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River beds are traditionally assumed to become mobile at a fixed value of nondimensional shear stress, but several flume and field studies have found that the critical value is higher in steep shallow flows. Explanations for this have been proposed in terms of the force balance on individual grains. The trend can also be understood in bulk‐flow terms if total flow resistance has “base” and “additional” components, the latter due to protruding immobile grains as well as any bedforms, and the stress corresponding to “additional” resistance is not available for grain movement in threshold conditions. A quantitative model based on these assumptions predicts that critical Shields stress increases with slope, critical stream power is near‐invariant with slope, and each has a secondary dependence on bed sorting. The proposed slope dependence is similar to what force‐balance models predict and consistent with flume data and most field data. Possible explanations are considered for the inability of this and other models to match the very low critical values of width‐averaged stress and power reported for some low‐gradient gravel bed rivers. Key Points New conceptual explanation for increase in critical Shields stress with slope Model predicts secondary dependence on bed sorting New model for critical stream power as spinoff

Investigations utilizing a one-dimensional sediment routing model demonstrate that moderate inputs of water and sediment at tributary junctions greatly increase physical heterogeneity in the recipient channel. Simulated physical heterogeneity is most sensitive to the ratios of tributary to mainstream bed load flux and bed load grain size and is less sensitive to relative discharge. Within the model, aggradation drives the processes that augment habitat variability, and in general, any aggradational confluence will be associated with elevated physical diversity. Model output reveals elevated physical diversity at two scales: between distinctive upstream and downstream zones separated by a confluence step and within each zone as a function of local environmental gradients. Total diversity increases as tributary sediment load and caliber increase relative to the mainstream. The ecological implications of the patterns and magnitude of tributary-induced physical heterogeneity are considered, and testable hypotheses are presented. Results highlight the need to accurately characterise patterns of sediment production, delivery, and routing in order to predict local tributary impacts and thereby understand patterns of habitat diversity and biodiversity at network scales.

The Obsessive Compulsive Cognitions Working Group (OCCWG) created the Interpretation of Intrusions Inventory (III) to measure appraisals (interpretations) of mental intrusions. Validation attempts by the OCCWG suggest that the three appraisal mechanisms hypothesized to comprise the III are better described as a single construct. The underlying factor structure of the III was investigated with university students (n = 307). Confirmatory factor analyses were conducted on the theoretically-derived three-factor model and on the empirically-derived one-factor model of the III. Both models failed to adequately fit the data. Thus, an exploratory factor analysis was conducted, which produced a two-factor model consisting of appraisals of Responsibility and Importance/Control of Thoughts. The new factors exhibited good predictive validity, as they predicted the severity of obsessive-compulsive symptoms and subtypes of obsessive-compulsive disorder (OCD).[PUBLICATION ABSTRACT]

Cognitive theory of obsessions hypothesizes that faulty appraisals of intrusive thoughts are paramount in the development and persistence of obsessive-compulsive disorder (OCD). Types of faulty appraisals include interpretations of excessive responsibility for preventing an adverse outcome (responsibility), appraisals of exaggerated personal importance (importance of thoughts), and interpretations that focus on having total control over one's own thoughts (control of thoughts). Previous research suggests that importance and control of thoughts appraisals (Ferguson, Jarry, & Jackson, 2006) and beliefs (Obsessive Compulsive Cognitions Working Group, 2005) are better described as one construct. Although there are numerous experimental studies suggesting that appraisals of excessive responsibility lead to more severe OCD symptoms, only two have demonstrated this effect with importance of thoughts appraisals (Teachman, Woody, & Magee, 2006; Teachman & Clerkin, 2007), and none have experimentally examined the combined effect of importance appraisals and efforts at mental control. The present research investigates the impact of an experimental manipulation of importance appraisals and attempts at mental control on the severity of OCD associated manifestations. Participants had an unwanted mental intrusion provoked through the use of a well-established intrusive thought provocation procedure (Rachman, Shafran, Mitchell, Trant, & Teachman, 1996). Appraisals of importance were experimentally manipulated by systematically varying information given to participants about having an intrusive thought (i.e., whether it is meaningful or not). Attempts at mental control were manipulated using a thought suppression task, as suppression is a common strategy used by people in response to an intrusive thought in order to regain mental control. Results revealed that participants who were exposed to importance interpretations, and those who were not given any feedback about their intrusive thought (Control group), reported more severe dysfunctional appraisals of importance and mental control, as well as higher levels of OCD associated symptoms than did those who had their intrusive thought normalized. Participants who were instructed to exercise mental control via thought suppression did not report more severe levels of obsessive-compulsive symptoms than did those who were not given such instructions. Finally, the findings clearly suggest that psychoeducational information to normalize mental intrusions is beneficial.

