Groups and semigroups with a one-counter word problem

We prove that a finitely generated semigroup whose word problem is a one-counter language has a linear growth function. This provides us with a very strong restriction on the structure of such a semigroup, which, in particular, yields an elementary proof of a result of Herbst, that a group with a one-counter word problem is virtually cyclic. We prove also that the word problem of a group is an intersection of finitely many one-counter languages if and only if the group is virtually abelian

The molecular basis of color vision in colorful fish: Four Long Wave-Sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites

<p>Abstract</p> <p>Background</p> <p>Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of elaborate coloration in male guppies (<it>Poecilia reticulata</it>) is also associated with opsin gene diversity, we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the family Poeciliidae.</p> <p>Results</p> <p>Sequences of four LWS opsin genes were amplified from the guppy genome and from mRNA isolated from adult guppy eyes. Variation in expression was quantified using qPCR. Three of the four genes encode opsins predicted to be most sensitive to different wavelengths of light because they vary at key amino acid positions. This family of LWS opsin genes was produced by a diversity of duplication events. One, an intronless gene, was produced prior to the divergence of families Fundulidae and Poeciliidae. Between-gene PCR and DNA sequencing show that two of the guppy LWS opsins are linked in an inverted orientation. This inverted tandem duplication event occurred near the base of the poeciliid tree in the common ancestor of <it>Poecilia </it>and <it>Xiphophorus</it>. The fourth sequence has been uncovered only in the genus <it>Poecilia</it>. In the guppies surveyed here, this sequence is a hybrid, with the 5' end most similar to one of the tandem duplicates and the 3' end identical to the other.</p> <p>Conclusion</p> <p>Enhanced wavelength discrimination, a possible consequence of opsin gene duplication and divergence, might have been an evolutionary prerequisite for color-based sexual selection and have led to the extraordinary coloration now observed in male guppies and in many other poeciliids.</p

Understanding Shape and Centroid Deviations in 39 Strong Lensing Galaxy Clusters in Various Dynamical States

Through observational tests of strong lensing galaxy clusters, we can test simulation derived structure predictions that follow from $\Lambda$ Cold Dark Matter ($\Lambda$CDM) cosmology. The shape and centroid deviations between the total matter distribution, stellar matter distributions, and hot intracluster gas distribution serve as an observational test of these theoretical structure predictions. We measure the position angles, ellipticities, and locations/centroids of the brightest cluster galaxy (BCG), intracluster light (ICL), the hot intracluster medium (ICM), and the core lensing mass for a sample of strong lensing galaxy clusters from the SDSS Giant Arcs Survey (SGAS). We utilize HST WFC3/IR imaging data to measure the shapes/centroids of the ICL and BCG distributions and use Chandra ACIS-I X-ray data to measure the shapes/centroids of ICM. Additionally, we measure the concentration parameter c and asymmetry parameter A to incorporate cluster dynamical state into our analysis. Using this multicomponent approach, we attempt to constrain the astrophysics of our strong lensing cluster sample and evaluate the different components in terms of their ability to trace out the DM halo of clusters in various dynamical states.Comment: 6 pages, 4 figures, to appear in Proc. of the mm Universe 2023 conference, Grenoble (France), June 2023, published by F. Mayet et al. (Eds), EPJ Web of conferences, EDP Science

Zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase II clinical efficacy studies

Zanamivir is a highly selective neuraminidase (NA) inhibitor with demonstrated clinical efficacy against influenza A and B virus infections. In phase II clinical efficacy trials (NAIB2005 and NAIB2008), virological substudies showed mean reductions in virus shedding after 24 h of treatment of 1.5 to 2.0 log(10) 50% tissue culture infective doses compared to a placebo, with no reemergence of virus after the completion of therapy. Paired isolates (n = 41) obtained before and during therapy with zanamivir demonstrated no shifts in susceptibility to zanamivir when measured by NA assays, although for a few isolates NA activity was too low to evaluate. In plaque reduction assays in MDCK cells, the susceptibility of isolates to zanamivir was extremely variable even at baseline and did not correlate with the speed of resolution of virus shedding. Isolates with apparent limited susceptibility to zanamivir by plaque reduction proved highly susceptible in vivo in the ferret model. Further sequence analysis of paired isolates revealed no changes in the hemagglutinin and NA genes in the majority of isolates. The few changes observed were all natural variants. No amino acid changes that had previously been identified in vitro as being involved with reduced susceptibility to zanamivir were observed. These studies highlighted problems associated with monitoring susceptibility to NA inhibitors in the clinic, in that no reliable cell-based assay is available. At present the NA assay is the best available predictor of susceptibility to NA inhibitors in vivo, as measured in the validated ferret model of infection

Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte-Binding Protein Homologue-5 in Kalifabougou, Mali

Reticulocyte-binding homologues (RH) are a ligand family that mediates merozoite invasion of erythrocytes in Plasmodium falciparum. Among the five members of this family identified so far, only P. falciparum reticulocyte-binding homologue-5 (PfRH5) has been found to be essential for parasite survival across strains that differ in virulence and route of host-cell invasion. Based on its essential role in invasion and early evidence of sequence conservation, PfRH5 has been prioritized for development as a vaccine candidate. However, little is known about the extent of genetic variability of RH5 in the field and the potential impact of such diversity on clinical outcomes or on vaccine evasion. Samples collected during a prospective cohort study of malaria incidence conducted in Kalifabougou, in southwestern Mali, were used to estimate genetic diversity, measure haplotype prevalence, and assess the within-host dynamics of PfRH5 variants over time and in relation to clinical malaria. A total of 10 nonsynonymous polymorphic sites were identified in the Pfrh5 gene, resulting in 13 haplotypes encoding unique protein variants. Four of these variants have not been previously observed. Plasmodium falciparum reticulocyte-binding homologue-5 had low amino acid haplotype (h = 0.58) and nucleotide (π = 0.00061) diversity. By contrast to other leading blood-stage malaria vaccine candidate antigens, amino acid differences were not associated with changes in the risk of febrile malaria in consecutive infections. Conserved B- and T-cell epitopes were identified. These results support the prioritization of PfRH5 for possible inclusion in a broadly cross-protective vaccine

Small Region, Big Impact: Highly Anisotropic Lyman-continuum Escape from a Compact Starburst Region with Extreme Physical Properties

Extreme, young stellar populations are considered the primary contributor to cosmic reionization. However, how Lyman-continuum (LyC) escapes these galaxies remains highly elusive because LyC escape can vary on sub-galactic scales that are technically challenging to observe in LyC emitters. We investigate the Sunburst Arc: a strongly lensed, LyC emitter at $z=2.37$. This galaxy reveals the exceptionally small scale (tens of parsecs) physics of LyC escape thanks to high magnification from strong lensing. Analyzing HST broadband and narrowband imaging, we find that the small ($<$100 pc) LyC leaking region shows distinctly extreme properties: a very blue UV slope ($\beta=-2.9\pm0.1$), high ionization state ([OIII]$\lambda 5007$/[OII]$\lambda 3727=11\pm3$ and [OIII]$\lambda 5007$/H$\beta=6.8\pm0.4$), strong oxygen emission (EW([OIII])$=1095\pm 40 \r{A}$), and high Lyman-$\alpha$ escape fraction ($0.3\pm 0.03$), none of which are found in any non-leaking regions of the galaxy. Moreover, a UV slope comparison with starburst population models indicates that the leaking region's UV emission consists of nearly ``pure'' stellar light with minimal contamination from surrounding nebular continuum emission and dust extinction. These results suggest a highly directional LyC escape such that LyC is produced and escapes from a small, extreme starburst region where the stellar feedback from an ionizing star cluster may create an anisotropic ``pencil beam'' viewing geometry in the surrounding gas. As a result, unabsorbed LyC directly escapes through these perforated hole(s). Importantly, such anisotropic escape processes imply that unfavorable sightline effects are a crucial contributor to the significant scatters between galaxy properties and LyC escape fraction in observations and that strong lensing uniquely reveals the small-scale physics that regulates the ionizing budget of galaxies for reionization.Comment: 17 pages, 5 figures, 3 tables, submitted to ApJ Letters. Comments welcom

Standardized research protocols enable transdisciplinary research of climate variation impacts in corn production systems

The important questions about agriculture, climate, and sustainability have become increasingly complex and require a coordinated, multifaceted approach for developing new knowledge and understanding. A multistate, transdisciplinary project was begun in 2011 to study the potential for both mitigation and adaptation of corn-based cropping systems to climate variations. The team is measuring the baseline as well as change of the system\u27s carbon (C), nitrogen (N), and water footprints, crop productivity, and pest pressure in response to existing and novel production practices. Nine states and 11 institutions are participating in the project, necessitating a well thought out approach to coordinating field data collection procedures at 35 research sites. In addition, the collected data must be brought together in a way that can be stored and used by persons not originally involved in the data collection, necessitating robust procedures for linking metadata with the data and clearly delineated rules for use and publication of data from the overall project. In order to improve the ability to compare data across sites and begin to make inferences about soil and cropping system responses to climate across the region, detailed research protocols were developed to standardize the types of measurements taken and the specific details such as depth, time, method, numbers of samples, and minimum data set required from each site. This process required significant time, debate, and commitment of all the investigators involved with field data collection and was also informed by the data needed to run the simulation models and life cycle analyses. Although individual research teams are collecting additional measurements beyond those stated in the standardized protocols, the written protocols are used by the team for the base measurements to be compared across the region. A centralized database was constructed to meet the needs of current researchers on this project as well as for future use for data synthesis and modeling for agricultural, ecosystem, and climate sciences

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Discovery and characterization of small molecules that target the Ral GTPase

The Ras-like GTPases RalA and B are important drivers of tumor growth and metastasis. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here, we used protein structure analysis and virtual screening to identify drug-like molecules that bind a site on the GDP-form of Ral. Compounds RBC6, RBC8 and RBC10 inhibited Ral binding to its effector RalBP1, Ral-mediated cell spreading in murine fibroblasts and anchorage-independent growth of human cancer cell lines. Binding of RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasma resonance and 15N-HSQC NMR. RBC8 and BQU57 show selectivity for Ral relative to Ras or Rho and inhibit xenograft tumor growth similar to depletion of Ral by siRNA. Our results show the utility of structure-based discovery for development of therapeutics for Ral-dependent cancers

Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 μg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation