bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple Approximation To The Bias Of Gene-Envinornment Interactions In Case/Control Studies With Silent Disease
Authors: Lobach Iryna , Sampson Joshua , Lobach Siarhei , Alekseyenko Alexander , Pryatinska Alexandra , He Tao , Zhang Li
Published: October 2018

One of the most important research areas in case-control Genome-Wide Association Studies is to determine how the effect of a genotype varies across the environment or to measure the gene-environment interaction (GxE). We consider the scenario when some of the “healthy” controls actually have the disease and when the frequency of these latent cases varies by the environmental variable of interest. In this scenario, performing logistic regression of clinically defined case status on the genetic variant, environmental variable, and their interaction will result in biased estimates of GxE interaction. Here, we derive a general theoretical approximation to the bias in the estimates of the GxE interaction and show, through extensive simulation, that this approximation is accurate in finite samples. Moreover, we apply this approximation to evaluate the bias in the effect estimates of the genetic variants related to mitochondrial proteins a large-scale Prostate Cancer study.
Using experimental data and information criteria to guide model selection for reaction–diffusion problems in mathematical biology
Authors: Warne David J. , Baker Ruth E. , Simpson Matthew J.
Published: October 2018

Reaction–diffusion models describing the movement, reproduction and death of individuals within a population are key mathematical modelling tools with widespread applications in mathematical biology. A diverse range of such continuum models have been applied in various biological contexts by choosing different flux and source terms in the reaction–diffusion framework. For example, to describe collective spreading of cell populations, the flux term may be chosen to reflect various movement mechanisms, such as random motion (diffusion), adhesion, haptotaxis, chemokinesis and chemotaxis. The choice of flux terms in specific applications, such as wound healing, is usually made heuristically, and rarely is it tested quantitatively against detailed cell density data. More generally, in mathematical biology, the questions of model validation and model selection have not received the same attention as the questions of model development and model analysis. Many studies do not consider model validation or model selection, and those that do often base the selection of the model on residual error criteria after model calibration is performed using nonlinear regression techniques. In this work, we present a model selection case study, in the context of cell invasion, with a very detailed experimental data set. Using Bayesian analysis and information criteria, we demonstrate that model selection and model validation should account for both residual errors and model complexity. These considerations are often overlooked in the mathematical biology literature. The results we present here provide a clear methodology that can be used to guide model selection across a range of applications. Furthermore, the case study we present provides a clear example where neglecting the role of model complexity can give rise to misleading outcomes.
Adaptive eQTLs reveal the evolutionary impacts of pleiotropy and tissue-specificity, while contributing to health and disease in human populations
Authors: Quiver Melanie H. , Lachance Joseph
Published: October 2018

Regulatory DNA has the potential to be adaptive, and large numbers of expression quantitative trait loci (eQTLs) have recently been identified in humans. For the first time, a comprehensive study of adaptive eQTLs is possible. Many eQTLs have large allele frequency differences between populations, and these differences can be due to natural selection. Here, we combined population branch statistics with tissue-specific eQTL data to identify positively selected loci in human populations. Adaptive eQTLs tend to affect fewer tissues than non-adaptive eQTLs. Because the tissue breadth of an eQTL can be viewed as a measure of pleiotropy, these results suggest that pleiotropy can inhibit adaptation. The proportion of eQTLs that are adaptive varies by tissue, and we find that eQTLs that regulate expression in testis, thyroid, blood, or sun-exposed skin are enriched for adaptive outliers. By contrast, eQTLs that regulate expression in the cerebrum or female-specific tissues have a relative lack of adaptive outliers. These results reveal tissues that have been the targets of adaptation during the last 100,000 years of human evolution. The strongest adaptive signal in many regions of the human genome is an eQTL, including an eQTL associated with the Duffy blood group and malaria resistance. Scans of selection also reveal that many adaptive eQTLs are closely linked to disease-associated loci. Taken together, our results indicate that adaptive eQTLs have played an important role in human evolution.
Fast two-photon volumetric imaging of an improved voltage indicator reveals electrical activity in deeply located neurons in the awake brain
Authors: Chavarha Mariya , Villette Vincent , Dimov Ivan K. , Pradhan Lagnajeet , Evans Stephen W. , Shi Dongqing , Yang Renzhi , Chamberland Simon , Bradley Jonathan , Mathieu Benjamin , St-Pierre Francois , Schnitzer Mark J. , Bi Guoqiang , Toth Katalin , Ding Jun , Dieudonné Stéphane , Lin Michael Z.
Published: October 2018

