Fibrational induction rules for initial algebras

This paper provides an induction rule that can be used to prove properties of data structures whose types are inductive, i.e., are carriers of initial algebras of functors. Our results are semantic in nature and are inspired by Hermida and Jacobs’ elegant algebraic formulation of induction for polynomial data types. Our contribution is to derive, under slightly different assumptions, an induction rule that is generic over all inductive types, polynomial or not. Our induction rule is generic over the kinds of properties to be proved as well: like Hermida and Jacobs, we work in a general fibrational setting and so can accommodate very general notions of properties on inductive types rather than just those of particular syntactic forms. We establish the correctness of our generic induction rule by reducing induction to iteration. We show how our rule can be instantiated to give induction rules for the data types of rose trees, finite hereditary sets, and hyperfunctions. The former lies outside the scope of Hermida and Jacobs’ work because it is not polynomial; as far as we are aware, no induction rules have been known to exist for the latter two in a general fibrational framework. Our instantiation for hyperfunctions underscores the value of working in the general fibrational setting since this data type cannot be interpreted as a set

TESTING THE MEDIATING ROLE OF LEADERS’ BACKGROUND ON THE EFFECTS OF NATIONALITY ON GLOBAL MINDSET

This study investigated the impact of nationality on the development of global mindset through an online survey administered to 243 leaders in the U.S. and Germany. The study found no statistically significant difference in global mindset between U.S. and German citizens; however, it did find that dual citizens have significantly higher global mindsets than citizens of a single country. The study also found that the effects of nationality on global mindset are mediated by the personal, educational, and professional factors in the leader’s background. These findings suggest that fundamental factors, such as education and experience, are more important to global mindset than nationality

Therapeutic CFTR correction normalizes systemic and lung-specific S1P level alterations associated with heart failure

Heart failure (HF) is among the main causes of death worldwide. Alterations of sphingosine-1-phosphate (S1P) signaling have been linked to HF as well as to target organ damage that is often associated with HF. S1P’s availability is controlled by the cystic fibrosis transmembrane regulator (CFTR), which acts as a critical bottleneck for intracellular S1P degradation. HF induces CFTR downregulation in cells, tissues and organs, including the lung. Whether CFTR alterations during HF also affect systemic and tissue-specific S1P concentrations has not been investigated. Here, we set out to study the relationship between S1P and CFTR expression in the HF lung. Mice with HF, induced by myocardial infarction, were treated with the CFTR corrector compound C18 starting ten weeks post-myocardial infarction for two consecutive weeks. CFTR expression, S1P concentrations, and immune cell frequencies were determined in vehicle- and C18-treated HF mice and sham controls using Western blotting, flow cytometry, mass spectrometry, and qPCR. HF led to decreased pulmonary CFTR expression, which was accompanied by elevated S1P concentrations and a pro-inflammatory state in the lungs. Systemically, HF associated with higher S1P plasma levels compared to sham-operated controls and presented with higher S1P receptor 1-positive immune cells in the spleen. CFTR correction with C18 attenuated the HF-associated alterations in pulmonary CFTR expression and, hence, led to lower pulmonary S1P levels, which was accompanied by reduced lung inflammation. Collectively, these data suggest an important role for the CFTR-S1P axis in HF-mediated systemic and pulmonary inflammation

Ivacaftor therapy post myocardial infarction augments systemic inflammation and evokes contrasting effects with respect to tissue inflammation in brain and lung

Acquired cystic fibrosis transmembrane regulator (CFTR) dysfunctions have been associated with several conditions, including myocardial infarction (MI). Here, CFTR is downregulated in brain, heart, and lung tissue and associates with inflammation and degenerative processes. Therapeutically increasing CFTR expression attenuates these effects. Whether potentiating CFTR function yields similar beneficial effects post-MI is unknown. The CFTR potentiator ivacaftor is currently in clinical trials for treatment of acquired CFTR dysfunction associated with chronic obstructive pulmonary disease and chronic bronchitis. Thus, we tested ivacaftor as therapeutic strategy for MI-associated target tissue inflammation that is characterized by CFTR alterations. MI was induced in male C57Bl/6 mice by ligation of the left anterior descending coronary artery. Mice were treated with ivacaftor starting ten weeks post-MI for two consecutive weeks. Systemic ivacaftor treatment ameliorates hippocampal neuron dendritic atrophy and spine loss and attenuates hippocampus-dependent memory deficits occurring post-MI. Similarly, ivacaftor therapy mitigates MI-associated neuroinflammation (i.e., reduces higher proportions of activated microglia). Systemically, ivacaftor leads to higher frequencies of circulating Ly6C+ and Ly6Chi cells compared to vehicle-treated MI mice. Likewise, an ivacaftor-mediated augmentation of MI-associated pro-inflammatory macrophage phenotype characterized by higher CD80-positivity is observed in the MI lung. In vitro, ivacaftor does not alter LPS-induced CD80 and tumor necrosis factor alpha mRNA increases in BV2 microglial cells, while augmenting mRNA levels of these markers in mouse macrophages and differentiated human THP-1-derived macrophages. Our results suggest that ivacaftor promotes contrasting effects depending on target tissue post-MI, which may be largely dependent on its effects on different myeloid cell types

Potent inhibitory activity of chimeric oligonucleotides targeting two different sites of human telomerase

Suppression of telomerase activity in tumor cells has been considered as a new anticancer strategy. Here, we present chimeric oligonucleotides (chimeric ODNs) as a new type of telomerase inhibitor that contains differently modified oligomers to address two different sites of telomerase: the RNA template and a suggested protein motif. We have shown previously that phosphorothioate-modified oligonucleotides (PS ODNs) interact in a length-dependent rather than in a sequence-dependent manner, presumably with the protein part of the primer-binding site of telomerase, causing strong inhibition of telomerase. In the present study, we demonstrate that extensions of these PS ODNs at their 3'-ends with an antisense oligomer partial sequence covering 11 bases of the RNA template cause significantly increased inhibitory activity, with IC(50) values between 0.60 and 0.95 nM in a Telomeric Repeat Amplification Protocol (TRAP) assay based on U-87 cell lysates. The enhanced inhibitory activity is observed regardless of whether the antisense part is modified (phosphodiester, PO; 2'-O-methylribosyl, 2'-OMe/PO; phosphoramidate, PAM). However, inside intact U-87 cells, these modifications of the antisense part proved to be essential for efficient telomerase inhibition 20 hours after transfection. In particular, the chimeric ODNs containing PAM or 2'-OMe/PO modifications, when complexed with lipofectin, were most efficient telomerase inhibitors (ID(50) = 0.04 and 0.06 microM, respectively). In conclusion, ODNs of this new type emerged as powerful inhibitors of human telomerase and are, therefore, promising candidates for further investigations of the anticancer strategy of telomerase inhibition

Spin-Selective Electron Transport Through Single Chiral Molecules

The interplay between chirality and magnetism has been a source of fascination among scientists for over a century. In recent years, chirality-induced spin selectivity (CISS) has attracted renewed interest. It has been observed that electron transport through layers of homochiral molecules leads to a significant spin polarization of several tens of percent. Despite the abundant experimental evidence gathered through mesoscopic transport measurements, the exact mechanism behind CISS remains elusive. In this study, we report spin-selective electron transport through single helical aromatic hydrocarbons that were sublimed in vacuo onto ferromagnetic cobalt surfaces and examined with spin-polarized scanning tunneling microscopy (SP-STM) at a temperature of 5 K. Direct comparison of two enantiomers under otherwise identical conditions revealed magnetochiral conductance asymmetries of up to 50% when either the molecular handedness was exchanged or the magnetization direction of the STM tip or Co substrate was reversed. Importantly, our results rule out electron-phonon coupling and ensemble effects as primary mechanisms responsible for CISS.Comment: 15 pages, 4 figures, plus Supporting Informatio

Role of the QBO in modulating the influence of the 11 year solar cycle on the atmosphere using constant forcings

We present a set of six 20 year experiments made with a state-of-the-art chemistry-climate model that incorporates the atmosphere from the surface to the lower thermosphere. The response of the middle atmosphere to the 11 year solar cycle, its impact on the troposphere, and especially the role of an externally prescribed stratospheric quasi-biennial oscillation (QBO) is investigated with NCAR's Whole Atmosphere Community Climate Model (WACCM3). The model experiments use either fixed solar cycle inputs or fixed solar cycle together with prescribed QBO phase. The annual mean solar response in temperature and ozone in the upper stratosphere is in qualitative agreement with other modeling and observational studies and does not depend on the presence of the imposed QBO. However, the solar response in the middle to lower stratosphere differs significantly for the two QBO phases. During solar maxima a weaker Brewer-Dobson circulation with relative downwelling, warming, and enhanced ozone occurs in the tropical lower stratosphere during QBO east conditions, while a stronger circulation, cooling, and decreased ozone exists during QBO west conditions. The net ozone increase during QBO east is the combined result of production and advection, whereas during QBO west the effects cancel each other and result in little net ozone changes. Especially during Southern Hemisphere late winter to early spring, the solar response at polar latitudes switches sign between the two QBO phases and qualitatively confirms observations and other recent model studies. During a poleward downward modulation of the polar night jet and a corresponding modulation of the Brewer-Dobson circulation in time, solar signals are detected all the way down to the extratropical troposphere. Possible limitations of the model experiments with respect to the fixed solar cycle conditions or the prescribed QBO phases, as well as the constant sea surface temperatures, are discussed

Generic Fibrational Induction

This paper provides an induction rule that can be used to prove properties of data structures whose types are inductive, i.e., are carriers of initial algebras of functors. Our results are semantic in nature and are inspired by Hermida and Jacobs' elegant algebraic formulation of induction for polynomial data types. Our contribution is to derive, under slightly different assumptions, a sound induction rule that is generic over all inductive types, polynomial or not. Our induction rule is generic over the kinds of properties to be proved as well: like Hermida and Jacobs, we work in a general fibrational setting and so can accommodate very general notions of properties on inductive types rather than just those of a particular syntactic form. We establish the soundness of our generic induction rule by reducing induction to iteration. We then show how our generic induction rule can be instantiated to give induction rules for the data types of rose trees, finite hereditary sets, and hyperfunctions. The first of these lies outside the scope of Hermida and Jacobs' work because it is not polynomial, and as far as we are aware, no induction rules have been known to exist for the second and third in a general fibrational framework. Our instantiation for hyperfunctions underscores the value of working in the general fibrational setting since this data type cannot be interpreted as a set.Comment: For Special Issue from CSL 201

Kinetic models with randomly perturbed binary collisions

We introduce a class of Kac-like kinetic equations on the real line, with general random collisional rules, which include as particular cases models for wealth redistribution in an agent-based market or models for granular gases with a background heat bath. Conditions on these collisional rules which guarantee both the existence and uniqueness of equilibrium profiles and their main properties are found. We show that the characterization of these stationary solutions is of independent interest, since the same profiles are shown to be solutions of different evolution problems, both in the econophysics context and in the kinetic theory of rarefied gases