formations are fractures filled with lime-mud, i.e. neptunian dykes, which penetrated into the cracks of the phyllite. The presence of foraminifers and the geotectonic situation of the unit imply marine origin. Considering that these beds are neptunian dykes, their age must be younger than the paleozoic metamorphic event. They must be older than the Early Cretaceous dyke emplacement in the region, based on cross-cutting relation with limonite stained calcite veins, related to the volcanic activity (Dabi et al., 2011) In this region (Tisza-megaunit) continental rift-related alkali basaltic submarine volcanism was widespread during the Early Cretaceous epoch, when hypabyssal basaltic bodies (intrusive pillow basalts) intruded into unconsolidated sediments. Along these magmatic bodies low temperature hydrothermal circulation of seawater hydrolyzed basaltic glass and mafic minerals, and huge amount of Fe(II) was released and got into the lime mud that was saturated with anaerobic water, where iron oxidizing microorganisms thrived (Jáger et al., 2012).We propose a very similar paleoenvironmental model for Ófalu occurence, where low temperature, reductive iron-rich hydrothermal fluids penetrated soft sediments and contributed to the flourishing of iron-oxidizers. Due to subsequent tectonic events, these iron-rich sediments got into the fissures of the Ófalu metamorphic complex. This model is strenghtened by some borehole and outcrops where the Lower Cretaceous interpillow sediments and hyaloclastites rich in iron oxydes and intrusive pillow basalt can be found close to our investigated section. (Hetényi et al., 1976) This study was supported by the Developing Competitiveness of Universities in the South Transdanubian Region (SROP-4.2.1.B-10/2/KONV-2010-0002). Dabi, G., Siklósy, Z., Schubert, F., Bajnóczi, B., M. Tóth, T., 2011. The relevance of vein texture in understanding the past hydraulic behaviour of a crystalline rock mass: reconstruction of the palaeohydrology of the Mecsekalja Zone, South Hungary. Geofluids, 11, 309-327. Hetényi, R., Földi, M., Hámor, G., Nagy, I., Bilik, I., Jantsky, B. 1976. Magyarázó a Mecsek hegység földtani térképéhez 10 000-es sorozat. MÁFI Budapest (in hungarian). Jáger, V., Molnár, F., Buchs, D. & Koděra, P. 2012: The connection between iron ore formations and "mud-shrimp" colonizations around sunken wood debris and hydrothermal sediments in a Lower Cretaceous continental rift basin, Mecsek Mts., Hungary. — Earth-Science Reviews 114/3-4, 250-278.
In Germany more than 99 % of fens have lost their carbon and nutrient sink function due to heavy drainage and agricultural land use especially during the last decades and thus resulted in compression and heavy peat loss (CHARMAN 2002; JOOSTEN & CLARKE 2002; SUCCOW & JOOSTEN 2001; AUGUSTIN et al. 1996; KUNTZE 1993). Therefore fen peatlands play an important part (4-5 %) in the national anthropogenic trace gas budget. But only a small part of drained and agricultural used fens in NE Germany can be restored. Knowledge of the influence of land use to trace gas exchange is important for mitigation of the climate impact of the anthropogenic peatland use. We study carbon exchanges of several fen peatland use areas between soil and atmosphere at different sites in NE-Germany. Our research covers peatlands of supposed strongly climate forcing land use (cornfield and intensive pasture) and of probably less forcing, alternative types (meadow and extensive pasture) as well as rewetted (formerly drained) areas and near-natural sites like a low-degraded fen and a wetted alder woodland. We measured trace gas fluxes with manual and automatic chambers in periodic routines since spring 2007. The used chamber technique bases on DROESLER (2005). In total we now do research at 22 sites situated in 5 different locations covering agricultural, varying states of rewetted and near-natural treatments. We present results of at least 2 years of measurements and show significant differences in their annual trace gas balances depending on the genesis of the observed sites and the seasonal dynamics. Crosswise comparison of different site treatments combined with the seasonal environmental observations give good hints for the identification of main flux driving parameters. That is that a reduced intensity in land use as a supposed mitigating treatment did not show the expected effect, though a normal meadow treatment surprisingly resulted in the lowest balances in both years. For implementing a further trace gas flux model observations will proceed at least until the end of year 2011. Regarding restoration sites we present newly installed locations of observing especially methane fluxes. To assure our results (presented at last years EGU conference, GIEBELS et al. 2009) from our in 2005 rewetted site we started observations at sites with advanced states of rewetting and alternative management respectively. I.e. one alternative aim to mitigate the heavy methane efflux after rewetting is observed at a site with removed canopy. Other experiments are conducted by freshly reforested alders and reed grass. References: Augustin, J., Merbach, W., Käding, H., Schnidt, W. & Schalitz, G. 1996. Lachgas- und Methanemissionen aus degradierten Niedermoorstandorten Nordostdeutschlands unter dem Einfluß unterschiedlicher Bewirtschaftung. Alfed-Wegener-Stiftung (ed.): Von den Ressourcen zum Recycling: Geoanalytik-Geomanagement-Geoinformatik. Ernst & Sohn Verlag. Berlin Charman, D. 2002: Peatland and environmental change. John Wiley & Sons, LTD, Chichester Droesler, M. 2005. Trace Gas Exchange and climatic relevance of bog ecosystems, Southern Germany, phD-thesis, TU München, München Giebels, M., Augustin, J., Minke, M., Halle, E., Beyer, M., Ehrig, B., Leitholdt, E., Chojnicki, B., Juszczak, R., Serba, T. 2009. Anthropogenic impact on the carbon cycle of fen peatlands in NE-Germany, EGU General Assembly 2009 Joosten, H. & Clarke, D. 2002: Wise use of mires and peatlands-background and principles including a framework for decision-making. International Mire Conservation Group and International Peat Society (eds.), Finland Kuntze 1993: Moore als Senken und Quellen für C und N, Mitt. Deutsche Bodenkundliche Gesellschaft 69, 277-280 Succow, M. & Joosten, H. 2001: Landschaftsökologische Moorkunde, 2nd edition, Schweizerbart'sche Verlagsbuchhandlung, Stuttgart
In Germany more than 99 % of fens have lost their carbon and nutrient sink function due to heavy drainage and agricultural land use especially during the last decades and thus resulted in compression and heavy peat loss (CHARMAN 2002; JOOSTEN & CLARKE 2002; SUCCOW & JOOSTEN 2001; AUGUSTIN et al. 1996; KUNTZE 1993). Therefore fen peatlands play an important part (4-5 %) in the national anthropogenic trace gas budget. But only a small part of drained and agricultural used fens in NE Germany can be restored. Knowledge of the influence of land use to trace gas exchange is important for mitigation of the climate impact of the anthropogenic peatland use. We study carbon exchanges of several fen peatland use areas between soil and atmosphere at different sites in NE-Germany. Our research covers peatlands of supposed strongly climate forcing land use (cornfield and intensive pasture) and of probably less forcing, alternative types (meadow and extensive pasture) as well as rewetted (formerly drained) areas and near-natural sites like a low-degraded fen and a wetted alder woodland. We measured trace gas fluxes with manual and automatic chambers in periodic routines since spring 2007. The used chamber technique bases on DROESLER (2005). In total we now do research at 22 sites situated in 5 different locations covering agricultural, varying states of rewetted and near-natural treatments. We present results of at least 2 years of measurements and show significant differences in their annual carbon balances depending on the genesis of the observed sites and the seasonal dynamics. Crosswise comparison of different site treatments combined with the seasonal environmental observations give good hints for the identification of main flux driving parameters. That is that a reduced intensity in land use as a supposed mitigating treatment did not show the expected effect, though a normal meadow treatment surprisingly resulted in the lowest CO2 balances in both years. For implementing a further trace gas flux model observations will proceed at least until the end of year 2011. Regarding restoration sites we present newly installed locations of observing especially methane fluxes. To assure our results (presented at last years EGU conference, GIEBELS et al. 2009) from our in 2005 rewetted site we started observing carbon exchange at sites with advanced states of rewetting and alternative management respectively. I.e. one alternative aim to mitigate the heavy methane efflux after rewetting is observed at a site with removed canopy. Other experiments are conducted by freshly reforested alders and reed grass. References: Augustin, J., Merbach, W., Käding, H., Schnidt, W. & Schalitz, G. 1996. Lachgas- und Methanemissionen aus degradierten Niedermoorstandorten Nordostdeutschlands unter dem Einfluß unterschiedlicher Bewirtschaftung. Alfed-Wegener-Stiftung (ed.): Von den Ressourcen zum Recycling: Geoanalytik-Geomanagement-Geoinformatik. Ernst & Sohn Verlag. Berlin Charman, D. 2002: Peatland and environmental change. John Wiley & Sons, LTD, Chichester Droesler, M. 2005. Trace Gas Exchange and climatic relevance of bog ecosystems, Southern Germany, phD-thesis, TU München, München Giebels, M., Augustin, J., Minke, M., Halle, E., Beyer, M., Ehrig, B., Leitholdt, E., Chojnicki, B., Juszczak, R., Serba, T. 2009. Anthropogenic impact on the carbon cycle of fen peatlands in NE-Germany, EGU General Assembly 2009 Joosten, H. & Clarke, D. 2002: Wise use of mires and peatlands-background and principles including a framework for decision-making. International Mire Conservation Group and International Peat Society (eds.), Finland Kuntze 1993: Moore als Senken und Quellen für C und N, Mitt. Deutsche Bodenkundliche Gesellschaft 69, 277-280 Succow, M. & Joosten, H. 2001: Landschaftsökologische Moorkunde, 2nd edition, Schweizerbart'sche Verlagsbuchhandlung, Stuttgart
This study investigated the slope carbonates of two Miocene carbonate systems: the Maltese Islands (in the Central Mediterranean) and the Marion Plateau (Northeastern Australia, drilled during ODP Leg 194). The aim of the study was to trace the impact of the Miocene cooling steps (events Mi1-Mi6) in these carbonate systems, especially the Mi3 event, which took place around 13.6 Ma and deeply impacted the marine oxygen isotope record. This event also profoundly impacted oceanographic and climatic patterns, eventually leading to the establishment of the modern ice-house world. In particular, East Antarctica became ice covered at that period. The rational behind the present study was to investigate the impact that this event had on shallow water systems in order to complement the deep-sea record and hence acquire a more global perspective on Miocene climate change. The Maltese Islands were investigated for trends in bulk-rock carbon and oxygen isotopes, as well as bulk-rock mineralogy, clay minerals analysis and organic geochemisty. Results showed that the mid Miocene cooling event deeply impacted sedimentation at that location by changing sedimentation from carbonate to clay-rich sediments. Moreover, it was discovered that each phase of Antarctic glaciation, not just the major mid Miocene event, resulted in higher terrigenous input on Malta. Mass accumulation rates revealed that this was linked to increased runoff during periods when Antarctica was glaciated, and thus that the carbonate sediments were “diluted” by clay-rich sediments. The model subsequently developed to explain this implies feedback from Antarctic glaciations creating cold, dense air masses that push the ITCZ Northward, thus increasing precipitation on the North African subcontinent. Increased precipitation (or stronger African monsoon) accelerated continental weathering and runoff, thus bringing more terrigenous sediment to the paleo-location of the slope sediments of Malta. Spectral analysis of carbonate content and organic matter geochemical analysis furthermore suggest that the clay-rich intervals are similar to sapropelic deposits. On the Marion Plateau, trends in oxygen and carbon isotopes were obtained by measuring Cibicidoides spp foraminifers. Moreover, carbonate content was reconstructed using a chemical method (coulometer). Results show that the mid Miocene cooling step profoundly affected this system: a major drop in accumulation rates of carbonates occurs precisely at 13.8 Ma, around the time of the East Antarctic ice sheet formation. Moreover, sedimentation changes occurred at that time, carbonate fragments coming from neritic environments becoming less abundant, planktonic foraminifer content increasing and quartz and reworked glauconite being deposited. Conversely, a surprising result is that the major N12-N14 sea-level fall occurring around 11.5 Ma did not impact the accumulation of carbonates on the slope. This was unexpected since carbonate platform are very sensitive to sea-level changes. The model developed to explain that mass accumulation rates of carbonates diminished around 13.6 Ma (Mi3 Event) instead of 11.5 Ma (N12-N14 event), suggests that oceanic currents were controlling slope carbonate deposition on the Marion Plateau prior to the mid-Miocene, and that the mid Miocene event considerably increase their strength, hence reducing the amount of carbonate being deposited on slope sites. Moreover, by combining results from deep-sea oxygen isotopes with sea-level estimates based on coastal onlaps made during Leg 194, we constrain the amplitude of the N12-N14 sea-level fall to 90 meters. When integrating isotopic results from this study, this amplitude is lowered to 70 meters. A general conclusion of this work is that the mid Miocene climatic shift did impact carbonate systems, at least at the two locations studied. However, the nature of this response was highly dependant on the regional settings, in particular the presence of land mass (Malta) and the absence of a barrier to shelter from the effects of open ocean (Marion Plateau). Im Rahmen dieser Doktorarbeit wurden die Hangkarbonate von zwei miozänen heterozoischen Karbonatsystemen näher untersucht: die Malta Inselgruppe (zentrales Mittelmeer) und das Marion Plateau (Nordost Australien, ODP Leg 194). Die Auswirkungen der mittelmiozänen Abkühlung (Mi3), die auf 13.6 Ma datiert wird und starken Einfluß auf die Sauerstoffisotopenkurve hatte, in den oben genannten Flachwassersystemen stellten das Ziel dieser Arbeit dar. Dieses Abkühlungsereignis beeinflußte außerdem sehr stark die ozeanographischen und klimatischen Muster, die im weiteren Verlauf zum modernen Eishausklima führten. So steht insbesondere die Vereisung von Ostantarktika mit diesem Ereignis in Verbindung. Diese Arbeit untersucht den Einfluß dieses Ereignisses auf Flachwassersysteme, um vorliegende Untersuchungen in Tiefwassersystemen zu ergänzen und so zum globalen Verständnis des miozänen Klimawechsels beizutragen. Die Profile auf der Maltainselgruppe wurden mit Hilfe von Kohlenstoff- und Sauerstoffisotopen Auswertungen im Gesamtgestein, Gesamtgesteinmineralogie, Tonmineralanalyse und organischer Geochemie untersucht. Durch einen Wechsel von karbonatischeren zu tonigeren Sedimenten beeinflußte das mittelmiozäne Abkühlungsereignis die Sedimentation in diesem Gebiet sehr stark. Weiterhin wurde beobachtet, daß jede Phase der antarktischen Vereisung, nicht nur das mittelmiozäne Hauptereignis, zu einem erhöhten terrigenen Eintrag in den Hangsedimenten der Maltainselgruppe führte. Akkumulationsraten zeigen, daß dieser erhöhte terrigene Eintrag den einzelnen Vereisungsperioden zusammenhängt und die karbonatischen Sedimente durch tonreiche Sedimente “verunreinigt” wurden. Das daraufhin entwickelte Modell erklärt diesen erhöhten terrigenen Eintrag mit einer nordwärtigen Verlagerung der innertropischen Konvergenzzone durch die Bildung von kalten, dichten Luftmassen, die zu verstärkten Niederschlägen in Nordafrika führten. Diese verstärkten Niederschläge (oder verstärkter afrikanischer Monsun) beeinflußten die kontinentale Verwitterung und den Eintrag, mit der Folge, daß verstärkt terrigene Sedimente im Bereich der Hangsedimente der Maltainselgruppe abgelagert wurden. Die tonreichen Intervalle weisen Ähnlichkeiten zu sapropelischen Ablagerungen auf, was mit Hilfe der Spektral analyse des Karbonatgehalts und der geochemischen Analyse des organischen Materials gezeigt wurde. Auf dem Marion Plateau wurden die Sauerstoff- und Kohlenstoffisotopenkurven anhand von Foraminiferen der Gattung Cibicidoides spp. rekonstruiert. Der Karbonatgehalt wurde mit Hilfe einer chemischen Methode (Coulometer) ermittelt. Genauso wie die Sedimente der Maltainselgruppe beeinflußte das mittelmiozäne Abkühlungsereignis (Mi3) auch die Sedimente auf dem Marion Plateau. So kam es bei 13,8 Ma, in etwa zur Zeit der Vereisung von Ostantarktika, zu einem Abfall der Karbonatakkumulationsraten. Weiterhin traten Änderungen in der Zusammensetzung der Sedimente auf, so nehmen neritische Karbonatfragmente ab, der planktische Foraminiferengehalt nimmt zu und es wurden verstärkt Quarz und Glaukonit abgelagert. Ein überraschendes Ergebnis ist die Tatsache, daß der große N12-N14 Meeresspiegelabfall um 11,5 Ma die Akkumulationsraten der Karbonate auf dem Hang nicht beeinflußte. Dieses Ergebnis ist umso erstaunlicher, da Karbonatplattformen normalerweise sehr sensitiv auf Meeresspiegeländerungen reagieren. Der Grund, warum sich die Karbonatakkumulationsraten schon um 13,6 Ma (Mi3) und nicht erst um 11,5 Ma (N12-N14) verringerten, liegt in der Tatsache, daß die ozeanischen Strömungen die Karbonatsedimentation auf dem Hang des Marion Plateau schon im Miozän kontrollierten. Das mittelmiozäne Ereignis (Mi3) erhöhte die Stärke diese Strömungen und als eine Ursache wurde die Karbonatakkumulation auf den Hängen reduziert. Die Amplitude des N12-N14 Meeresspiegelabfalls liegt bei 90 m unter der Berücksichtigung der Sauerstoffisotopendaten aus der Tiefsee und Berechnungen des Meeresspiegels anhand des “coastal onlaps”, die während Leg 194 gemacht wurden. Die Isotopendaten dieser Arbeit weisen hingegen auf einen verringerten Meeresspiegelabfall von 70 m hin. Als allgemeine Schlußfolgerung kann gesagt werden, daß der mittelmiozäne Klimaumschwung die Karbonatsysteme zumindest an den beiden untersuchten Lokalitäten beeinflußt hat. Allerdings waren die Auswirkungen sehr von den unterschiedlichen lokalen Gegebenheiten abhängig. Insbesondere wirkten sich die Anwesenheit einer Landmasse (Malta) und die Abwesenheit einer Barriere vor den Einflüssen des offenen Ozeans (Marion Plateau) stark auf die Ablagerung der Karbonate aus.
