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The direct dimetalation of phenylacetylene and of (1-naphthy1)acetylene at the acetylenic as well as the ortho position can be achieved by an equimolar mixture of n-butyllithium and potassium tert-butoxide. Metalation at the ortho position was shown by subsequent reaction with trimethylchlorosilane (TMSC1) resulting in the formation of the ortho-silylated disilyl compounds o-TMSC6H4CeTMS and 2-TMS-1-Cl&C%CTMS. Under similar conditions C6H5C=CBut and 1-CloH7C=CBut gave the meta-silylated compound and a mixture of 3-, 4-, and 5-silylated derivatives, respectively. Ab initio calculations show that the ortho metalation of ethynylbenzene and 1-ethynylnaphthalene can be explained by the much higher coordination energy of the metalating reagent with the CECM rather than with the C=CR moiety.

In the Netherlands, there is a vigorous debate on ammonia emissions, atmospheric concentrations and deposition between stakeholders and research institutions. In this article, we scrutinise some aspects of the ammonia discourse. In particular, we want to improve the understanding of the methodology for handling experimentally determined ammonia emissions. We show that uncertainty in published results is substantial. This uncertainty is under-or even unreported, and as a result, data in national emission inventories are overconfident by a wide margin. Next, we demonstrate that the statistical handling of data on atmospheric ammonia concentrations to produce national yearly atmospheric averages is oversimplified and consequently atmospheric concentrations are substantially overestimated. Finally, we show that the much-discussed 'ammonia gap'either the discrepancy between calculated and measured atmospheric ammonia concentrations or the difference observed between estimated NH 3 emission levels and those indicated by atmospheric measurementsis an expression of the widespread overconfidence placed in atmospheric modelling.

In this paper, we review European legislation in the field of micronutrient food supplements and find it wanting. It is shown that the precautionary principle, embedded in European food legislation, pre-empts innovative developments in this field. In view of the scientific advances in micronutrients research, we subsequently critique the precautionary perspective and propose a novel outlook on micronutrients food supplements regulation. However, this requires a transition from the "survival" approach of the current deficiency-related RDAs to a "health-optimization" approach of a n(ew)-RDA. Genomic integrity is central in this envisioned transition.

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This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.e. functional utility of the LNT model) while offering the possibility of significant reductions in cancer incidence should the hormetic dose-response model predictions be correct. The dose yielding the 10(-4) cancer risk therefore yields the optimized toxicologically based "regulatory sweet spot".

In this contribution, we show that current scientific methodologies used in nutrition science and by regulatory agencies, such as the randomized control trial, limit our understanding of nutrition and health as they are to crude to capture the subtle pleiotropic nature of most nutrients. Thereby, regulatory agencies such as the European Food Safety Authority curb the development of scientific knowledge and industrial innovations within the nutritional field. In order to develop insights into the health impact of certain food and food-components, we need to realize that health is adaptation set within a homeostatic range. Increased performance of health, i.e., the maximum stimulation of health, typically seems 30-60% greater than the control group, with a width of no more than about a factor of ten, clarifying the difficulty of documenting responses of food-endogenous components within the homeostatic range of healthy people. A strategy to record subtle responses of food components is the summation of procentual effects of relevant health outcomes. We illustrate this approach with the action of flavanols on vascular health, specifically endothelial function.

Low-dose radiation therapy (LD-RT) has historically been a successful treatment for pneumonia and is clinically established as an immunomodulating therapy for inflammatory diseases. The ongoing COVID-19 pandemic has elicited renewed scientific interest in LD-RT and multiple small clinical trials have recently corroborated the historical LD-RT findings and demonstrated preliminary efficacy and immunomodulation for the treatment of severe COVID-19 pneumonia. The present review explicates archival medical research data of LD-RT and attempts to translate this into modernized evidence, relevant for the COVID-19 crisis. Additionally, we explore the putative mechanisms of LD-RT immunomodulation, revealing specific downregulation of proinflammatory cytokines that are integral to the development of the COVID-19 cytokine storm induced hyperinflammatory state. Radiation exposure in LD-RT is minimal compared to radiotherapy dosing standards in oncology care and direct toxicity and long-term risk for secondary disease are expected to be low. The recent clinical trials investigating LD-RT for COVID-19 confirm initial treatment safety. Based on our findings we conclude that LD-RT could be an important treatment option for COVID-19 patients that are likely to progress to severity. We advocate the further use of LD-RT in carefully monitored experimental environments to validate its effectiveness, risks and mechanisms of LD-RT.