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Migratory birds that experience poor overwintering conditions are often late to arrive at the breeding grounds, which is known to depress individual fitness. Despite the importance of this carryover effect, few studies have investigated how individuals can modify migratory behaviors en route to reduce delays on arrival and whether accelerating migration incurs survival costs. To examine this, we used Motus Wildlife Tracking System to track individual American redstarts (Setophaga ruticilla) as they migrated from wintering grounds in Southwest Jamaica through Florida en route to their breeding areas. We leveraged long-term data on spring departure timing and breeding latitude to quantify the relative departure dates (early vs. delayed) of tagged individuals, which we then related to individual migration rates and apparent annual survival. Compared to those initiating migration earlier, individuals that departed relatively late (10-day delay) migrated at a 43% faster rate, which decreased their annual survival by 6.3%. Our results are consistent with the hypothesis that spring migrants use speed to compensate for departure delays despite incurring survival costs. This compensatory behavior may potentially underly differential survival during spring migration and may be particularly widespread across short-lived migratory birds generally considered time-constrained.

This preliminary study quantified tibia cartilage thickness (Cart.Th), subchondral bone plate thickness (SBPl.Th) and subchondral trabecular bone (STB) microarchitecture in subjects with varus- or valgus- malaligned knees diagnosed with end-stage knee osteoarthritis (OA) and compared them to controls (non-OA). Tibial plateaus from 25 subjects with knee-OA (undergoing knee arthroplasty) and 15 cadavers (controls) were micro-CT scanned (17 µm/voxel). Joint alignment was classified radiographically for OA subjects (varus-aligned n = 18, valgus-aligned n = 7). Cart.Th, SBPl.Th, STB bone volume fraction (BV/TV) and their medial-to-lateral ratios were analyzed in anteromedial, anterolateral, posteromedial and posterolateral subregions. Varus-OA and valgus-OA were compared to controls. Compared to controls (1.19-1.54 mm), Cart.Th in varus-OA was significantly lower anteromedially (0.58 mm, -59%) and higher laterally (2.19-2.47 mm, +60-63%); in valgus-OA, Cart.Th was significantly higher posteromedially (1.86 mm, +56%). Control medial-to-lateral Cart.Th ratios were around unity (0.8-1.1), in varus-OA significantly below (0.2-0.6) and in valgus-OA slightly above (1.0-1.3) controls. SBPl.Th and BV/TV were significantly higher medially in varus-OA (0.58-0.72 mm and 37-44%, respectively) and laterally in valgus-OA (0.60-0.61 mm and 32-37%), compared to controls (0.26-0.47 mm and 18-37%). In varus-OA, the medial-to-lateral SBPl.Th and BV/TV ratios were above unity (1.4-2.4) and controls (0.8-2.1); in valgus-OA they were closer to unity (0.8-1.1) and below controls. Varus- and valgus-OA tibia differ significantly from controls in Cart.Th, SBPl.Th and STB microarchitecture depending on joint alignment, suggesting structural changes in OA may reflect differences in medial-to-lateral load distribution upon the tibial plateau. Here we identified an inverse relationship between cartilage thickness and underlying subchondral bone, suggesting a whole-joint response in OA to daily stimuli.

Objective To screen a library of potential therapeutic compounds for a woman with Lennox‐Gastaut syndrome due to a Y302C GABRB3 (c.905A>G) mutation. Methods We compared the electrophysiological properties of cells with wild‐type or the pathogenic GABRB3 mutation. Results Among 1320 compounds, multiple candidates enhanced GABRB3 channel conductance in cell models. Vinpocetine, an alkaloid derived from the periwinkle plant with anti‐inflammatory properties and the ability to modulate sodium and channel channels, was the lead candidate based on efficacy and safety profile. Vinpocetine was administered as a dietary supplement over 6 months, reaching a dosage of 20 mg three times per day, and resulted in a sustained, dose‐dependent reduction in spike‐wave discharge frequency on electroencephalograms. Improved language and behavior were reported by family, and improvements in global impression of change surveys were observed by therapists blinded to intervention. Significance Vinpocetine has potential efficacy in treating patients with this mutation and possibly other GABRB3 mutations or other forms of epilepsy. Additional studies on pharmacokinetics, potential drug interactions, and safety are needed.

The size of the pectoral muscle is an important component of body condition in birds and has been linked to indices of fitness and migratory performance. Bauchinger et al. (2011. Journal of Ornithology 152: 507–514) developed, calibrated, and validated an aluminum “muscle meter” device that estimates the size of pectoral muscles noninvasively. To make this tool more widely available, we created a CAD model from 3D‐scan data of the aluminum muscle meter that can be 3D‐printed in durable plastic for ~ $30 USD. We tested this device on seven species of songbirds in Jamaica, The Bahamas, Cameroon, Equatorial Guinea, and Michigan. We demonstrate that the breast muscle meter measurements are (1) repeatable among users, (2) correlated with a four‐category visual breast muscle scoring system, and (3) correlated with scaled mass index (an index of body condition). Muscle scores from our device outperformed the traditional four‐category muscle scoring system in predicting scaled mass index. Finally, with our device, we quantified the increasing breast muscle size of American Redstarts (Setophaga ruticilla) from March through May as they prepared for spring migration. Given the precision of the 3D‐scanning hardware used to generate our 3D image for printing, we produced a plastic muscle meter that is as precise and useful as the aluminum original, but more cost‐effective and widely available.

Premise Measuring plant productivity is critical to understanding complex community interactions. Many traditional methods for estimating productivity, such as direct measurements of biomass and cover, are resource intensive, and remote sensing techniques are emerging as viable alternatives. Methods We explore drone-based remote sensing tools to estimate productivity in a tallgrass prairie restoration experiment and evaluate their ability to predict direct measures of productivity. We apply these various productivity measures to trace the evolution of plant productivity and the traits underlying it. Results The correlation between remote sensing data and direct measurements of productivity varies depending on vegetation diversity, but the volume of vegetation estimated from drone-based photogrammetry is among the best predictors of biomass and cover regardless of community composition. The commonly used normalized difference vegetation index (NDVI) is a less accurate predictor of biomass and cover than other equally accessible vegetation indices. We found that the traits most strongly correlated with productivity have lower phylogenetic signal, reflecting the fact that high productivity is convergent across the phylogeny of prairie species. This history of trait convergence connects phylogenetic diversity to plant community assembly and succession. Discussion Our study demonstrates (1) the importance of considering phylogenetic diversity when setting management goals in a threatened North American grassland ecosystem and (2) the utility of remote sensing as a complement to ground measurements of grassland productivity for both applied and fundamental questions.

Featuring high biocompatibility, the emerging field of gas therapy has attracted extensive attention in the medical and scientific communities. Currently, considerable research has focused on the gasotransmitter nitric oxide (NO) owing to its unparalleled dual roles in directly killing cancer cells at high concentrations and cooperatively sensitizing cancer cells to other treatments for synergistic therapy. Of particular note, recent state-of-the-art studies have turned our attention to the chemical design of various endogenous/exogenous stimuli-responsive NO-releasing nanomedicines and their biomedical applications for on-demand NO-sensitized synergistic cancer therapy, which are discussed in this Minireview. Moreover, the potential challenges regarding NO gas therapy are also described, aiming to advance the development of NO nanomedicines as well as usher in new frontiers in this fertile research area.