Hämoglobin-A1c (HbA1c) ist ein Hämoglobin (Hb)-Subtypus, der durch nicht-enzymatische Glykierung des N-terminalen Valinrestes der Hämoglobin-beta-Kette entsteht. Das gemessene Verhältnis von HbA1c zum Gesamt-Hämoglobin (5-20 % bei Diabetikern) repräsentiert den Mittelwert der Blutglucosekonzentration über einen zweimonatigen Zeitraum und stellt zur Beurteilung der diabetischen Stoffwechsellage eine Ergänzung zur Akutkontrolle der Glukosekonzentration dar. Ziel der vorliegenden Arbeit war es, einen amperometrischen Biosensor für die Bestimmung des medizinisch relevanten Parameters HbA1c zu entwickeln. Durch Selektion geeigneter Bioerkennungselemente und deren Immobilisierung unter Erhalt der Bindungsfunktion für die Zielmoleküle Hämoglobin bzw. HbA1c wurden spezifische, hochaffine und regenerationsstabile Sensoroberflächen geschaffen. Für die Entwicklung des HbA1c-Biosensors wurden zwei Konzepte - Enzymsensor und Immunosensor - miteinander verglichen. Die enzymatische Umsetzung von HbA1c erfolgte mit der Fructosylamin Oxidase (FAO) aus Pichia pastoris N 1-1 unter Freisetzung von H2O2, welches sowohl optisch über eine Indikatorreaktion als auch elektrochemisch nach Einschluss der FAO in PVA-SbQ und Fixierung des Immobilisats vor einer H2O2-Elektrode nachgewiesen wurde. Die Kalibration des Enzymsensors mit der HbA1c-Modellsubstanz Fructosyl-Valin ergab Nachweisgrenzen, die ausserhalb des physiologisch relevanten HbA1c-Konzentrationsbereich lagen. Aus der Umsetzung von glykierten Peptiden mit einer nicht HbA1c analogen Aminosäurensequenz, z.B. Fructosyl-Valin-Glycin wurde zudem eine geringe HbA1c-Spezifität abgeleitet. Für den Immunosensor wurden zwei heterogene Immunoassay-Formate unter Verwendung von hochaffinen und spezifischen Antikörpern in Kombination mit Glucose Oxidase (GOD) als Markerenzym zum Nachweis von HbA1c untersucht. Beim indirekt-kompetitiven Immunoassay wurde anstelle des kompletten HbA1c-Moleküls das glykierte Pentapeptid Fructosyl-Valin-Histidin-Leucin-Threonin-Prolin (glkPP) als Kompetitor und Affinitätsligand immobilisiert und so eine regenerierfähige Oberfläche geschaffen. Beim Sandwich-Immunoassay wurde im ersten Schritt Gesamt-Hämoglobin an die mit Haptoglobin (Hp) modifizierte Festphase angereichert und im zweiten Schritt der gebundene HbA1c-Anteil nachgewiesen. Für die Konstruktion des HbA1c-Immunosensors wurden Affinitätsmatrizen durch Modifizierung von Cellulose-Dialysemembranen mit glkPP bzw. Hp hergestellt. Grundlegend studiert wurde die Aktivierung der Cellulose-Membranen mit 1,1'-Carbonyldiimidazol (CDI) und 1-Cyano-4-dimethylaminopyridintetrafluoroborat (CDAP) als Aktivierungsagenzien. Eine gerichtete Immobilisierung der Liganden wurde realisiert, indem glkPP über dessen C-Terminus (einzige Carboxylatgruppe) und Hp über dessen periodat-oxidiertem Kohlenhydratrest an die amino- oder hydrazidfunktionalisierte Membranen kovalent gekoppelt wurden. Mit dem Einsatz der glkPP- und Hp-modifizierten Membranen in der elektrochemischen Messzelle war erstmalig der biosensorische Nachweis von HbA1c möglich. Als Transduktor diente eine Pt-Elektrode, an der das von der GOD generierte H2O2 umgesetzt und ein mit der HbA1c-Konzentration korrelierendes Stromsignal erzeugt wurde. Die Immunosensoren zeigten Ansprechzeiten von 3 s. Mit dem Immunosensor auf Basis des indirekt-kompetitiven Testprinzips wurde eine Kalibrationskurve für HbA1c im Bereich von 0,25-30 µg/ml (3,9-465 nM, CV 3-9 %) mit Assayzeiten von 60 min und mit dem Immunosensor im Sandwich-Format eine Kalibrationskurve im Bereich von 0,5-5 µg/ml (7,8-78 nM; 5-50 % HbA1c vom Gesamt-Hb, CV 6-10 %, 3 h) aufgenommen. Hemoglobin-A1c (HbA1c) is a hemoglobin subtype formed by non-enzymatic reaction of glucose with the N-terminus of the beta-polypeptide chains. As it reflects the glycemic status of diabetics over the preceding 8-12 weeks, the determination of HbA1c has become an established procedure in the management of diabetes mellitus. It is measured as the percentage of total hemoglobin. Up to 5 % HbA1c are considered as normal whereas in diabetic subjects it could be elevated from 5-20 %. In addition to amperometric biosensors for glucose self monitoring which have been successfully applied in diabetes management, biosensors for HbA1c would be an useful supplement for a comprehensive diabetes control. Objective of this work was to develop and compare amperometric biosensors for determination of HbA1c based on enzymatic and immunochemical methods. For the enzyme based HbA1c assay a novel fructosamine oxidase (FAO) derived from marine yeast Pichia pastoris, strain N1-1 was utilized. It recognizes and oxidatively degrades fructosyl-valine (FV) which corresponds to the glycated N-terminus of the beta-chain of HbA1c and therefore is regarded as a model compound for HbA1c. Hydrogen peroxide which is liberated by the FAO during FV conversion was indicated optically in a horseradish peroxidase (POD) coupled reaction and electrochemically. For the biosensor the FAO was embedded in polyvinyl alcohol-stylbazole (PVA-SbQ) and fixed it in front of a Pt-electrode. So far, the measuring range of FV did not cover the clinically relevant range of HbA1c. Low specificity was assumed since enzyme activity also was obtained with glycated peptides, e.g. fructosyl-valine-glycine, not corresponding to the glycated N-terminus of the hemoglobin-beta-chain. For the immunosensor two immunoassays formats - heterogeneous sandwich and heterogeneous competitive - were tested. The assays were designed as follows: The competitive immunoassay was based on the immobilized synthetic glycated pentapeptide fructosyl-valine-histidine-leucine-threonine-proline (glkPP) utilized as HbA1c analogue. The peptide has an amino acid sequence corresponding to the N-terminus of the hemoglobin beta-chains and is capable for competition together with the HbA1c of the sample for the amount of a glucose oxidase (GOD)-labelled anti-HbA1c antibody. In the sandwich-type assay haptoglobin (Hp), a natural hemoglobin binding molecule with antibody characteristic properties, was used as bioreceptor for enrichment of total hemoglobin onto the surface. In a subsequent step the HbA1c fraction was quantified by a GOD-labelled HbA1c specific antibody. Cellulose dialysis membrane was used as the solid support for immobilization of Hp and glkPP near the sensor surface. For activation of the membrane two reagents, 1,1‧-carbonyldiimidazole (CDI) and 1-cyano-4-dimethylamino pyridinium tetrafluoroborate (CDAP), were compared with respect to the degree of activation and coupling efficiency. Site-directed immobilization of Hp and glkPP was achieved by coupling Hp via its carbohydrate residue and glkPP via its C-terminus to the activated membrane using a bis-amine or bis-hydrazide spacer. The affinity membranes were placed in front of a modified Clark-type hydrogen peroxide electrode in an electrochemical measuring cell and HbA1c analysis was carried out within the stirred cell. Detection of the bound GOD-label was achieved by measurement of the electrocatalytic oxidation of hydrogen peroxide at +600 mV vs. Ag/AgCl. The indication was done in only 3 s. For the competitive principle a typical inhibition curve with a linear range between 0,25-30 µg/ml (3,9-465 nM, CV 3-9 %, 60 min per sample) HbA1c was obtained. Due to the high functional stability of the peptide multiple regeneration of the affinity surface was possible without loss of binding capacity. With the sandwich assay configuration the clinically relevant range could easily be covered (calibration curve: 5-50 % HbA1c corresponding to 7,8-78 nM, CV 6-10 %, 3 h per sample).
In recent years, there has been a dramatic increase in available compute capacities. However, these “Grid resources” are rarely accessible in a continuous stream, but rather appear scattered across various machine types, platforms and operating systems, which are coupled by networks of fluctuating bandwidth. It becomes increasingly difficult for scientists to exploit available resources for their applications. We believe that intelligent, self-governing applications should be able to select resources in a dynamic and heterogeneous environment: Migrating applications determine a resource when old capacities are used up. Spawning simulations launch algorithms on external machines to speed up the main execution. Applications are restarted as soon as a failure is detected. All these actions can be taken without human interaction. A distributed compute environment possesses an intrinsic unreliability. Any application that interacts with such an environment must be able to cope with its failing components: deteriorating networks, crashing machines, failing software. We construct a reliable service infrastructure by endowing a service environment with a peer-to-peer topology. This “Grid Peer Services” infrastructure accommodates high-level services like migration and spawning, as well as fundamental services for application launching, file transfer and resource selection. It utilizes existing Grid technology wherever possible to accomplish its tasks. An Application Information Server acts as a generic information registry to all participants in a service environment. The service environment that we developed, allows applications e.g. to send a relocation requests to a migration server. The server selects a new computer based on the transmitted resource requirements. It transfers the application's checkpoint and binary to the new host and resumes the simulation. Although the Grid's underlying resource substrate is not continuous, we achieve persistent computations on Grids by relocating the application. We show with our real-world examples that a traditional genome analysis program can be easily modified to perform self-determined migrations in this service environment. In den vergangenen Jahren ist es zu einer dramatischen Vervielfachung der verfügbaren Rechenzeit gekommen. Diese 'Grid Ressourcen' stehen jedoch nicht als kontinuierlicher Strom zur Verfügung, sondern sind über verschiedene Maschinentypen, Plattformen und Betriebssysteme verteilt, die jeweils durch Netzwerke mit fluktuierender Bandbreite verbunden sind. Es wird für Wissenschaftler zunehmend schwieriger, die verfügbaren Ressourcen für ihre Anwendungen zu nutzen. Wir glauben, dass intelligente, selbstbestimmende Applikationen in der Lage sein sollten, ihre Ressourcen in einer dynamischen und heterogenen Umgebung selbst zu wählen: Migrierende Applikationen suchen eine neue Ressource, wenn die alte aufgebraucht ist. 'Spawning'-Anwendungen lassen Algorithmen auf externen Maschinen laufen, um die Hauptanwendung zu beschleunigen. Applikationen werden neu gestartet, sobald ein Absturz endeckt wird. Alle diese Verfahren können ohne menschliche Interaktion erfolgen. Eine verteilte Rechenumgebung besitzt eine natürliche Unverlässlichkeit. Jede Applikation, die mit einer solchen Umgebung interagiert, muss auf die gestörten Komponenten reagieren können: schlechte Netzwerkverbindung, abstürzende Maschinen, fehlerhafte Software. Wir konstruieren eine verlässliche Serviceinfrastruktur, indem wir der Serviceumgebung eine 'Peer-to-Peer'-Topology aufprägen. Diese “Grid Peer Service” Infrastruktur beinhaltet Services wie Migration und Spawning, als auch Services zum Starten von Applikationen, zur Dateiübertragung und Auswahl von Rechenressourcen. Sie benutzt existierende Gridtechnologie wo immer möglich, um ihre Aufgabe durchzuführen. Ein Applikations-Information- Server arbeitet als generische Registratur für alle Teilnehmer in der Serviceumgebung. Die Serviceumgebung, die wir entwickelt haben, erlaubt es Applikationen z.B. eine Relokationsanfrage an einen Migrationsserver zu stellen. Der Server sucht einen neuen Computer, basierend auf den übermittelten Ressourcen-Anforderungen. Er transferiert den Statusfile des Applikation zu der neuen Maschine und startet die Applikation neu. Obwohl das umgebende Ressourcensubstrat nicht kontinuierlich ist, können wir kontinuierliche Berechnungen auf Grids ausführen, indem wir die Applikation migrieren. Wir zeigen mit realistischen Beispielen, wie sich z.B. ein traditionelles Genom-Analyse-Programm leicht modifizieren lässt, um selbstbestimmte Migrationen in dieser Serviceumgebung durchzuführen.
1-Methylpyren (MP) ist hepatokanzerogen in neugeborenen männlichen Mäusen. Durch Hydroxylierung an der benzylischen Stelle und anschließende Sulfonierung wird MP zu DNA-reaktivem 1-Sulfooxymethylpyren (SMP) aktiviert. In der Ratte führt die Exposition des benzylischen Alkohols, 1-Hydroxymethylpyren (HMP), zur DNA-Adduktbildung in verschiedenen Geweben. Eventuelle Konsequenz der Toxifizierung ist die Ausscheidung entsprechender Mercaptursäure und Nukleosidaddukt im Harn, welche aufgrund ihrer Herkunft als Biomarker eignen könnten. In dieser Arbeit wird die Ausscheidung der Mercaptursäure und des N2-Desoxyguanosinadduktes in HMP-exponierten Ratten untersucht. Nach der Applikation von HMP bzw. MP wurden weniger als 1 % der Dosis als MPMA über Urin und Faeces ausgeschieden (0 - 48 h). Die Ausscheidung erfolgt hauptsächlich in den ersten 24 h nach der Applikation. MPdG konnte weder in Urin noch in Faeces der HMP-behandelten Tieren identifiziert werden. Nach direkter SMP-Applikation wurde MPdG nur in sehr geringe Menge (weniger als 0,9 ppm in 12 h) im Urin gefunden. Aufgrund der geringen Menge eignet sich MPdG nicht als Biomarker. MPMA dagegen, lässt sich analytisch gut erfassen. Es sollte daher untersucht werden, ob MPMA die Toxifizierung des HMP wiederspiegelt. Die Voraussetzung dafür ist die Kenntnisse über das Metabolismusmuster von HMP. Es wurde daher umfassende Untersuchungen zum Metabolismus des HMP durchgeführt. Die Ergebnisse zeigten, dass mehr als 80 % der Metaboiten in ihrer oxidierten Form (PCS, deren Glucuronsäure-Konjugate sowie phenolische Sulfatester der PCS) ausgeschieden wurden. Demnach spielt die Oxidation des HMP zu PCS eine sehr wichtige Rolle bei der Detoxifizierung und Ausscheidung von HMP. Ferne konnte nachgewiesen werden, dass die Enzyme Alkohol- und Aldehyd-Dehydrogenase an der Oxidation von HMP beteiligt waren. Die Inhibitoren Disulfiram und Ethanol der o. g. Enzyme wurde daher zur Modulation der Detoxifizierung in vivo eingesetzt. Die Veränderungen in der Toxifizierung von HMP zu SMP wurden durch die SMP-Konzentration im Plasma, die DNA-Addukthäufigkeit und die MPMA-Ausscheidung erfasst. Die Vorbehandlung von Disulfiram und Ethanol führte zu tendentielle Erhöhung der SMP-Konzentration im Plasma, DNA-Addukthäufigkeit in der Leber und die MPMA-Ausscheidung. Bemerkenswert ist jedoch, dass bereits eine Dosis von 0,2 g Ethanol/kg Körpermasse bereits zu statistisch signifikanten Erhöhungen der MPMA-Ausscheidung bei weiblichen Ratten. 1-Methylpyrene is hepatocarcinogenic in rodents. It is metabolized primarily to 1-hydroxymethylpyrene (HMP) by various cDNA-expressed rat and human cytochromes P450. HMP is activated to a highly reactive sulfuric acid ester, 1-sulfooxymethylpyrene (SMP), by sulphotransferases. In the rat, this activation pathway leads to the formation of DNA adducts in various tissues. Possible consequences of the toxification could be the excretion of the corresponding mercapturic acid and nucleosidadduct in urine and feces. Because of their origin, these substances should reflex the toxification process may be used as biomarkers. We investigate the excretion of 1-methylpyrenyl-mercapturic acid (MPMA) and the excretion of N2-(1-methylpyrenyl)-desoxyguanosin (MPdG) in urine and feces of HMP-treated rats. These studies showed that only a minor portion (< 1 %) of the administered dose of 1-HMP was excreted as mercapturic acid. MPdG could not be identified in urine and feces of HMP-treated rats. Treating rats with the active spieces sulfooxymethylpyrene, 0.9 ppm of the dose was found excreted within 12 h. I now investigated the alternative metabolic pathways of HMP. More than 50 % of the dose (administered intraperitoneally) was excreted as free 1-pyrenyl carboxylic acid and its glucuronic acid conjugate primarily in the urine. Other major urinary metabolites were phenolic sulpho conjugates of ring-oxidized 1-pyrenyl carboxylic acid (> 30 %). Minor metabolites were phenolic sulpho conjugates of HMP (< 5 %). The glucuronic acid conjugate of HMP was found in very small amounts. In total, > 80 % of the metabolites excreted were oxidized at the exocyclic carbon. This side-chain oxidation, probably catalyzed by alcohol and aldehyde dehydrogenases, appears to represent a detoxification pathway. Indeed, administration of ethanol shortly before the administration of HMP to rats increased the levels of SMP detected in blood, of DNA adducts formed in tissues and of mercapturic acid excreted. These effects were observed even at very low dose levels of ethanol (0.2 g per kg body weight). Similar effects were shown after administration of Disulfiram, an inhibitor of aldehyde dehydrogenase.
In order to face the rapidly increasing need for computational resources of various scientific and engineering applications one has to think of new ways to make more efficient use of the worlds current computational resources. In this respect, the growing speed of wide area networks made a new kind of distributed computing possible: Metacomputing or (distributed) Grid computing. This is a rather new and uncharted field in computational science. The rapidly increasing speed of networks even outperforms the average increase of processor speed: Processor speeds double on average each 18 month whereas network bandwidths double every 9 months. Due to this development of local and wide area networks Grid computing will certainly play a key role in the future of parallel computing. This type of distributed computing, however, distinguishes from the traditional parallel computing in many ways since it has to deal with many problems not occurring in classical parallel computing. Those problems are for example heterogeneity, authentication and slow networks to mention only a few. Some of those problems, e.g. the allocation of distributed resources along with the providing of information about these resources to the application have been already attacked by the Globus software. Unfortunately, as far as we know, hardly any application or middle-ware software takes advantage of this information, since most parallelizing algorithms for finite differencing codes are implicitly designed for single supercomputer or cluster execution. We show that although it is possible to apply classical parallelizing algorithms in a Grid environment, in most cases the observed efficiency of the executed code is very poor. In this work we are closing this gap. In our thesis, we will - show that an execution of classical parallel codes in Grid environments is possible but very slow - analyze this situation of bad performance, nail down bottlenecks in communication, remove unnecessary overhead and other reasons for low performance - develop new and advanced algorithms for parallelisation that are aware of a Grid environment in order to generelize the traditional parallelization schemes - implement and test these new methods, replace and compare with the classical ones - introduce dynamic strategies that automatically adapt the running code to the nature of the underlying Grid environment. The higher the performance one can achieve for a single application by manual tuning for a Grid environment, the lower the chance that those changes are widely applicable to other programs. In our analysis as well as in our implementation we tried to keep the balance between high performance and generality. None of our changes directly affect code on the application level which makes our algorithms applicable to a whole class of real world applications. The implementation of our work is done within the Cactus framework using the Globus toolkit, since we think that these are the most reliable and advanced programming frameworks for supporting computations in Grid environments. On the other hand, however, we tried to be as general as possible, i.e. all methods and algorithms discussed in this thesis are independent of Cactus or Globus. Die immer dichtere und schnellere Vernetzung von Rechnern und Rechenzentren über Hochgeschwindigkeitsnetzwerke ermöglicht eine neue Art des wissenschaftlich verteilten Rechnens, bei der geographisch weit auseinanderliegende Rechenkapazitäten zu einer Gesamtheit zusammengefasst werden können. Dieser so entstehende virtuelle Superrechner, der selbst aus mehreren Grossrechnern besteht, kann dazu genutzt werden Probleme zu berechnen, für die die einzelnen Grossrechner zu klein sind. Die Probleme, die numerisch mit heutigen Rechenkapazitäten nicht lösbar sind, erstrecken sich durch sämtliche Gebiete der heutigen Wissenschaft, angefangen von Astrophysik, Molekülphysik, Bioinformatik, Meteorologie, bis hin zur Zahlentheorie und Fluiddynamik um nur einige Gebiete zu nennen. Je nach Art der Problemstellung und des Lösungsverfahrens gestalten sich solche "Meta-Berechnungen" mehr oder weniger schwierig. Allgemein kann man sagen, dass solche Berechnungen um so schwerer und auch um so uneffizienter werden, je mehr Kommunikation zwischen den einzelnen Prozessen (oder Prozessoren) herrscht. Dies ist dadurch begründet, dass die Bandbreiten bzw. Latenzzeiten zwischen zwei Prozessoren auf demselben Grossrechner oder Cluster um zwei bis vier Grössenordnungen höher bzw. niedriger liegen als zwischen Prozessoren, welche hunderte von Kilometern entfernt liegen. Dennoch bricht nunmehr eine Zeit an, in der es möglich ist Berechnungen auf solch virtuellen Supercomputern auch mit kommunikationsintensiven Programmen durchzuführen. Eine grosse Klasse von kommunikations- und berechnungsintensiven Programmen ist diejenige, die die Lösung von Differentialgleichungen mithilfe von finiten Differenzen zum Inhalt hat. Gerade diese Klasse von Programmen und deren Betrieb in einem virtuellen Superrechner wird in dieser vorliegenden Dissertation behandelt. Methoden zur effizienteren Durchführung von solch verteilten Berechnungen werden entwickelt, analysiert und implementiert. Der Schwerpunkt liegt darin vorhandene, klassische Parallelisierungsalgorithmen zu analysieren und so zu erweitern, dass sie vorhandene Informationen (z.B. verfügbar durch das Globus Toolkit) über Maschinen und Netzwerke zur effizienteren Parallelisierung nutzen. Soweit wir wissen werden solche Zusatzinformationen kaum in relevanten Programmen genutzt, da der Grossteil aller Parallelisierungsalgorithmen implizit für die Ausführung auf Grossrechnern oder Clustern entwickelt wurde.
One of the rules-of-thumb of colloid and surface physics is that most surfaces are charged when in contact with a solvent, usually water. This is the case, for instance, in charge-stabilized colloidal suspensions, where the surface of the colloidal particles are charged (usually with a charge of hundreds to thousands of e, the elementary charge), monolayers of ionic surfactants sitting at an air-water interface (where the water-loving head groups become charged by releasing counterions), or bilayers containing charged phospholipids (as cell membranes). In this work, we look at some model-systems that, although being a simplified version of reality, are expected to capture some of the physical properties of real charged systems (colloids and electrolytes). We initially study the simple double layer, composed by a charged wall in the presence of its counterions. The charges at the wall are smeared out and the dielectric constant is the same everywhere. The Poisson-Boltzmann (PB) approach gives asymptotically exact counterion density profiles around charged objects in the weak-coupling limit of systems with low-valent counterions, surfaces with low charge density and high temperature (or small Bjerrum length). Using Monte Carlo simulations, we obtain the profiles around the charged wall and compare it with both Poisson-Boltzmann (in the low coupling limit) and the novel strong coupling (SC) theory in the opposite limit of high couplings. In the latter limit, the simulations show that the SC leads in fact to asymptotically correct density profiles. We also compare the Monte Carlo data with previously calculated corrections to the Poisson-Boltzmann theory. We also discuss in detail the methods used to perform the computer simulations. After studying the simple double layer in detail, we introduce a dielectric jump at the charged wall and investigate its effect on the counterion density distribution. As we will show, the Poisson-Boltzmann description of the double layer remains a good approximation at low coupling values, while the strong coupling theory is shown to lead to the correct density profiles close to the wall (and at all couplings). For very large couplings, only systems where the difference between the dielectric constants of the wall and of the solvent is small are shown to be well described by SC. Another experimentally relevant modification to the simple double layer is to make the charges at the plane discrete. The counterions are still assumed to be point-like, but we constraint the distance of approach between ions in the plane and counterions to a minimum distance D. The ratio between D and the distance between neighboring ions in the plane is, as we will see, one of the important quantities in determining the influence of the discrete nature of the charges at the wall over the density profiles. Another parameter that plays an important role, as in the previous case, is the coupling as we will demonstrate, systems with higher coupling are more subject to discretization effects than systems with low coupling parameter. After studying the isolated double layer, we look at the interaction between two double layers. The system is composed by two equally charged walls at distance d, with the counterions confined between them. The charge at the walls is smeared out and the dielectric constant is the same everywhere. Using Monte-Carlo simulations we obtain the inter-plate pressure in the global parameter space, and the pressure is shown to be negative (attraction) at certain conditions. The simulations also show that the equilibrium plate separation (where the pressure changes from attractive to repulsive) exhibits a novel unbinding transition. We compare the Monte Carlo results with the strong-coupling theory, which is shown to describe well the bound states of systems with moderate and high couplings. The regime where the two walls are very close to each other is also shown to be well described by the SC theory. Finally, Using a field-theoretic approach, we derive the exact low-density ("virial") expansion of a binary mixture of positively and negatively charged hard spheres (two-component hard-core plasma, TCPHC). The free energy obtained is valid for systems where the diameters d_+ and d_- and the charge valences q_+ and q_- of positive and negative ions are unconstrained, i.e., the same expression can be used to treat dilute salt solutions (where typically d_+ ~ d_- and q_+ ~ q_-) as well as colloidal suspensions (where the difference in size and valence between macroions and counterions can be very large). We also discuss some applications of our results. Eine der Faustregeln der Kolloid- und Oberflächenphysik ist, dass die meisten Oberflächen geladen sind, wenn sie mit einem Lösungsmittel, normalerweise Wasser, in Kontakt treten. Dies ist zum Beispiel bei ladungsstabilisierten Kolloidalen Suspensionen der Fall, bei denen die Oberfläche der Kolloidteilchen geladen ist (gewöhnlich mit einer Ladung von mehreren Hunderttausend Elementarladungen), oder bei Monoschichten ionischer Tenside, die auf einer Luft-Wasser Grenzfläche sitzen (wobei die wasserliebenden Kopfgruppen durch die Freisetzung von Gegenionen geladen werden), sowie bei Doppelschichten, die geladene phospholipide enthalten (wie Zellmembranen). In dieser Arbeit betrachten wir einige Modellsysteme, die zwar eine vereinfachte Fassung der Realität darstellen, von denen wir aber dennoch erwarten koennen, dass wir mit ihrer Hilfe einige physikalische Eigenschaften realer geladener Systeme (Kolloide und Elektrolyte) einfangen können.
In this work we consider statistical learning problems. A learning machine aims to extract information from a set of training examples such that it is able to predict the associated label on unseen examples. We consider the case where the resulting classification or regression rule is a combination of simple rules - also called base hypotheses. The so-called boosting algorithms iteratively find a weighted linear combination of base hypotheses that predict well on unseen data. We address the following issues: o The statistical learning theory framework for analyzing boosting methods. We study learning theoretic guarantees on the prediction performance on unseen examples. Recently, large margin classification techniques emerged as a practical result of the theory of generalization, in particular Boosting and Support Vector Machines. A large margin implies a good generalization performance. Hence, we analyze how large the margins in boosting are and find an improved algorithm that is able to generate the maximum margin solution. o How can boosting methods be related to mathematical optimization techniques? To analyze the properties of the resulting classification or regression rule, it is of high importance to understand whether and under which conditions boosting converges. We show that boosting can be used to solve large scale constrained optimization problems, whose solutions are well characterizable. To show this, we relate boosting methods to methods known from mathematical optimization, and derive convergence guarantees for a quite general family of boosting algorithms. o How to make Boosting noise robust? One of the problems of current boosting techniques is that they are sensitive to noise in the training sample. In order to make boosting robust, we transfer the soft margin idea from support vector learning to boosting. We develop theoretically motivated regularized algorithms that exhibit a high noise robustness. o How to adapt boosting to regression problems? Boosting methods are originally designed for classification problems. To extend the boosting idea to regression problems, we use the previous convergence results and relations to semi-infinite programming to design boosting-like algorithms for regression problems. We show that these leveraging algorithms have desirable theoretical and practical properties. o Can boosting techniques be useful in practice? The presented theoretical results are guided by simulation results either to illustrate properties of the proposed algorithms or to show that they work well in practice. We report on successful applications in a non-intrusive power monitoring system, chaotic time series analysis and a drug discovery process. --- Anmerkung: Der Autor ist Träger des von der Mathematisch-Naturwissenschaftlichen Fakultät der Universität Potsdam vergebenen Michelson-Preises für die beste Promotion des Jahres 2001/2002. In dieser Arbeit werden statistische Lernprobleme betrachtet. Lernmaschinen extrahieren Informationen aus einer gegebenen Menge von Trainingsmustern, so daß sie in der Lage sind, Eigenschaften von bisher ungesehenen Mustern - z.B. eine Klassenzugehörigkeit - vorherzusagen. Wir betrachten den Fall, bei dem die resultierende Klassifikations- oder Regressionsregel aus einfachen Regeln - den Basishypothesen - zusammengesetzt ist. Die sogenannten Boosting Algorithmen erzeugen iterativ eine gewichtete Summe von Basishypothesen, die gut auf ungesehenen Mustern vorhersagen. Die Arbeit behandelt folgende Sachverhalte: o Die zur Analyse von Boosting-Methoden geeignete Statistische Lerntheorie. Wir studieren lerntheoretische Garantien zur Abschätzung der Vorhersagequalität auf ungesehenen Mustern. Kürzlich haben sich sogenannte Klassifikationstechniken mit großem Margin als ein praktisches Ergebnis dieser Theorie herausgestellt - insbesondere Boosting und Support-Vektor-Maschinen. Ein großer Margin impliziert eine hohe Vorhersagequalität der Entscheidungsregel. Deshalb wird analysiert, wie groß der Margin bei Boosting ist und ein verbesserter Algorithmus vorgeschlagen, der effizient Regeln mit maximalem Margin erzeugt. o Was ist der Zusammenhang von Boosting und Techniken der konvexen Optimierung? Um die Eigenschaften der entstehenden Klassifikations- oder Regressionsregeln zu analysieren, ist es sehr wichtig zu verstehen, ob und unter welchen Bedingungen iterative Algorithmen wie Boosting konvergieren. Wir zeigen, daß solche Algorithmen benutzt werden koennen, um sehr große Optimierungsprobleme mit Nebenbedingungen zu lösen, deren Lösung sich gut charakterisieren laesst. Dazu werden Verbindungen zum Wissenschaftsgebiet der konvexen Optimierung aufgezeigt und ausgenutzt, um Konvergenzgarantien für eine große Familie von Boosting-ähnlichen Algorithmen zu geben. o Kann man Boosting robust gegenüber Meßfehlern und Ausreissern in den Daten machen? Ein Problem bisheriger Boosting-Methoden ist die relativ hohe Sensitivität gegenüber Messungenauigkeiten und Meßfehlern in der Trainingsdatenmenge. Um dieses Problem zu beheben, wird die sogenannte 'Soft-Margin' Idee, die beim Support-Vector Lernen schon benutzt wird, auf Boosting übertragen. Das führt zu theoretisch gut motivierten, regularisierten Algorithmen, die ein hohes Maß an Robustheit aufweisen. o Wie kann man die Anwendbarkeit von Boosting auf Regressionsprobleme erweitern? Boosting-Methoden wurden ursprünglich für Klassifikationsprobleme entwickelt. Um die Anwendbarkeit auf Regressionsprobleme zu erweitern, werden die vorherigen Konvergenzresultate benutzt und neue Boosting-ähnliche Algorithmen zur Regression entwickelt. Wir zeigen, daß diese Algorithmen gute theoretische und praktische Eigenschaften haben. o Ist Boosting praktisch anwendbar? Die dargestellten theoretischen Ergebnisse werden begleitet von Simulationsergebnissen, entweder, um bestimmte Eigenschaften von Algorithmen zu illustrieren, oder um zu zeigen, daß sie in der Praxis tatsächlich gut funktionieren und direkt einsetzbar sind. Die praktische Relevanz der entwickelten Methoden wird in der Analyse chaotischer Zeitreihen und durch industrielle Anwendungen wie ein Stromverbrauch-Überwachungssystem und bei der Entwicklung neuer Medikamente illustriert.
