bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Disease Experience across the Life Span for Individuals with Osteogenesis Imperfecta: Challenges and Opportunities for Patient-Reported Outcomes (PROs) Measurement
Authors: Tosi Laura L. , Floor Marianne K. , Dollar Christina M. , Gillies Austin P. ,   Members of the Brittle Bone Disease Consortium, Hart Tracy S. , Cuthbertson David , Sutton V. Reid , Krischer Jeffrey P.
Published: September 2018

Background

Patient reported outcome (PRO) information is crucial for establishing better patient-provider communication, improving shared decision making between clinicians and patients, and assessing patient responses to therapeutic interventions and increasing satisfaction with care. We used the Brittle Bones Disease Consortium (BBDC) Contact Registry for People with OI, managed by the Rare Disease Clinical Research Network (RDCRN) to (1) to evaluate the construct validity of the Patient-Reported Outcome Measurement Information System®(PROMIS®) to record important components of the disease experience among individuals with OI; and (2) explore the feasibility of using a registry to recruit individuals with OI to report on health status. Our long-term goal is to enhance communication of health and disease management findings back to the OI community, especially those who do not have access to major OI clinical centers.

Results

We demonstrated the construct validity of PROMIS instruments in OI. Our results confirm that the scores from most domains differ significantly from the general US population: individuals with OI have worse symptom burden and functioning. We found no excessive floor or ceiling effects. Our study demonstrates that the BBDC Contact Registry can be used to recruit participants for online health status surveys. However, there are numerous challenges that must be addressed: lack of self-knowledge of OI type, under-representation of men, limited ethnic diversity, and imperfect questionnaire completion rates.

Conclusion

Our pilot study demonstrated the feasibility of using a contact registry to recruit respondents from the OI community and to obtain analyzable PROMIS data regarding disease experience. Because the results differ from the general population and avoid excessive floor and ceiling effects, PROMIS instruments can be used to assess response to therapeutic interventions in individuals with OI. Future directions will include (1) development and validation of an OI-specific patient-based classification system that aggregates persons with similar clinical characteristics and risks for complications to identify treatment needs; and (2) integrating these PRO tools into routine patient care and research studies.
Spatio-temporal modelling ofLeishmania infantuminfection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil
Authors: Buckingham-Jeffery Elizabeth , Hill Edward M. , Datta Samik , Dilger Erin , Courtenay Orin
Published: September 2018

Background

The parasiteLeishmania infantumcauses zoonotic visceral leishmaniasis (VL), a potentially fatal vector-borne disease of canids and humans. Zoonotic VL poses a significant risk to public health, with regions of Latin America being particularly afflicted by the disease.

Leishmania infantumparasites are transmitted between hosts during blood feeding by infected female phlebotomine sand flies. With a principal reservoir host ofL. infantumbeing domestic dogs, limiting prevalence in this reservoir may result in a reduced risk of infection for the human population. To this end, a primary focus of research efforts has been to understand disease transmission dynamics among dogs. One way this can be achieved is through the use of mathematical models.

Methods

We have developed a stochastic, spatial, individual-based mechanistic model ofL. infantumtransmission in domestic dogs. The model framework was applied to a rural Brazilian village setting with parameter values informed by fieldwork and laboratory data. To ensure household and sand fly populations were realistic, we statistically fit distributions for these entities to existing survey data. To identify the model parameters of highest importance, we performed a stochastic parameter sensitivity analysis of the prevalence of infection among dogs to the model parameters.

Results

We computed parametric distributions for the number of humans and animals per household and a non-parametric temporal profile for sand fly abundance. The stochastic parameter sensitivity analysis determined prevalence ofL. infantuminfection in dogs to be most strongly affected by the sand fly associated parameters and the proportion of immigrant dogs already infected withL. infantumparasites.

Conclusions

Establishing the model parameters with the highest sensitivity of averageL. infantuminfection prevalence in dogs to their variation helps motivate future data collection efforts focusing on these elements. Moreover, the proposed mechanistic modelling framework provides a foundation that can be expanded to explore spatial patterns of zoonotic VL in humans and to assess spatially targeted interventions.
Predictive model in the presence of missing data: the centroid criterion for variable selection
Authors: Gaudart Jean , Adalian Pascal , Leonetti George
Published: September 2018

Introduction

In many studies, covariates are not always fully observed because of missing data process. Usually, subjects with missing data are excluded from the analysis but the number of covariates can be greater than the size of the sample when the number of removed subjects is high. Subjective selection or imputation procedures are used but this leads to biased or powerless models.

The aim of our study was to develop a method based on the selection of the nearest covariate to the centroid of a homogeneous cluster of covariates. We applied this method to a forensic medicine data set to estimate the age of aborted fetuses.

Analysis

Methods

We measured 46 biometric covariates on 50 aborted fetuses. But the covariates were complete for only 18 fetuses.

First, to obtain homogeneous clusters of covariates we used a hierarchical cluster analysis.

Second, for each obtained cluster we selected the nearest covariate to the centroid of the cluster, maximizing the sum of correlations (the centroid criterion).

Third, with the covariate selected this way, the sample size was sufficient to compute a classical linear regression model.

We have shown the almost sure convergence of the centroid criterion and simulations were performed to build its empirical distribution.

We compared our method to a subjective deletion method, two simple imputation methods and to the multiple imputation method.

Results

The hierarchical cluster analysis built 2 clusters of covariates and 6 remaining covariates. After the selection of the nearest covariate to the centroid of each cluster, we computed a stepwise linear regression model. The model was adequate (R2=90.02%) and the cross-validation showed low prediction errors (2.23 10−3).

The empirical distribution of the criterion provided empirical mean (31.91) and median (32.07) close to the theoretical value (32.03).

The comparisons showed that deletion and simple imputation methods provided models of inferior quality than the multiple imputation method and the centroid method.

Conclusion

When the number of continuous covariates is greater than the sample size because of missing process, the usual procedures are biased. Our selection procedure based on the centroid criterion is a valid alternative to compose a set of predictors.
Human Migration and the Spread of the Nematode ParasiteWuchereria bancrofti
Authors: Small Scott T. , Labbé Frédéric , Coulibaly Yaya I. , Nutman Thomas B. , King Christopher L. , Serre David , Zimmerman Peter A.
Published: September 2018

The human disease lymphatic filariasis causes the debilitating effects of elephantiasis and hydrocele. Lymphatic filariasis currently affects the lives of 90 million people in 52 countries. There are three nematodes that cause lymphatic filariasis,Brugia malayi, B. timori, andWuchereria bancrofti, but 90% of all cases of lymphatic filariasis are caused solely byW. bancrofti. Here we use population genomics to identify the geographic origin ofW. bancroftiand reconstruct its spread. Previous genomic sequencing efforts have suffered from difficulties in obtaining Wb DNA. We used selective whole genome amplification to enrichW. bancroftiDNA from infected blood samples and were able to analyze 47 whole genomes ofW. bancroftifrom endemic locations in Haiti, Mali, Kenya, and Papua New Guinea. Our results are consistent with a Southeast Asia or East Asia origin forW. bancroftispread around the globe by infecting migrating populations of humans. Austronesians probably introducedW. ban-croftito Madagascar where later migrations moved it to continental Africa. From Africa,W. bancroftispread to the New World during the transatlantic slave trade. The greater genetic diversity ofW. bancroftipopulations from Haiti are also consistent with genetic admixture from multiple source populations. Genome scans for locally adapted haplotypes identified genes associated with human immune suppression and insecticide sensitivity. Locally adapted haplotypes may provide a foundation to understand the distribution ofW. bancrofticompared to that of other filarial nematodes and how populations may differ in response to eradication efforts.
Recruit symbiosis establishment and Symbiodiniceae composition influenced by adult corals and reef sediment
Authors: Ali A , Kriefall N , Emery LE , Kenkel CD , Matz MV , Davies SW
Published: September 2018

For most reef-building corals, the establishment of symbiosis occurs via horizontal transmission, where juvenile coral recruits acquire their algal symbionts (family Symbiodiniaceae) from their surrounding environment post-settlement. This transmission strategy allows corals to interact with a diverse array of symbionts, potentially facilitating adaptation to the newly settled environment. We exposed aposymbiotic Pseudodiploria strigosa recruits from the Flower Garden Banks to natal reef sediment (C-S+), symbiotic adult coral fragments (C+S-), sediment and coral fragments (C+S+), or seawater controls (C-S-) and quantified rates of symbiont uptake and Symbiodiniaceae community composition within each recruit using metabarcoding of the ITS2 locus. The most rapid uptake was observed in C+S+ treatments and this combination also led to the highest symbiont alpha diversity in recruits. While C-S+ treatments exhibited the next highest uptake rate, only one individual recruit successfully established symbiosis in the C+S-treatment, suggesting that sediment both serves as a direct symbiont source for coral recruits and promotes (or, potentially, mediates) transmission from adult coral colonies. In turn, presence of adult corals facilitated uptake from the sediment, perhaps via chemical signaling. Taken together, our results reinforce the key role of sediment in algal symbiont uptake by P. strigosa recruits and suggest that sediment plays a necessary, but perhaps not sufficient, role in the life cycle of the algal Symbiodinaceae symbionts.
Distinct nanoscale calcium channel and synaptic vesicle topographies contribute to the diversity of synaptic function
Authors: Rebola Nelson , Reva Maria , Kirizs Tekla , Szoboszlay Miklos , Moneron Gael , Nusser Zoltan , DiGregorio David A.
Published: September 2018

The nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+imaging, Ca2+chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modelling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled (∼10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity (∼50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus VGCC-SV arrangements are not canonical across CNS synapses and their diversity could underlie functional heterogeneity.
The geography of malaria elimination in Bangladesh: combining data layers to estimate the spatial spread of parasites
Authors: Chang Hsiao-Han , Wesolowski Amy , Sinha Ipsita , Jacob Christopher G , Mahmud Ayesha , Uddin Didar , Zaman Sazid Ibna , Hossain Md Amir , Faiz M Abul , Ghose Aniruddha , Sayeed Abdullah Abu , Rahman M Ridwanur , Islam Akramul , Karim Mohammad Jahirul , Rezwan M Kamar , Shamsuzzaman Abul Khair Mohammad , Jhora Sanya Tahmina , Aktaruzzaman M M , Miotto Olivo , Engø-Monsen Kenth , Kwiatkowski Dominic , Maude Richard J , Buckee Caroline O
Published: September 2018

Malaria control programs face difficult resource allocation decisions. Of particular concern for countries aiming for malaria elimination, the regular movement of individuals to and from endemic areas undermines local interventions by reintroducing infections and sustaining local transmission. Quantifying this movement of malaria parasites around a country has become a priority for national control programs, but remains methodologically challenging, particularly in areas with highly mobile populations. Here, we combined multiple data sources to measure the geographical spread of malaria parasites, including epidemiological surveillance data, travel surveys, parasite genetic data, and anonymized mobile phone data. We collected parasite genetic barcodes and travel surveys from 2,090 patients residing in 176 unions in southeast Bangladesh. We developed a genetic mixing index to quantify the likelihood of samples being local or imported. We then inferred the direction and intensity of parasite flow between locations using an epidemiological model, and estimated the proportion of imported cases assuming mobility patterns parameterized using the travel survey and mobile phone calling data. Our results show that each data source provided related but different information about the patterns of geographic spread of parasites. We identify a consistent north/south separation of the Chittagong Hill Tracts region in Bangladesh, and found that in addition to imported infections from forested regions, frequent mixing also occurs in low transmission but highly populated areas in the southwest. Thus, unlike risk maps generated from incidence alone, our maps provide evidence that elimination programs must address ongoing movement of parasites around the lower transmission areas in the southwest.
Characteristics of a SAR11 strain grown in batch and continuous culture
Authors: Grant Scott R. , Church Matthew J. , Ferrón Sara , Laws Edward A. , Rappé Michael S.
Published: September 2018

In this study, a strain of SAR11 subgroup IIIa (termed HIMB114) isolated from the tropical Pacific Ocean was grown in seawater-based batch and continuous culture in order to quantify cellular features and metabolism relevant to SAR11 ecology. We report the first direct measurements of cellular elemental quotas for nitrogen (N) and phosphorus (P) for SAR11: 1.4 ± 0.9 fg N and 0.44 ± 0.01 fg P, respectively, that were consistent with the small size of HIMB114 cells (average volume of 0.09 µm3). However, the mean carbon (C) cellular quota of 50 ± 47 fg C was anomalously high, but variable. Rates of phosphate (PO43-) uptake measured from both batch and continuous cultures were exceptionally slow: in chemostats growing at 0.3 d−1, HIMB114 took up 1.1 ± 0.3 amol P cell−1d−1, suggesting that <30% of the cellular P requirement of HIMB114 was met by PO43-assimilation. The mean rate of leucine incorporation, a measure of bacterial production, during late log phase growth of batch HIMB114 cultures was 0.042 ± 0.02 amol Leu cell−1h−1. While only weakly correlated with changes in specific growth rates, the onset of stationary phase resulted in decreases in cell-specific leucine incorporation that were proportional to changes in growth rate. Rates of cellular production, respiratory oxygen consumption, and changes in total organic C concentrations constrained cellular growth efficiencies to 13 ± 4%. Hence, despite the small, streamlined genome and diminutively sized cells, SAR11 strain HIMB114 appears to grow at efficiencies similar to naturally occurring bacterioplankton communities.

