Andreas Blauert, Das Urfehdewesen im deutschen Südwesten im Spätmittelalter und in der frühen Neuzeit

Urfehde denoted originally an oath to keep the peace taken by those released from gaol, forswearing vengeance for their confinement. The very need for such assurances provides a revealing testimony to the nature of public order in the early part of the period covered in this book : the precarious legitimacy of governments, their weakness and vulnerability, and, correspondingly, the capacity and even legitimacy of « private » persons to resort to violence against governments and their represen..

Andreas Blauert, Das Urfehdewesen im deutschen Südwesten im Spätmittelalter und in der frühen Neuzeit

Urfehde denoted originally an oath to keep the peace taken by those released from gaol, forswearing vengeance for their confinement. The very need for such assurances provides a revealing testimony to the nature of public order in the early part of the period covered in this book : the precarious legitimacy of governments, their weakness and vulnerability, and, correspondingly, the capacity and even legitimacy of « private » persons to resort to violence against governments and their represen..

Molt-inhibiting hormone stimulates vitellogenesis at advanced ovarian developmental stages in the female blue crab, Callinectes sapidus 2: novel specific binding sites in hepatopancreas and cAMP as a second messenger

The finding that molt-inhibiting hormone (MIH) regulates vitellogenesis in the hepatopancreas of mature Callinectes sapidus females, raised the need for the characterization of its mode of action. Using classical radioligand binding assays, we located specific, saturable, and non-cooperative binding sites for MIH in the Y-organs of juveniles (J-YO) and in the hepatopancreas of vitellogenic adult females. MIH binding to the hepatopancreas membranes had an affinity 77 times lower than that of juvenile YO membranes (KD values: 3.22 × 10-8 and 4.19 × 10-10 M/mg protein, respectively). The number of maximum binding sites (BMAX) was approximately two times higher in the hepatopancreas than in the YO (BMAX values: 9.24 × 10-9 and 4.8 × 10-9 M/mg protein, respectively). Furthermore, MIH binding site number in the hepatopancreas was dependent on ovarian stage and was twice as high at stage 3 than at stages 2 and 1. SDS-PAGE separation of [125I] MIH or [125I] crustacean hyperglycemic hormone (CHH) crosslinked to the specific binding sites in the membranes of the J-YO and hepatopancreas suggests a molecular weight of ~51 kDa for a MIH receptor in both tissues and a molecular weight of ~61 kDa for a CHH receptor in the hepatopancreas. The use of an in vitro incubation of hepatopancreas fragments suggests that MIH probably utilizes cAMP as a second messenger in this tissue, as cAMP levels increased in response to MIH. Additionally, 8-Bromo-cAMP mimicked the effects of MIH on vitellogenin (VtG) mRNA and heterogeneous nuclear (hn) VtG RNA levels. The results imply that the functions of MIH in the regulation of molt and vitellogenesis are mediated through tissue specific receptors with different kinetics and signal transduction. MIH ability to regulate vitellogenesis is associated with the appearance of MIH specific membrane binding sites in the hepatopancreas upon pubertal/final molt

Molt-inhibiting hormone stimulates vitellogenesis at advanced ovarian developmental stages in the female blue crab, Callinectes sapidus 1: an ovarian stage dependent involvement

To understand the hormonal coordination of the antagonism between molting and reproduction in crustaceans, the terminally anecdysial mature female Callinectes sapidus was used as a model. The regulatory roles of crustacean hyperglycemic hormone (CHH) and molt-inhibiting hormone (MIH) in vitellogenesis were examined. A competitive specific RIA was used to measure the levels of MIH and CHH in the hemolymphs of mature females at pre- and mid- vitellogenic stages, and their effects on vitellogenesis at early (early 2, E2) and mid vitellogenesis (3) stages were determined in vitro. A hepatopancreas fragments incubation system was developed and the levels of vitellogenin (VtG), as well as VtG mRNA and heterogeneous nuclear (hn)VtG RNA were determined using RIA or QPCR, respectively. MIH titers were four times higher at mid-vitellogenesis than at pre-vitellogenesis, while CHH levels in the hemolymph were constant. In the in vitro incubation experiments, MIH increased both VtG mRNA levels and secretion at ovarian stage 3. At stage E2, however, MIH resulted in a mixed response: downregulation of VtG mRNA and upregulation of hnVtG RNA. CHH had no effect on any of the parameters. Actinomycin D blocked the stimulatory effects of MIH in stage 3 animals on VtG mRNA and VtG, while cycloheximide attenuated only VtG levels, confirming the MIH stimulatory effect at this stage. MIH is a key endocrine regulator in the coordination of molting and reproduction in the mature female C. sapidus, which simultaneously inhibits molt and stimulates vitellogenesis