Four lines of Tribolium castaneum were selected in each of three replicates for increased ratio of (pupal-larval) to (adult-larval) weight gains, using selection for increased (pupal-larval) weight gain (PL), selection for decreased (adult-larval) weight gain (AL), direct selection for the ratio (R) and linear selection index of larval, pupal and adult weights (I), respectively, for four generations. Linear index was calculated with economic weights of m(2) -m(3) , m(3) -m(1) and m(1) -m(2) , respectively, with m(1) , m(2) and m(3) being the means for larval, pupal and adult weights. Selection to increase the ratio is considered to be a method to maximize the mean response in (adult-larval) weight while controlling the response in (pupal-adult) weight, and as a form of antagonistic selection to increase the weight gain during a given age period relative to the gain at another age period. Larval, pupal and adult weights were measured at 14, 21 and 28 days after adult emergence, respectively. The selected proportion was 20 % in all lines. The response observed for the ratio differed significantly among lines (p < 0.01), with the I and AL lines having the greatest responses. Line R was less effective in improving the objective of selection, while line PL appeared to be inappropriate. The observed responses for the numerator and denominator weight gains were positive in line PL, and negative in the AL, R and I lines. All lines apart from line PL decreased the (adult-larval) weight, holding (pupal-adult) weight constant. Larval weight showed the greatest influence on the response for the objective of selection. The results for this greater than 1 ratio are compared with results of others for smaller than 1 ratios, in which indirect selection for increased numerator is the more efficient alternative to the selection index. ZUSAMMENFASSUNG: Effizienz Selektionsverfahren zur Verbesserung des Quotienten der Gewichtsentwicklung zwischen Puppe/Larve und Käfer/Larve bei Tribolium. In den jeweils drei Versuchsserien zur Erhöhung des Quotienten (Gewicht von Puppe-Larve/Gewicht von Käfer-Larve) wurden vier Versuchsreihen von Tribolium castaneum untersucht: die Versuchsreihe PL wurde gewählt um die Differenz (Puppengewicht-Larvengewicht) zu erhöhen, die Versuchsreihe AL wurde gewählt um die Differenz (Käfergewicht-Larvengewicht) zu reduzieren, die Versuchsreihe R wurde direkt für den Koeffizienten gewählt und die Auswahl der Versuchsreihe I erfolgte über einen linearen Index, errechnet aus dem Gewicht von Larven, Puppen und Käfern über vier Generationen. Der lineare Index wurde berechnet aus den Gewichten von (m(2) -m(3) ), (m(3) -m(1) ) bzw. (m(1) -m(2) ), wobei m(1) , m(2) und m(3) die Mittelwerte für das Gewicht von Larven, Puppen bzw. Käfern sind. Die Auswahl zur Erhöhung des Quotienten ist eine Methode zur Maximierung des Durchschnittsgewichtsverhältnisses Käfer/Larve, sowie eine antagonische Auswahlform zur Erhöhung der Gewichtszunahme während einer bestimmten Wachstumsperiode im Vergleich zur Gewichtszunahme während einer anderen Wachstumsperiode. Das Selektionsverhältnis belief sich auf 20%. Die beim Quotienten beobachtete Antwort wies bedeutende Unterschiede zwischen Versuchsreihen auf (p < 0.01), wobei die höchsten Antworten bei den Versuchsreihen I und AL beobachtet wurden. Versuchsreihe R war am wenigsten effektiv, während Versuchsreihe PL nicht geeignet schien, das Auswahlziel zu verbessern. Die bei Nenner und Zähler beobachteten Antworten waren positiv bei der Versuchsreihe PL und negativ bei den anderen drei Versuchsreihen. Die Ergebnisse für diesen Quotient größer als 1 wurden mit denen anderer Versuche für Quotienten kleiner als 1 verglichen, bei denen die Auswahl zur Erhöhung des Zählers die effizienteste Alternative zum Auswahlindex ist. RESUMEN: Eficiencia de métodos de selección para incrementar el cociente entre la ganancia en peso de pupa-peso de larva y la ganancia en peso de adulto-peso de larva en Tribolium Cuatro líneas de Tribolium castaneum fueron seleccionadas en cada una de tres repeticiones para incrementar el cociente (peso de pupa-peso de larva)/(peso de adulto-peso de larva); la línea PL fue seleccionada para aumentar la diferencia (peso de pupa-pesp de larva), la línea AL fue seleccionada para disminuir la diferencia (peso de adulto-peso de larva), fa línea R fue seleccionada directamente para el cociente, y la línea I fue seleccionada por medio de un índice lineal basado en los pesos de larva, pupa y adulto, durante cuatro generaciones. El índice lineal se calculó con pesos económicos de (m(2) -m(3) ), (m(3) -m(1) ), y (m(1) -m(2) ) respectivamentee, siendo m(1) , m(2) , y m(3) los valores medios para el peso de larva, pupa y adulto. La selección para aumentar el cociente indicado es un método para maximizar la respuesta en (peso de adulto-peso de larva) controlando al tiempo la respuesta en (peso de pupa-peso de adulto), y es una forma de selección antagónica para aumentar la ganancia de peso durante un periodo de edad en relación con la ganancia en peso durante otro periodo. La proporción de selección due el 20 %. La respuesta observada en el cociente difería significativamente entre lineas (p < 0.01), teniendo las líneas I y AL las mayores respuestas. La línea R fue menos efectiva, mientras que la línea PL parecía inapropiada para mejorar el objetiyo de selección. Las respuestas observadas en el denominador y en el numerador fueron positivas en la línea PL, y negativas en las otras tres líneas. Los resultados para este cociente mayor que 1 se comparan con los de otros experimentos para cocientes menores que 1, en los que la selección para incrementar el numerador es la alternativa más eficiente al índice de selección. 1994 Blackwell Verlag GmbH.
Two different breeds of Andalusian sheep, 'Grazalema Merino' and 'Lebrijan Churro', and two different breeds of Andalusian goats, 'Andalusian White' and 'Andalusian Black', chosen by previous studies (Rodero et al. 1992a) as priority breeds for conservation, were studied. The systems used corresponded to ethnozootechnic characteristics, as well as the different biochemical-polymorphism variables. Farms were differentiated within breeds, or between themselves, and different tests were used of genetic and genotypic frequencies: Wright's indices, medium heterozygosities, Whalund's variances, G test of probability of reason, etc. Also Cavalli-Sforza's genetic distance was obtained. In the Andalusian Black and Grazalema Merino breeds, the Whalund's variances obtained were a result of selection, that has divided the breeds into distinct populations differentiated spatially. Medium heterozygosities of each breed do not differ much within themselves, but when each system is considered alone, discrepancies between ethnic groups are relevant. Wright's F indices demonstrated in the Andalusian White and Grazalema Merino breeds, genetic heterozygosities between populations or studied herds can be deduced, but this is not possible in the Andalusian Black. The F(IS) values indicated, despite the small size of the populations, that inbreeding has been avoided, probably because of the entry of foreign sires. In none of the breeds is there a significant excess of heterozygosis. The genetic distances between flocks within breeds do not differ from those found between breeds. RÉSUMÉ: On a travallé avec, differents troupeau des races de montons de l'Andalusie, Grazalema Merino et Lebrija Churro, et avec les races caprines Andalusian White et Andalusian Black, choisie entre les races Andaluciennes comme prioritaires pour la conservation, dans un etudie avant (Rodero et col. 1992a). Les sistémes utilicés dans cette travaille correspondent á charactérés etnozootechniques et á differents variables de polymorphism biochimique. Lorsque on fait differences entre troupeau, dedans de races, ou entre elles, on a utilicés differents preuves, á partir des fréquences géniques et génotipiques: l'index de Wright, hétérozygotie moyennes, variances de Whalund, preuve G de raison de probabilité, etc. Aussi le distance de Cavalli-Sforza. Comme conclusion, dans les races Andalusian Black et Grazalema Merino les variances de Whalund obtenues sont cosequences de l'action de la selection, donant different populations avec differentiation spaciale. Les hétérozygoties moyennes de chaque race sont parus, mais lorsque on considérent chaque systéme separé, les differences entre groupes ethniques sont importantes. Les indexes F de Wright demonstrent que, dans le races Andalusian White et Grazalema Merino on peuvent déduire d'heterozygoties génétique entre les populations ou troupeau analicées, dans le race Andalusian Black les differences valeurs de FIS indiquent que, malgré les petites dimensions des populations, on a evité la consanguinitée, due, probablement, á l'entrée d'étalons externes. Il n'y a pas, chez auqune race, d'un signifivative accroissement d'hétérizygosis. Les distances génétiques entre troupeau, dedans des races, en different pas des distances obtenues entre races. RESUMEN: Se ha trabajado con diferentes ganaderias de las razas ovinas andaluzas Merino de Grazalema y Churra Lebrijana, y con las caprinas Blanca Serrana y Negra Serrana, elegidas entre el resto de las razas de Andalucia como prioritarias pra la conservación, por estudio previo (Rodero y col., 1992a). Los sistemas utilizados en este trabajo corresponden tanto a caracteres etnozootécnicos como a diferentes variables de polimorfismos bioquimicos. Cuando se han diferenciado las ganaderias dentrde razas, o las ganaderias entre si, se han utilizado diferentes pruebas, a partir de las frecuencias genéticas y genotipicas: indices de Wright, heterocigosidades media, varianzas de Whalund, prueba G de razón de probabilidad, etc. También se obtuvieron las distancia genéticas de Cavalli-Sforza. Se concluye que en las razas Negra Serrana y Merino de Grazalema las varianzas de Whalund obtenidas son consecuencia de la acción de la selección que ha actuado dividiendo las razas en distintas poblaciones con diferenciación espacial. Las heterocigosidades medias de cada raza no difieren mucho entre si, pero cuando se considera cada sistema aisladamente, las discrepancias entre grupos étnicos son acusadas. Los indices F de Wright ponen de manifiesto que, mientras en las razas Blanca Serrana y Merino de Grazalema se pueden deducir heterocigosidades genéticas entre las problaciones o ganaderias estudiadas, no ocurre otro tanto en la raza Negra Serrana. Los valores de F(IS) parecen indicar que, a pesar del tamaño pequeño de las poblaciones, se ha evitado la consanguinidad, probablemente por la entrada de sementales externos. No se produce en ninguna de las razas un exceso significativo de heterocigosis. Las distancias genéticas entre ganaderias dentro de razas no difieren de lashalladas entre razas. ZUSAMMENFASSUNG: Es wurde mit verschiedenen andalusischen Zuchten der Schafrassen 'Grazalema Merino' and 'Lebrijan Churro' und der Ziegenrassen 'Andalusian White' und 'Andalusian Black' gearbeitet, die man von den andalusichen Rassen im Hinblick auf Erhaltung ausgewählt hat. Die benutzten Systeme in dieser Forschungsarbeit entsprechen Merkmalen, die sich sowohl auf ethnisch wie auch auf die verschiedenen Variablen des biochemischen Polimorfismius bezichen. Zur Unterschlidung von Zuchten innerhalb die Rassen oder von zuchten untereinander wurden verschiedene Tests benutzt, die von den genetischen und genotypischen Frequenzen ausgehen: Wright-Index, Durchschnittsheterozygositäten, Wahl und Varianz G-Test der Wahrscheinlichkeit, etc. Außerdem wurden die genetischen Distanzen nach Cavalli-Sforza errechnet. Man Kommt zum Schluß, daß in den Andalusian Black und Grazalema Merino die Wahl und Varianz das Ergebnis einer Selektionsaktivität ist, die die Rassen in Verschiedenen Populationen und unterschiedlichen Räumen aufgeteilt hat. Die durchschnittlichen Heterozygositäten jeder Rasse unterscheiden sich wenig voneinander, aber wenn man jedes System für sich betrachtet, stell man doch erhebliche Diskrepanzen zwischen den ethnischen Gruppen fest. Der Wright-Index offenbart, daß man in den Rassen Andalusian White und Grazalema Merino genetische Heterozygositäten ableiten kann zwischen den Populationen oder den untersuchten Zuchten; dies ist nicht der Fall inder Rasse Andalusian Black. Die F(IS) werte scheinen anzugeben, da trotz der kleinen Größe der Populationen die Blutsverwandschaft vermieden wurde, wahrscheinlich durch von außerhalb kommenden Böcken. In keiner der Rassen existiert übermässige Heterozygotie Die genetischen Distanzen zwischer der Zuchten unterscheiden sich nicht van dener der Rassen. 1997 Blackwell Verlag GmbH.