Objective Many previous studies of drug repurposing have relied on literature review followed by evaluation of a limited number of candidate compounds. Here, we demonstrate the feasibility of a more comprehensive approach using high-throughput screening to identify inhibitors of a gain-of-function mutation in the SCN8A gene associated with severe pediatric epilepsy. Methods We developed cellular models expressing wild-type or an R1872Q mutation in the Nav 1.6 sodium channel encoded by SCN8A. Voltage clamp experiments in HEK-293 cells expressing the SCN8A R1872Q mutation demonstrated a leftward shift in sodium channel activation as well as delayed inactivation; both changes are consistent with a gain-of-function mutation. We next developed a fluorescence-based, sodium flux assay and used it to assess an extensive library of approved drugs, including a panel of antiepileptic drugs, for inhibitory activity in the mutated cell line. Lead candidates were evaluated in follow-on studies to generate concentration-response curves for inhibiting sodium influx. Select compounds of clinical interest were evaluated by electrophysiology to further characterize drug effects on wild-type and mutant sodium channel functions. Results The screen identified 90 drugs that significantly inhibited sodium influx in the R1872Q cell line. Four drugs of potential clinical interest-amitriptyline, carvedilol, nilvadipine, and carbamazepine-were further investigated and demonstrated concentration-dependent inhibition of sodium channel currents. Significance A comprehensive drug repurposing screen identified potential new candidates for the treatment of epilepsy caused by the R1872Q mutation in the SCN8A gene.

Tibial subchondral bone plays an important role in knee osteoarthritis (OA). Microarchitectural characterisation of subchondral bone plate (SBP), underlying trabecular bone (STB) and relationships between microarchitecture in these compartments, however, is limited. The aim of this study was to characterise the spatial distribution of SBP thickness and porosity and STB microarchitecture, and relationships between compartments, in OA tibiae of varying joint alignment. Twenty-five tibial plateaus from end-stage knee-OA patients, with varus (n= 17) or non-varus (n= 8) alignment were micro-CT scanned (17µm/voxel). SBP and STB microarchitecture was quantified via a systematic mapping in 22 volumes of interest per knee (11 medial, 11 lateral). Significant within-condylar and between-condylar (medial vs. lateral) differences (p

Food selectivity by individuals with autism spectrum disorder (ASD) is often viewed in the behavioral literature as a problem with compliance and treated accordingly. However, when viewed as a problem with invariance, it may be appropriate to treat the problem by using procedures that increase variant food consumption. Lag schedules of reinforcement have been shown to increase variability in verbal and play behavior of children with ASD. Therefore, we attempted to evaluate the effects of a lag schedule of positive reinforcement on variant food consumption by a girl with ASD and food selectivity. Ultimately, a lack of baseline variability in consumption precluded an evaluation of the programmed lag schedule but suggested that a discovery research approach may be informative. Thus, additional treatment components were added and evaluated in a component analysis. Response blocking of invariant consumption appeared to establish a lag schedule of reinforcement that increased variability and variety in food consumption, which was maintained across changes in the value of the lag schedule. Some potential behavioral processes responsible for the effects and implications for future research are discussed. Copyright © 2016 John Wiley & Sons, Ltd.

Water movement between soil and the atmosphere is restricted by hardscapes in the urban environment. Some green infrastructure is intended to increase infiltration and storage of water, thus decreasing runoff and discharge of urban stormwater. Bioswales are a critical component of a water-sensitive urban design (or a low-impact urban design), and incorporation of trees into these green infrastructural components is believed to be a novel way to return stored water to the atmosphere via transpiration. This research was conducted in The Morton Arboretum's main parking lot, which is one of the first and largest green infrastructure installations in the midwestern United States. The parking lot is constructed of permeable pavers and tree bioswales. Trees in bioswales were evaluated for growth and condition and for their effects on water cycling via transpiration. Our data indicate that trees in bioswales accounted for 46 to 72% of total water outputs via transpiration, thereby reducing runoff and discharge from the parking lot. By evaluating the stomatal conductance, diameter growth, and condition of a variety of tree species in these bioswales, we found that not all species are equally suited for bioswales and that not all are equivalent in their transpiration and growth rates, thereby contributing differentially to the functional capacity of bioswales. We conclude that species with high stomatal conductance and large mature form are likely to contribute best to bioswale function.