Importance

While SAR11 bacteria contribute a significant fraction to the total picoplankton biomass in the ocean and likely are major players in organic C and nutrient cycling, the cellular characteristics and metabolic features of most lineages have either been only hypothesized from genomes or otherwise not measured in controlled laboratory experimentation. The dearth of data on even the most basic characteristics for what is arguably the most abundant heterotroph in seawater has limited the specific consideration of SAR11 in ocean ecosystem modeling efforts. In this study, we provide measures of cellular P, N, C, aerobic respiration and bacterial production for a SAR11 strain growing in natural seawater media that can be used to directly relate these features of SAR11 to biogeochemical cycling in the oceans. Through the development of a chemostat system to measure nutrient uptake during steady-state growth, we have also documented inorganic P uptake rates that allude to the importance of organic phosphorous to meet cellular P demands, even in the presence of non-limiting PO43-concentrations.
Genotyping by low-coverage whole-genome sequencing in intercross pedigrees from outbred founders: a cost efficient approach
Authors: Zan Yanjun , Payen Thibaut , Lillie Mette , Honaker Christa F. , Siegel Paul B. , Carlborg Örjan
Published: September 2018

Background

Experimental intercrosses between outbred founder populations are powerful resources for mapping loci contributing to complex traits (Quantitative Trait Loci or QTL). Here, we present an approach and accompanying software for high-resolution genotype imputation in such populations using whole-genome high coverage sequence data on founder individuals (∼30×) and low coverage sequence data on intercross individuals (∼0.4×). The method is illustrated in a large F2pedigree between lines of chickens that have been divergently selected for 40 generations for the same trait (body weight at 8 weeks of age).

Results

Described is how hundreds of individuals were whole-genome sequenced in a cost- and time-efficient manner using aTn5-based library preparation protocol optimized for this application. In total, 7.6M markers segregated in this pedigree and 10.0 to 13.7% were informative for imputing the founder line genotypes within the F0-F2families. The genotypes imputed from low coverage sequence data were consistent with the founder line genotypes estimated using SNP and microsatellite markers both at individual imputed sites (92%) and across the genome of individual chickens (93%). The resolution of the recombination breakpoints was high with 50% being resolved within <10kb.

Conclusions

A method for genotype imputation from low-coverage whole-genome sequencing in outbred intercrosses is described and evaluated. By applying it to an outbred chicken F2cross it is illustrated that it provides high quality, high-resolution genotypes in a time and cost efficient manner.
Expression of TorsinA in a heterologous yeast system reveals interactions with conserved lumenal domains of LINC and nuclear pore complexes
Authors: Chalfant Madeleine , Barber Karl W. , Borah Sapan , Thaller David , Lusk C. Patrick
Published: September 2018

DYT1 dystonia is caused by an in-frame deletion of a glutamic acid codon in the gene encoding the AAA+ ATPase TorsinA. TorsinA localizes within the lumen of the nuclear envelope/ER and binds to a membrane-spanning co-factor, LAP1 or LULL1, to form an ATPase; the substrate(s) of TorsinA remain ill defined. Here we use budding yeast, which lack Torsins, to interrogate TorsinA function. We show that TorsinA accumulates at nuclear envelope embedded spindle pole bodies (SPBs) in a way that requires its oligomerization and the conserved SUN-domain protein, Mps3. TorsinA is released from SPBs upon expression of LAP1 and stabilized by LAP1 mutants incapable of stimulating TorsinA ATPase activity, suggesting the recapitulation of a TorsinA-substrate cycle. While the expression of TorsinA or TorsinA-ΔE impacts the fitness of strains expressingmps3alleles, a genetic interaction with a conserved component of the nuclear pore complex, Pom152, is specific for TorsinA. This specificity is mirrored by a physical interaction between Pom152 and TorsinA, but not TorsinA-ΔE. These data suggest that TorsinA-nucleoporin interactions would be abrogated by TorsinA-ΔE, providing new experimental avenues to interrogate the molecular basis behind nuclear envelope herniations seen in cells lacking TorsinA function.
Identification of differentially methylated cell-types in Epigenome-Wide Association Studies
Authors: Zheng Shijie C , Breeze Charles E. , Beck Stephan , Teschendorff Andrew E.
Published: September 2018