The colloidal systems are present everywhere in many varieties such as emulsions (liquid droplets dispersed in liquid), aerosols (liquid dispersed in gas), foam (gas in liquid), etc. Among several new methods for the preparation of colloids, the so-called miniemulsion technique has been shown to be one of the most promising. Miniemulsions are defined as stable emulsions consisting of droplets with a size of 50-500 nm by shearing a system containing oil, water, a surfactant, and a highly water insoluble compound, the so-called hydrophobe 1. In the first part of this work, dynamic crystallization and melting experiments are described which were performed in small, stable and narrowly distributed nanodroplets (confined systems) of miniemulsions. Both regular and inverse systems were examined, characterizing, first, the crystallization of hexadecane, secondly, the crystallization of ice. It was shown for both cases that the temperature of crystallization in such droplets is significantly decreased (or the required undercooling is increased) as compared to the bulk material. This was attributed to a very effective suppression of heterogeneous nucleation. It was also found that the required undercooling depends on the nanodroplet size: with decreasing droplet size the undercooling increases. 2. It is shown that the temperature of crystallization of other n-alkanes in nanodroplets is also significantly decreased as compared to the bulk material due to a very effective suppression of heterogeneous nucleation. A very different behavior was detected between odd and even alkanes. In even alkanes, the confinement in small droplets changes the crystal structure from a triclinic (as seen in bulk) to an orthorhombic structure, which is attributed to finite size effects inside the droplets. An intermediate metastable rotator phase is of less relevance for the miniemulsion droplets than in the bulk. For odd alkanes, only a strong temperature shift compared to the bulk system is observed, but no structure change. A triclinic structure is formed both in bulk and in miniemulsion droplets. 3. In the next part of the thesis it is shown how miniemulsions could be successfully applied in the development of materials with potential application in pharmaceutical and medical fields. The production of cross-linked gelatin nanoparticles is feasible. Starting from an inverse miniemulsion, the softness of the particles can be controlled by varying the initial concentration, amount of cross-link agent, time of cross-linking, among other parameters. Such particles show a thermo-reversible effect, e.g. the particles swell in water above 37 °C and shrink below this temperature. Above 37 °C the chains loose the physical cross-linking, however the particles do not loose their integrity, because of the chemical cross-linking. Those particles have potential use as drug carriers, since gelatin is a natural polymer derived from collagen. 4. The cross-linked gelatin nanoparticles have been used for the biomineralization of hydroxyapatite (HAP), a biomineral, which is the major constituent of our bones. The biomineralization of HAP crystals within the gelatin nanoparticles results in a hybrid material, which has potential use as a bone repair material. 5. In the last part of this work we have shown that layers of conjugated semiconducting polymers can be deposited from aqueous dispersion prepared by the miniemulsion process. Dispersions of particles of different conjugated semiconducting polymers such as a ladder-type poly(para-phenylene) and several soluble derivatives of polyfluorene could be prepared with well-controlled particle sizes ranging between 70 - 250 nm. Layers of polymer blends were prepared with controlled lateral dimensions of phase separation on sub-micrometer scales, utilizing either a mixture of single component nanoparticles or nanoparticles containing two polymers. From the results of energy transfer it is demonstrated that blending two polymers in the same particle leads to a higher efficiency due to the better contact between the polymers. Such an effect is of great interest for the fabrication of opto-electronic devices such as light emitting diodes with nanometer size emitting points and solar cells comprising of blends of electron donating and electron accepting polymers. populärwissenschaftlicher Abstract: Kristallisation, Biomimetik und halbleitende Polymere in räumlich begrenzten Systemen: Äl und Wasser mischen sich nicht, man kann aber aus beiden Flüssigkeiten Emulsionen herstellen, bei denen Tröpfchen der einen Flüssigkeit in der anderen Flüssigkeit vorliegen. Das heit, es können entweder Ältröpfchen in Wasser oder Wassertröpfchen in Äl erzeugt werden. Aus täglichen Erfahrungen, z.B. beim Kochen wei man jedoch, dass sich eine Emulsion durch Schütteln oder Rühren herstellen lässt, diese jedoch nicht besonders stabil ist. Mit Hilfe von hohen Scherenergien kann man nun sehr kleine, in ihrer Gröe sehr einheitliche und auerdem sehr stabile Tröpfchen von 1/10000 mm erhalten. Eine solche Emulsion wird Miniemulsion genannt. In der Dissertation wurden nun z.B. Miniemulsionen untersucht, die aus kleinen Wassertröpfchen in einem Äl bestehen. Es konnte gezeigt werden, dass das Wasser in diesen Tröpfchen, also in den räumlich begrenzten Systemen, nicht bei 0 °C, sondern bei -22 °C kristallisierte. Wie lässt sich das erklären? Wenn man einen Eimer Wasser hat, dann bildet sich normalerweise bei 0 °C Eis, da nämlich in dem Wasser einige (manchmal ganz wenige) Keime (z.B. Schutzteilchen, ein Fussel etc.) vorhanden sind, an denen sich die ersten Kristalle bilden. Wenn sich dann einmal ein Kristall gebildet hat, kann das Wasser im gesamten Eimer schnell zu Eis werden. Ultrareines Wasser würde bei -22 °C kristallisieren. Wenn man jetzt die Menge Wasser aus dem Eimer in kleine Tröpfchen bringt, dann hat man eine sehr, sehr groe Zahl, nämlich 1017 Tröpfchen, in einem Liter Emulsion vorliegen. Die wenigen Schmutzpartikel verteilen auf sehr wenige Tröpfchen, die anderen Tröpfchen sind ultrarein. Daher kristallisieren sie erst bei -22 °C. Im Rahmen der Arbeit konnte auch gezeigt werden, dass die Miniemulsionen genutzt werden können, um kleine Gelatine-Partikel, also Nanogummibärchen, herzustellen. Diese Nanogummibärchen quellen bei Erhöhung der Temperatur auf ca. 38 °C an. Das kann ausgenutzt werden, um zum Beispiel Medikamente zunächst in den Partikeln im menschlichen Körper zu transportieren, die Medikamente werden dann an einer gewünschten Stelle freigelassen. In der Arbeit wurde auch gezeigt, dass die Gelatine-Partikel genutzt werden können, um die Natur nachzuahnen (Biomimetik). Innerhalb der Partikel kann nämlich gezielt Knochenmaterial aufgebaut werden kann. Die Gelatine-Knochen-Partikel können dazu genutzt werden, um schwer heilende oder komplizierte Knochenbrüche zu beheben. Gelatine wird nämlich nach einigen Tagen abgebaut, das Knochenmaterial kann in den Knochen eingebaut werden. LEDs werden heute bereits vielfältig verwendet. LEDs bestehen aus Halbleitern, wie z.B. Silizium. Neuerdings werden dazu auch halbleitende Polymere eingesetzt. Das groe Problem bei diesen Materialien ist, dass sie aus Lösungsmitteln aufgebracht werden. Im Rahmen der Doktorarbeit wurde gezeigt, dass der Prozess der Miniemulsionen genutzt werden kann, um umweltfreundlich diese LEDs herzustellen. Man stellt dazu nun wässrige Dispersionen mit den Polymerpartikeln her. Damit hat man nicht nur das Lösungsmittel vermieden, das hat nun noch einen weiteren Vorteil: man kann nämlich diese Dispersion auf sehr einfache Art verdrucken, im einfachsten Fall verwendet man einfach einen handelsüblichen Tintenstrahldrucker.
In der vorliegenden Arbeit habe ich wichtige Teilmechanismen der Erregungs-Sekretionskopplung in der Speicheldrüse der Schabe Periplaneta americana (L.) untersucht. Die Speicheldrüse ist von dopaminergen und serotonergen Fasern innerviert (Baumann et al., 2002). Beide Transmitter stimulieren eine unterschiedliche Reaktion der Drüse: Dopamin (DA) stimuliert die P-Zellen der Acini und die Ausführgangzellen, während Serotonin (5-HT) die P- und C-Zellen der Acini stimuliert, nicht jedoch die Ausführgangzellen. Der Endspeichel ist nach einer DA-Stimulierung proteinfrei. Dagegen enthält er nach einer 5-HT-Stimulierung Proteine, die von den C-Zellen sezerniert werden (Just & Walz, 1996). Im ersten Teil meiner Arbeit habe ich mittels Kapillarelektrophoretischer Analyse (CE-Analyse) die Elektrolytkonzentrationen im Endspeichel untersucht sowie die Raten der Flüssigkeitssekretion gemessen. Damit wollte ich klären, welche Transporter an der Sekretion des Primärspeichels und an dessen Modifikation beteiligt sind. Ausserdem wollte ich die Rolle der transportaktiven Epithelzellen der Ausführgänge für die Modifikation des Primärspeichels untersuchen. Dafür habe ich einen Vergleich der Elektrolytkonzentrationen im DA- und 5-HT-stimulierten Endspeichel durchgeführt. Der Elektrolytgehalt des DA- und 5-HT-stimulierten Endspeichels unterscheidet sich nicht signifikant voneinander. Er ist nach beiden Stimulierungen hypoosmotisch zum verwendeten Ringer. Die Ausführgangzellen werden durch DA stimuliert und modifizieren den Primärspeichel durch eine netto-Ionenreabsorption. Meine Versuche zeigen jedoch, dass auch die während einer 5-HT-Stimulierung der Drüse unstimulierten Ausführgangzellen den Primärspeichel modifizieren. In einer nachfolgenden Versuchsreihe habe ich den Einfluss von Ouabain, einem Hemmstoff der Na+-K+-ATPase, und Bumetanid, einem Hemmstoff des NKCC, auf die Raten der Flüssigkeitssekretion sowie den Elektrolytgehalt des Endspeichels untersucht. Ich habe gefunden, dass die Aktivität der Na+-K+-ATPase wichtig für die Modifikation des DA-stimulierten Primärspeichels ist. Im Gegensatz dazu ist sie für die Modifikation des 5-HT-stimulierten Primärspeichels nicht von Bedeutung. Bezüglich der Flüssigkeitssekretion habe ich keinen Einfluss der Na+-K+-ATPase-Aktivität auf die DA-stimulierten Sekretionsraten gefunden, dagegen ist die 5-HT-stimulierte Sekretionsrate in Anwesenheit von Ouabain gesteigert. Die Aktivität des NKCC ist für beide sekretorische Prozesse, die Ionen- und die Flüssigkeitssekretion, wichtig. Eine Hemmung des NKCC bewirkt eine signifikante Verringerung der Raten der Flüssigkeitssekretion nach DA- und 5-HT-Stimulierung sowie in beiden Fällen einen signifikanten Abfall der Ionenkonzentrationen im Endspeichel. Im zweiten Teil meiner Arbeit habe ich versucht, Änderungen der intrazellulären Ionenkonzentrationen in den Acinuszellen während einer DA- oder 5-HT-Stimulierung zu messen. Diese Experimente sollten mit der Methode des "ratiometric imaging" durchgeführt werden. Messungen mit dem Ca2+-sensitiven Fluoreszenzfarbstoff Fura-2 zeigten keinen globalen Anstieg in der intrazellulären Ca2+-Konzentration der P-Zellen. Aufgrund von Problemen mit einer schlechten Beladung der Zellen, einer starken und sich während der Stimulierung ändernden Autofluoreszenz der Zellen sowie Änderungen im Zellvolumen wurden keine Messungen mit Na+- und K+-sensitiven Fluoreszenzfarbstoffen durchgeführt. Im dritten Teil dieser Arbeit habe ich die intrazellulären Signalwege untersucht, die zwischen einer 5-HT-Stimulierung der Drüse und der Proteinsekretion vermitteln. Dazu wurde der Proteingehalt im Endspeichel biochemisch mittels eines modifizierten Bradford Assay gemessen. Eine erstellte Dosis-Wirkungskurve zeigt, dass die Rate der Proteinsekretion von der zur Stimulierung verwendeten 5-HT-Konzentration abhängt. In einer Serie von Experimenten habe ich die intrazellulären Konzentrationen von Ca2+, cAMP und / oder cGMP erhöht und anschließend den Proteingehalt im Endspeichel gemessen. Ein Anstieg der intrazellulären Ca2+-Konzentration aktiviert nur eine geringe Rate der Proteinsekretion. Dagegen kann die Steigerung der intrazellulären cAMP-Konzentration eine stärkere Proteinsekretion aktivieren, die sich nicht signifikant von der nach 5-HT-Stimulierung unterscheidet. Die cAMP-stimulierte Proteinsekretion kann durch gleichzeitige Erhöhung der intrazellulären Ca2+-Konzentration weiter gesteigert werden. Dagegen aktivierte eine Erhöhung der intrazellulären cGMP-Konzentration die Proteinsekretion nicht. Aufgrund dieser Ergebnisse postuliere ich die Existenz eines die Adenylatcyclase aktivierenden 5-HT-Rezeptors in der Basolateralmembran der C-Zellen. The aim of this PhD-work was to investigate major mechanisms of excitation-secretion coupling in the salivary gland of the cockroach Periplaneta americana (L.). This salivary gland is innervated by dopaminergic and serotonergic fibres (Baumann et al., 2002). The two transmitters stimulate different processes in the gland: Dopamine (DA) stimulates the p-cells of the acini and the salivary duct cells, whereas 5-HT (serotonin) activates the p- and the c-cells of the acini, but not the salivary duct cells. Final saliva is completely protein-free after dopamine stimulation. It contains proteins, which are secreted by the c-cells of the acini, after a 5-HT-stimulation (Just & Walz, 1996). In the first part of my work I measured the electrolytic composition of the final saliva by capillary electrophoretic analysis and measured the rates of fluid secretion, in order to answer the following questions: 1.) Which transporters affect the production of primary saliva and its modification? 2.) What is the function of the transport-active salivary duct cells for the modification of the primary saliva? Electrolytic composition of the DA- and 5-HT-stimulated final saliva is not significantly different from each other, and is hypoosmotic to the Ringer used. Salivary duct cells are stimulated by DA and modify the primary saliva by a netto ion-reabsorption. My experiments also show that the duct cells, which are unstimulated during a 5-HT-stimulation of the gland, modify the primary saliva. In the next series of experiments I investigated the effects of ouabain, an inhibitor of the Na+-K+-ATPase, and bumetanide, an inhibitor of the NKCC on the rates of fluid secretion and the electrolytic composition of the final saliva. I found, that the activity of the Na+-K+-ATPase is important for the modification of DA-stimulated primary saliva during its flow through the stimulated duct system. In contrast, it is not important for modification of the 5-HT-stimulated primary saliva. Inhibition of the Na+-K+-ATPase does not affect rates of DA-stimulated fluid secretion, but it increases the rates of 5-HT-stimulated fluid secretion. Activity of the NKCC is important for both secretory processes: the ion and the fluid secretion. Inhibition of the NKCC results in a significant drop in the rates of fluid secretion after DA- and 5-HT-stimulation, as well as a drop in electrolytic concentrations in the saliva. In the second part of my work, I tried to measure changes in the intracellular ionic concentrations (Ca2+, Na+, and K+) within the acinar cells during a DA- or 5-HT-stimulation. The experiments should be performed by ratiometric imaging. Measurements with the Ca2+-sensitive dye Fura-2 did not show any global increase in the intracellular Ca2+-concentration in the p-cells of the acini. Problems concerning a bad loading of the cells, a strong autofluorescence which changed during the time course of the stimulation, as well as changes in the cell volume were the reason, that no measurements using Na+- or K+-sensitive dyes were performed. In the third part of my work I investigated the intracellular signalling pathways, which activate protein secretion after 5-HT-stimulation of the gland. A modified Bradford Assay was used for measuring the protein content in the final saliva. In a dose-response curve I showed that rates of protein secretion are dependent on the 5-HT-concentrations used to stimulate the glands. In another set of experiments I increased the intracellular concentrations of Ca2+, cAMP and / or cGMP, and measured the protein content in the final saliva. An increase in the intracellular Ca2+-concentration activates only a low rate of protein secretion. After an increase in the intracellular cAMP-concentration a much higher rate of protein secretion can be activated, which is not significantly different from the 5-HT stimulated rate of protein secretion. The cAMP-stimulated protein secretion can be further increased by a simultaneous rise in the intracellular Ca2+-concentration. In contrast, cGMP does not activate protein secretion. Therefore I propose the expression of an adenylyl cyclase activating 5-HT-receptor in the basolateral membrane of the protein secreting c-cells.
