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21.
    
Zusammenfassung Es werden pharmakokinetische Modelle angegeben, um den Konzentrationsverlauf von Arzneimittelrückständen im Menschen zu berechnen, die mit der Nahrung aufgenommen werden. Dabei lassen sich zwei Kompartimentmodelle für die Kinetik in der Nahrung und im Menschen koppeln: Das erste System liefert die Anfangswerte (bzw. eine Folge von Anfangswerten) für das zweite System. Das Modell wird auf die Übertragung von Chloramphenicol durch Speisefische auf den Menschen und auf die Übertragung von Theophyin durch die Muttermilch auf gestillte Säuglinge angewendet. Durch Einführung einer günstigsten und ungünstigsten Parameterkombination werden Grenzverläufe für die Blutspiegel berechnet, die als Grundlage einer Rückstandsbewertung dienen können.
Residues of active substances following the consumption of contaminated food —Status report on the evaluation of residues based on two drugs
Summary Pharmacokinetic models are presented for the computation of time courses of blood levels of drugs in man following the consumption of contaminated food. Mathematically, two linear systems of differential equations are set up for the donor organism (e.g., trout) and for the recipient, (e.g., man), where the first system generates the initial conditions for the second. Models of this kind are applied to the transfer of chloramphenicol to man via carp and trout (which had previously been administered this drug) and to the transfer of theophylline to infants via breast milk. Limiting concentration profiles are computed by constructing the most favourable and most adverse combinations of parameters with respect to drug elimination in both the donor and recipient organism.
  相似文献   
22.
With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10−6). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.  相似文献   
23.
Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD01, are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.  相似文献   
24.
In this paper, a novel concept of a thermo-mechanical MEMS actuator using aluminum thin-film heaters on a thermal oxide for electrical insulation is presented. The actuator is part of an universal tensile testing platform for thermo-mechanical material characterization of one dimensional materials on a micro- and nano-scopic scale under different environmental conditions, as varying temperatures, pressure, moisture or even vacuum and is realised in BDRIE technology. It is shown, that the actuator concept fulfills the requirements for the use in a tensile loading stage along with heterogeneously integrated nanofunctional elements, following a specimen centered approach in line with bottom-up self-assembly processes. Simulation and experiment agree very well in the thermal and mechanical domain and allow subsequent optimisation of the actuator performance.  相似文献   
25.
By the very nature of information technology (IT), change and dynamism have always been significant drivers on its path to further development—and it has traditionally been the Western countries leading these. Now the picture is changing. The new high growth economies of the world (also known as BRIC countries) are increasingly pressing forward as active IT development drivers. Internal IT organizations of international companies are experiencing these global shifts firsthand and are facing changes in their traditional roles. This exploratory research is aimed at clarifying the context of the impact of high growth economies on such IT departments of Western-rooted enterprises. Forty-six interviews were conducted with IT managers, HR managers and expatriates emphasizing the importance of intercultural interaction, maturing IT economies, change in IT landscape and entrepreneurship.  相似文献   
26.
Battery life is a major concern on portable devices like smartphones and tablet PCs. On these devices, games constitute the class of most popular applications and are at the same time highly compute-intensive. Every game consists of several states like the loading, main menu and the gaming state. Each of those states has its own workload characteristics, e.g., the loading phase is likely to be memory bound and the main menu state is less interactive than the gaming state. We propose an interception technique that allows to profile the game and detect its current state based on the game’s communication with the underlying OS. Current power management governors are unaware of the running applications and scale the processor’s voltage and frequency merely based on the system’s utilization. We provide the game’s state information and workload profile to our governor which selects the processing frequency such that the desired frame rate of the current state is ensured. This leads to an optimal choice of processing frequencies and thereby significantly reduces power consumption. We have implemented the scheme on an Android-based Samsung Galaxy Nexus smartphone using popular games like Jetpack Joyride and Temple Run. We reduced the CPU’s power consumption by up to 43.2 % compared to the Android interactive governor without impacting the gaming experience. Motivated by these results we propose a power management API that would allow game developers to significantly reduce the power consumption of their game using simple API calls.  相似文献   
27.
