Pufendorf, Samuel

During the last two decades, Samuel von Pufendorf’s (1632–1694) natural law philosophy has become the subject of renewed and growing attentiveness among intellectual historians and philosophers (Seidler 2015). In the late-seventeenth century and early eighteenth century, Pufendorf was the most widely-read moral and political philosopher in Europe, whose reputation is most clearly exemplified in the impressive number of translations and editions of his works. Pufendorfian natural law theory offered a shared vocabulary and conceptual possibilities for the discussion of morality, politics and interstate relations for numerous eighteenth-century thinkers, such as Christian Thomasius, the authors of the Scottish Enlightenment and Jean-Jacques Rousseau. Pufendorf spent large parts of his career in princely courts and portrayed the history of states and their natural law foundations in his widely circulated historical works (Seidler 1997). Moreover, he also wrote on the issues of theology and church-state relations (Döring 1992, Zurbuchen 1998).Peer reviewe

Measurement of dynamic voltage variation effect on instrument transformers for power grid applications

Within the framework of distribution and transmission grids, the knowledge of Instrument Transformers (ITs) behavior in distorted conditions is a topic of great interest. Its relevance stems from the ITs wide use in metering, protection, monitoring and control applications, where their role is to reduce voltage and current to levels compatible with measuring instrument inputs. In force standards require that the performance of measuring instruments is assessed under realistic conditions. On the contrary, performance tests of ITs are generally carried out only at rated conditions, so that their behavior under actual waveforms is not fully known. To cover this gap, a suitable setup for the traceable test of Voltage instrument Transformers (VTs) under a quite large set of static and time-varying test waveforms is developed. The paper, after a short description of the setup, shows the performance of two commercial VTs under some power quality events, that are amplitude and phase modulations and voltage dips

Transient expression of reck under hepatic ischemia/reperfusion conditions is associated with mapk signaling pathways

In this study, we demonstrated the involvement of matrix metalloproteinases (MMPs) in hepatic ischemia/reperfusion (I/R) injury. Our aim is to evaluate the impact of reperfusion on I/R-related changes in RECK, an MMP modulator, and mitogen-activated protein kinase (MAPKs) pathways (ERK, p38, and JNK). Male Wistar rats were either subjected to 60 min partial-hepatic ischemia or sham-operated. After a 60 min or 120 min reperfusion, liver samples were collected for analysis of MMP-2 and MMP-9 by zymography and RECK, TIMP-1, and TIMP-2 content, MAPKs activation (ERK1/2, JNK1/2, and p38), as well as iNOS and eNOS by Western blot. Serum enzymes AST, ALT, and alkaline-phosphatase were quantified. A transitory decrease in hepatic RECK and TIMPs was associated with a transitory increase in both MMP-2 and MMP-9 activity and a robust activation of ERK1/2, JNK1/2, and p38 were detected at 60 min reperfusion. Hepatic expression of iNOS was maximally upregulated at 120 min reperfusion. An increase in eNOS was detected at 120 min reperfusion. I/R evoked significant hepatic injury in a time-dependent manner. These findings provide new insights into the underlying molecular mechanisms of reperfusion in inducing hepatic injury: a transitory decrease in RECK and TIMPs and increases in both MAPK and MMP activity suggest their role as triggering factors of the organ dysfunction

Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA-ISA working group

Background: This guideline has been developed jointly by the European Society of Haematology and International Society of Amyloidosis recommending non-transplant chemotherapy treatment for patients with AL amyloidosis. / Methods: A review of literature and grading of evidence as well as expert recommendations by the ESH and ISA guideline committees. / Results and Conclusions: The recommendations of this committee suggest that treatment follows the clinical presentation which determines treatment tolerance tempered by potential side effects to select and modify use of drugs in AL amyloidosis. All patients with AL amyloidosis should be considered for clinical trials where available. Daratumumab-VCD is recommended from most untreated patients (VCD or VMDex if daratumumab is unavailable). At relapse, the two guiding principles are the depth and duration of initial response, use of a class of agents not previously exposed as well as the limitation imposed by patients’ fitness/frailty and end organ damage. Targeted agents like venetoclax need urgent prospective evaluation. Future prospective trials should include advanced stage patients to allow for evidence-based treatment decisions. Therapies targeting amyloid fibrils or those reducing the proteotoxicity of amyloidogenic light chains/oligomers are urgently needed

Interleukin-15 is required for immunosurveillance and immunoprevention of HER2/neu-driven mammary carcinogenesis

We previously demonstrated that HER2/neu-driven mammary carcinogenesis can be prevented by an interleukin-12 (IL-12)-adjuvanted allogeneic HER2/neu-expressing cell vaccine. Since IL-12 can induce the release of interleukin-15 (IL-15), in the present study we investigated the role played by IL-15 in HER2/neu driven mammary carcinogenesis and in its immunoprevention

Search for AL amyloidosis risk factors using Mendelian randomization

In amyloid light chain (AL) amyloidosis, amyloid fibrils derived from immunoglobulin light chain are deposited in many organs, interfering with their function. The etiology of AL amyloidosis is poorly understood. Summary data from genome-wide association studies (GWASs) of multiple phenotypes can be exploited by Mendelian randomization (MR) methodology to search for factors influencing AL amyloidosis risk. We performed a 2-sample MR analyzing 72 phenotypes, proxied by 3461 genetic variants, and summary genetic data from a GWAS of 1129 AL amyloidosis cases and 7589 controls. Associations with a Bonferroni-defined significance level were observed for genetically predicted increased monocyte counts (P = 3.8 × 10−4) and the tumor necrosis factor receptor superfamily member 17 (TNFRSF17) gene (P = 3.4 × 10−5). Two other associations with the TNFRSF (members 6 and 19L) reached a nominal significance level. The association between genetically predicted decreased fibrinogen levels may be related to roles of fibrinogen other than blood clotting. be related to its nonhemostatic role. It is plausible that a causal relationship with monocyte concentration could be explained by selection of a light chain–producing clone during progression of monoclonal gammopathy of unknown significance toward AL amyloidosis. Because TNFRSF proteins have key functions in lymphocyte biology, it is entirely plausible that they offer a potential link to AL amyloidosis pathophysiology. Our study provides insight into AL amyloidosis etiology, suggesting high circulating levels of monocytes and TNFRSF proteins as risk factors