Die Landschaften Mitteleuropas sind das Resultat einer langwierigen Geschichte menschlicher Landnutzung mit ihren unterschiedlichen, z.T. konkurrierenden Nutzungsansprüchen. Durch eine überwiegend intensive Beanspruchung haben die direkten und indirekten Auswirkungen der Landnutzung in vielen Fällen zu Umweltproblemen geführt. Die Disziplin der Landschaftsökologie hat es sich zur Aufgabe gemacht, Konzepte für eine nachhaltige Nutzung der Landschaft zu entwickeln. Eine wichtige Fragestellung stellt dabei die Abschätzung der möglichen Folgen von Landnutzungsänderungen dar. Für die Analyse der relevanten Prozesse in der Landschaft werden häufig mathematische Modelle eingesetzt, welche es erlauben die Landschaft unter aktuellen Verhältnissen oder hinsichtlich veränderter Rahmenbedingungen zu untersuchen. Die hypothetische Änderung der Landnutzung, die als Landnutzungsszenario bezeichnet wird, verkörpert eine wesentliche Modifikation der Rahmenbedingungen, weil Landnutzung mageblich Einfluss auf die natürlichen Prozesse der Landschaft nimmt. Während die Antriebskräfte einer solchen Änderung überwiegend von sozio-ökonomischen und politischen Entscheidungen gesteuert werden, orientiert sich die exakte Verortung der Landnutzungsänderungen an den naturräumlichen Bedingungen und folgt z.T. erkennbaren Regeln. Anhand dieser Vorgaben ist es möglich, räumlich explizite Landnutzungsszenarien zu entwickeln, die als Eingangsdaten für die Modellierung verschiedener landschaftsökologischer Fragestellungen wie z.B. für die Untersuchung des Einflusses der Landnutzung auf den Wasserhaushalt, die Erosionsgefahr oder die Habitatqualität dienen können. Im Rahmen dieser Dissertation wurde das rasterbasierte deterministische Allokationsmodell luck (Land Use Change Scenario Kit) für die explizite Verortung der Landnutzungsänderungen entwickelt. Es basiert auf den in der Landschaftsökologie üblichen räumlichen Daten wie Landnutzung, Boden sowie Topographie und richtet sich bei der Szenarienableitung nach den Leitbildern der Landschaftsplanung. Das Modell fut auf der Hypothese, dass das Landnutzungsmuster als Funktion seiner landschaftsökologischen Faktoren beschrieben werden kann. Das Veränderungspotenzial einer Landnutzungseinheit resultiert im Modell aus einer Kombination der Bewertung der relativen Eignung des Standortes für die jeweilige Landnutzung und der Berücksichtigung von Standorteigenschaften der umliegenden Nachbarn. Die Durchführung der Landnutzungsänderung im Modell ist iterativ angelegt, um den graduellen Prozess des Landschaftswandels nachvollziehen zu können. Als Fallbeispiel für die Anwendung solcher räumlich expliziten Landnutzungsszenarien dient die Fragestellung, inwieweit Landnutzungsänderungen die Hochwasserentstehung beeinflussen. Um den Einfluss auf die Hochwasserentstehung für jede der Landnutzungskategorien – bebaute, landwirtschaftlich genutzte und naturnahe Flächen – abschätzen zu können, wird im Landnutzungsmodell luck exemplarisch für jede Kategorie ein Teilmodell für die Veränderung von Landnutzung angeboten: 1) Ausdehnung der Siedlungsfläche: Dieses Teilmodell fut auf der Annahme, dass sich Siedlungen nur in direkter Nachbarschaft bereits bestehender Bebauung und bevorzugt entlang von Entwicklungsachsen ausbreiten. Steile Hangneigungen stellen für potenzielle Standorte ein Hemmnis bei der Ausbreitung dar. 2) Stilllegung von Grenzertragsackerflächen: Gemä der Hypothese, dass sich die Stilllegung von Ackerflächen an der potenziellen Ertragsleistung der Standorte orientiert, werden in diesem Teilmodell alle Ackerstandorte dahingehend bewertet und die Flächen mit der geringsten Leistungsfähigkeit stillgelegt. Bei homogenen Gebietseigenschaften werden die Stilllegungsflächen zufällig auf die Ackerfläche verteilt. 3) Etablierung von Schutzgebieten in Ufer- und Auenbereichen: Ausgehend von der These, dass sich entlang von Flüssen sensible Flächen befinden, deren Schutz positive Folgen für das Leistungsvermögen der Landschaft haben kann, werden in diesem Teilmodell schützenswerte Ufer- und Auenbereiche auf derzeit landwirtschaftlich genutzten Flächen ausgewiesen. Die Gröe der Schutzgebietsfläche orientiert sich an der Morphologie der umgebenden Landschaft. Die drei Teilmodelle wurden hinsichtlich der implizierten Hypothesen mit vielen unterschiedlichen Ansätzen validiert. Das Resultat dieser intensiven Analyse zeigt für jedes Teilmodell eine zufriedenstellende Tauglichkeit. Die Modellierung der Landnutzungsänderungen wurden in drei mesoskaligen Flusseinzugsgebieten mit einer Fläche zwischen 100 und 500 km² durchgeführt, die sich markant in ihrer Landnutzung unterscheiden. Besonderer Wert wurde bei der Gebietsauswahl darauf gelegt, dass eines der Gebiete intensiv landwirtschaftlich genutzt wird, eines dicht besiedelt und eines vorwiegend bewaldet ist. Im Hinblick auf ihre Relevanz für die vorliegende Fragestellung wurden aus bestehenden Landnutzungstrends die Szenarien für (1) die prognostizierte Siedlungsfläche für das Jahr 2010, (2) die möglichen Konsequenzen des EU-weiten Beschlusses der Agenda 2000 und (3) die Novelle des Bundesnaturschutzgesetzes aus dem Jahr 2001 abgeleitet. Jedes Szenario wurde mit Hilfe des Modells auf die drei Untersuchungsgebiete angewendet. Dabei wurden für die Siedlungsausdehnung in allen drei Gebieten realistische Landnutzungsmuster generiert. Einschränkungen ergeben sich bei der Suche nach Grenzertragsstilllegungsflächen. Hier hat unter homogenen Gebietseigenschaften die zufällige Verteilung von Flächen für die Stilllegung zu einem unrealistischen Ergebnis geführt. Die Güte der Schutzgebietsausweisung ist mageblich an die aktuelle Landnutzung der Aue und die Morphologie des Geländes gebunden. Die besten Ergebnisse werden erzielt, wenn die Flächen in den Ufer- und Auenbereichen mehrheitlich unter derzeitiger Ackernutzung stehen und der Flusslauf sich in das Relief eingetieft hat. Exemplarisch werden für jeden Landnutzungstrend die hydrologischen Auswirkungen anhand eines historischen Hochwassers beschrieben, aus denen jedoch keine pauschale Aussage zum Einfluss der Landnutzung abgeleitet werden kann. Die Studie demonstriert die Bedeutung des Landnutzungsmusters für die natürlichen Prozesse in der Landschaft und unterstreicht die Notwendigkeit einer räumlich expliziten Modellierung für landschaftsökologische Fragestellungen in der Mesoskala. Today′s landscapes in Central Europe are the result of a long history of land-use, which is characterised by many different demands. The immediate and long-term consequences of predominantly intensive land-use have led to environmental problems in many cases. Therefore it is necessary to develop strategies for the maintenance of landscape efficiency which take into account the different claims of utilisation. In this context the estimation of possible impacts of land-use changes represents an important statement of problem. For the analysis of the relevant processes within the landscape, it is common to apply mathematical models. Such models enable the investigation of the landscape under current conditions or with regard to modified boundary conditions. A hypothetic alteration of land-use, which is termed as land-use scenario, represents a substantial modification of the boundary conditions, because land-use exerts a strong influence on the natural processes of the landscape. While the driving forces are predominantly governed by socio-economical and political decisions, the exact location of land-use changes within the landscape mainly depends on the natural conditions and follows partly transparent rules. With these presumptions it is possible to develop land-use scenarios, which can serve as input data for the modelling of different questions of landscape ecology such as the influence of land-use on the water balance, the danger of erosion or the quality of habitat characteristics. In the context of this thesis the grid-based deterministic allocation model luck (Land Use Change Scenario Kit) for the allocation of land-use changes was developed. It is based upon the types of spatial data, which are commonly used in landscape ecology, such as information on land-use, soils as well as topography. The derivation of scenarios follows the approaches of landscape planning. The model is based upon the hypothesis, that land-use structure can be described as a function of its landscape ecological factors. The potential of a site to become subject to land-use changes, results from a combination of its local qualities and the site characteristics of its neighbourhood. Land-use change is realised iteratively in order to simulate the gradual process of changes in the landscape. The influence of land-use changes on flood generation serves as a case study to demonstrate the need for spatial explicit land-use scenarios. For each land-use category – built up areas, agriculturally used areas and natural/semi-natural land – the model luck offers a submodel for investigating the effect of land-use changes on flood generation: 1) Expansion of settlement area: This submodel is based upon the assumption that settlements spread only in the neighbourhood of already existing built-up areas and preferentially along infrastructural axes of development. Steep slopes inhibit the spreading on potential locations. 2) Set-aside of marginal yield sites under agricultural use: Setting-aside of arable land is based on the hypothesis that the selection of arable land to be set-aside depends on the potential yield efficiency of the locations. Within this submodel all fields under agricultural use are valued to that effect and the ones with the least productive efficiency are selected as set-aside locations. In case of homogeneous area qualities the set-aside locations are selected randomly. 3) Establishment of protected areas in waterside and ripearian areas: This submodel takes into consideration that the protection of sensitive areas along the river courses may have positive consequences for the efficiency of the landscape. Therefore this submodel establishes protection zones on waterside and ripearian sites under currently agricultural use, that might be of value for nature conservation. The size of the protection area depends on the morphology of the surrounding landscape. The three submodels were validated with respect to the implied hypotheses by the help of many different approaches. The result of this intensive analysis shows a satisfying suitability for each of the submodels. The simulation of land-use changes was carried out for three mesoscale river catchments with an area between 100 and 500 km². Special attention was paid to the fact that these areas should be markingly different in their land-use: One study area is predominantly under intensive agricultural use, one is densely populated and the third one is covered by forest in large parts of the area. With regard to their relevance to the onhand question from existing land-use trends scenarios were derived for the prognosed settlement area for the year 2010, for the possible consequences of the EU-wide agreement of Agenda 2000 and for the amending federal conservation law dating to the year 2001, which enhances the enlargement of protected areas. Each scenario was applied to the three study areas utilizing the model luck. For the expansion of the settlement areas in all three study areas realistic land-use patterns were generated. Limitations arose only in the context of the search for marginal yield fields. Here, the random distribution of areas to be set-aside under homogeneous conditions led to unrealistic results. The quality of the establishment of protected areas in waterside and ripearian areas is substantially bound to current land-use and the morphology of the area. The best results for this submodel are achieved if waterside and ripearian areas are mainly arable land and if the river has lowered its course into the morphology. The hydrological consequences are described exemplarily for each land-use trend with a historical flood event. The interpretation of the hydrographs does not allow global statements about the influence of land-use. The study demonstrates the significance of land-use pattern for the natural processes in the landscape and underlines the necessity of spatially explicit modelling for landscape ecological questions at the mesoscale.
Erstes wissenschaftliches Beobachtungsinstrument liefert eindrucksvolle Bilder Entsprechend dem straffen Zeitplan wird das ESO Very Large Teleskop Projekt (VLT-Projekt) auf dem Cerro Paranal in Nord-Chile verwirklicht: die volle Betriebsbereitschaft des ersten der vier 8,2m-Einzelteleskope wird Anfang des nächsten Jahres erreicht sein. Am 15. September 1998 wurde ein weiterer wichtiger Meilenstein erfolgreich, rechtzeitig und innerhalb des Kostenplans erreicht. Nur wenige Tage nach seiner Montage am ersten 8,2m-Einzelteleskop des VLT (UT1) konnte FORS1 ( FO cal R educer and S pectrograph) als erstes einer Gruppe leistungsfähiger und komplexer wissenschaftlicher Instrumente seine Beobachtungstätigkeit beginnen. Von Anfang an konnte es eine Reihe exzellenter astronomischer Bilder aufnehmen. Dieses bedeutende Ereignis eröffnet eine Fülle neuer Möglichkeiten für die europäische Astronomie. FORS - ein Höhepunkt an Komplexität FORS1 und das zukünftige Zwillingsinstrument (FORS2) sind das Ergebnis einer der eingehendsten und fortschrittlichsten technologischen Studien, die je für ein Instrument der bodengebundenen Astronomie durchgeführt wurden. Dieses einzigartige Instrument ist nun im Cassegrain-Fokus installiert und verschwindet beinahe, trotz seiner Dimensionen von 3 x 1.5m (Gewicht 2.3t), unterhalb des riesigen 53 m 2 großen Zerodurspiegels. Um die große Spiegelfläche und die hervorragende Bildqualität von UT1 optimal auszunützen, wurde FORS speziell so konstruiert, daß es die lichtschwächsten und entferntesten Objekte im Weltall untersuchen kann. Bald wird dieses komplexe VLT-Instrument den europäischen Astronomen erlauben, die derzeitigen Beobachtungshorizonte entscheidend zu erweitern. Die beiden FORS-Instrumente sind Vielzweck-Beobachtungsinstrumente, die in mehreren unterschiedlichen Beobachtungsarten eingesetzt werden können. Beispielsweise können Bilder mit zwei verschiedenen Abbildungsmaßstäben (Vergrößerungen) sowie Spektren mit unterschiedlicher spektraler Auflösung von einzelnen oder mehreren Objekten aufgenommen werden. Dabei erlaubt der schnelle Wechsel zwischen den unterschiedlichen Beobachtungsarten z.B. zunächst die Aufnahme und direkt anschließend die Spektroskopie weit entfernter Galaxien. Damit kann dann u.a. die stellare Zusammensetzung und die Entfernung bestimmt werden. Als eines der leistungsfähigsten astronomischen Instrumente seiner Art wird FORS1 ein wahres Arbeitspferd für die Untersuchung des fernen Universums darstellen. Der Bau von FORS Das FORS-Projekt wird unter ESO-Kontrakt von einem Konsortium dreier deutscher astronomischer Institute durchgeführt, der Landessternwarte Heidelberg und den Universitäts-Sternwarten von Göttingen and München. Bis zur Beendigung des Projekts werden die beteiligten Institute Arbeit im Umfang von ca. 180 Mann-Jahren eingebracht haben. Bei der Landessternwarte Heidelberg lag die Leitung des Projekts. Hier wurde außerdem das gesamte optische System konstruiert, die Beschaffung der Komponenten der abbildenden Optik und der Zusatzoptiken für Spektroskopie und Polarimetrie durchgeführt und die spezielle Computersoftware geschrieben, mit der die von FORS gelieferten Daten verarbeitet und ausgewertet werden. Darüber hinaus wurde in der Werkstatt der Sternwarte ein Teleskopsimulator gebaut, mit dem alle wesentlichen Funktionen von FORS in Europa getestet werden konnten, bevor das Instrument zum Paranal (Chile) transportiert wurde. An der Universitäts-Sternwarte Göttingen wurden Konstruktion, Herstellung und Zusammenbau der gesamten Mechanik von FORS durchgeführt. Der größte Teil der Präzisionsteile, insbesondere der Multispalteinheit, wurde in der feinmechanischen Werkstatt der Sternwarte hergestellt. Die Beschaffung der großen Instrumentengehäuse und Flansche, die Computeranalysen für mechanische und thermische Stabilität des empfindlichen Spektrographen und die Herstellung der speziellen Werkzeuge für Handhabung, Wartung und Justierung lag ebenso in der Verantwortung dieser Sternwarte wie die Tests der zahlreichen opto- und elektromechanischen Funktionen. Die Universitäts-Sternwarte München war verantwortlich für das Projektmanagement, Integration und Test des gesamten Instruments im Labor, für Planung und Einbau aller Elektronik und Elektromechanik, sowie für Entwicklung und Test der gesamten Software, die FORS in allen Teilen vollständig per Computer steuert (z.B. Filter- und Grismräder, Verschlüsse, Spalteinheit für die Vielspaltspektroskopie, Masken, alle optischen Komponenten, Elektromotoren, Encoder usw.). Zusätzlich wurde Computersoftware geschrieben, mit der die komplexen astronomischen Beobachtungen mit FORS vorbereitet werden und das Verhalten des Instruments durch eine ständige Kontrolle der gesammelten wissenschaftlichen Daten überwacht wird. Als Gegenleistung für den Bau von FORS erhalten die Astronomen der drei beteiligten Institute des FORS-Konsortiums eine gewisse Anzahl von Nächten an "garantierter Beobachtungszeit" am VLT. In dieser Beobachtungszeit werden verschiedene Forschungsprojekte durchgeführt, deren Themen unter anderem von kleinen Körpern im äußeren Sonnensystem über Untersuchungen von Sternen im Endstadium und den von ihnen abgestoßenen Gaswolken bis zur Erforschung ferner Galaxien und Quasare reichen, die Aufschluß über die frühen Zeiten unseres Universums geben. Erste Tests von FORS1 am VLT-UT1: ein großartiger Erfolg Nach sorgfältiger Vorbereitung hat das FORS-Konsortium nun mit der Inbetriebnahme ("Commissioning") des Instruments begonnen. Dazu gehören ein eingehender Nachweis der spezifizierten Leistungsfähigkeit am Teleskop, die Überprüfung der korrekten Funktionsweise unter Softwaresteuerung vom Kontrollraum auf Paranal, und am Ende dieses Prozesses eine Demonstration, daß das Instrument seinen angestrebten wissenschaftlichen Zweck erfüllt. Während der Durchführung dieser Tests gelangen dem Commissioning-Team auf Paranal eine Reihe von Aufnahmen verschiedener astronomischer Objekte, von denen einige hier wiedergegeben sind. Sie wurden alle mit FORS in der Standardauflösung gewonnen (Bildfeldgröße 6.8 x 6.8 Bogenminuten, Pixelgröße 0.20 Bogensekunden) und zeigen einige der eindrucksvollen Möglichkeiten, die das neue Instrument bietet. Spiralgalaxie NGC 1288 ESO PR Photo 37a/98 ESO PR Photo 37a/98 [Preview - JPEG: 800 x 908 pix - 224k] [High-Res - JPEG: 3000 x 3406 pix - 1.5Mb] Farbaufnahme der Spiralgalaxie NGC 1288, aufgenommen in der ersten Beobachtungsnacht von FORS ("Nacht des ersten Lichts"). Das erste Photo zeigt eine Dreifarbenaufnahme der schönen Spiralgalaxie NGC 1288 im südlichen Sternbild Fornax. PR Photo 37a/98 umfaßt das gesamte Feld, das mit der 2048 x 2048 Pixel großen CCD-Kamera abgebildet wurde. Es wurde aus drei CCD-Aufnahmen zusammengesetzt, die bei gutem Seeing in verschiedenen Farben in der "Nacht des ersten Lichts" (15. September 1998) aufgenommen wurden. Diese Galaxie mit einem Durchmesser von rund 200000 Lichtjahren ist etwa 300 Millionen Lichtjahre entfernt, ihre Fluchtgeschwindigkeit beträgt 4500 km/sec. Technische Informationen : Photo 37a/98 ist ein Komposit von drei Aufnahmen in den drei Filtern B (420nm, 6 Minuten belichtet), V (530nm, 3 Minuten) und I (800nm, 3 Minuten) während einer Periode mit 0.7 Bogensekunden Seeing. Das gezeigte Feld ist 6.8 x 6.8 Bogenminuten groß. Norden ist links, Osten unten. Entfernter Galaxienhaufen ESO PR Photo 37b/98 ESO PR Photo 37b/98 [Preview - JPEG: 657 x 800 pix - 248k] [High-Res - JPEG: 2465 x 3000 pix - 1.9Mb] Ein ungewöhnlicher Galaxienhaufen in der Umgebung des Quasars PB5763 . ESO PR Photo 37c/98 ESO PR Photo 37c/98 [Preview - JPEG: 670 x 800 pix - 272k] [High-Res - JPEG: 2512 x 3000 pix - 1.9Mb] Vergrößerung von PR Photo 37b/98; sie zeigt mehr Einzelheiten des ungewöhnlichen Galaxienhaufens. Die nächsten Photos