A Linearization Beam-Hardening Correction Method for X-Ray Computed Tomographic Imaging of Structural Ceramics

Computed tomographic (CT) imaging with both monochromatic and polychromatic x-ray sources can be a powerful NDE method for characterization (e. g., measurement of density gradients) as well as flaw detection (e. g., detection of cracks, voids, inclusions) in ceramics. However, the use of polychromatic x-ray sources can cause image artifacts and overall image degradation through beam hardening (BH) effects [1]. Beam hardening occurs because (i) x-ray attenuation in a given material is energy dependent and (ii) data collection in CT systems is not energy selective. Without an appropriate correction, the BH effect prevents the establishment of an absolute scale for density measurement. Thus, quantitative density comparisons between samples of the same material but of different geometrical shape becomes unreliable [2]

Single-cell analysis uncovers a novel influenza A virus-derived defective interfering particle for antiviral therapy

Single-cell analysis of virus-infected cells (Heldt and Kupke et al., 2015) enables the characterization of individual highly productive cells, which may support strategies to improve cell culture-based vaccine production. However, the definition of poor producer single cells can also yield valuable information. Here we show that low-productive single Madin-Darby canine kidney (MDCK) cells, infected with influenza A virus (IAV) of strain A/PR/8/34 (PR8), were affected by a yet unrecognized form of defective-interfering particle (DIP). Conventional DIPs (cDIPs) typically contain a deleted form of the viral genome and are therefore unable to reproduce in an infection. However, upon complementation by the co-infection with fully infectious standard virus (STV), interference with the normal viral life cycle can be observed. Interestingly, considering their ability to suppress STV replication, cDIPs are of growing interest for clinical application, i.e. for their use as antivirals (Dimmock and Easton, 2014). Single-cell infection experiments revealed a surprisingly high variability in IAV replication with progeny virus yields that ranged from 0 to roughly 1000 plaque-forming units (PFU) per cell. Intriguingly, low-productive cells (0-10 PFU) displayed an abnormal phenotype, which was caused by the co-infection of a subpopulation of virus, in the following termed OP7 virus. Sequences of the genomic viral RNA (vRNA) of OP7 virions showed a significant amount of nucleotide substitutions in one of the eight vRNA segments, affecting its promotor, encoded proteins and virus packaging signals. We showed that these alterations were all directed towards the predominant genomic replication and packaging of the mutated vRNA over other genome segments. Concurrently, OP7 virions lacked a large fraction of other vRNAs, which constitute its defect in virus replication. Finally, co-infection experiments showed strong interference of OP7 virus with IAV replication, as indicated by a dramatic reduction in the infectivity of released virions. This interference was directed against relevant homologous and heterologous IAV strains, including strains of the current influenza season. Furthermore, we demonstrated interference in human cell lines. Therefore, OP7 virions are a novel form of IAV-derived DIPs with a non-deleted but mutated genomic RNA segment. First, it seems reasonable to investigate the presence of OP7 virions in seed virus preparations, as they can reduce virus titers in a production process, similar to cDIPs (Frensing et al., 2014). Second, OP7 virus may be used for antiviral therapy. As they are not able to reproduce on their own, they may be administered to organisms with no harm. The presence of OP7 virions can then inhibit the propagation of IAV of a natural infection. In addition, the induction of the innate immune response, observed upon infection with OP7 virus, can even further promote the antiviral effect. In the future, the design of efficient production systems for OP7 virions and the execution of animal trials may facilitate its utilization as a novel antiviral agent. References Heldt and Kupke et al. (2015) Nature Commun 6, 8938 Dimmock and Easton (2014) J Virol 88(10), 5217-5227 Frensing et al. (2014) Appl Microbiol Biotechnol 98, 8999-9008 Patent Patent pending for usage of OP7 virions as an antiviral agen

Supplementary health insurance as a tool for risk-selection in mandatory basic health insurance markets

As the share of supplementary health insurance (SI) in health care finance is likely to grow, SI may become an increasingly attractive tool for risk-selection in basic health insurance (BI). In this paper, we develop a conceptual framework to assess the probability that insurers will use SI for favourable risk-selection in BI. We apply our framework to five countries in which risk-selection via SI is feasible: Belgium, Germany, Israel, the Netherlands, and Switzerland. For each country, we review the available evidence of SI being used as selection device. We find that the probability that SI is and will be used for risk-selection substantially varies across countries. Finally, we discuss several strategies for policy makers to reduce the chance that SI will be used for risk-selection in BI market