bluuebunny/crossref_metadata_2025 huggingface dataset:
A systematic mixed-integer differential evolution approach for water network operational optimization
Authors: Zhao Wanqing , Beach Thomas H. , Rezgui Yacine
Published: September 2018

The operational management of potable water distribution networks presents a great challenge to water utilities, as reflected by the complex interplay of a wide range of multidimensional and nonlinear factors across the water value chain including the network physical structure and characteristics, operational requirements, water consumption profiles and the structure of energy tariffs. Nevertheless, both continuous and discrete actuation variables can be involved in governing the water network, which makes optimizing such networks a mixed-integer and highly constrained decision-making problem. As such, there is a need to situate the problem holistically, factoring in multidimensional considerations, with a goal of minimizing water operational costs. This paper, therefore, proposes a systematic optimization methodology for (near) real-time operation of water networks, where the operational strategy can be dynamically updated using a model-based predictive control scheme with little human intervention. The hydraulic model of the network of interest is thereby integrated and successively simulated with different trial strategies as part of the optimization process. A novel adapted mixed-integer differential evolution (DE) algorithm is particularly designed to deal with the discrete-continuous actuation variables involved in the network. Simulation results on a pilot water network confirm the effectiveness of the proposed methodology and the superiority of the proposed mixed-integer DE in comparison with genetic algorithms. It also suggests that 23.69% cost savings can be achieved compared with the water utility's current operational strategy, if adaptive pricing is adopted for all the pumping stations.
Asymmetry of the atomic-level stress tensor in homogeneous and inhomogeneous materials
Authors: Rigelesaiyin Ji , Diaz Adrian , Li Weixuan , Xiong Liming , Chen Youping
Published: September 2018

The stress tensor is described as a symmetric tensor in all classical continuum mechanics theories and in most existing statistical mechanics formulations. In this work, we examine the theoretical origins of the symmetry of the stress tensor and identify the assumptions and misinterpretations that lead to its symmetric property. We then make a direct measurement of the stress tensor in molecular dynamics simulations of four different material systems using the physical definition of stress as force per unit area acting on surface elements. Simulation results demonstrate that the stress tensor is asymmetric near dislocation cores, phase boundaries, holes and even in homogeneous material under a shear loading. In addition, the atomic virial stress and Hardy stress formulae are shown to significantly underestimate the stress tensor in regions of stress concentration.
Indirect ecological effects interact with community genetic effects in a host–parasite system and dramatically reduce parasite burden
Authors: Khudr Mouhammad Shadi , Purkiss Samuel Alexander , Hager Reinmar
Published: September 2018

Community genetic (CG) effects and ecological factors create a complex set of interactions that are key drivers of evolutionary dynamics in ecological systems. To date, most studies investigating trait variation have focused on either effects of intraspecific genetic variation or on genotype by environment (GxE) interactions in isolation. Poorly investigated but very important are the interactions between CGs and indirect ecological effects (IEEs) that are caused by plant–soil interactions. Here, we tested how CGs in a cabbage host and its aphid parasite depended on the ecological conditions under which the host was grown. We established microcosms of different cabbage cultivars and aphid genotypes on soils inoculated with samples of other soils previously trained with onion. We hypothesized that such IEEs will have significantly different outcomes for ecosystems than predicted from simpler CG or GxE studies. Our analysis demonstrated a large IEE that differed by context and aphid genotype causing reduced parasite population sizes by up to 90%. The IEE is induced by insect-repellent properties and the microbiome of the onion. Our results highlight the importance of interacting IEEs and CGs for ecosystems dynamics showing that IEEs offer sustainable solutions by dramatically reducing parasite burden on cash crops.
Host defences against avian brood parasitism: an endocrine perspective
Authors: Abolins-Abols Mikus , Hauber Mark E.
Published: September 2018

Host defences against avian brood parasites are the outcome of well-documented coevolutionary arms races, yet important questions about variation in hosts' antiparasitic response traits remain poorly understood. Why are certain defences employed by some species or individuals and not by others? Here, we propose that understanding variability in and the evolution of host defences can be facilitated by the study of the underlying physiological mechanisms. Specifically, because antiparasitic strategies involve behaviours that have been shown to be hormonally regulated in other contexts, we hypothesize that host responses to brood parasites are likely to be mediated by related endocrine mechanisms. We outline the hallmarks of the endocrine bases of parasite defence-related avian behaviours, review the current understanding of antiparasitic host tactics and propose testable hypotheses about the hormonal mechanisms that may mediate host defences. We consider these mechanisms in a life-history framework and discuss how endocrine factors may shape variation in host defences. By providing a hypothesis-driven mechanistic framework for defences against parasitism, this perspective should stimulate the study of their endocrine bases to enhance our understanding of the intricate arms races in avian host–parasite systems.
Rapid energy expenditure estimation for assisted and inclined loaded walking
Authors: Slade Patrick , Troutman Rachel , Kochenderfer Mykel J. , Collins Steven H. , Delp Scott L.
Published: September 2018

Background

Estimating energy expenditure with indirect calorimetry requires expensive equipment and provides slow and noisy measurements. Rapid estimates using wearable sensors would enable techniques like optimizing assistive devices outside a lab. Existing methods correlate data from wearable sensors to measured energy expenditure without evaluating the accuracy of the estimated energy expenditure for activity conditions or subjects not included in the correlation process. Our goal is to assess data-driven models that are capable of rapidly estimating energy expenditure for new conditions and subjects.

Methods

We developed models that estimated energy expenditure from two datasets during walking conditions with (1) ankle exoskeleton assistance and (2) various loads and inclines. The estimation was portable and rapid, using input features that are possible to measure with wearable sensors and restricting the input data length to a single gait cycle or four second interval. The performance of the models was evaluated for three use cases. The first case estimated energy expenditure during walking conditions for subjects with some subject specific training data available. The second case estimated all conditions in the dataset for a new subject not included in the training data. The third case estimated new conditions for a new subject. The models also ordered the magnitude of energy expenditure across all conditions for a new subject.

Results

The average errors in energy expenditure estimation during assisted walking conditions were 4.4%, 8.0%, and 8.1% for the three use cases, respectively. The average errors in energy expenditure estimation during inclined and loaded walking conditions were 6.1%, 9.7%, and 11.7% for the three use cases. The models ordered the magnitude of energy expenditure with a maximum and average percentage of correctly ordered conditions of 56% and 43% for assisted walking and 85% and 55% for incline and loaded walking.

Conclusions

Our data-driven models determined the accuracy of energy expenditure estimation for three use cases. For experiments where the accuracy of a data-driven model is sufficient, standard indirect calorimetry can be replaced. The energy expenditure ordering could aid in selecting optimal assistance conditions. The models, code, and datasets are provided for reproduction and extension of our results.
Gelbox — An Interactive Simulation Tool for Gel Electrophoresis
Authors: Gingold Chaim , Douglas Shawn M.
Published: September 2018

Gel electrophoresis enables separation and visualization of biomolecules such as DNA, RNA, or proteins. Like many powerful tools, mastering the use of gels and making the information gained from them productive, can be dificult. Gelbox is a simulation tool that helps users understand how changing experimental input parameters can affect the data output from gel electrophoresis. Our simulation model handles a wide range of settings, including many “suboptimal” values that may be useful for troubleshooting common mistakes made by novices.
Trends in millennial adolescent mental health and health related behaviours over ten years: a population cohort comparison study
Authors: Patalay Praveetha , Gage Suzanne H
Published: September 2018

Background

There is evidence that mental health problems are increasing and substance use behaviours are decreasing. This paper aimed to investigate recent trends in mental ill-health and health-related behaviours in two cohorts of UK adolescents in 2005 and 2015.

Method

Trends in harmonised mental ill-health (depressive symptoms, self-harm, anti-social behaviours, parent reported difficulties) and health related behaviours (substance use, weight, weight perception, sleep, sexual intercourse) were examined at age 14 in two UK birth cohorts; Avon Longitudinal Study of Parents and Children (ALSPAC, N=5627, born 1991-92) and Millennium Cohort Study (MCS, N=11318, born 2000-02). Prevalences and trend estimates are presented unadjusted and using propensity score matching and entropy balancing.

Results

Depressive symptoms (9% to ∼15%) and self-harm (11.8% to ∼14.5%) increased over the 10 years. Parent-reported emotional difficulties, conduct problems, hyperactivity and peer problems were higher in 2015 compared to 2005 (5.7 – 9% to 9 – 18%).Conversely, substance use (tried smoking 9% to 3%; tried alcohol 52% to ∼43%, cannabis 4.6% to ∼4%), sexual activity (2% to ∼1%) and anti-social behaviours (6.2 – 40.1% to 1.6 – 28%) were less common or no different. Adolescents in 2015 were spending less time sleeping, had higher BMIs and a greater proportion perceived themselves as overweight.

Conclusion

Given health-related behaviours are often cited as risk-factors for poor mental health, our findings suggest relationships between these factors might be more complex and dynamic in nature than currently understood. Striking increases in mental health difficulties, BMI and poor sleep related behaviours highlight an increasing public health challenge.
Different analysis methods of Scottish and English child physical activity data explain the majority of the difference between the national prevalence estimates
Authors: Williamson Chloë , Kelly Paul , Strain Tessa
Published: September 2018

Background

The percentage of children in Scotland and England meeting the aerobic physical activity recommendation differ greatly according to the estimates derived from the respective national health surveys. The Scottish Health Survey (SHeS) usually estimates that over 70% meet the guidelines; Health Survey for England (HSE) estimates are usually below 25%. It is plausible that these differences originate from different analysis methods. The HSE monitor the percentage of children that undertake 60 minutes of moderate-to-vigorous physical activity on each day of the week (‘the daily minimum method’ (DMM)). The SHeS monitor the proportion that undertake at least seven sessions of moderate-to-vigorous physical activity, with an average daily duration over 60 minutes (‘the average method’ (WAM)). We aimed to establish how great an influence this difference in analysis methods has on the prevalence estimates.

Methods

Physical activity data from 5-15 year olds in the 2015 HSE and SHeS were reanalysed (weighted n=3840 and 965, respectively). Two comparable pairs of estimates were derived: a DMM and WAM estimate from the HSE not including travel to/from school, and WAM estimates from the HSE and the SHeS including travel to/from school. It is not possible to calculate a DMM estimate from the SHeS due to the way the questions are asked. Results were presented for the total samples, and by sex and age sub-groups.

