Uniqueness and Non-uniqueness in the Einstein Constraints

The conformal thin sandwich (CTS) equations are a set of four of the Einstein equations, which generalize the Laplace-Poisson equation of Newton's theory. We examine numerically solutions of the CTS equations describing perturbed Minkowski space, and find only one solution. However, we find {\em two} distinct solutions, one even containing a black hole, when the lapse is determined by a fifth elliptic equation through specification of the mean curvature. While the relationship of the two systems and their solutions is a fundamental property of general relativity, this fairly simple example of an elliptic system with non-unique solutions is also of broader interest.Comment: 4 pages, 4 figures; abstract and introduction rewritte

E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family.

E2F transcription factors are central regulators of cell division and cell fate decisions. E2F4 often represents the predominant E2F activity in cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. This role for E2F4 is independent of the RB family. Furthermore, E2F4 functionally interacts with chromatin regulators associated with gene activation and we observed decreased histone acetylation at the promoters of cell cycle genes and E2F targets upon loss of E2F4 in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that provide insights into the biology of rapidly dividing cells

PCB 47, 51, 68 – Bestimmung von PCB 47, 51, 68 in der Luft am Arbeitsplatz mittels Gaschromatographie (GC-ECD)

This analytical method is a validated measurement procedure for the determination of the three tetrachlorinated biphenyls PCB 47 [2437-79-8], PCB 51 [68194-04-7] and PCB 68 [73575-52-7] in workplace air in a concentration range of 0.16 to 0.62 μg/m3. It was developed to detect PCB that only may be generated during the manufacture of silicone products with peroxidic crosslinking with bis(2,4-dichlorobenzoyl) peroxide. By measurement in manufacturing plants it could be proven that the PCB to be investigated are present exclusively in vapour form. For this reason, the method was only validated for vaporous samples. There are currently no valid evaluation criteria for these PCB. Therefore, the German Occupational Exposure Limit Value for the sum of all PCB (5 × sum of the 6 indicator PCB [28, 52, 101, 138, 152, 180]) of 3 μg/m3 was used as the assessment standard for each congener. For sampling, a defined volume of air is drawn through a sorbent tube filled with Florisil. The flow rate is set to 1 l/min and sampling duration is 4 hours (which correspond to a sampling volume of 240 l). The PCB are extracted with n-hexane at 40 °C in an ultrasonic bath and subsequently analysed using gas chromatography with electron capture detection. The quantitative determination is based on a calibration function. The limit of quantification is 0.11 μg/m3 based on an air sample volume of 240 l. The mean recovery is 96% and the expanded uncertainty for the validation range of 0.16 to 0.62 μg/m3 is 22 to 24%

1,2-Dichloroethane – Method for the determination of 1,2-dichloroethane in workplace air using gas chromatography (GC-MS)

This analytical method is a validated measurement procedure for the determination of 1,2-dichloroethane [107-06-2] after personal or stationary sampling. Sampling is performed by drawing a defined volume of air through an adsorption tube made of stainless steel packed with Chromosorb 106 using a suitable flow-regulated pump. After thermal desorption, the 1,2-dichloroethane retained on the adsorbens is analysed using gas chromatography with flame ionisation detection and mass spectrometry. The relative limit of quantification (LOQ) is 0.009 mg 1,2-dichloroethane/m3 for an air sample volume of 1.2 l. The mean recovery for 1,2-dichloroethane was 101%. The concentration-dependent expanded uncertainty was 20% to 21%. This analytical method has been accredited by the accident insurance companies for the detection in workplace air of substances that are carcinogenic, mutagenic or toxic to reproduction. This method has been tested and recommended for the determination of 1,2-dichloroethane in work areas by the German Social Accident Insurance (DGUV). Both personal and stationary sampling can be performed for measurements in order to evaluate work areas

Isolation and characterization of a cDNA encoding rat liver cytosolic epoxide hydrolase and its functional expression in Escherichia coli

A cDNA of 1992 base pairs encoding the complete rat liver cytosolic epoxide hydrolase has been isolated using a polymerase chain reaction-derived DNA fragment (Arand, M., Knehr, M., Thomas, H., Zeller, H. D., and Oesch, F. (1991) FEBS Lett. 294, 19-22) known to represent the 3'-end of the cytosolic epoxide hydrolase mRNA. Sequence analysis revealed an open reading frame of 1662 nucleotides corresponding to 554 amino acids (M(r) = 62,268). The DNA sequence obtained did not display significant homology to the sequences of microsomal epoxide hydrolase or leukotriene A4 hydrolase or to any other DNA included in the EMBL Data Bank (release 32). On Northern blotting of rat liver RNA, a single mRNA species was detected that was strongly induced on treatment of the animal with fenofibrate, a potent peroxisome proliferator. The most significant structure of the deduced protein is a modified peroxisomal targeting signal (Ser-Lys-Ile) at the carboxyl terminus that is regarded to be responsible for the unusual dual localization of the cytosolic epoxide hydrolase in peroxisomes as well as in the cytosol. In addition, a leucine zipper-like motif was identified at the amino terminus. Its possible implication for the observed dimeric structure of cytosolic epoxide hydrolase is discussed. The isolated cDNA was expressed in bacteria to yield a catalytically active enzyme. Specific activity of the crude lysate obtained exceeded that of rat liver cytosols from maximally induced animals by a factor of 8

Mode of action-based risk assessment of genotoxic carcinogens

The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B$_{1}$, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs