On the Union Closed Fragment of Existential Second-Order Logic and Logics with Team Semantics

We present syntactic characterisations for the union closed fragments of existential second-order logic and of logics with team semantics. Since union closure is a semantical and undecidable property, the normal form we introduce enables the handling and provides a better understanding of this fragment. We also introduce inclusion-exclusion games that turn out to be precisely the corresponding model-checking games. These games are not only interesting in their own right, but they also are a key factor towards building a bridge between the semantic and syntactic fragments. On the level of logics with team semantics we additionally present restrictions of inclusion-exclusion logic to capture the union closed fragment. Moreover, we define a team based atom that when adding it to first-order logic also precisely captures the union closed fragment of existential second-order logic which answers an open question by Galliani and Hella

Pharmacogenetics of ophthalmic topical β-blockers

Glaucoma is the second leading cause of blindness worldwide. The primary glaucoma risk factor is elevated intraocular pressure. Topical β-blockers are affordable and widely used to lower intraocular pressure. Genetic variability has been postulated to contribute to interpersonal differences in efficacy and safety of topical β-blockers. This review summarizes clinically significant polymorphisms that have been identified in the β-adrenergic receptors (ADRB1, ADRB2 and ADRB3). The implications of polymorphisms in CYP2D6 are also discussed. Although the candidate-gene approach has facilitated significant progress in our understanding of the genetic basis of glaucoma treatment response, most drug responses involve a large number of genes, each containing multiple polymorphisms. Genome-wide association studies may yield a more comprehensive set of polymorphisms associated with glaucoma outcomes. An understanding of the genetic mechanisms associated with variability in individual responses to topical β-blockers may advance individualized treatment at a lower cost

Effects of Pulvinar Inactivation on Spatial Decision-making between Equal and Asymmetric Reward Options

The ability to selectively process visual inputs and to decide between multiple movement options in an adaptive manner is critical for survival. Such decisions are known to be influenced by factors such as reward expectation and visual saliency. The dorsal pulvinar connects to a multitude of cortical areas that are involved in visuospatial memory and integrate information about upcoming eye movements with expected reward values. However, it is unclear whether the dorsal pulvinar is critically involved in spatial memory and reward-based oculomotor decision behavior. To examine this, we reversibly inactivated the dorsal portion of the pulvinar while monkeys performed a delayed memory saccade task that included choices between equally or unequally rewarded options. Pulvinar inactivation resulted in a delay of saccade initiation toward memorized contralesional targets but did not affect spatial memory. Furthermore, pulvinar inactivation caused a pronounced choice bias toward the ipsilesional hemifield when the reward value in the two hemifields was equal. However, this choice bias could be alleviated by placing a high reward target into the contralesional hemifield. The bias was less affected by the manipulation of relative visual saliency between the two competing targets. These results suggest that the dorsal pulvinar is involved in determining the behavioral desirability of movement goals while being less critical for spatial memory and reward processing

Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding

BACKGROUND: The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. However, in a number of recent studies, a prevalence of antagonistic epistasis (the tendency of multiple mutations to have a mitigating rather than reinforcing effect) has been observed. RESULTS: We studied in silico the net amount and form of epistatic interactions in RNA secondary structure folding by measuring the fraction of neutral mutants as a function of mutational distance d. We found a clear prevalence of antagonistic epistasis in RNA secondary structure folding. By relating the fraction of neutral mutants at distance d to the average neutrality at distance d, we showed that this prevalence derives from the existence of many compensatory mutations at larger mutational distances. CONCLUSIONS: Our findings imply that the average direction of epistasis in simple fitness landscapes is directly related to the density with which fitness peaks are distributed in these landscapes

Evolution of digital organisms at high mutation rates leads to survival of the flattest

Darwinian evolution favours genotypes with high replication rates, a process called 'survival of the fittest'. However, knowing the replication rate of each individual genotype may not suffice to predict the eventual survivor, even in an asexual population. According to quasi-species theory, selection favours the cloud of genotypes, interconnected by mutation, whose average replication rate is highest. Here we confirm this prediction using digital organisms that self-replicate, mutate and evolve. Forty pairs of populations were derived from 40 different ancestors in identical selective environments, except that one of each pair experienced a 4-fold higher mutation rate. In 12 cases, the dominant genotype that evolved at the lower mutation rate achieved a replication rate >1.5-fold faster than its counterpart. We allowed each of these disparate pairs to compete across a range of mutation rates. In each case, as mutation rate was increased, the outcome of competition switched to favour the genotype with the lower replication rate. These genotypes, although they occupied lower fitness peaks, were located in flatter regions of the fitness surface and were therefore more robust with respect to mutations

Adaptive Radiation from Resource Competition in Digital Organisms

Species richness often peaks at intermediate productivity and decreases as resources become more or less abundant. The mechanisms that produce this pattern are not completely known, but several previous studies have suggested environmental heterogeneity as a cause. In experiments with evolving digital organisms and populations of fixed size, maximum species richness emerges at intermediate productivity, even in a spatially homogeneous environment, owing to frequency-dependent selection to exploit an influx of mixed resources. A diverse pool of limiting resources is sufficient to cause adaptive radiation, which is manifest by the origin and maintenance of phenotypically and phylogenetically distinct groups of organisms

Nano- and micro-structures in lunar zircon from Apollo 15 and 16 impactites: implications for age interpretations

Meteorite impact processes are ubiquitous on the surfaces of rocky and icy bodies in the Solar System, including the Moon. One of the most common accessory minerals, zircon, when shocked, produces specific micro-structures that may become indicative of the age and shock conditions of these impact processes. To better understand the shock mechanisms in zircon from Apollo 15 and 16 impact breccias, we applied transmission electron microscopy (TEM) and studied nano-structures in eight lunar zircons displaying four different morphologies from breccias 15455, 67915, and 67955. Our observations revealed a range of shock-related features in zircon: (1) planar and non-planar fractures, (2) “columnar” zircon rims around baddeleyite cores, (3) granular textured zircon, in most cases with sub-µm-size inclusions of monoclinic ZrO2 (baddeleyite) and cubic ZrO2 (zirconia), (4) silica-rich glass and metal inclusions of FeS and FeNi present at triple junctions in granular zircon and in baddeleyite, (5) inclusions of rutile in shocked baddeleyite, (6) amorphous domains, (7) recrystallized domains. In many grain aggregates, shock-related micro-structures overprint each other, indicating either different stages of a single impact process or multiple impact events. During shock, some zircons were transformed to diaplectic glass (6), and others (7) were completely decomposed into SiO2 and Zr-oxide, evident from the observed round shapes of cubic zirconia and silica-rich glass filling triple junctions of zircon granules. Despite the highly variable effect on textures and Zr phases, shock-related features show no correlation with relatively homogeneous U–Pb or 207Pb/206Pb ages of zircons. Either the shock events occurred very soon after the solidification or recrystallization of the different Zr phases, or the shock events were too brief to result in noticeable Pb loss during shock metamorphism

Effects of Pulvinar Inactivation on Spatial Decision-making between Equal and Asymmetric Reward Options

The ability to selectively process visual inputs and to decide between multiple movement options in an adaptive manner is critical for survival. Such decisions are known to be influenced by factors such as reward expectation and visual saliency. The dorsal pulvinar connects to a multitude of cortical areas that are involved in visuospatial memory and integrate information about upcoming eye movements with expected reward values. However, it is unclear whether the dorsal pulvinar is critically involved in spatial memory and reward-based oculomotor decision behavior. To examine this, we reversibly inactivated the dorsal portion of the pulvinar while monkeys performed a delayed memory saccade task that included choices between equally or unequally rewarded options. Pulvinar inactivation resulted in a delay of saccade initiation toward memorized contralesional targets but did not affect spatial memory. Furthermore, pulvinar inactivation caused a pronounced choice bias toward the ipsilesional hemifield when the reward value in the two hemifields was equal. However, this choice bias could be alleviated by placing a high reward target into the contralesional hemifield. The bias was less affected by the manipulation of relative visual saliency between the two competing targets. These results suggest that the dorsal pulvinar is involved in determining the behavioral desirability of movement goals while being less critical for spatial memory and reward processing

Differentiating between hydrothermal and diagenetic carbonate using rare earth element and yttrium (REE+Y) geochemistry: a case study from the Paleoproterozoic George Fisher massive sulfide Zn deposit, Mount Isa, Australia

Carbonate minerals are ubiquitous in most sediment-hosted mineral deposits. These deposits can contain a variety of carbonate types with complex paragenetic relationships. When normalized to chondritic values (CN), rare-earth elements and yttrium (REE+YCN) can be used to constrain fluid chemistry and fluid-rock interaction processes in both low- and high-temperature settings. Unlike other phases (e.g., pyrite), the application of in situ laser ablation-inductively coupled plasma-mass spectroscopy (LA-ICP-MS) data to the differentiation of pre-ore and hydrothermal carbonates remains relatively untested. To assess the potential applicability of carbonate in situ REE+Y data, we combined transmitted light and cathodoluminescence (CL) petrography with LA-ICP-MS analysis of carbonate mineral phases from (1) the Proterozoic George Fisher clastic dominated (CD-type) massive sulfide deposit and from (2) correlative, barren host rock lithologies (Urquhart Shale Formation). The REE+YCN composition of pre-ore calcite suggests it formed during diagenesis from diagenetic pore fluids derived from ferruginous, anoxic seawater. Hydrothermal and hydrothermally altered calcite and dolomite from George Fisher is generally more LREE depleted than the pre-ore calcite, whole-rock REE concentrations, and shale reference values. We suggest this is the result of hydrothermal alteration by saline Cl--rich mineralizing fluids. Furthermore, the presence of both positive and negative Eu/Eu* values in calcite and dolomite indicates that the mineralizing fluids were relatively hot (>250°C) and cooled below 200–250°C during ore formation. This study confirms the hypothesis that in situ REE+Y data can be used to differentiate between pre-ore and hydrothermal carbonate and provide important constraints on the conditions of ore formation

Balancing Robustness and Evolvability

Can a single unifying mathematical framework help to explain robustness - the ability of organisms to persist in the face of changing conditions - at all biological scales, from biochemical to ecological