Diminishing returns from increased clock frequencies and instruction-level parallelism have forced computer architects to adopt architectures that exploit wider parallelism through multiple processor cores. While emerging many-core architectures have progressed at a remarkable rate, concerns arise regarding the performance and productivity of numerous parallel-programming tools for application development. Development of parallel applications on many-core processors often requires developers to familiarize themselves with unique characteristics of a target platform while attempting to maximize performance and maintain correctness of their applications. The family of partitioned global address space PGAS programming models comprises the current state of the art in balancing performance and programmability. One such PGAS approach is SHMEM, a lightweight, shared-memory programming library that has demonstrated high performance and productivity potential for parallel-computing systems with distributed-memory architectures. In the paper, we present research, design, and analysis of a new SHMEM infrastructure specifically crafted for low-level PGAS on modern and emerging many-core processors featuring dozens of cores and more. Our approach with a new library known as TSHMEM is investigated and evaluated atop two generations of Tilera architectures, which are among the most sophisticated and scalable many-core processors to date, and is intended to enable similar libraries atop other architectures now emerging. In developing TSHMEM, we explore design decisions and their impact on parallel performance for the Tilera TILE-Gx and TILEPro many-core architectures, and then evaluate the designs and algorithms within TSHMEM through microbenchmarking and applications studies with other communication libraries. Our results with barrier primitives provided by the Tilera libraries show dissimilar performance between the TILE-Gx and TILEPro; therefore, TSHMEM's barrier design takes an alternative approach and leverages the on-chip mesh network to provide consistent low-latency performance. In addition, our experiments with TSHMEM show that naive collective algorithms consistently outperformed linear distributed collective algorithms when executed in an SMP-centric environment. In leveraging these insights for the design of TSHMEM, our approach outperforms the OpenSHMEM reference implementation, achieves similar to positive performance over OpenMP and OSHMPI atop MPICH, and supports similar libraries in delivering high-performance parallel computing to emerging many-core systems. Copyright © 2015 John Wiley & Sons, Ltd.

Seasonal variability in groundwater pumping is common in many places, but resulting effects of seasonal pumping stress on the quality of water produced by public-supply wells are not thoroughly understood. Analysis of historical water-quality samples from public-supply wells completed in deep basin-fill aquifers in Modesto, California (134 wells) and Albuquerque, New Mexico (95 wells) indicates that several wells have seasonal variability in concentrations of contaminants of concern. In Modesto, supply wells are more likely to produce younger groundwater with higher nitrate and uranium concentrations during the summer (high) pumping season than during the winter (low) pumping season. In Albuquerque, supply wells are more likely to produce older groundwater with higher arsenic concentrations during the winter pumping season than during the summer pumping season. Seasonal variability in contaminant concentrations in Modesto is influenced primarily by effects of summer pumping on vertical hydraulic gradients that drive migration of shallow groundwater through the aquifer to supply wells. Variability in Albuquerque is influenced primarily by the period of time that a supply well is idle, allowing its wellbore to act as a conduit for vertical groundwater flow and contaminant migration. However, both processes are observed in each study area. Similar findings would appear to be likely in other alluvial basins with stratified water quality and substantial vertical head gradients. Results suggest that even in aquifers dominated by old groundwater, changes to seasonal pumping patterns and/or to depth of well completion can help reduce vulnerability to selected contaminants of either natural or anthropogenic origin.

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv β3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (

Biological nanoparticles, including viruses and extracellular vesicles (EVs), are of interest to many fields of medicine as biomarkers and mediators of or treatments for disease. However, exosomes and small viruses fall below the detection limits of conventional flow cytometers due to the overlap of particle-associated scattered light signals with the detection of background instrument noise from diffusely scattered light. To identify, sort, and study distinct subsets of EVs and other nanoparticles, as individual particles, we developed nanoscale Fluorescence Analysis and Cytometric Sorting (nanoFACS) methods to maximise information and material that can be obtained with high speed, high resolution flow cytometers. This nanoFACS method requires analysis of the instrument background noise (herein defined as the “reference noise”). With these methods, we demonstrate detection of tumour cell-derived EVs with specific tumour antigens using both fluorescence and scattered light parameters. We further validated the performance of nanoFACS by sorting two distinct HIV strains to >95% purity and confirmed the viability (infectivity) and molecular specificity (specific cell tropism) of biological nanomaterials sorted with nanoFACS. This nanoFACS method provides a unique way to analyse and sort functional EV- and viral-subsets with preservation of vesicular structure, surface protein specificity and RNA cargo activity.