Optical waveguides with compound multiperiodic grating nanostructures for refractive index sensing

The spectral characteristics and refractive index sensitivity of compound multiperiodic grating waveguides are investigated in theory and experiment. Compound gratings are formed by superposition of two or more monoperiodic gratings. Compared to monoperiodic photonic crystal waveguides, compound grating waveguides offer more degrees of design freedom by choice of component grating periods and duty cycles. Refractive index sensing is achieved by evaluating the wavelength or intensity of guided mode resonances in the reflection spectrum. We designed, fabricated, and characterized 24 different compound multiperiodic nanostructured waveguides for refractive index sensing. Simulations are carried out with the Rigorous Coupled Wave Algorithm (RCWA). The resulting spectra, resonance sensitivities, and quality factors are compared to monoperiodic as well as to three selected aperiodic nanostructures (Rudin-Shapiro, Fibonacci, and Thue-Morse). The refractive index sensitivity of the TE resonances is similar for all types of investigated nanostructures. For the TM resonances the compound multiperiodic nanostructures exhibit higher sensitivity values compared to the monoperiodic nanostructure and similar values as the aperiodic nanostructures. No significant influence of the compound grating duty cycles on the sensitivity is observed

Skepticism Motivated: On the Skeptical Import of Motivated Reasoning

Empirical work on motivated reasoning suggests that our judgments are influenced to a surprising extent by our wants, desires and preferences (Kahan 2016; Lord, Ross, and Lepper 1979; Molden and Higgins 2012; Taber and Lodge 2006). How should we evaluate the epistemic status of beliefs formed through motivated reasoning? For example, are such beliefs epistemically justified? Are they candidates for knowledge? In liberal democracies, these questions are increasingly controversial as well as politically timely (Beebe et al. 2018; Lynch forthcoming, 2018; Slothuus and de Vreese 2010). And yet, the epistemological significance of motivated reasoning has been almost entirely ignored by those working in mainstream epistemology. We aim to rectify this oversight. Using politically motivated reasoning as a case study, we show how motivated reasoning gives rise to three distinct kinds of skeptical challenges. We conclude by showing how the skeptical import of motivated reasoning has some important ramifications for how we should think about the demands of intellectual humility

Causality and CPT violation from an Abelian Chern-Simons-like term

We study a class of generalized Abelian gauge field theories where CPT symmetry is violated by a Chern-Simons-like term which selects a preferred direction in spacetime. Such Chern-Simons-like terms may either emerge as part of the low-energy effective action of a more fundamental theory or be produced by chiral anomalies over a nonsimply connected spacetime manifold. Specifically, we investigate the issues of unitarity and causality. We find that the behaviour of these gauge field theories depends on whether the preferred direction is spacelike or timelike. For a purely spacelike preferred direction, a well-behaved Feynman propagator exists and microcausality holds, which indicates the possibility of a consistent quantization of the theory. For timelike preferred directions, unitarity or causality is violated and a consistent quantization does not seem to be possible.Comment: LaTeX, 27 pages, v4: to appear in NP

Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation

Abstract: The human voltage gated potassium channel Kv1.5 that conducts the IKurcurrent is akey determinant of the atrial action potential. Its mutations have been linked to hereditary formsof atrial fibrillation (AF), and the channel is an attractive target for the management of AF. Thedevelopment of IKurblockers to treat AF resulted in small molecule Kv1.5 inhibitors. The selectivityof the blocker for the target channel plays an important role in the potential therapeutic applicationof the drug candidate: the higher the selectivity, the lower the risk of side effects. In this respect,small molecule inhibitors of Kv1.5 are compromised due to their limited selectivity. A wide range ofpeptide toxins from venomous animals are targeting ion channels, including mammalian channels.These peptides usually have a much larger interacting surface with the ion channel compared tosmall molecule inhibitors and thus, generally confer higher selectivity to the peptide blockers. Wefound two peptides in the literature, which inhibited IKur: Ts6 and Osu1. Their affinity and selectivityfor Kv1.5 can be improved by rational drug design in which their amino acid sequences could bemodified in a targeted way guided by in silico docking experiments

Arcanolysin is a cholesterol-dependent cytolysin of the human pathogen Arcanobacterium haemolyticum

Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis, wound infections, and a variety of occasional invasive diseases. Since its initial discovery in 1946, this Gram positive organism has been known to have hemolytic activity, yet no hemolysin has been previously reported. A. haemolyticum also displays variable hemolytic activity on laboratory blood agar that is dependent upon which species the blood is derived. Here we describe a cholesterol-dependent cytolysin (CDC) secreted by A. haemolyticum, designated arcanolysin (aln), which is present in all strains (n = 52) tested by DNA dot hybridization. Among the known CDCs, ALN is most closely related to pyolysin (PLO) from Trueperella (formerly Arcanobacterium) pyogenes. The aln probe, however, did not hybridize to DNA from T. pyogenes. The aln open reading frame has a lower mol %G+C (46.7%) than the rest of the A. haemolyticum genome (53.1%) and is flanked by two tRNA genes, consistent with probable acquisition by horizontal transfer. The ALN protein (~ 64 kDa) contains a predicted signal sequence, a putative PEST sequence, and a variant undecapeptide within domain 4, which is typically important for function of the toxins. The gene encoding ALN was cloned and expressed in Escherichia coli as a functional recombinant toxin. Recombinant ALN had hemolytic activity on erythrocytes and cytolytic activity on cultured cells from human, rabbit, pig and horse origins but was poorly active on ovine, bovine, murine, and canine cells. ALN was less sensitive to inhibition by free cholesterol than perfringolysin O, consistent with the presence of the variant undecapeptide. ALN is a newly identified CDC with hemolytic activity and unique properties in the CDC family and may be a virulence determinant for A. haemolyticum