Results

The HSE WAM estimate was 31.7 (95% CI: 30.2-33.3) percentage points higher than the DMM estimate (54.3% (95% CI: 52.6-56.0) and 22.6% (95% CI: 21.2-24.1) respectively). The magnitude of this difference differed by age group but not sex. When comparable WAM estimates were derived from the SHeS and the HSE, the SHeS was 11.8 percentage points higher (73.6% (95% CI: 69.8-77.1) and 61.8% (95% CI: 60.2-63.5) respectively). The magnitude of this difference differed by age group and sex.

Conclusions

The results indicate that the difference in the analysis method explains the majority (approximately 30 percentage points) of the difference in the child physical activity prevalence estimates between Scotland and England. These results will help those involved in national surveillance to determine how to increase comparability between the U.K. home nations.
Modulation of electrocorticographic seizure features predicts response to closed-loop brain stimulation
Authors: Kokkinos Vasileios , Sisterson Nathaniel D. , Wozny Thomas A. , Richardson R. Mark
Published: September 2018

Why does closed-loop invasive brain stimulation improve seizure control in some patients with epilepsy, but not others? The RNS System, the only FDA-approved bi-directional brain-computer interface, has been shown to improve seizure control in patients with refractory epilepsy, although the mechanisms behind this success are undefined. We analyzed recordings from the RNS System and discovered two main categories of electrophysiological signatures of stimulation-induced modulation of the seizure network. Direct effects included ictal inhibition and early frequency modulation but did not correlate with improved clinical outcomes. Only indirect effects, those occurring remote from triggered stimulation, predicted improved clinical outcomes. These indirect effects, which included spontaneous ictal inhibition, frequency modulation, fragmentation, and ictal duration modulation, may reflect progressive local epileptogenic network compartmentalization that hinders the spread of pathological synchrony from recruiting neuronal populations. Our findings suggest that responsiveness to RNS may be explained by chronic stimulation-induced modulation of seizure network activity, rather than direct effects on each detected seizure.
Field evaluation of malachite green loop-mediated isothermal amplification as a malaria parasite detection tool in a health post in Roraima state, Brazil
Authors: Kudyba Heather M. , Louzada Jaime , Ljolje Dragan , Kudyba Karl A. , Muralidharan Vasant , Oliveira-Ferreira Joseli , Lucchi Naomi W.
Published: September 2018

Malaria is a debilitating parasitic disease that causes significant morbidity and mortality. Microscopic detection of parasites is currently the “gold standard” diagnostic. This technique is limited in its ability to detect low-density infections, is time consuming, and requires a highly trained microscopist. Malaria epidemiological surveillance studies especially aimed at the detection of low-density infection and asymptomatic cases will require more sensitive and user-friendly tools. We have shown previously that the molecular-based, colorimetric malachite green loop-mediated isothermal amplification (MG-LAMP) assay is a valuable tool for diagnosing malaria infection in a laboratory setting. In this study, we field evaluated this assay in a malaria diagnostic post in Roraima, Brazil. We prospectively collected 91 patient samples and performed microscopy, MG-LAMP, and real-time PCR (PET-PCR) to detect Plasmodium infection. Two independent readers were used to score the MG-LAMP tests to assess whether the sample was positive (blue/green) or negative (clear). There was 100% agreement between the two readers (Kappa=1). All tests detected 33 positive samples, but both the MG-LAMP and PET-PCR detected 6 and 7 more positive samples, respectively. The PET-PCR assay detected 6 mixed infections (defined as infection with both P. falciparum and P. vivax) while microscopy detected one and MG-LAMP detected two of these mixed infections. Microscopy did not detect any Plasmodium infection in 26 of the enrolled asymptomatic cases while MG-LAMP detected five and PET-PCR assay three positive cases. Overall, MG-LAMP provided a simpler and user-friendly molecular method for malaria diagnosis that is more sensitive than microscopy. Additionally, MG- LAMP has the capacity to test 38 samples per run (one hour), allowing for the screening of large number of samples which is appealing when large-scale studies are necessary e.g. in community surveillance studies. The current MG-LAMP assay was limited in its ability to detect mixed infection when compared to the PET-PCR, but otherwise proved to be a powerful tool for malaria parasite detection in the field and opens new perspectives in the implementation of surveillance studies in malaria elimination campaigns.
SeqTailor: a user-friendly webserver for the extraction of DNA or protein sequences from next-generation sequencing data
Authors: Zhang Peng , Boisson Bertrand , Casanova Jean-Laurent , Abel Laurent , Itan Yuval
Published: September 2018

Human whole-genome sequencing generally reveals about 4,000,000 genetic variants, including 20,000 coding variants, in each individual studied. These data are mostly stored as VCF-format files. Although many variant analysis methods accept VCF files as input, many other tools require DNA or protein sequences, particularly for splicing prediction, sequence alignment, phylogenetic analysis, and structure prediction. However, there is currently no existing online tool for extracting DNA or protein sequences for genomic variants from VCF files with user-defined parameters in a user-friendly, efficient, and standardized manner. We developed the SeqTailor webserver to bridge this gap. It can be used for the rapid extraction of (1) DNA sequences around genetic variants, with customizable window sizes, from the hg19 or hg38 human reference genomes; and (2) protein sequences encoded by the DNA sequences around genetic variants, with built-in SnpEff annotation and customizable window sizes, from human canonical transcripts. The SeqTailor webserver streamlines the sequence extraction process, and accelerates the analysis of genetic variant data with software requiring DNA or protein sequences. SeqTailor will facilitate the study of human genomic variation, by increasing the feasibility of sequence-based analysis and prediction. The SeqTailor webserver is freely available from http://shiva.rockefeller.edu/SeqTailor/.
Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity
Authors: Park Jeehae , Estrada Javier , Johnson Gemma , Ricci-Tam Chiara , Bragdon Meghan , Shulgina Yekaterina , Cha Anna , Gunawardena Jeremy , DePace Angela H.
Published: September 2018

Developmental enhancers integrate graded concentrations of input transcription factors (TFs) to create sharp gene expression boundaries. Here we examine the hunchback P2 (HbP2) enhancer which drives a sharp expression pattern in the Drosophila blastoderm embryo in response to the transcriptional activator Bicoid (Bcd). We systematically interrogate cis and transfactors that influence the shape and position of expression driven by HbP2, and find that the prevailing model, based on cooperative binding of Bcd to HbP2 is not adequate. We demonstrate that other proteins, such as pioneer factors, mediator and histone modifiers influence the shape and position of the HbP2 expression pattern. By comparing our results to theory, we assess how higher-order cooperativity and energy expenditure impact boundary location and sharpness. Our results emphasize that the bacterial view of transcription regulation, where pairwise interactions between regulatory proteins dominate, must be re-examined in animals, where multiple molecular mechanisms collaborate to shape the gene regulatory function.
Recovery and analysis of transcriptome subsets from pooled single-cell RNA-seq libraries
Authors: Riemondy Kent A. , Ransom Monica , Alderman Christopher , Gillen Austin E. , Fu Rui , Finlay-Schultz Jessica , Kirkpatrick Gregory , Paola Di Jorge , Kabos Peter , Sartorius Carol A. , Hesselberth Jay R.
Published: September 2018

Single-cell RNA sequencing (scRNA-seq) methods generate sparse gene expression profiles for thousands of single cells in a single experiment. The information in these profiles is sufficient to classify cell types by distinct expression patterns but the high complexity of scRNA-seq libraries often prevents full characterization of transcriptomes from individual cells. To extract more focused gene expression information from scRNA-seq libraries, we developed a strategy to physically recover the DNA molecules comprising transcriptome subsets, enabling deeper interrogation of the isolated molecules by another round of DNA sequencing. We applied the method in cell-centric and gene-centric modes to isolate cDNA fragments from scRNA-seq libraries. First, we resampled the transcriptomes of rare, single megakaryocytes from a complex mixture of lymphocytes and analyzed them in a second round of DNA sequencing, yielding up to 20-fold greater sequencing depth per cell and increasing the number of genes detected per cell from a median of 1,313 to 2,002. We similarly isolated mRNAs from targeted T cells to improve the reconstruction of their VDJ-rearranged immune receptor mRNAs. Second, we isolatedCD3DmRNA fragments expressed across cells in a scRNA-seq library prepared from a clonal T cell line, increasing the number of cells with detectedCD3Dexpression from 59.7% to 100%. Transcriptome resampling is a general approach to recover targeted gene expression information from single-cell RNA sequencing libraries that enhances the utility of these costly experiments, and may be applicable to the targeted recovery of molecules from other single-cell assays.
Mutant p53 triggers a dynamin-1/APPL1 endosome feedback loop that regulates β1 integrin recycling and migration
Authors: Lakoduk Ashley M. , Roudot Philippe , Mettlen Marcel , Grossman Heather M. , Schmid Sandra L. , Chen Ping-Hung
Published: September 2018

Multiple mechanisms contribute to cancer cell progression and metastatic activity, including changes in endocytic trafficking and signaling of cell surface receptors. We report that gain-of-function (GOF) mutant p53 expression enhances β integrin and EGF receptor recycling and increases cell migration by triggering a positive feedback loop involving the activation of dynamin-1 (Dyn1) and accumulation of a spatially-restricted subpopulation of APPL1-positive ‘perimeter’ endosomes. DNM1 is upregulated at both the mRNA and protein levels in a manner dependent on expression of GOF mutant p53. Perimeter APPL1 endosomes are required for rapid recycling of EGFR and β1 integrins and modulate Akt signaling and Dyn1 activation to create the positive feedback loop that culminates in increased focal adhesion turnover and cell migration. Thus, Dyn1- and Akt-dependent perimeter APPL1 endosomes function as a nexus, integrating signaling and receptor trafficking, that can be co-opted by cancer cells for mutant p53-driven migration and invasion.
The entopeduncular nucleus drives lateral habenula responses to negative but not positive or neutral affective stimuli
Authors: Li Hao , Pullmann Dominika , Jhou Thomas C.
Published: September 2018

Lateral habenula (LHb) neurons are activated by negative motivational stimuli and play key roles in the pathophysiology of depression. Early reports indicated the possibility that rostral entopeduncular nucleus (rEPN) neurons drive these LHb responses, but this influence remains untested. We find that both rEPN and LHb neurons in rats exhibit similar activation/inhibition patterns after negative/positive motivational stimuli, but that the rEPN influence on LHb firing is surprisingly selective. Temporary rEPN inactivation decreases LHb basal and burst firing, and eliminates LHb responses to footshock-predictive cues occurring 40-100ms but not 10-30ms post-stimulus, nor on responses to positive/neutral motivational stimuli. Additionally, rEPN inactivation partially but not fully reduces LHb responses to signaled footshocks, while excitotoxic rEPN lesions only partially diminish footshock-induced cFos in the LHb and its rostromedial tegmental nucleus targets. Together, our findings indicate an important but selective role of the rEPN in driving LHb responses to motivational stimuli.
Accounting for ambiguity in ancestral sequence reconstruction
Authors: Oliva A. , Pulicani S. , Lefort V. , Bréhélin L. , Guindon S.
Published: September 2018

The reconstruction of ancestral genetic sequences from the analysis of contemporaneous data is a powerful tool to improve our understanding of molecular evolution. Various statistical criteria defined in a phylogenetic framework can be used to infer nucleotide, aminoa-cid or codon states at internal nodes of the tree, for every position along the sequence. These criteria generally select the state that maximises (or minimises) a given criterion. Although it is perfectly sensible from a statistical perspective, that strategy fails to convey useful information about the level of uncertainty associated to the inference. The present study introduces a new criterion for ancestral nucleotide reconstruction that selects a single state whenever the signal conveyed by the data is strong, and a combination of multiple states otherwise. Simulations demonstrate the benefit of this approach with a substantial increase in the accuracy of ancestral sequence reconstruction without significantly compromising on the precision of the solutions returned.
Acute inhibition of heterotrimeric kinesin-2 function reveals mechanisms of intraflagellar transport in mammalian cilia
Authors: Engelke Martin F. , Waas Bridget , Kearns Sarah E. , Suber Ayana , Boss Allison , Allen Benjamin L. , Verhey Kristen J.
Published: September 2018

The trafficking of components within cilia, called intraflagellar transport (IFT), is powered by kinesin-2 and dynein-2 motors. Loss of function in any subunit of the heterotrimeric KIF3A/KIF3B/KAP kinesin-2 motor prevents ciliogenesis in mammalian cells and has hindered an understanding of how kinesin-2 motors function in IFT. We used a chemical-genetic approach to engineer an inhibitable KIF3A/KIF3B (i3A/i3B) kinesin-2 motor that is capable of rescuing WT motor function inKif3a/Kif3bdouble-knockout cells. Inhibitor addition blocks ciliogenesis or, if added to ciliated cells, blocks IFT within two minutes, which leads to a complete loss of primary cilia within six hours. The kinesin-2 family members KIF3A/KIF3C and KIF17 cannot rescue ciliogenesis inKif3a/Kif3bdouble-knockout cells nor delay the disassembly of full-formed cilia upon i3A/i3B inhibition. These data suggest that KIF3A/KIF3B/KAP is the sole and essential motor for cilia assembly and function in mammalian cells, indicating a species-specific adaptation of kinesin-2 motors for IFT function.
Trafficking of Cholesterol from Lipid Droplets to Mitochondria in Bovine Luteal Cells: Acute Control of Progesterone Synthesis1
Authors: Plewes Michele R. , Cordes Crystal , Przgrodzka Emilia , Talbott Heather , Wood Jennifer , Cupp Andrea , Davis John S.
Published: September 2018

The corpus luteum (CL) is a transient endocrine gland that synthesizes and secretes the steroid hormone, progesterone. Progesterone biosynthesis is a complex process, converting cholesterol via a series of enzymatic reactions, into progesterone. Lipid droplets in luteal cells store cholesterol in the form of cholesterol esters, which can be utilized for steroidogenesis. In small luteal cells, luteinizing hormone (LH) increases intracellular cAMP concentrations leading to activation of protein kinase A (PKA), which phosphorylates downstream proteins, such as hormone sensitive lipase (HSL). Phosphorylation of HSL at Ser563 leads to increased HSL activation and association with lipid droplets, events which theoretically release cholesterol, which can be used for progesterone synthesis. Bovine CL were obtained from a local abattoir, dispersed, and luteal cells were enriched for SLC via centrifugal elutriation. Our results reveal that LH, forskolin, and cAMP induce HSL phosphorylation at Ser563and Ser660. Moreover, inhibiting HSL activity attenuates LH-induced P4 synthesis. Confocal analysis revealed that LH stimulates translocation of HSL to lipid droplets and mitochondria. Furthermore, LH increased trafficking of cholesterol from the lipid droplets to the mitochondria which was dependent on both PKA and HSL activation. These results demonstrate cholesterol stored in lipid droplets are utilized for LH-induced progesterone biosynthesis. Likewise, PKA-induced activation of HSL is required for release and trafficking of cholesterol from the lipid droplets to the mitochondria. Taken together, these findings support a role for a PKA/HSL signaling pathway in response to LH and demonstrate the dynamic relationship between PKA, HSL, and the lipid droplets in the synthesis of progesterone.

Highlights

LH and PKA induce HSL phosphorylation at Ser563and Ser660

HSL is required for optimal LH-induced P4 synthesis

LH stimulates translocation of HSL to lipid droplets and mitochondria

LH stimulated trafficking of cholesterol from lipid droplets to mitochondria
Loss of TLE3 Promotes Mitochondrial Program in Beige Adipocytes and Improves Glucose Metabolism
Authors: Pearson Stephanie , Loft Anne , Rahbhandari Prashant , Simcox Judith , Lee Sanghoon , Donato Anthony , Tontonoz Peter , Mandrup Susanne , Villanueva Claudio J.
Published: September 2018

Prolonged cold exposure stimulates the recruitment of beige adipocytes within white adipose tissue. Beige adipocytes depend on mitochondrial oxidative phosphorylation to drive thermogenesis. The transcriptional mechanisms that promote remodeling in adipose tissue are not well understood. Here we demonstrate that the transcriptional coregulator TLE3 is induced with aging and inhibits mitochondrial gene expression in beige adipocytes. Conditional deletion of TLE3 in adipocytes prevents age- and diet-induced weight gain by promoting mitochondrial oxidative metabolism and increasing energy expenditure, thereby improving glucose control. Using chromatin immunoprecipitation and deep sequencing we found that TLE3 occupies distal enhancers in proximity to nuclear-encoded mitochondrial genes and that many of these enhancers are also enriched for EBF transcription factors. TLE3 interacts with EBF2 and blocks its ability to promote the thermogenic transcriptional program. Collectively, these studies demonstrate that TLE3 mediates age-dependent beige adipose thermogenic decline through inhibition of EBF2 transcriptional activity. Inhibition of TLE3 may provide a novel therapeutic approach for obesity and diabetes.
Comprehensive Genomic Characterization of Breast Tumors with BRCA1 and BRCA2 Mutations
Authors: Lal Avantika , Ramazzotti Daniele , Weng Ziming , Liu Keli , Ford James M. , Sidow Arend
Published: September 2018

Background

Germline mutations in the BRCA1 and BRCA2 genes predispose carriers to breast and ovarian cancer, and there remains a need to identify the specific genomic mechanisms by which cancer evolves in these patients. Here we present a systematic genomic analysis of breast tumors with BRCA1 and BRCA2 mutations.

Methods

We analyzed genomic data from breast tumors, with a focus on comparing tumors with BRCA1/BRCA2 gene mutations with common classes of sporadic breast tumors.

Results

We identify differences between BRCA-mutated and sporadic breast tumors in patterns of point mutation, DNA methylation and structural variation. We show that structural variation disproportionately affects tumor suppressor genes and identify specific driver gene candidates that are enriched for structural variation.

Conclusions

Compared to sporadic tumors, BRCA-mutated breast tumors show signals of reduced DNA methylation, more ancestral cell divisions, and elevated rates of structural variation that tend to disrupt highly expressed protein-coding genes and known tumor suppressors. Our analysis suggests that BRCA-mutated tumors are more aggressive than sporadic breast cancers because loss of the BRCA pathway causes multiple processes of mutagenesis and gene dysregulation.
The crystal structure of an essential high-temperature requirement protein HtrA1 (Rv1223) from Mycobacterium tuberculosis reveals its unique features
Authors: Singh Khundrakpam Herojit , Yadav Savita , Kumar Deepak , Biswal Bichitra Kumar
Published: September 2018

High-temperature requirement A (HtrA) proteins, which are members of the heat-shock-induced serine protease family, are involved in extracytoplasmic protein quality control and bacterial survival strategies under stress conditions, and are associated with the virulence of several pathogens; they are therefore major drug targets. Mycobacterium tuberculosis possesses three putative HtrAs: HtrA1 (Rv1223), HtrA2 (Rv0983) and HtrA3 (Rv0125). Each has a cytoplasmic region, a transmembrane helix and a periplasmic region. Here, the crystal structure of the periplasmic region consisting of a protease domain (PD) and a PDZ domain from an M. tuberculosis HtrA1 mutant (mHtrA1S387A) is reported at 2.7 Å resolution. Although the mHtrA1S387A PD shows structural features similar to those of other HtrAs, its loops, particularly L3 and LA, display different conformations. Loop L3 communicates between the PDs of the trimer and the PDZ domains and undergoes a transition from an active to an inactive conformation, as reported for an equivalent HtrA (DegS). Loop LA, which is responsible for higher oligomer formation owing to its length (50 amino acids) in DegP, is very short in mHtrA1S387A (five amino acids), as in mHtrA2 (also five amino acids), and therefore lacks essential interactions for the formation of higher oligomers. Notably, a well ordered loop known as the insertion clamp in the PDZ domain interacts with the protease domain of the adjacent molecule, which possibly aids in the stabilization of a trimeric functional unit of this enzyme. The three-dimensional structure of mHtrA1S387A presented here will be useful in the design of enzyme-specific antituberculosis inhibitors.
The unspeakable truth of accounting
Authors: Bassnett Susan , Frandsen Ann-Christine , Hoskin Keith
Published: September 2018

Purpose

The purpose of this paper is to investigate accounting as first visible-sign statement form, and also as the first writing, and analyse its systematic differences, syntactic and semantic, from subsequent speech-following (glottographic) writing forms. The authors consider how accounting as non-glottographic (and so “unspeakable”) writing form renders “glottography” a “subsystem of writing” (Hyman, 2006), while initiating a mode of veridiction which always and only names and counts, silently and synoptically. The authors also consider the translation of this statement form into the graphs, charts, equations, etc., which are central to the making of modern scientific truth claims, and to remaking the boundaries of “languaging” and translatability.

Design/methodology/approach

As a historical–theoretical study, this draws on work reconceptualising writing vs speech (e.g. Harris, 1986; 2000), the statement vs the word (e.g. Foucault, 1972/2002) and the parameters of translation (e.g. Littau, 2016) to re-think the conceptual significance of accounting as constitutive of our “literate modes” of thinking, acting and “languaging in general”.

Findings

Specific reflections are offered on how the accounting statement, as mathematically regularised naming of what “ought” to be counted, is then evaluated against what is counted, thus generating a first discourse of the norm and a first accounting-based apparatus for governing the state. The authors analyse how the non-glottographic statement is constructed and read not as linear flow of signs but as simulacrum; and on how the accounting statement poses both the practical issue of how to translate non-linear flow statements, and the conceptual problem of how to think this statement form’s general translatability, given its irreducibility to the linear narrative statement form.

Originality/value

The paper pioneers in approaching accounting as statement form in a way that analyses the differences that flow from its non-glottographic status.
SLAPPing accountability out of the public sphere
Authors: Murphy Daniel , Moerman Lee
Published: September 2018

Purpose

The purpose of this paper is to investigate the disruption to civic accountability by strategic corporate action in the form of SLAPP suits.

Design/methodology/approach

This paper provides empirical evidence of the discursive processes underpinning participatory and emancipatory accountability regimes through the lens of deliberative democracy and the Habermasian ideal of the public sphere.

Findings

Within this paper, it is argued that the strategic use of SLAPPs by corporations presents a danger to both mechanistic and virtuous forms of accountability regardless of what deliberative democratic theory is adopted. Habermas’ theory of communicative action and notion of the “public sphere” is utilised to demonstrate how SLAPPs can result in the colonisation of public discursive arenas to prevent others providing alternative (in form) and counter (in view) accounts of corporate behaviour and thus act to limit opportunities for corporate accountability.

Social implications

This paper throws light on a practice being utilised by corporations to limit public participation in democratic and participatory accountability processes. Strategic use of SLAPPs limit the “ability” for citizens to provide an alternative “account” of corporate behaviour.

Originality/value

This paper is original in that it analyses the impact on accountability of strategic corporate practice of issuing SLAPP suits to “chill” public political discussion and limit protest about issues of social and civic importance. The paper extends the critical accounting literature into improving dialogic and participatory accountability regimes.
Factors affecting Chinese farmers’ microcredit participation
Authors: Qin Ming , Wachenheim Cheryl Joy , Wang Zhigang , Zheng Shi
Published: September 2018

Purpose

The purpose of this paper is to investigate factors affecting use of microcredit among farmers in Northern China.

Design/methodology/approach

A two-stage Heckman model is used to estimate the effect of farmer and family characteristics and loan and lending environment on likelihood of farmer participation in microcredit and the value of loans taken. Data from 342 first-hand observations in Northern China were used.

Findings

Social capital, production cost, non-labor family members, income, guarantee group membership, village head loan guarantee, and messenger use were found to increase use of microcredit. The same factors were found to affect the value of loans among participating farmers except a guarantor requirement for the loan replaces membership in a guarantee group.

Practical implications

Results support that there is demand for microcredit among farmers and that they are willing to take steps to obtain it including seeking membership in a household guarantee group. Identification of faced constraints facilitates understanding of supply-side efforts with potential to decrease financial exclusion with a focus on external-to-market intervention.

Originality/value

Pivotal findings are the importance of guarantee group membership for loan approval and that this requirement hinders farmers’ ability to obtain credit. Three alternatives are suggested to overcome this constraint including excluding low-risk borrowers from a group guarantee requirement; charging higher interest rates on high risk loans not supported by a guarantee; and development of insurance options to replace the guarantee.
Managerial assignments of credit and blame: a five-country study of leadership desirability
Authors: Lakshman C. , Gok Kubilay , Vo Linh Chi
Published: September 2018

Purpose

Although the international business literature has examined leader traits that are desirable in different cultures, it has not examined critical behaviors or managerial attributions of credit and blame. Credit and blame attributions have important consequences for the desirability of leadership across cultures. Arguing that these types of managerial attributions are likely to have a strong impact on what constitutes desirable leadership; the authors examine them in five countries, namely, USA, France, India, Turkey and Vietnam. The purpose of this paper is to contribute by examining the influence of credit and blame attributions on subordinate satisfaction and leadership perceptions (desirability), unaddressed in the literature.

Design/methodology/approach

The model was tested using questionnaire responses of subordinates in a variety of business organizations, from the five countries indicated, including manufacturing, telecommunication, financial and other services.

Findings

Using the implicit leadership theory, the authors contribute by demonstrating the importance of these attributions for leadership perceptions in five different cultures. The results are supportive of the hypotheses and suggest the important moderating role of subordinate performance for leadership perceptions. The authors discuss findings in the context of the literature, highlight contributions and identify limitations and future directions.

Originality/value

Using the implicit leadership theory, the authors contribute by demonstrating the importance of these attributions for leadership perceptions in five different cultures.
The impact of external and internal corporate governance mechanisms on agency costs
Authors: Schäuble Jonas
Published: September 2018

Purpose

The purpose of this paper is to investigate the impact of external and internal corporate governance mechanisms on agency costs.

Design/methodology/approach

The author uses data from German firms that were listed in the regulated market of the Frankfurt Stock exchange during 2006-2011. Agency costs were measured using stochastic frontier analysis, a relatively new approach to estimate agency costs. The regression analysis is applied to test the model.

Findings

The results indicate that an industry specialized audit firm, the presence of a large audit firm, abnormal audit fees, management ownership and variable management compensation are significantly negatively associated with the level of a firms’ agency costs. In contrast, this seems not to be true for the existence of an audit committee for which the results of the paper document a non-significant association.

Originality/value

The paper contributes to the existing literature in several ways. First, the research design is to the best of the authors’ knowledge the first that investigates the influence of different corporate governance mechanisms on the level of agency costs. Second, previous studies are mainly focused on the US audit market. This focus on the US audit market leaves uncertainties regarding the direction and magnitude of the empirical relationship in the European and German environmental context. Finally, the paper provides initial empirical evidence for a sample of German IFRS listed companies (IFRS – International Financial Reporting Standards).
CPW fed circularly polarized wideband pie-shaped monopole antenna for multi-antenna techniques
Authors: Arun Henridass , M. Gulam Nabi Alsath
Published: September 2018

Purpose

This paper aims to present the design and implementation of a circularly polarized co-planar waveguide (CPW) fed wideband pie-shaped monopole antenna for multi-antenna techniques. Multi-antenna techniques are promising solutions for higher data rate and enhanced reliability of wireless applications. They find numerous applications in 4G/5G networks and in most wireless standards such as wireless local area networks (WLAN), wireless fidelity and worldwide interoperability for microwave access systems to enhance the channel capacity without additional spectrum by means of multi-path propagation techniques.

Design/methodology/approach

The antenna is designed to operate at three WLAN frequency bands of 4.8, 5.2 and 5.8 GHz. The measured 10 dB impedance bandwidth of the proposed antenna element is 1.2 GHz (24.23 per cent). The proposed CPW fed, pie-shaped monopole antenna has a gain of 5.4 dB and an efficiency of 72.8 per cent at 4.8 GHz.

Findings

To use the proposed antenna in a multi-antenna environment, the antennas have to be placed in a close proximity to each other. The close proximity introduces strong mutual coupling between the antennas, which in turn degrades the performance of multi-antenna systems. A multi-antenna system with two antenna elements has been constructed with an edge to edge spacing of 0.24 λ0 (15 mm), and the mutual coupling level is −17 dB. To enhance the isolation between the antenna elements, a shorting pin-based interconnected semicircles enclosed decoupling structure is proposed, which improves the isolation by a factor of 12.67 dB at 4.8 GHz.

Originality/value

To validate the performance of the proposed multi-antenna in working environment, the performance metrics such as envelope correlation coefficient (ECC), diversity gain (DG) and total active reflection coefficient (TARC) are computed for the proposed multiple-input multiple-output (MIMO) antenna. The ECC value is 0.000366 at center frequency and below 0.09 for the entire operating bandwidth, which is well below the acceptable level of 0.5 as per 3GPP standard. The DG value lies above 9.5 dB for the entire operating bandwidths and it is well above the minimum value of 3 dB. The TARC values are calculated based on S parameters, and it proves that the proposed antenna a good candidate for the multi-antenna systems.
Nonlinear interval eigenvalue problems for damped spring-mass system
Authors: Chakraverty Snehashish , Mahato Nisha Rani
Published: September 2018

Purpose

In structural mechanics, systems with damping factor get converted to nonlinear eigenvalue problems (NEPs), namely, quadratic eigenvalue problems. Generally, the parameters of NEPs are considered as crisp values but because of errors in measurement, observation or maintenance-induced errors, the parameters may have uncertain bounds of values, and such uncertain bounds may be considered in terms of closed intervals. As such, this paper aims to deal with solving nonlinear interval eigenvalue problems (NIEPs) with respect to damped spring-mass systems having interval parameters.

Design/methodology/approach

Two methods, namely, linear sufficient regularity perturbation (LSRP) and direct sufficient regularity perturbation (DSRP), have been proposed for solving NIEPs based on sufficient regularity perturbation method for intervals. LSRP may be used for solving NIEPs by linearizing the eigenvalue problems into generalized interval eigenvalue problems, and DSRP may be considered as a direct solution procedure for solving NIEPs.

Findings

LSRP and DSRP methods help in computing the lower and upper eigenvalue and eigenvector bounds for NIEPs which contain the crisp eigenvalues. Further, the DSRP method is computationally efficient compared to LSRP.

Originality/value

The efficiency of the proposed methods has been validated by example problems of NIEPs. Moreover, the procedures may be extended for other nonlinear interval eigenvalue application problems.