wurden von einer 5-minütigen Aufnahme im Nahen Infrarot reproduziert, die ebenfalls in der "Nacht des ersten Lichts" von FORS1 (15. September 1998) gewonnen wurde. PR Photo 37b/98 zeigt einen Himmelsausschnitt in der Nähe des Quasars PB5763, in dem auch ein ungewöhnlicher, sehr weit entfernter Haufen von Galaxien zu sehen ist. Er besteht aus einer großen Zahl lichtschwacher Galaxien, die bisher noch nicht eingehend untersucht wurden. Dieser Haufen ist ein gutes Beispiel für die Art von Objekten, auf die viel Beobachtungszeit mit FORS verwendet werden wird, sobald der reguläre Beobachtungsbetrieb begonnen hat. Eine Vergrößerung des gleichen Feldes ist in PR Photo 37c/98 wiedergegeben. Sie zeigt die einzelnen Mitglieder dieses Galaxienhaufens im Detail. Man beachte besonders die interessante spindelförmige Galaxie, die anscheinend einen äquatorialen Ring aufweist. Neben einer schönen Spiralgalaxie sind auch noch viele weitere lichtschwache Galaxien zu erkennen. Sie sind entweder Zwerggalaxien und Mitglieder des Haufens oder befinden sich sehr viel weiter entfernt im Hintergrund des Haufens. Technische Informationen : PR Photos 37b/98 (als Negativ reproduziert) und 37c/98 (Positiv) stammen von einer Aufnahme, die bei 0.8 Bogensekunden Seeing durch ein I-Filter (nahes Infrarot, 800nm) gewonnen wurde. Die Belichtungszeit betrug 5 Minuten, und es wurde eine Flatfield-Korrektur durchgeführt. Das gezeigte Feld ist 6.8 x 6.8 Bogenminuten bzw. 2.5 x 2.3 Bogenminuten groß. Norden ist links oben, Osten links unten. Spiralgalaxie NGC 1232 ESO PR Photo 37d/98 ESO PR Photo 37d/98 [Preview - JPEG: 800 x 912 pix - 760k] [High-Res - JPEG: 3000 x 3420 pix - 5.7Mb] Ein Farbbild der Spiralgalaxie NGC 1232, aufgenommen am 21. September 1998. ESO PR Photo 37e/98 ESO PR Photo 37e/98 [Preview - JPEG: 800 x 961 pix - 480k] [High-Res - JPEG: 3000 x 3602 pix - 3.5Mb] Vergrößerung des Zentrums von PR Photo 37d/98. Dieses spektakuläre Bild der großen Spiralgalaxie NGC 1232 (Photo 37d/98) wurde am 21. September 1998 unter guten Beobachtungsbedingungen erhalten. Es wurde aus drei Einzelaufnahmen im ultravioletten, blauen und roten Licht zusammengesetzt. Die Farben der verschiedenen Regionen sind deutlich sichtbar: Das Zentralgebiet enthält ältere, rötlich leuchtende Sterne (Photo 37e/98), während die Spiralarme von jungen, bläulichen Sternen und roten Sternentstehungsgebieten bevölkert sind. Man beachte die gestörte Begleitgalaxie am linken Rand (Photo 37d/98), die wie der griechische Buchstabe "Theta" aussieht. NGC 1232 liegt 20 Grad südlich des Himmelsäquators im Sternbild Eridanus. Obwohl die Entfernung dieser Galaxie ungefähr 100 Millionen Lichtjahre beträgt, kann man auf Grund der exzellenten Bildqualität einen unglaublichen Reichtum an Details erkennen. Bei dieser Entfernung entspricht die Kantenlänge des Bildfeldes etwa 200000 Lichtjahren oder etwa der doppelten Größe unserer Milchstraße. Technische Informationen : Photos 37d/98 und 37e/98 sind ein Komposit von drei Aufnahmen in den drei Filtern U (360nm, 10 Minuten belichtet), B (420nm, 6 Minuten) und R (600nm, 2 Minuten 30 Sekunden) während einer Periode mit 0.7 Bogensekunden Seeing. Das gezeigte Feld ist 6.8 x 6.8 Bogenminuten bzw. 1.6 x 1.8 Bogenminuten groß. Norden ist oben, Osten links. Note: [1] Diese Pressemitteilung wird gemeinsam (auf Englisch und Deutsch) von der Europäischen Südsternwarte, der Landessternwarte Heidelberg und den Universitäts-Sternwarten Göttingen und München herausgegeben. An English Version of this Press Release is also available. Zugang zu ESO Presseinformationen ESO Presseinformationen werden im World Wide Web zur Verfügung gestellt (URL: http://www.eso.org/outreach/press-rel/). ESO Pressephotos dürfen veröffentlicht werden, wenn die Europäische Südsternwarte als Urheber genannt wird.
Semi-arid areas are, due to their climatic setting, characterized by small water resources. An increasing water demand as a consequence of population growth and economic development as well as a decreasing water availability in the course of possible climate change may aggravate water scarcity in future, which often exists already for present-day conditions in these areas. Understanding the mechanisms and feedbacks of complex natural and human systems, together with the quantitative assessment of future changes in volume, timing and quality of water resources are a prerequisite for the development of sustainable measures of water management to enhance the adaptive capacity of these regions. For this task, dynamic integrated models, containing a hydrological model as one component, are indispensable tools. The main objective of this study is to develop a hydrological model for the quantification of water availability in view of environmental change over a large geographic domain of semi-arid environments. The study area is the Federal State of Ceará (150 000 km2) in the semi-arid north-east of Brazil. Mean annual precipitation in this area is 850 mm, falling in a rainy season with duration of about five months. Being mainly characterized by crystalline bedrock and shallow soils, surface water provides the largest part of the water supply. The area has recurrently been affected by droughts which caused serious economic losses and social impacts like migration from the rural regions. The hydrological model Wasa (Model of Water Availability in Semi-Arid Environments) developed in this study is a deterministic, spatially distributed model being composed of conceptual, process-based approaches. Water availability (river discharge, storage volumes in reservoirs, soil moisture) is determined with daily resolution. Sub-basins, grid cells or administrative units (municipalities) can be chosen as spatial target units. The administrative units enable the coupling of Wasa in the framework of an integrated model which contains modules that do not work on the basis of natural spatial units. The target units mentioned above are disaggregated in Wasa into smaller modelling units within a new multi-scale, hierarchical approach. The landscape units defined in this scheme capture in particular the effect of structured variability of terrain, soil and vegetation characteristics along toposequences on soil moisture and runoff generation. Lateral hydrological processes at the hillslope scale, as reinfiltration of surface runoff, being of particular importance in semi-arid environments, can thus be represented also within the large-scale model in a simplified form. Depending on the resolution of available data, small-scale variability is not represented explicitly with geographic reference in Wasa, but by the distribution of sub-scale units and by statistical transition frequencies for lateral fluxes between these units. Further model components of Wasa which respect specific features of semi-arid hydrology are: (1) A two-layer model for evapotranspiration comprises energy transfer at the soil surface (including soil evaporation), which is of importance in view of the mainly sparse vegetation cover. Additionally, vegetation parameters are differentiated in space and time in dependence on the occurrence of the rainy season. (2) The infiltration module represents in particular infiltration-excess surface runoff as the dominant runoff component. (3) For the aggregate description of the water balance of reservoirs that cannot be represented explicitly in the model, a storage approach respecting different reservoirs size classes and their interaction via the river network is applied. (4) A model for the quantification of water withdrawal by water use in different sectors is coupled to Wasa. (5) A cascade model for the temporal disaggregation of precipitation time series, adapted to the specific characteristics of tropical convective rainfall, is applied for the generating rainfall time series of higher temporal resolution. All model parameters of Wasa can be derived from physiographic information of the study area. Thus, model calibration is primarily not required. Model applications of Wasa for historical time series generally results in a good model performance when comparing the simulation results of river discharge and reservoir storage volumes with observed data for river basins of various sizes. The mean water balance as well as the high interannual and intra-annual variability is reasonably represented by the model. Limitations of the modelling concept are most markedly seen for sub-basins with a runoff component from deep groundwater bodies of which the dynamics cannot be satisfactorily represented without calibration. Further results of model applications are: (1) Lateral processes of redistribution of runoff and soil moisture at the hillslope scale, in particular reinfiltration of surface runoff, lead to markedly smaller discharge volumes at the basin scale than the simple sum of runoff of the individual sub-areas. Thus, these processes are to be captured also in large-scale models. The different relevance of these processes for different conditions is demonstrated by a larger percentage decrease of discharge volumes in dry as compared to wet years. (2) Precipitation characteristics have a major impact on the hydrological response of semi-arid environments. In particular, underestimated rainfall intensities in the rainfall input due to the rough temporal resolution of the model and due to interpolation effects and, consequently, underestimated runoff volumes have to be compensated in the model. A scaling factor in the infiltration module or the use of disaggregated hourly rainfall data show good results in this respect. The simulation results of Wasa are characterized by large uncertainties. These are, on the one hand, due to uncertainties of the model structure to adequately represent the relevant hydrological processes. On the other hand, they are due to uncertainties of input data and parameters particularly in view of the low data availability. Of major importance is: (1) The uncertainty of rainfall data with regard to their spatial and temporal pattern has, due to the strong non-linear hydrological response, a large impact on the simulation results. (2) The uncertainty of soil parameters is in general of larger importance on model uncertainty than uncertainty of vegetation or topographic parameters. (3) The effect of uncertainty of individual model components or parameters is usually different for years with rainfall volumes being above or below the average, because individual hydrological processes are of different relevance in both cases. Thus, the uncertainty of individual model components or parameters is of different importance for the uncertainty of scenario simulations with increasing or decreasing precipitation trends. (4) The most important factor of uncertainty for scenarios of water availability in the study area is the uncertainty in the results of global climate models on which the regional climate scenarios are based. Both a marked increase or a decrease in precipitation can be assumed for the given data. Results of model simulations for climate scenarios until the year 2050 show that a possible future change in precipitation volumes causes a larger percentage change in runoff volumes by a factor of two to three. In the case of a decreasing precipitation trend, the efficiency of new reservoirs for securing water availability tends to decrease in the study area because of the interaction of the large number of reservoirs in retaining the overall decreasing runoff volumes. Semiaride Gebiete sind auf Grund der klimatischen Bedingungen durch geringe Wasserressourcen gekennzeichnet. Ein zukünftig steigender Wasserbedarf in Folge von Bevölkerungswachstum und ökonomischer Entwicklung sowie eine geringere Wasserverfügbarkeit durch mögliche Klimaänderungen können dort zu einer Verschärfung der vielfach schon heute auftretenden Wasserknappheit führen. Das Verständnis der Mechanismen und Wechselwirkungen des komplexen Systems von Mensch und Umwelt sowie die quantitative Bestimmung zukünftiger Veränderungen in der Menge, der zeitlichen Verteilung und der Qualität von Wasserressourcen sind eine grundlegende Voraussetzung für die Entwicklung von nachhaltigen Maßnahmen des Wassermanagements mit dem Ziel einer höheren Anpassungsfähigkeit dieser Regionen gegenüber künftigen Änderungen. Hierzu sind dynamische integrierte Modelle unerlässlich, die als eine Komponente ein hydrologisches Modell beinhalten. Vorrangiges Ziel dieser Arbeit ist daher die Erstellung eines hydrologischen Modells zur großräumigen Bestimmung der Wasserverfügbarkeit unter sich ändernden Umweltbedingungen in semiariden Gebieten. Als Untersuchungsraum dient der im semiariden tropischen Nordosten Brasiliens gelegene Bundestaat Ceará (150 000 km2). Die mittleren Jahresniederschläge in diesem Gebiet liegen bei 850 mm innerhalb einer etwa fünfmonatigen Regenzeit. Mit vorwiegend kristallinem Grundgebirge und geringmächtigen Böden stellt Oberflächenwasser den größten Teil der Wasserversorgung bereit. Die Region war wiederholt von Dürren betroffen, die zu schweren ökonomischen Schäden und sozialen Folgen wie Migration aus den ländlichen Gebieten geführt haben. Das hier entwickelte hydrologische Modell Wasa (Model of Water Availability in Semi-Arid Environments) ist ein deterministisches, flächendifferenziertes Modell, das aus konzeptionellen, prozess-basierten Ansätzen aufgebaut ist. Die Wasserverfügbarkeit (Abfluss im Gewässernetz, Speicherung in Stauseen, Bodenfeuchte) wird mit täglicher Auflösung bestimmt. Als räumliche Zieleinheiten können Teileinzugsgebiete, Rasterzellen oder administrative Einheiten (Gemeinden) gewählt werden. Letztere ermöglichen die Kopplung des Modells im Rahmen der integrierten Modellierung mit Modulen, die nicht auf der Basis natürlicher Raumeinheiten arbeiten. Im Rahmen eines neuen skalenübergreifenden, hierarchischen Ansatzes werden in Wasa die genannten Zieleinheiten in kleinere räumliche Modellierungseinheiten unterteilt. Die ausgewiesenen Landschaftseinheiten erfassen insbesondere die strukturierte Variabilität von Gelände-, Boden- und Vegetationseigenschaften entlang von Toposequenzen in ihrem Einfluss auf Bodenfeuchte und Abflussbildung. Laterale hydrologische Prozesse auf kleiner Skala, wie die für semiaride Bedingungen bedeutsame Wiederversickerung von Oberflächenabfluss, können somit auch in der erforderlichen großskaligen Modellanwendung vereinfacht wiedergegeben werden. In Abhängigkeit von der Auflösung der verfügbaren Daten wird in Wasa die kleinskalige Variabilität nicht räumlich explizit sondern über die Verteilung von Flächenanteilen subskaliger Einheiten und über statistische Übergangshäufigkeiten für laterale Flüsse zwischen den Einheiten berücksichtigt. Weitere Modellkomponenten von Wasa, die spezifische Bedingungen semiarider Gebiete berücksichtigen, sind: (1) Ein Zwei-Schichten-Modell zur Bestimmung der Evapotranspiration berücksichtigt auch den Energieumsatz an der Bodenoberfläche (inklusive Bodenverdunstung), der in Anbetracht der meist lichten Vegetationsbedeckung von Bedeutung ist. Die Vegetationsparameter werden zudem flächen- und zeitdifferenziert in Abhängigkeit vom Auftreten der Regenzeit modifiziert. (2) Das Infiltrationsmodul bildet insbesondere Oberflächenabfluss durch Infiltrationsüberschuss als dominierender Abflusskomponente ab. (3) Zur aggregierten Beschreibung der Wasserbilanz von im Modell nicht einzeln erfassbaren Stauseen wird ein Speichermodell unter Berücksichtigung verschiedener Größenklassen und ihrer Interaktion über das Gewässernetz eingesetzt. (4) Ein Modell zur Bestimmung der Entnahme durch Wassernutzung in verschiedenen Sektoren ist an Wasa gekoppelt. (5) Ein Kaskadenmodell zur zeitlichen Disaggregierung von Niederschlagszeitreihen, das in dieser Arbeit speziell für tropische konvektive Niederschlagseigenschaften angepasst wird, wird zur Erzeugung höher aufgelöster Niederschlagsdaten verwendet. Alle Modellparameter von Wasa können von physiographischen Gebietsinformationen abgeleitet werden, sodass eine Modellkalibrierung primär nicht erforderlich ist. Die Modellanwendung von Wasa für historische Zeitreihen ergibt im Allgemeinen eine gute Übereinstimmung der Simulationsergebnisse für Abfluss und Stauseespeichervolumen mit Beobachtungsdaten in unterschiedlich großen Einzugsgebieten. Die mittlere Wasserbilanz sowie die hohe monatliche und jährliche Variabilität wird vom Modell angemessen wiedergegeben. Die Grenzen der Anwendbarkeit des Modell-konzepts zeigen sich am deutlichsten in Teilgebieten mit Abflusskomponenten aus tieferen Grundwasserleitern, deren Dynamik ohne Kalibrierung nicht zufriedenstellend abgebildet werden kann. Die Modellanwendungen zeigen weiterhin: (1) Laterale Prozesse der Umverteilung von Bodenfeuchte und Abfluss auf der Hangskala, vor allem die Wiederversickerung von Oberflächenabfluss, führen auf der Skala von Einzugsgebieten zu deutlich kleineren Abflussvolumen als die einfache Summe der Abflüsse der Teilflächen. Diese Prozesse sollten daher auch in großskaligen Modellen abgebildet werden. Die unterschiedliche Ausprägung dieser Prozesse für unterschiedliche Bedingungen zeigt sich an Hand einer prozentual größeren Verringerung der Abflussvolumen in trockenen im Vergleich zu feuchten Jahren. (2) Die Niederschlagseigenschaften haben einen sehr großen Einfluss auf die hydrologische Reaktion in semiariden Gebieten. Insbesondere die durch die grobe zeitliche Auflösung des Modells und durch Interpolationseffekte unterschätzten Niederschlagsintensitäten in den Eingangsdaten und die daraus folgende Unterschätzung von Abflussvolumen müssen im Modell kompensiert werden. Ein Skalierungsfaktor in der Infiltrationsroutine oder die Verwendung disaggregierter stündlicher Niederschlagsdaten zeigen hier gute Ergebnisse. Die Simulationsergebnisse mit Wasa sind insgesamt durch große Unsicherheiten gekennzeichnet. Diese sind einerseits in Unsicherheiten der Modellstruktur zur adäquaten Beschreibung der relevanten hydrologischen Prozesse begründet, andererseits in Daten- und Parametersunsicherheiten in Anbetracht der geringen Datenverfügbarkeit. Von besonderer Bedeutung ist: (1) Die Unsicherheit der Niederschlagsdaten in ihrem räumlichen Muster und ihrer zeitlichen Struktur hat wegen der stark nicht-linearen hydrologischen Reaktion einen großen Einfluss auf die Simulationsergebnisse. (2) Die Unsicherheit von Bodenparametern hat im Vergleich zu Vegetationsparametern und topographischen Parametern im Allgemeinen einen größeren Einfluss auf die Modellunsicherheit. (3) Der Effekt der Unsicherheit einzelner Modellkomponenten und -parameter ist für Jahre mit unter- oder überdurchschnittlichen Niederschlagsvolumen zumeist unterschiedlich, da einzelne hydrologische Prozesse dann jeweils unterschiedlich relevant sind. Die Unsicherheit einzelner Modellkomponenten- und parameter hat somit eine unterschiedliche Bedeutung für die Unsicherheit von Szenarienrechnungen mit steigenden oder fallenden Niederschlagstrends. (4) Der bedeutendste Unsicherheitsfaktor für Szenarien der Wasserverfügbarkeit für die Untersuchungsregion ist die Unsicherheit der den regionalen Klimaszenarien zu Grunde liegenden Ergebnisse globaler Klimamodelle. Eine deutliche Zunahme oder Abnahme der Niederschläge bis 2050 kann gemäß den hier vorliegenden Daten für das Untersuchungsgebiet gleichermaßen angenommen werden. Modellsimulationen für Klimaszenarien bis zum Jahr 2050 ergeben, dass eine mögliche zukünftige Veränderung der Niederschlagsmengen zu einer prozentual zwei- bis dreifach größeren Veränderung der Abflussvolumen führt. Im Falle eines Trends von abnehmenden Niederschlagsmengen besteht in der Untersuchungsregion die Tendenz, dass auf Grund der gegenseitigen Beeinflussung der großen Zahl von Stauseen beim Rückhalt der tendenziell abnehmenden Abflussvolumen die Effizienz von neugebauten Stauseen zur Sicherung der Wasserverfügbarkeit zunehmend geringer wird. --- Anmerkung: Der Autor ist Träger des von der Universitätsgesellschaft Potsdam e.V. vergebenen Wissenschaftspreises zur Förderung des wissenschaftlichen Nachwuchses für die beste Dissertation des Jahres 2002/2003 an der Universität Potsdam.
Nine Middle Triassic paleogeographical maps comprising the uppermost Upper Bunter, Lower to Middle Muschelkalk and Upper Muschelkalk to Lower Keuper time frame (Diedrich 2008b) show the marine ingression and regression cycle of the Middle Triassic Germanic Basin (Diedrich 2010c). For bathymetrical and palaeoenvironmental interpretations especially reptiles and their footprints are used. This Germanic Basin as analogon for the Arabian Gulf (Knaust 1997), north of the Tethys, was under marine and finally terrestrial influenced sediments in a time frame (after Kozur and Bachmann 2008) between 247.2 My (Myophoria Fm, Aegean, Lower Anisian) to 237.9 My (Grabfeld Fm, Longobardian, Lower Ladinian). In a duration of 9.3 My the Germanic Basin was filled up mainly with marine carbonates and at the end by siliciclastics influenced by the northern Tethys through the Silesian, Carpathian and later the Burgundian Gates which connected the Germanic Basin to the Northern Tethys. With the marine ingression from the East via the Silesian Gate (Poland) a ten to hundred kilometers extended intertidal flat to sabkha facies belt surrounded first only the central and then the Western Germanic Basin (Winterswijk, Netherlands). Those intertidal zones were used mainly by two different small reptiles as their primary habitat. Hereby they left Millions of the small tom medium sized footprints of the ichnogenera Rhynchosauroides and Procolophonichnium (Diedrich 2005, 2008a). Larger terrestrial and beach and sabkha adapted reptiles were Tanystrophaeus antiquus and unknown archosaurs, which are recorded only by their footprints. At the beginning of the ingression at the uppermost Bunter a shallow marine invertebrate fauna and coastal reptiles appeared in the Germanic Basin which must have originated mainly from the Northern Tethys. Especially all marine reptiles immigrated from the Tethys which is proven not only by assamblaged Tethyan cephalopod Ceratite species (cf. Diedrich 2008a). The coastal intertidal zones appeared with mud cracked biolaminate and sabkha dolomites ("Biolaminate and Sabkha facies") and expanded further west and south within the Lower Muschelkalk Winterswijk Fm (Aegean/Bithynian boundary), Osnabrück Fm, and Jena Fm (Bithynian to Pelsonian) (Diedrich and Trostheide 2007, Diedrich 2008a). The intertidal zones changed their extensions several times in the Lower Muschalkalk due to the less eustatically and more tectonically controlled very shallow relief cratonic basin morphology and were more stable in the western part of the flat carbonate ramp basin (Winterswijk, Netherlands) and in coastal zones in general. In the Germanic Basin centre (Rüdersdorf to Gogolin, Germany/Poland) the conditions were all that time under very shallow carbonate sand barr (Oolithtic, Terebratula or Shell bioclastic facies) or shallow subtidal ("Wellenkalk facies") conditions, whereas even extended seagrass meadows in shallow carbonate facies types are indirectly proven by invertebrate communities, especially snails. Those algae attracted especially placodontids which were the "Triassic seacows" feeding on such algae (Diedrich, 2010a), which immigrated with Paraplacodus, Placodus and Cyamodus already with the first Lower Muschelkalk ingression sequence. Also other reptiles such as nothosaurs Nothosaurus (small species), Cymatosaurus, the pachypleurosaurids Dactylosaurus, Neusticosaurus or Serpianosaurus must have originated from the tethys and were shallow marine and even lagoonary adapted paraxial swimming smaller marine reptiles. This "Lower Muschelkalk" time was highly tectonically active represented by several seismic layers (slumps, sigmoidal shocked layers, etc.) (cf. Schwarz 1975, Rüffer 1996, Knaust 2000, Diedrich 2008a), which were also reaching the intertidal beach zones, possibly even with tsunamite hazard events (Diedrich 2008b, 2009b). Such tsunamis or quick floodings due to storm events must have had hazardous impacts on marine reptiles or fishes, and the beach inhabiting terrestrial reptiles, which could have been killed by high amounts which explains the presence of many skeletons, bonebeds, and footprint preservations in the Germanic Basin biolaminate and lagoonal facies. With a high seismic peak during the Middle Muschelkalk Karlstadt Fm (Pelsonian/Illyrian boundary) in the intertidal zones up to 19 tectonically shocked biolaminate layers (locality Bernburg, Central Germany, Diedrich 2009b) prove the beginning of the Alpine tectonics and its raise (fold belt structure: Müller et al. 1964), but also the opening of the Carpathian Gate (graben structure: Szulc 1998), from which the epicenters were estimated by two main slickenside directions. Those can be found all over the Germanic Basin "Lower Muschelkalk" sediments (Szulc 1998, Föhlisch 2007, Diedrich 2009b). This time period of the Pelsonian/Illyrian boundary gave even such extended intertidal zones, that reptiles left Millions of tracks all over those biolaminate facies types, allowing those to migrate and distribute East (Bohemian Island) - West (Rhenisch Massif, London-Brabant Massif) due to "intertidal flat bridges". Therefore chirotherid archosaur trackmakers left Chirotherium, Isochirotherium and Brachychirotherium trackways quite abundantly not anymore in the typical Bunter red sandstone facies; now they appeared in the new environments, the intertidal biolaminates such as well documented at Bernburg (Central Germany, Diedrich 2009b), but also on other Middle Triassic coast east of the Massif Central (Demathieu 1985) or the Alps (e.g. Avanzini 2002). The only surviving marine reptiles were smaller lagoonal adapted pachypleurosaurs such as the common Anarosaurus and smaller sized Nothosaurus. Placodontids disappeared with the loss of the palaeoenvironment of the macroalgae meadows and seem to have migrated to the Carpathian gate and northern Tethys, where those habitats were still present. The dramatical habitat change with terrestrial territory loss, and marginal marine beach zone extensions seem to be also the reason for the beginning of the dinosaur raise in the world. Within the Middle Muschelkalk Heilbronn and Diemel Formations a massive sea level fall caused a new extension of intertidal zones and sabkhas, but also halite and gypsum evaporates ("Domolite-evaporate facies") in the basin center including the southern Germanic Basin branch (region Tübingen/Stuttgart, Southwestern Germany). The "Middle Muschelkalk" shallow relief and lagoon to intertidal dominated period changed again drastically within a new tectonic active "Upper Muschelkalk" time and strong "ingression" of the northern Tethys into the Germanic Basin within the Illyrian time (Bad Sulza Fm, Trochitenkalk Fm). A shallow marine, with shallow water carbonates filled Germanic Basin developed again, but this time with different consequences onto the former coastal zones, in which intertidal biolaminated and sabkhas disappeared as a result of steeper coastal morphologies. Whereas in the first ingression a shallow marine reptile fauna was present (Nothosaur-Pachypleurosaur taphocoenosis, Lower Bad Sulza Fm, Diedrich in prep.). The fauna changed with the main transgression within the Upper Bad Sulza Fm to a Placodontid-Pistosaur taphocoenosis with more open marine adapted forms (Diedrich in prep.). At those time also crinoid bioherms developed massively all over the central and southern Germanic Basin in front of the costs at the "steeper coast margins" (which were still hot high angled), as a "crinoid belt" (e.g. Aigner and Bachmann 1991), which was responsible for massive crinoidal limestones (= "Trochitenkalk facies"). In this period again "Triassic seacows" seem to have populated well the entire Germanic Basin, and here again seagrass meadow areas documented by benthic invertebrate palaeocommunities (Diedrich 2009a, 2010a). The marine macroplants must have built extended meadows on the shallow marine and oxygen-rich seafloor conditions of the "Tonplatten facies" on which many different invertebrates settled in- or epifaunistic. This tectonical deepening controlled situation continued with the Meißner Fm and aequivalent Formations and its cephalopod Ceratite rich "Tonplatten facies", whereas the "maximum flooding" (if the term can be used here in a cratonic and tectonically controlled basin: cf. definition of marine cycles in: Aigner and Bachmann 1991) was in the compressus biozone (ceratite biozone, middle Meißner Fm, Anisian/Ladinian boundary, cf. Diedrich 2009a). The high stand is underlined by now full adapted marine reptiles such as nothosaurs (Nothosaurus mirabilis, Simosaurus gaillardodti), pistosaurs (Pistosaurus longaevus) and especially the open marine ichtyosaurs (Shastasaurus, Mixosaurus, Omphtalmosaurus) support the full marine and highest water level conditions. The "regression" or better suggested here "basin uplifting" started in the upper Meißner Fm with a reducing carbonate sedimentation which was overtaken slowly by terrestrial sediments already within the Warburg/Erfurt Formations (Fassanian/Longobardian boundary, Lower Ladinian). The fresh water and clay mineral influence caused a reduction of the marine benthic community biodiversity and the development of brackish lagoons, in which some invertebrate faunas and dominantly small marine reptiles pachypleurosaurs lived. At that time all placodontid reptiles disappeared, which must have been the chain reaction of the macroalgae loss and environmental changes. A change of terrestrial influence and periodic marine influence is documented in repeating intercalated massive dolomites (Alberti-Bed, Anthraconit-Bed and others) and clay layers of the Lower Keuper Erfurt and especially Grabfeld Fm (Longobardian). In this final period the Lower Keuper Germanic Basin was less and less marine influenced, finally dominated at that time on the limnic influenced costs by large amphibians such as Mastodonsaurus, Gerrhothorax or Plagiosuchus, which were found especially at southern German and Central german sites (Schoch and Wild 1999, Diedrich 2010b), including the famous southern German "Grenzbonebed" (Fassanian/Longobardian boundary) (Reif 1982, Hagdorn 1990). This bonebed already contains a strongly reduced marine reptile fauna with pachypleurosaurs and giant lagoon-adapted nothosaurs (N. giganteus, S. gaillardoti) and few marine hypersaline adapted shells such as Costatoria costata (cf. Hagdorn et al. 2009). The absence of cephalopod ceratites and rare nautilid presence are the last proves for the periodic restricted lagoon situations- being comparable in its facies and reptile fauna to the lagoon of the Northern Tethys Monte San Giorgio, Switzerland/Italy (e.g. De Zanche and Farabegoli 1988, Furrer 1995) to which the Germanic Basin was connected through the Burgundian Gate, France. The marine influence and marine sediment fill of the Germanic Basin stopped finally at the beginning of the Middle Keuper (lower Upper Triassic), diachronously more earlier in northern Germany (Warburg/Erfurt Fm, cf.: Kozur and Bachmann 2008, Diedrich 2010b) as in southern Germany (cf. Hagdorn et al. 2009) indicating a periodic marine influence from the Northern Tethys through the Burgundian Gate. At the final tectonical stage (last seismits in the Grabfeld Fm, Longobardian: cf. Bachmann and Aref 2005) no intertidal flats nor biolamnintes developed anymore in a low relief Germanic Basin morphology, which reason can be explained be the carbonate reduction, strong terrigenous clay input, and brakish-lagoonary conditions, in which cyanobacterial mats of the low-relief intertidal zones could not develop. References Aigner, T. and Bachmann, G.H. 1991. Sequence Stratigraphy of the German Muschelkalk. In: Hagdorn, H. and Seilacher, A. (Eds.): Muschelkalk. Schöntaler Symposium. 15-18. Goldschneck-Verlag, Stuttgart. Avanzini, M. 2002. Dinosauromorph tracks from the Middle Triassic (Anisian) of the Southern Alps (Valle di Non-Italy). Bolletino della Società Paleontologica Italiana, 41 (1), 37-40. Bachmann, G.H. and Aref, M.A.M., 2005. A seismite in Triassic gypsum deposits (Grabfeld Formation, Ladinian), Southwest Germany. Sedimentary Geology 180, 75-89. De Zanche, V. and Farabegoli, E. 1988. Anisian paleogeographic evolution in the Central-Western Southern Alps. Memoirs Scientifique Geologique 40, 399-411. Demathieu, G.R. 1985. Trace fossil assemblages in Middle Triassic marginal marine deposits, eastern border of the Massif Central, France. Societe Economie Paléontologie et Mineralogie, Special Publications, 35, 53-66. Diedrich, C. 2005. Actuopalaeontological trackway experiments with Iguana on intertidal flat carbonates of the Arabian Gulf - a comparison to fossil Rhynchosauroides tracks of Triassic carbonate tidal flat megatracksites in the European Germanic Basin. Senckenbergiana maritime, 35 (2), 203-220. Diedrich, C. 2008a. Millions of reptile tracks - Early to Middle Triassic carbonate tidal flat migration bridges of Central Europe. Palaeogeography, Palaeoclimatology, Palaeoecology, 259, 410-423. Diedrich, C. 2008b. Palaeogeographic evolution of the marine Middle Triassic marine Germanic Basin changements - with emphasis on the carbonate tidal flat and shallow marine habitats of reptiles in Central Pangaea. 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