Identification of a Novel Drug Lead That Inhibits HCV Infection and Cell-to-Cell Transmission by Targeting the HCV E2 Glycoprotein

Hepatitis C Virus (HCV) infects 200 million individuals worldwide. Although several FDA approved drugs targeting the HCV serine protease and polymerase have shown promising results, there is a need for better drugs that are effective in treating a broader range of HCV genotypes and subtypes without being used in combination with interferon and/or ribavirin. Recently, two crystal structures of the core of the HCV E2 protein (E2c) have been determined, providing structural information that can now be used to target the E2 protein and develop drugs that disrupt the early stages of HCV infection by blocking E2’s interaction with different host factors. Using the E2c structure as a template, we have created a structural model of the E2 protein core (residues 421–645) that contains the three amino acid segments that are not present in either structure. Computational docking of a diverse library of 1,715 small molecules to this model led to the identification of a set of 34 ligands predicted to bind near conserved amino acid residues involved in the HCV E2: CD81 interaction. Surface plasmon resonance detection was used to screen the ligand set for binding to recombinant E2 protein, and the best binders were subsequently tested to identify compounds that inhibit the infection of Huh-7 cells by HCV. One compound, 281816, blocked E2 binding to CD81 and inhibited HCV infection in a genotype-independent manner with IC50’s ranging from 2.2 µM to 4.6 µM. 281816 blocked the early and late steps of cell-free HCV entry and also abrogated the cell-to-cell transmission of HCV. Collectively the results obtained with this new structural model of E2c suggest the development of small molecule inhibitors such as 281816 that target E2 and disrupt its interaction with CD81 may provide a new paradigm for HCV treatment

Phylogenetic analysis of Andinia (Pleurothallidinae; Orchidaceae) and a systematic re-circumscription of the genus

Most of the species studied in this paper have previously been placed in either Pleurothallis or Lepanthes. However, at one time or another, members of the group have also been placed in the genera Andinia, Brachycladium, Lueranthos, Masdevalliantha, Neooreophilus, Oreophilus, Penducella, Salpistele and Xenosia. Phylogenetic analyses of nuclear ITS and plastid matK sequences indicate that these species form a strongly supported clade that is only distantly related to Lepanthes and is distinct from Pleurothallis and Salpistele. Since this clade includes the type species of Andinia, A. dielsii, and it has taxonomic precedence over all other generic names belonging to this group, Andinia is re-circumscribed and expanded to include 72 species segregated into five subgenera: Aenigma, Andinia, Brachycladium, Masdevalliantha and Minuscula. The required taxonomic transfers are made herein. We hypothesize that convergent evolution towards a similar pollinator syndrome involving deceit pollination via pseudocopulation by Diptera resulted in a similar floral morphology between species of subgenus Brachycladium and species of Lepanthes; hence the prior placement of the species of subgenus Brachycladium in Lepanthes. Species of the re-circumscribed Andinia are confined exclusively to the Andes, ranging from about 1,200 to 3,800 m, from Colombia south to Bolivia, making the generic name very apt. Elevational distributions of the individual clades are discussed in relation to the possible evolutionary diversification of the most species-rich clade, subgenus Brachycladium.La mayoría de las especies aquí estudiadas han sido previamente incluidas ya sea en el género Pleurothallis o en Lepanthes. Sin embargo, en un momento u otro, miembros del grupo también han sido colocados en los géneros Andinia, Brachycladium, Lueranthos, Masdevalliantha, Neooreophilus, Oreophilus, Penducella, Salpistele y Xenosia. Análisis filogenéticos de secuencias de las regiones ITS y matK indican que estas especies forman un clado fuertemente soportado que está solo distantemente relacionado con Lepanthes y que es diferente de las especies de Pleurothallis y Salpistele. Ya que este clado incluye la especie tipo de Andinia, A. dielsii y que tiene precedencia taxonómica sobre los demás nombres genéricos que pertenecen al grupo, se re-circunscribe y expande el género Andinia para incluir 72 especies segregadas en cinco subgéneros: Aenigma, Andinia, Brachycladium, Masdevalliantha y Minuscula y se hacen las transferencias taxonómicas requeridas. Hipotetizamos que la evolución convergente hacia un síndrome de polinización similar que involucra la polinización por engaño por medio de la pseudocópula por Diptera, resultó en una morfología floral similar entre las especies del subgénero Brachycladium y las especies de Lepanthes; de ahí la ubicación previa de las especies del subgénero Brachycladium en Lepanthes. Las especies de Andinia están confinadas exclusivamente a los Andes, distribuidas aproximadamente desde 1200 m a 3800 m desde Colombia hasta Bolivia, haciendo del nombre genérico uno muy adequado. Se discuten las distribuciones altitudinales de los clados individuales en relación a la posible diversificacion evolutiva del clado con más especies, el cual corresponde al subgénero Brachycladium.Universidad de Costa Rica/[814-B1-239]/UCR/Costa RicaUniversidad de Costa Rica/[814-B3-075]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Agroalimentarias::Jardín Botánico Lankester (JBL