Imaging of transmembrane voltage deep in brain tissue with cellular resolution has the potential to reveal information processing by neuronal circuits in living animals with minimal perturbation. Multi-photon voltage imaging in vivo, however, is currently limited by speed and sensitivity of both indicators and imaging methods. Here, we report the engineering of an improved genetically encoded voltage indicator, ASAP3, which exhibits up to 51% fluorescence responses in the physiological voltage range, sub-millisecond activation kinetics, and full responsivity under two-photon illumination. We also introduce an ultrafast local volume excitation (ULOVE) two-photon scanning method to sample ASAP3 signals in awake mice at kilohertz rates with increased stability and sensitivity. ASAP3 and ULOVE allowed continuous single-trial tracking of spikes and subthreshold events for minutes in deep locations, with subcellular resolution, and with repeated sampling over multiple days. By imaging voltage in visual cortex neurons, we found evidence for cell type-dependent subthreshold modulation by locomotion. Thus, ASAP3 and ULOVE enable continuous high-speed high-resolution imaging of electrical activity in deeply located genetically defined neurons during awake behavior.
Pixel Quantum Efficiency Differences and Variance Stabilization for sCMOS Single Molecule Localization Microscopy Data Analysis
Authors: Babcock Hazen P. , Huang Fang
Published: October 2018

Optimal analysis of single molecule localization microscopy (SMLM) data acquired with a CMOS camera requires compensation for single pixel differences in gain, offset and readout noise. For some CMOS cameras we found that it is also necessary to compensate for pixel differences in sensitivity or relative quantum efficiency (RQE). We present the modifications to the original sCMOS analysis algorithm necessary to correct for these RQE differences. We also discuss the use of the Anscombe transform (AT) for variance stabilization. Removing the variance dependence on the mean allows simpler least squares fitting approaches to achieve the Cramer-Rao bound on the mixed Poisson and Gaussian distributed data typically acquired with an sCMOS camera.
Gastrocnemius fascicles are shorter and more pennate throughout the first month following acute Achilles tendon rupture
Authors: Hullfish Todd J. , O’Connor Kathryn M , Baxter Josh R.
Published: October 2018

The purpose of this study was to characterize the short-term effects of Achilles tendon ruptures on medial gastrocnemius. We hypothesized that the fascicles of the medial gastrocnemius muscle of the injured Achilles tendon would be shorter and more pennate immediately following the injury and would persist throughout 4 weeks post-injury. B-mode longitudinal ultrasound images of the medial gastrocnemius were acquired in 10 adults who suffered acute Achilles tendon ruptures and were treated non-operatively. Ultrasound images were acquired during the initial clinical visit following injury as well as two and four weeks following this initial clinical visit. Resting muscle structure was characterized by measuring fascicle length, pennation angle, muscle thickness, and muscle echo intensity in both the injured and contralateral (control) limbs. Fascicle length was 15% shorter (P< 0.001) and pennation angle was 21% greater (P< 0.001) in the injured muscle compared to the uninjured (control) muscle at the presentation of injury (week 0). These differences in fascicle length and pennation angle persisted throughout the 4 weeks after the injury (P< 0.008). Muscle thickness changes were not detected at any of the post-injury visits (difference < 4%,P> 0.04). Echo intensity of the injured limb was 8% lower at the presentation of the injury and 11% lower (P= 0.008) than the contralateral muscle at 2 weeks following injury (P< 0.001) but returned to within 1% by 4 weeks (P= 0.393). Our results suggest that Achilles tendon ruptures elicit rapid changes in the configuration and quality of the medial gastrocnemius, which may explain long-term functional deficits.
Large-scale neuron cell classification of single-channel and multi-channel extracellularrecordings in the anterior lateral motor cortex
Authors: Parikh Rohan
Published: October 2018

Identification of neuron cell type helps us connect neural circuitry and behavior; greater specificity in cell type and subtype classification provides a clearer picture of specific relationships between the brain and behavior. With the advent of high-density probes, large-scale neuron classification is needed, as typical extracellular recordings are identity-blind to the neurons they record. Current methods for identification of neurons include optogenetic tagging and intracellular recordings, but are limited in that they are expensive, time-consuming, and have a limited scope. Therefore, a more automated, real-time method is needed for large-scale neuron identification. Data from two recordings was incorporated into this research; the single-channel recording included data from three neuron types in the motor cortex: FS, IT, and PT neurons. The multi-channel recording contained data from two neuron subtypes also in the motor cortex: PT_L and PT_U neurons. This allowed for an examination of both general neuron classification and more specific subtype classification, which was done via artificial neural networks (ANNs) and machine learning (ML) algorithms. For the single-channel neuron classification, the ANNs achieved 91% accuracy, while the ML algorithms achieved 98% accuracy, using the raw electrical waveform. The multi-channel classification, which was significantly more difficult due to the similarity between the neuron types, yielded an ineffective ANN, reaching 68% accuracy, while the ML algorithms reached 81% using 8 calculated features from the waveform. Thus, to distinguish between different neuron cell types and subtypes in the motor cortex, both ANNs and specific ML algorithms can facilitate rapid and accurate near real-time large-scale classification.
Independent mechanisms for acquired salt tolerance versus growth resumption induced by mild ethanol pretreatment inSaccharomyces cerevisiae
Authors: McDaniel Elizabeth A. , Stuecker Tara N. , Veluvolu Manasa , Gasch Audrey P. , Lewis Jeffrey A.
Published: October 2018

All living organisms must recognize and respond to various environmental stresses throughout their lifetime. In natural environments, cells frequently encounter fluctuating concentrations of different stressors that can occur in combination or sequentially. Thus, the ability to anticipate an impending stress is likely ecologically relevant. One possible mechanism for anticipating future stress is acquired stress resistance, where cells pre-exposed to a mild sub-lethal dose of stress gain the ability to survive an otherwise lethal dose of stress. We have been leveraging wild strains ofSaccharomyces cerevisiaeto investigate natural variation in the yeast ethanol stress response and its role in acquired stress resistance. Here, we report that a wild vineyard isolate possesses ethanol-induced cross-protection against severe concentrations of salt. Because this phenotype correlates with ethanol-dependent induction of theENAgenes, which encode sodium efflux pumps already associated with salt resistance, we hypothesized that variation inENAexpression was responsible for differences in acquired salt tolerance across strains. Surprisingly, we found that theENAgenes were completely dispensable for ethanol-induced survival of high salt concentrations in the wild vineyard strain. Instead, theENAgenes were necessary for the ability to resume growth on high concentrations of salt following a mild ethanol pretreatment. Surprisingly, this growth acclimation phenotype was also shared by the lab yeast strain despite lack ofENAinduction under this condition. This study underscores that cross protection can affect both viability and growth through distinct mechanisms, both of which likely confer fitness effects that are ecologically relevant.

IMPORTANCE

Microbes in nature frequently experience “boom or bust” cycles of environmental stress. Thus, microbes that can anticipate the onset of stress would have an advantage. One way microbes anticipate future stress is through acquired stress resistance, where cells exposed to a mild dose of one stress gain the ability survive an otherwise lethal dose of a subsequent stress. In the budding yeastSaccharomyces cerevisiae,certain stressors can cross protect against high salt concentrations, though the mechanisms governing this acquisition of higher stress resistance are not well understood. In this study, we took advantage of wild yeast strains to understand the mechanism underlying ethanol-induced cross protection against high salt concentrations. We found that mild ethanol stress allows cells to resume growth on high salt, which involves a novel role for a well-studied salt transporter. Overall, this discovery highlights how leveraging natural variation can provide new insights into well-studied stress defense mechanisms.
Individual variation in the dear enemy phenomenon via territorial vocalizations in red squirrels
Authors: Robertson Jack Graham , Boutin Stan , Humphries Murray M , Dantzer Ben , Lane Jeffrey E , McAdam Andrew G
Published: October 2018

Territoriality arises when the benefits of resources exceed the costs of defending them. The dear enemy phenomenon, where familiar territorial neighbours refrain from intruding on one another and mutually reduce their defensive efforts, allows for reduction of these costs but requires discrimination between conspecifics. We hypothesized that territorial vocalizations in red squirrels (Tamiasciurus hudsonicus) are used for this discrimination. We performed a speaker replacement experiment where red squirrels (n = 41) were temporarily removed from their territories and replaced with a speaker broadcasting their own call, an unfamiliar call, or silence. Contrary to our prediction, there were no differences in overall intrusion risk among our three playbacks, but the identity of intruders did vary. Existing variation in familiarity within territorial neighbourhoods should be considered, rather than the binary classification of familiar or stranger, when studying dear enemy effects. We also discuss the variable importance of silence in acoustic territorial populations.
Predicting Intra- and Intertypic Recombination in Enterovirus 71
Authors: Woodman Andrew , Lee Kuo-Ming , Janissen Richard , Gong Yu-Nong , Dekker Nynke , Shih Shin-Ru , Cameron Craig E.
Published: October 2018

Enteroviruses are well known for their ability to cause neurological damage and paralysis. The model enterovirus is poliovirus (PV), the causative agent of poliomyelitis, a condition characterized by acute flaccid paralysis. A related virus, enterovirus 71 (EV-A71), causes similar clinical outcomes in recurrent outbreaks throughout Asia. Retrospective phylogenetic analysis has shown that recombination between circulating strains of EV-A71 produces the outbreak-associated strains which exhibit increased virulence and/or transmissibility. While studies on the mechanism(s) of recombination in PV are ongoing in several laboratories, little is known about factors that influence recombination in EV-A71. We have developed a cell-based assay to study recombination of EV-A71 based upon previously reported assays for poliovirus recombination. Our results show that: (1) EV-A71 strain-type and RNA sequence diversity impacts recombination frequency in a predictable manner that mimics the observations found in nature; (2) recombination is primarily a replicative process mediated by the RNA-dependent RNA polymerase (RdRp); (3) a mutation shown to reduce recombination in PV (L420A) similarly reduces EV-A71 recombination suggesting conservation in mechanism(s); and (4) sequencing of intertypic recombinant genomes indicates that template-switching is by a mechanism that requires some sequence homology at the recombination junction and that the triggers for template-switching may be sequence independent. The development of this recombination assay will permit further investigation on the interplay between replication, recombination and disease.
Processing of grassland soil C-N compounds into soluble and volatile molecules is depth stratified and mediated by genomically novel bacteria and archaea
Authors: Diamond Spencer , Andeer Peter , Li Zhou , Crits-Christoph Alex , Burstein David , Anantharaman Karthik , Lane Katherine R. , Thomas Brian C. , Pan Chongle , Northen Trent , Banfield Jillian F.
Published: October 2018