M. Ikegami  G. Xu  S. Honma  D.L. Dietrich 《Fuel》2003,82(3):293-304
This report presents an investigation on the combustion of single droplets comprised of heavy oil and oil mixtures blending diesel light oil (LO) and a heavy oil residue (HOR). The tests were conducted in a microgravity facility that offered 10 s of free-fall time. Fine wire thermocouples supported the droplets, resulting in a measurement of droplet temperature history. Additional data were the droplet and flame size history. The results identified four distinctive burning stages between ignition and extinction for heavy oil (C class) and HOR-LO blends. They are, in succession, the start-up, inner evaporation, thermal decomposition (pyrolysis) and polymerization stages. The start-up stage denoted an initial transient period, where the LO components burned from the droplet surface and the droplet temperature increased rapidly. The latter three stages featured pronounced droplet swellings and contractions caused by fuel evaporation and decomposition inside the droplet. An evaporation temperature demarcated the start-up stage from the inner evaporation stage, and this temperature corresponded to a plateau in the temperature history of the droplet. Two additional temperatures, termed the decomposition and polymerization temperatures, indicated the ends of the evaporation and decomposition stages. These temperatures were similarly identified by plateaus or inflection points in the time-temperature diagram. The evaporation temperature gradually decreased with increasing the initial LO mass fraction in the droplet, whereas the other two temperatures were almost independent of the oil composition. All three temperatures increased with decreasing initial droplet diameter, but the dependence was very slight. Based on the results, the combustion of heavy oil droplets appears to be dominated by a distillation-like vaporization mechanism, because of the rapid mass transport within the droplets caused by the disruptive burning.  相似文献   
28.
The selfdiffusion coefficients of acetone and benzene are studied in the systems acetone/poly(methylmethacrylate) and benzene/poly(methylmethacrylate) by means of the spin echo technique as function of concentration and temperature. From the dependence of temperature, the activation energies are calculated as function of concentration. The dependence of concentration of the selfdiffusion coefficients is discussed using the theory of Free Volume according to FUJITA. The Free Volume of the poly(methylmethacrylate) is calculated as function of temperature.  相似文献   
29.
Apolipoprotein E (apoE), an important determinant of plasma lipoprotein metabolism, has three common alleles (ε2, ε3, and ε4). Population studies have shown that the risk of diseases characterized by oxidative damage, such as coronary heart disease and Alzheimer’s disease, is significantly higher in ɛ4 carriers. We evaluated the association between apoE genotypes and plasma F2-isoprostane levels, an index of lipid peroxidation, in humans. Two hundred seventy-four healthy subjects (104 males, 170 females; 46.9±13.0 yr; 200 whites, 74 blacks; 81 nonsmokers, 64 passive smokers, and 129 active smokers) recruited for a randomized clinical antioxidant intervention trial were included in this analysis. ApoE genotype was determined by PCR and restriction enzyme digestion. Free plasma F2-isoprostane was measured by GC-MS. Genotype groups were compared using multiple regression analysis with adjustment for sex, age, race, smoking status, body mass index, plasma ascorbic acid, and β-carotene. Subjects with ε3/ε4 and ε4/ε4 genotype (ε4-carriers) and with ε2/ε3 and ε3/ε3 (non-ε4-carriers) were pooled for analysis. In subjects with high cholesterol levels (total cholesterol above 200 mg/dl), plasma F2-isoprostane levels were 29% higher in ε4 carriers than in non-ε4-carriers (P=0.0056). High-cholesterol subjects that are ε4 carriers have significantly higher levels of lipid peroxidation as assessed by circulating F2-isoprostane levels.  相似文献   
30.
Given the strong increase in regulatory requirements for business processes the management of business process compliance becomes a more and more regarded field in IS research. Several methods have been developed to support compliance checking of conceptual models. However, their focus on distinct modeling languages and mostly linear (i.e., predecessor-successor related) compliance rules may hinder widespread adoption and application in practice. Furthermore, hardly any of them has been evaluated in a real-world setting. We address this issue by applying a generic pattern matching approach for conceptual models to business process compliance checking in the financial sector. It consists of a model query language, a search algorithm and a corresponding modelling tool prototype. It is (1) applicable for all graph-based conceptual modeling languages and (2) for different kinds of compliance rules. Furthermore, based on an applicability check, we (3) evaluate the approach in a financial industry project setting against its relevance for decision support of audit and compliance management tasks.  相似文献   
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