Singularly Perturbed Monotone Systems and an Application to Double Phosphorylation Cycles

The theory of monotone dynamical systems has been found very useful in the modeling of some gene, protein, and signaling networks. In monotone systems, every net feedback loop is positive. On the other hand, negative feedback loops are important features of many systems, since they are required for adaptation and precision. This paper shows that, provided that these negative loops act at a comparatively fast time scale, the main dynamical property of (strongly) monotone systems, convergence to steady states, is still valid. An application is worked out to a double-phosphorylation ``futile cycle'' motif which plays a central role in eukaryotic cell signaling.Comment: 21 pages, 3 figures, corrected typos, references remove

Categorizing Different Approaches to the Cosmological Constant Problem

We have found that proposals addressing the old cosmological constant problem come in various categories. The aim of this paper is to identify as many different, credible mechanisms as possible and to provide them with a code for future reference. We find that they all can be classified into five different schemes of which we indicate the advantages and drawbacks. Besides, we add a new approach based on a symmetry principle mapping real to imaginary spacetime.Comment: updated version, accepted for publicatio

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205254/Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.info:eu-repo/semantics/publishedVersio

Human Health Risk Assessment For Arsenic: A Critical Review

Millions of people are exposed to arsenic resulting in a range of health implications.This paper provides an up-to-date review of the different sources of arsenic (water, soil and food), indicators of human exposure (biomarker assessment of hair, nail, urine and blood), epidemiological and toxicological studies on carcinogenic and non-carcinogenic health outcomes, and risk assessment approaches. The review demonstrates a need for more work evaluating the risks of different arsenic species such as; arsenate, arsenite monomethylarsonic acid, monomethylarsonous acid, dimethylarsinic acid and dimethylarsinous acid as well as a need to better integrate the different exposure sources in risk assessments