Soil microbial activity drives the carbon and nitrogen cycles and is an important determinant of atmospheric trace gas turnover, yet most soils are dominated by organisms with unknown metabolic capacities. Even Acidobacteria, among the most abundant bacteria in soil, remain poorly characterized, and functions across groups such as Verrucomicrobia, Gemmatimonadetes, Chloroflexi, Rokubacteria are understudied. Here, we resolved sixty metagenomic, and twenty proteomic datasets from a grassland soil ecosystem and recovered 793 near-complete microbial genomes from 18 phyla, representing around one third of all organisms detected. Importantly, this enabled extensive genomics-based metabolic predictions for these understudied communities. Acidobacteria from multiple previously unstudied classes have genomes that encode large enzyme complements for complex carbohydrate degradation. Alternatively, most organisms we detected encode carbohydrate esterases that strip readily accessible methyl and acetyl groups from polymers like pectin and xylan, forming methanol and acetate, the availability of which could explain high prevalences of C1 metabolism and acetate utilization in genomes. Organism abundances among samples collected at three soil depths and under natural and amended rainfall regimes indicate statistically higher associations of inorganic nitrogen metabolism and carbon degradation in deep and shallow soils, respectively. This partitioning decreased in samples under extended spring rainfall indicating long term climate alteration can affect both carbon and nitrogen cycling. Overall, by leveraging natural and experimental gradients with genome-resolved metabolic profiles, we link organisms lacking prior genomic characterization to specific roles in complex carbon, C1, nitrate, and ammonia transformations and constrain factors that impact their distributions in soil.
The glucocorticoid receptor ligand-binding domain confers drug-gated protein regulation inC. elegans
Authors: Monsalve Gabriela C. , Yamamoto Keith R. , Ward Jordan D.
Published: October 2018

Controlling protein activity and localization is a key tool in modern biology. Mammalian steroid receptor ligand-binding domains (LBDs) fusions have been used in a range of organisms and cell-types to inactivate proteins of interest until the cognate steroid ligand is applied. Here, we demonstrate that the glucocorticoid receptor LBD confers ligand-gated control of a heterologous gene expression system (Q system) and the DAF-16 transcription factor inC. elegans. These experiments demonstrate provide a powerful tool for temporal control of protein activity, and will bolster existing tools used to modulate gene expression and protein activity in this animal.
Smed-egfr-4 is required for planarian eye regeneration
Authors: Emili Elena , Pallarès Maclà Esteve , Romero Rafael , Cebrlà Francesc
Published: October 2018

Planarians are amazing animals that can regenerate a whole body from a tiny piece of them thanks to their pluripotent stem cells, the neoblasts. Planarian neoblasts include both pluripotent stem cells and specialized lineage-committed progenitors that give rise to all the mature cell types during regeneration and homeostatic cell turnover in these plastic animals. Little is known, however, about the mechanisms that regulate neoblast differentiation. Recently, it has been shown that Smed-egfr-1, a homologue of the epidermal growth factor receptor (EGFR) family is required for the final differentiation of the gut progenitors into mature cells but not for their specification. As planarians have several EGFR homologues it has been proposed that they could have diverged functionally to regulate the differentiation of the different cell types found in these animals. Here, we report on the function of Smed-egfr-4 on eye regeneration. The silencing of this gene by RNAi results in animals regenerating smaller eyes compared to controls. The numbers of both eye mature cell types, photoreceptor neurons and eye-cup pigment cells, are significantly decreased in the Smed-egfr-4(RNAi) animals. In contrast, the number of eye progenitor cells expressing the specific markers Smed-ovo and Smed-sp6-9 is increased. These results suggest that Smed-egfr-4 would be required not for the specification of eye progenitor cells but rather for their final differentiation and support the idea that in planarians the EGFR pathway could play a general role regulating the differentiation of lineage-committed progenitors.
Quantitative insights into the cyanobacterial cell economy
Authors: Zavřel Tomáš , Faizi Marjan , Loureiro Cristina , Poschmann Gereon , Stühler Kai , Sinetova Maria , Zorina Anna , Steuer Ralf , Červený Jan
Published: October 2018

Phototrophic microorganisms are promising resources for green biotechnology. Compared to heterotrophic microorganisms, however, the cellular economy of phototrophic growth is still insufficiently understood. We provide a quantitative analysis of light-limited, light-saturated, and light-inhibited growth of the cyanobacteriumSynechocystissp. PCC 6803 using a reproducible cultivation setup. We report key physiological parameters, including growth rate, cell size, and photosynthetic activity over a wide range of light intensities. Intracellular proteins were quantified to monitor proteome allocation as a function of growth rate. Among other physiological adaptations, we identify an upregulation of the translational machinery and downregulation of light harvesting components with increasing light intensity and growth rate. The resulting growth laws are discussed in the context of a coarse-grained model of phototrophic growth and available data obtained by a comprehensive literature search. Our insights into quantitative aspects of cyanobacterial adaptations to different growth rates have implications to understand and optimize photosynthetic productivity.
Nitrogen addition pulse has minimal effect in big sagebrush (Artemisia tridentata) communities on the Pinedale Anticline, Wyoming (USA)
Authors: Beltz Christopher W. , Mobley Megan L. , Burke Ingrid C.
Published: October 2018

