A Digital Delay Model Supporting Large Adversarial Delay Variations

Dynamic digital timing analysis is a promising alternative to analog simulations for verifying particularly timing-critical parts of a circuit. A necessary prerequisite is a digital delay model, which allows to accurately predict the input-to-output delay of a given transition in the input signal(s) of a gate. Since all existing digital delay models for dynamic digital timing analysis are deterministic, however, they cannot cover delay fluctuations caused by PVT variations, aging and analog signal noise. The only exception known to us is the $\eta$-IDM introduced by F\"ugger et al. at DATE'18, which allows to add (very) small adversarially chosen delay variations to the deterministic involution delay model, without endangering its faithfulness. In this paper, we show that it is possible to extend the range of allowed delay variations so significantly that realistic PVT variations and aging are covered by the resulting extended $\eta$-IDM

Exploring the evolution and function of Canoe’s intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis

One central question for cell and developmental biologists is defining how epithelial cells can change shape and move during embryonic development without tearing tissues apart. This requires robust yet dynamic connections of cells to one another, via the cell-cell adherens junction, and of junctions to the actin and myosin cytoskeleton, which generates force. The last decade revealed that these connections involve a multivalent network of proteins, rather than a simple linear pathway. We focus on Drosophila Canoe, homolog of mammalian Afadin, as a model for defining the underlying mechanisms. Canoe and Afadin are complex, multidomain proteins that share multiple domains with defined and undefined binding partners. Both also share a long carboxy-terminal intrinsically disordered region (IDR), whose function is less well defined. IDRs are found in many proteins assembled into large multiprotein complexes. We have combined bioinformatic analysis and the use of a series of canoe mutants with early stop codons to explore the evolution and function of the IDR. Our bioinformatic analysis reveals that the IDRs of Canoe and Afadin differ dramatically in sequence and sequence properties. When we looked over shorter evolutionary time scales, we identified multiple conserved motifs. Some of these are predicted by AlphaFold to be alpha-helical, and two correspond to known protein interaction sites for alpha-catenin and F-actin. We next identified the lesions in a series of eighteen canoe mutants, which have early stop codons across the entire protein coding sequence. Analysis of their phenotypes are consistent with the idea that the IDR, including the conserved motifs in the IDR, are critical for protein function. These data provide the foundation for further analysis of IDR function. © 2023 Gurley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Biological Mechanisms Underlying Physical Fitness and Sports Performance

The concept of mechanism in biology has three distinct meanings. It may refer to a philosophical thesis about the nature of life and biology, to the internal workings of a machine-like structure, or to the causal explanation of a particular phenomenon. In this Special Issue, we try to discuss these possible biological mechanisms that underlie the beneficial effects of physical fitness and sports performance, as well their importance and role/influences on physical health.Despite the significant body of knowledge regarding the physiological and physical effects of different training methods (based on dimensions of load), some of the biological causes for those changes are still unknown. Additionally, few studies have focused on the natural biological variability in humans and how specific properties of humans may justify different effects for the same training intervention. Thus, more original research is needed to provide plausible biological mechanisms that may explain the physiological and physical effects of exercise and training in humans.In this Special Issue, we gather the contributions that describe and list the links between physical fitness, sports performance, and human biology

Molecular Techniques Reveal Wide Phyletic Diversity of Heterotrophic Microbes Associated with Discodermia spp. (Porifera: Demospongiae)

Sponges are well known to harbor large numbers of heterotrophic microbes within their mesohyl. Studies to determine the diversity of these associated microbes have been attempted for only a few shallow water species. We cultured various microorganisms from several species of Discodermia collected from deep water using the \u27Johnson-Sea-Link\u27 manned submersibles, and characterised them by standard microbiological identification methods. Characterisation of a small proportion (ca. 10%) of the total and potential eubacterial isolate collection with molecular systematics techniques revealed a wide diversity of microbes. Phylogenetic analyses of 32 small subunit (SSU) 16S-like rRNA gene sequences from different micorbes indicated high levels of taxonomic diversity assoiated with this genus of sponge. For example, bacteria from at least five cubacterial subdivisions - gamma, alpha, beta, Cytophaga and Gram positive - were isolated from the mesohyl of Discodermia. Several strains were unidentifiable from current sequence databases. No overlap was found between sequences of 24 isolates and 8 sequences obtained by PCR and cloning directly from sponge samples. The abundance and diversity of microbes associated with sponges such as Discodermia suggest that they may play important roles in marine microbial ecology, dispersal and evolution

Lack of Chemical Defense in Two Species of Stalked Crinoids: Support for the Predation Hypothesis for Mesozoic Bathymetric Restriction

Methanol/dichloromethane extracts of (1) the arms and pinnules, and (2) the stalk and cirri of the deep water stalked crinoids Endoxocrinus parrae (Gervais) and Neocrinus decorus (Carpenter) were imbedded at ecologically relevant volumetric concentrations in alginate food pellets containing 2% krill as a feeding stimulant and presented in situ to an assemblage of shallow-water reef fish. Experimental pellets were highly palatable to reef fish; no significant differences in pellet consumption occurred between experimental pellets containing extracts from either species of stalked crinoid or control pellets. Small pieces of cirri, stalks, calyx, arms and pinnules of both species were also tested in in situ feeding assays. While immediate consumption by fish was not apparent, Blue Headed Wrasse (Thalassoma bifasciatum (Block)) and Dusky Damselfish (Stegastes fuscus (Cuvier)) bit at pieces of each body component. Similar fish biting behaviors were also observed when two living Endoxocrinus parrae were deployed on the shallow reef. Observations indicate that neither species of stalked crinoid is chemically defended from predation by a natural assemblage of reef fish. This supports the predation hypothesis that restriction of stalked crinoids in deep-water habitats may have resulted from the Mesozoic radiation of durophagous fishes in shallow seas, resulting in a reduction of stalked crinoids from shallow water