Salkovskis' (1989) cognitive-behavioural model of obsessive-compulsive disorder (OCD) posits that appraisals of intrusive thoughts that lead to symptoms of OCD are those in which the person perceives him or herself to be responsible for the occurrence of the intrusion and/or the perceived catastrophic outcomes (content) associated with the unwanted thought. Since Salkovskis' contribution, other cognitive theorists have acknowledged the importance of the appraisals (interpretations) of intrusive thoughts in the development and maintenance of OCD. The Obsessive Compulsive Cognitions Working Group (OCCWG) created the Interpretation of Intrusions Inventory (III), a self-report scale containing three subscales (Control of Thoughts, Importance of Thoughts, and Responsibility). Each subscale is designed to capture different types of appraisals of mental intrusions. Three hundred and seven undergraduate students at the University of Windsor completed the III. To provide an independent replication of the factor structure of the III, and to assess the hypothesis that its items are better conceptualized as representing a two-factor structure (of items that assess occurrence and content) related to responsibility appraisals, exploratory and confirmatory factor analyses were conducted. (Abstract shortened by UMI.)

We discuss some of the key open questions regarding the formation and evolution of globular clusters (GCs) during galaxy formation and assembly within a cosmological framework. The current state of the art for both observations and simulations is described, and we briefly mention directions for future research. The oldest GCs have ages greater than or equal to 12.5 Gyr and formed around the time of reionization. Resolved colour-magnitude diagrams of Milky Way GCs and direct imaging of lensed proto-GCs at z∼6 with the James Webb Space Telescope (JWST) promise further insight. GCs are known to host multiple populations of stars with variations in their chemical abundances. Recently, such multiple populations have been detected in ∼2 Gyr old compact, massive star clusters. This suggests a common, single pathway for the formation of GCs at high and low redshift. The shape of the initial mass function for GCs remains unknown; however, for massive galaxies a power-law mass function is favoured. Significant progress has been made recently modelling GC formation in the context of galaxy formation, with success in reproducing many of the observed GC-galaxy scaling relations.

About half of the satellites in the Andromeda galaxy (M 31), all with the same sense of rotation about their host, form a planar subgroup that is extremely wide but also very thin. The Andromeda galaxy's orbiting companions Giant spiral galaxies are assembled from smaller systems through a process known as hierarchical clustering. In orbit around these giants are dwarf galaxies, which are presumably remnants of the galactic progenitors. Recent studies of the dwarf galaxies of the Milky Way have led some astronomers to suspect that their orbits are not randomly distributed. This suspicion, which challenges current theories of galaxy formation, is now bolstered by the discovery of a plane of dwarf galaxies corotating as a coherent pancake-like structure around the Andromeda galaxy, the Milky Way's close neighbour and in many respects its 'twin'. The structure is extremely thin yet contains about half of the dwarf galaxies in the Andromeda system. The authors report that 13 of the 15 satellites in the plane share the same sense of rotation. Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way 1 . It has previously been suspected 2 that dwarf galaxies may not be isotropically distributed around our Galaxy, because several are correlated with streams of H  i emission, and may form coplanar groups 3 . These suspicions are supported by recent analyses 4 , 5 , 6 , 7 . It has been claimed 7 that the apparently planar distribution of satellites is not predicted within standard cosmology 8 , and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion 9 , 10 , 11 . Here we report the existence of a planar subgroup of satellites in the Andromeda galaxy (M 31), comprising about half of the population. The structure is at least 400 kiloparsecs in diameter, but also extremely thin, with a perpendicular scatter of less than 14.1 kiloparsecs. Radial velocity measurements 12 , 13 , 14 , 15 reveal that the satellites in this structure have the same sense of rotation about their host. This shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way’s disk and with the vector between the Milky Way and Andromeda.

Accelerating growth and global expansion of antimicrobial resistance has deepened the need for discovery of novel antimicrobial agents. Antimicrobial peptides have clear advantages over conventional antibiotics which include slower emergence of resistance, broad-spectrum antibiofilm activity, and the ability to favourably modulate the host immune response. Broad bacterial susceptibility to antimicrobial peptides offers an additional tool to expand knowledge about the evolution of antimicrobial resistance. Structural and functional limitations, combined with a stricter regulatory environment, have hampered the clinical translation of antimicrobial peptides as potential therapeutic agents. Existing computational and experimental tools attempt to ease the preclinical and clinical development of antimicrobial peptides as novel therapeutics. This Review identifies the benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens, highlights advances in the deployment of novel promising antimicrobial peptides, and underlines the needs and priorities in designing focused development strategies taking into account the most advanced tools available.

Alcohol Use Disorder (AUD) is a chronic, relapsing syndrome diagnosed by a heterogeneous set of behavioral signs and symptoms. There are no laboratory tests that provide direct objective evidence for diagnosis. Microarray and RNA-Seq technologies enable genome-wide transcriptome profiling at low costs and provide an opportunity to identify biomarkers to facilitate diagnosis, prognosis, and treatment of patients. However, access to brain tissue in living patients is not possible. Blood contains cellular and extracellular RNAs that provide disease-relevant information for some brain diseases. We hypothesized that blood gene expression profiles can be used to diagnose AUD. We profiled brain (prefrontal cortex, amygdala, and hypothalamus) and blood gene expression levels in C57BL/6J mice using RNA-seq one week after chronic intermittent ethanol (CIE) exposure, a mouse model of alcohol dependence. We found a high degree of preservation (rho range: [0.50, 0.67]) between blood and brain transcript levels. There was small overlap between blood and brain DEGs, and considerable overlap of gene networks perturbed after CIE related to cell-cell signaling (e.g., GABA and glutamate receptor signaling), immune responses (e.g., antigen presentation), and protein processing / mitochondrial functioning (e.g., ubiquitination, oxidative phosphorylation). Blood gene expression data were used to train classifiers (logistic regression, random forest, and partial least squares discriminant analysis), which were highly accurate at predicting alcohol dependence status (maximum AUC: 90.1%). These results suggest that gene expression profiles from peripheral blood samples contain a biological signature of alcohol dependence that can discriminate between CIE and Air subjects.

Abstract Rationale In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of the epithelial sodium channel (ENaC) have therapeutic potential in CF airways to reduce hyperstimulated sodium and fluid absorption to levels that can restore airway hydration. Objectives To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function. Methods Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy), and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured using a lactate dehydrogenase assay. Measurements and Main Results QUB-TL1 inhibits extracellularly located channel activating proteases (CAPs), including prostasin, matriptase, and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells. QUB-TL1–mediated CAP inhibition results in diminished ENaC-mediated Na+ absorption in CF airway epithelial cells caused by internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1–mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase–mediated ENaC activation and Pseudomonas aeruginosa exotoxin A–induced cell death. Conclusions QUB-TL1 corrects aberrant CAP activities, providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CF transmembrane conductance regulator mutation.