Nitrogen additions are known to elicit variable responses in semi-arid ecosystems, with responses increasing with precipitation. The response of semi-arid ecosystems to nitrogen are important to understand due to their large spatial extent worldwide and the global trend of increasingly available nitrogen. In this study, we evaluated the impact of a single nitrogen addition pulse on a semi-arid big sagebrush (Artemisia tridentata) ecosystem in western Wyoming. This is important given that sagebrush ecosystems are poorly understood, despite their prevalence in the western US. In addition, large-scale nitrogen additions have begun on sagebrush landscapes in Wyoming in order to mitigate population declines in mule deer (Odocoileus hemionus). The study objectives were (1) to evaluate the effectiveness of a nitrogen fertilization pulse in increasing sagebrush biomass and forage quality, and (2) to assess effects of nitrogen addition on soil biogeochemistry and vegetation community structure. We fertilized 15 plots across 5 locations in western Wyoming using a single pulse of urea (5.5g N m−2). In addition, we immobilized available nitrogen through surface hay treatments (250g hay/m2). Nitrogen additions failed to increase growth of sagebrush, alter nitrogen content of sagebrush leaders, or alter greenhouse gas efflux from soils. The plant community also remained unchanged; total cover, species richness, and community composition were all unaffected by our treatment application. Over the two years of this study, we did not find indications of nitrogen limitation of ecosystem processes, despite a wet growing season in 2014. Thus, we have found a general lack of response to nitrogen in sagebrush ecosystems and no treatment effect of a single pulse of N to sagebrush biomass or forage quality.
Research challenges in Africa – an exploratory study on the experiences and opinions of African researchers
Authors: Ngongalah Lem , Emerson Wepngong , Rawlings Ngwa Niba , Muleme Musisi James
Published: October 2018

Background

Insufficient research is a major impediment to growth, development and advancement of health in Africa. Africa produces less than 1% of global research output. Meanwhile, African countries face some of the toughest challenges worldwide, most of which can only be tackled through robust and efficient research. Addressing the barriers to conducting research in Africa is a step towards improving research capacity and output. This study aimed to identify the key challenges affecting research practice and output in Africa; and to highlight priority areas for improvement.

Methods

A cross-sectional survey was administered through an online questionnaire, including participants from six countries in Sub-Saharan Africa. Participants included research professionals, research students, research groups and academics.

Results

A total of 424 participants responded to this survey. The ability to conduct and produce high-quality research was seen to be influenced by multiple factors, most of which were related to the research environment in African countries. Priority areas for improvement included providing more training, raising awareness on the importance of research in Africa, encouraging governments to commit to research and increasing collaboration between researchers in Africa.

Conclusion

The conditions under which research is done in Africa are severely flawed and do not encourage engagement in research, or continuity of research activity. African governments need to develop initiatives that accelerate and support research and research-based education in Africa, in order to build a solid foundation for research, increase research capacity, and enable institutions to provide valuable training and develop sustainable research opportunities in Africa.
New classification of intrinsic disorder in the Human proteome
Authors: Deiana Antonio , Forcelloni Sergio , Porrello Alessandro , Giansanti Andrea
Published: October 2018

We propose a new, sequence-only, classification of intrinsically disordered human proteins which is based on two parameters: dr, the percentage of disordered residues, and Ld, the length of the longest disordered segment in the sequence. Depending on dr and Ld, we distinguish five variants: i)ordered proteins(ORDs); ii)not disordered proteins(NDPsj; (iii)proteins with intrinsically disordered regions(PDRs); iv)intrinsically disordered proteins(IDPs) and v)proteins with fragmenteddisorder (FRAGs). PDRs have been considered in the general category of intrinsically disordered proteins for a long time. We show that PDRs are closer to globular, ordered proteins (ORDs and NDPs) than to disordered ones (IDPs), both in amino acid composition and functionally. Moreover, NDPs and PDRs are uniformly spread over several functional protein classes, whereas IDPs are concentrated only on two, namelynucleic acid binding proteinsandtranscription factors, which are just a subset of the functions that are commonly associated with protein intrinsic disorder. As a conclusion, PDRs and IDPs should be considered, in future classifications, as distinct variants of disordered proteins, with different physical-chemical properties and functional spectra.
Reverse GWAS: Using Genetics to Identify and Model Phenotypic Subtypes
Authors: Dahl Andy , Cai Na , Ko Arthur , Laakso Markku , Pajukanta Päivi , Flint Jonathan , Zaitlen Noah
Published: October 2018

Recent and classical work has revealed biologically and medically significant subtypes in complex diseases and traits. However, relevant subtypes are often unknown, unmeasured, or actively debated, making automatic statistical approaches to subtype definition particularly valuable. We propose reverse GWAS (RGWAS) to identify and validate subtypes using genetics and multiple traits: while GWAS seeks the genetic basis of a given trait, RGWAS seeks to define trait subtypes with distinct genetic bases. Unlike existing approaches relying on off-the-shelf clustering methods, RGWAS uses a bespoke decomposition, MFMR, to model covariates, binary traits, and population structure. We use extensive simulations to show these features can be crucial for power and calibration. We validate RGWAS in practice by recovering known stress subtypes in major depressive disorder. We then show the utility of RGWAS by identifying three novel subtypes of metabolic traits. We biologically validate these metabolic subtypes with SNP-level tests and a novel polygenic test: the former recover known metabolic GxE SNPs; the latter suggests genetic heterogeneity may explain substantial missing heritability. Crucially, statins, which are widely prescribed and theorized to increase diabetes risk, have opposing effects on blood glucose across metabolic subtypes, suggesting potential have potential translational value.

Author summary

Complex diseases depend on interactions between many known and unknown genetic and environmental factors. However, most studies aggregate these strata and test for associations on average across samples, though biological factors and medical interventions can have dramatically different effects on different people. Further, more-sophisticated models are often infeasible because relevant sources of heterogeneity are not generally known a priori. We introduce Reverse GWAS to simultaneously split samples into homogeneoues subtypes and to learn differences in genetic or treatment effects between subtypes. Unlike existing approaches to computational subtype identification using high-dimensional trait data, RGWAS accounts for covariates, binary disease traits and, especially, population structure; these features are each invaluable in extensive simulations. We validate RGWAS by recovering known genetic subtypes of major depression. We demonstrate RGWAS is practically useful in a metabolic study, finding three novel subtypes with both SNP- and polygenic-level heterogeneity. Importantly, RGWAS can uncover differential treatment response: for example, we show that statin, a common drug and potential type 2 diabetes risk factor, may have opposing subtype-specific effects on blood glucose.
An Analysis of Decision Under Risk in Rats
Authors: Constantinople Christine M. , Piet Alex T. , Brody Carlos D.
Published: October 2018

Prospect Theory is the predominant behavioral economic theory describing decision-making under risk. It accounts for near universal aspects of human choice behavior whose prevalence may reflect fundamental neural mechanisms. We now apply Prospect Theory’s framework to rodents, using a task in which rats chose between guaranteed and probabilistic rewards. Like humans, rats distorted probabilities and showed diminishing marginal sensitivity, in which they were less sensitive to differences in larger rewards. They exhibited reference dependence, in which the valence of outcomes (gain or loss) was determined by an internal reference point reflecting reward history. The similarities between rats and humans suggest conserved neural substrates, and enable application of powerful molecular/circuit tools to study mechanisms of psychological phenomena from behavioral economics.
Tailoring structural and magnetic properties of Mn3−x
Fe
x
Ga alloys towards multifunctional applications
Authors: Liu Z.H. , Tang Z. J. , Tan J. G. , Zhang Y. J. , Wu Z. G. , Wang X. T. , Liu G. D. , Ma X. Q.
Published: October 2018

This study investigated the structural and magnetic properties of Mn3−x
Fe
x
Ga alloys (x = 0, 0.2, 0.4, 0.6, 0.8, 1) under different heat-treatment conditions. A tetragonal structure was observed in samples that were heat treated at 623 K for three days followed by quenching in ice water. These tetragonal alloys present large coercive fields in the range 0.8–5 kOe and low saturation magnetization, and have great potential for application in spin-transfer torque-based devices. A hexagonal structure was observed in samples subjected to heat treatment at 883 K for three days following quenching in ice water. A moderate decrease in the coercive field has been observed for the hexagonal alloys compared with those with a tetragonal structure. However, the Mn3−x
Fe
x
Ga alloys with a hexagonal structure exhibit other attractive magnetic properties, including collinear and non-collinear magnetic properties, holding high promise for technological applications. A face-centred-cubic (f.c.c.) structure was observed when subjected to annealing at 1073 K for three days followed by quenching in ice water. In contrast to the tetragonal and hexagonal structures, all f.c.c. alloys exhibit antiferromagnetic behaviour. This versatile material can display a wide range of multi-functionalities attributed to its tuneable crystal structure. This investigation will guide the design of multiple structures of these materials in order to utilise the wide functionalities for practical applications.
Unprecedented three-dimensional hydrogen-bonded hex topological chiral lanthanide–organic frameworks built from an achiral ligand
Authors: Qin Tao , Feng Zhe , Yang Jie , Shen Xuan , Zhu Dunru
Published: October 2018

The design and preparation of chiral metal–organic frameworks (CMOFs) from achiral ligands are a big challenge. Using 3-nitro-4-(pyridin-4-yl)benzoic acid (HL) as a new linker, a total of eight chiral lanthanide–organic frameworks (LOFs), namely poly[diaquatris[μ2-3-nitro-4-(pyridin-4-yl)benzoato-κ2
O:O′]lanthanide(III)], L- and D-[Ln(C12H7N2O4)3(H2O)2]
n
[(1), Ln = Eu; (2), Ln = Gd; (3), Ln = Dy; (4), Ln = Tb], were hydrothermally synthesized without chiral reagents and determined by X-ray crystallography. Crystal structure analyses show that L-(1)–(4) crystallize in the hexagonal P65 space group and are isomorphous and isostructural, while the enantiomers D-(1)–(4) crystallize in the hexagonal P61 space group. All LnIII ions are octacoordinated by six carboxyl O atoms of six 3-nitro-4-(pyridin-4-yl)benzoate ligands and two water molecules in a dodecahedral geometry. A one-dimensional neutral helical [Ln2(CO2)3]
n
chain is observed in (1)–(4) as a chiral origin. These helical chains are further interconnected via directional hydrogen-bonding interactions between pyridyl groups and water molecules to construct a three-dimensional (3D) homochiral network with hex topology. The present CMOF structure is the first chiral 3D hydrogen-bonded hex-net and shows good water stability. Solid-state circular dichroism (CD) signals revealed that (1)–(4) crystallized through spontaneous resolution. Furthermore, (1) and (4) display a strong red and green photoluminescence at room temperature, respectively, but their intensities reduce to almost half at 200 °C. Notably, upon excitation under visible light (463 nm), a circularly polarized luminescence (CPL) of (1) in the solid state is observed for the first time, with a g
lum value of 2.61 × 10−2.
Aircraft model for the automatic taxi directional control design
Authors: Krawczyk Mariusz , Szczepanski Cezary Jerzy , Zajdel Albert
Published: October 2018

Purpose

This paper aims to present a concept of an automatic directional control system of remotely piloted aerial system (RPAS) during the taxiing phase. In particular, it shows the initial stages of the control laws synthesis-mathematical model and simulation of taxiing aircraft. Several reasons have emerged in recent years that make the automation of taxiing an important design challenge including decreased safety, performance and pilot workload.

Design/methodology/approach

The adapted methodology follows the model-based design approach in which the control system and the aircraft are mathematically modelled to allow control laws synthesis. The computer simulations are carried out to analyse the model behaviour.

Findings

Chosen methodology and modelling technique, especially tire-ground contact model, resulted in a taxiing aircraft model that can be used for directional control law synthesis. Aerodynamic forces and moments were identified in the wind tunnel tests for the full range of the slip angle. Simulations allowed to compute the critical speeds for different taxiway conditions in a 90° turn.

Practical implications

The results can be used for the taxi directional control law synthesis and simulation of the control system. The computed critical speeds can be treated as a safety limits.

Originality/value

The taxi directional control system has not been introduced to the RPAS yet. Therefore, the model of taxiing aircraft including aerodynamic characteristics for the full range of the slip angle has a big value in the process of design and implementation of the future auto taxi systems. Moreover, computed speed safety limits can be used by designers and standards creators.
Oscillation mode flight data analysis based on FFT
Authors: Fu Jingcheng , Huang Jun , Wang Li-Bo , Song Lei
Published: October 2018

Purpose

The purpose of this paper is to propose an identification method of acquiring aircraft mode characteristics based on fast Fourier transform and half-power bandwidth method, aiming at the common oscillation met in flight test.

Design/methodology/approach

The feasibility of this method is demonstrated through derivation; the robustness analysis is conducted through three examples, and finally the method was applied on a set of sideslip angle record from flight test.

Findings

The derivation and numerical analysis both show that the presented method can have high accuracy and good robustness under coupled mode and noise condition.

Practical implications

The method proposed is of robustness, and it is concise and easy to apply on flight data record.

Originality/value

This paper demonstrates the feasibility of half power bandwidth to be applied on oscillation mode characteristics identification from flight data record, which is different from other method applied.
Gender disaggregated effects of microcredit on capital accumulation in rural households
Authors: Isoto Rosemary Emegu , Kraybill David Simon
Published: October 2018

Purpose

The purpose of this paper is to contribute to the literature on microcredit impacts by quantifying the gender disaggregated effects of long-term borrowing on capital accumulation in order to address the existing gap. Separate models are estimated for male-headed and female-headed households to determine if the effects of microcredit differ between these gender types.

Design/methodology/approach

The paper adopts the method proposed by Deaton (1990) in which he specifies a model without borrowing restrictions whereby the household maximizes an inter-temporal utility function. To account for self-selection and endogeneity of micro credit, the fixed effects instrumental variable approach is used. Data are disaggregated by gender and analyzed separately.

Findings

The paper finds that micro credit indeed increases productive assets and human capital but has no significant effect on non-productive assets. One striking result is that after disaggregating the data by gender, the authors find no effect of micro credit on women-headed households.

Practical implications

The paper provides an empirical evidence for the need to address gender issues in finance and lending. Furthermore, targeted lending particularly to women makes a great difference in the fight against poverty.

Originality/value

This paper fills the gap on gender and micro credit impacts on capital accumulation in a developing country context.
Investigate the role of distributed leadership and strategic flexibility in fostering business model innovation
Authors: Liao Suqin , Liu Zhiying , Fu Lihua , Ye Peichi
Published: October 2018

Purpose

The purpose of this paper is to examine whether the new distributed leadership patterns is an important driver for innovating business model. By synthesizing insights from the dynamic capabilities perspective, it also explores how and when distributed leadership enhances the business model innovation (BMI) by involving strategic flexibility as a mediator and environmental dynamism as important contingency.

Design/methodology/approach

A survey via questionnaire was conducted with 262 CEOs and 262 senior managers from Chinese high-tech companies that provided the research data. Structural equation modeling and linear regression analyses were used to test the time-lagged data, and then the main research questions were responded to.

Findings

The analysis reveals that distributed leadership has a significant direct influence on BMI, and that distributed leadership also indirectly affects BMI by enhancing strategic flexibility. Environmental dynamism strengthens the positive effect of distributed leadership on BMI under strategic flexibility.

Originality/value

This paper advances and enriches the emerging stream of BMI research. It presents an innovative conceptual analysis of the antecedents of BMI, and it shows a possible solution for BMI that complements extant research that considers which and how the leadership style of the organizations affects the business model change.
Measuring the impact of human resource development (HRD) practices on employee performance in small and medium scale enterprises
Authors: Otoo Frank Nana Kweku , Mishra Mridula
Published: October 2018

Purpose

The purpose of this paper is to examine the impact of human resource development practices on employee performance in small and medium scale enterprises.

Design/methodology/approach

An integrated research model was developed by combining principal factors from existing literature. Data were collected through questionnaire from 500 employees of the selected SME’s. The validity of the model and hypotheses was tested using structural equation modeling. The reliability and validity of the dimensions are established through confirmatory factor analysis.

Findings

The results indicate that some human resource development practices impact employee performance. Performance appraisal however does not impact employee performance of the firms studied.

Research limitations/implications

The research was undertaken in small and medium scale enterprises, and the analysis based on cross-sectional data which cannot be generalized across a broader range of sectors.

Practical implications

The findings of the study will help stakeholders, policy makers and management of SME’s in espousing appropriate and well-articulated HRD practices to improve employee competencies and enhance organizational effectiveness.

Originality/value

This study extends the literature by empirically adducing evidence that, human resource development practices impact employee performance of small and medium scale enterprises in Ghana.
Australian education policy from the 1970s: an autobiographical approach
Authors: Campbell Craig , Connors Lyndsay
Published: October 2018

Purpose

The purpose of this paper is to illuminate the history of national education policy through an interview with one of its significant makers and critics, Lyndsay Connors, a former Australian Schools Commissioner.

Design/methodology/approach

The paper occurs as an interview. The text is based on a revised conversation held as an event of the Australian and New Zealand History of Education Conference held at the University of Canberra, on 26 September 2017.

Findings

Australian educational policy is peculiarly complex, and apparently “irrational”. This appears especially so in relation to the government, tax-raised, funding of government and non-government schools. A combination of the peculiarities of Australian federalism in relation to education, political expediency, popular exhaustion with the “state aid” debate, the power of entrenched interest groups and the distancing of democratic decision making from the decision-making process in relation to education all play a part.

Originality/value

The originality of this contribution to a research journal lies in its combination of autobiography with historical policy analysis.
Navigating political terrain in organizations: the crucial role of leaders and HR
Authors: Javad Shahina , S.D. Sumod
Published: October 2018

Purpose

This paper aims to look at how to understand and identify sources office politics and how to manage it successfully for the betterment of organizations.

Design/methodology/approach

This briefing is prepared by independent writers who add their own impartial comments and place the article in context.

Findings

Politics is present in all organizations only the degree of politics varies among them. What matters is how successfully this minefield is navigated to achieve goals and mission of organizations. Managers and organizations could adopt some successful personal and HR strategies to manage office politics effectively.

Practical implications

The paper suggests some leader-level personal strategies and organizational-level HR strategies to harness office politics for the benefit of people and organizations.

Originality/value

This paper helps managers to identify the presence and sources of politics in their organizations.
Emotional labor’s impact on hoteliers outside the workplace
Authors: McGinley Sean , Wei Wei
Published: October 2018

Purpose

The purpose of this paper is to examine why and how emotional labor influences hotel employee behavior outside the workplace.

Design/methodology/approach

Both qualitative and quantitative approaches were used. First, 21 entry-level hotel managers were interviewed, and grounded theory was used for the analysis of the interview data (Study 1). Then, 410 survey responses were collected from hotel employees, and the data were analyzed using a PROCESS model (Study 2).

Findings

The results of Study 1 indicated that people relied on social support networks and alcohol to cope with emotional labor. Specific hypotheses were tested in Study 2, which found that emotional labor leads to more partying when life and work responsibilities are in conflict.

Practical implications

This research provides strategic guidance for hotel managers to help employees cope with emotional labor by better managing life-work conflict.

Originality/value

This research represents an early attempt to elucidate the effects of emotional labor on individual behavior outside the workplace. Conditions were found across the two studies that suggest the role of emotional labor in increasing alcohol consumption among hotel employees.