An outstanding challenge of Epigenome-Wide Association Studies (EWAS) performed in complex tissues is the identification of the specific cell-type(s) responsible for the observed differential DNA methylation. Here, we present a novel statistical algorithm, called CellDMC, which is able to identify not only differentially methylated positions, but also the specific cell-type(s) driving the differential methylation. We provide extensive validation of CellDMC on in-silico mixtures of DNA methylation data generated with different technologies, as well as on real mixtures from epigenome-wide-association and cancer epigenome studies. We demonstrate how CellDMC can achieve over 90% sensitivity and specificity in scenarios where current state-of-the-art methods fail to identify differential methylation. By applying CellDMC to a smoking EWAS performed in buccal swabs, we identify differentially methylated positions occurring in the epithelial compartment, which we validate in smoking-related lung cancer. CellDMC may help towards the identification of causal DNA methylation alterations in disease.
Electroporation of short hairpin RNAs for rapid and efficient gene knockdown in the starlet sea anemone, Nematostella vectensis
Authors: Karabulut Ahmet , He Shuonan , Chen Cheng-Yi , McKinney Sean A. , Gibson Matthew C.
Published: September 2018

A mechanistic understanding of evolutionary developmental biology requires the development of novel techniques for the manipulation of gene function in phylogenetically diverse organismal systems. Recently, gene-specific knockdown by microinjection of short hairpin RNA (shRNA) has been applied in the sea anemone Nematostella vectensis, a cnidarian model organism. Due to the unusual architecture of the cnidarian microRNA processing pathway, the shRNA approach is unusually effective for sequence-specific knockdown of a gene of interest. However, the time- and labor-intensive process of microinjection limits access to this technique and its application in large scale experiments. To address this issue, here we present an electroporation protocol for shRNA delivery into Nematostella eggs. This method leverages the speed and simplicity of electroporation, enabling users to manipulate gene expression in hundreds of Nematostella eggs or embryos within minutes. We provide a detailed description of the experimental procedure, including reagents, electroporation conditions, preparation of Nematostella vectensis eggs, and follow-up care of experimental animals. Finally, we demonstrate the knockdown of several endogenous and exogenous genes with known phenotypes and discuss the potential applications of this method.
Thalamocortical dynamics underlying spontaneous transitions in beta power in Parkinsonism
Authors: Reis Carolina , Sharott Andrew , Magill Peter J. , van Wijk Bernadette , Parr Thomas , Zeidman Peter , Friston Karl , Cagnan Hayriye
Published: September 2018

Parkinson’s disease (PD) is a neurodegenerative condition in which aberrant oscillatory synchronization of neuronal activity at beta frequencies (15-35 Hz) across the cortico-basal ganglia-thalamocortical circuit is associated with debilitating motor symptoms, such as bradykinesia and rigidity. Mounting evidence suggests that the magnitude of beta synchrony in the parkinsonian state fluctuates over time, but the mechanisms by which thalamocortical circuitry regulates the dynamic properties of cortical beta in PD are poorly understood. Using the recently developed generic dynamic causal modelling framework, we recursively optimised a set of plausible models of the thalamocortical circuit (n=144) to infer the neural mechanisms that best explain the transitions between low and high beta power states observed in recordings of field potentials made in the motor cortex of anesthetized Parkinsonian rats. Bayesian model comparison suggests that upregulation of cortical rhythmic activity in the beta-frequency band results from changes in the coupling strength both between and within the thalamus and motor cortex. Specifically, our model indicates that high levels of cortical beta synchrony are mainly achieved by a delayed (extrinsic) input from thalamic relay cells to deep pyramidal cells and a fast (intrinsic) input from middle pyramidal cells to superficial pyramidal cells. We therefore hypothesize that beta synchronisation at the cortical level could selectively be modulated via interventions that are capable of finely regulating cortical excitability in a spatial (delivered to either the superficial or deep cortical laminae) and time specific manner.
How yeast cells find their mates
Authors: Henderson Nicholas T. , Clark-Cotton Manuella R. , Zyla Trevin R. , Lew Daniel J.
Published: September 2018

Accurate detection of extracellular chemical gradients is essential for many cellular behaviors. Gradient sensing is challenging for small cells, which experience little difference in ligand concentrations on the up-gradient and down-gradient sides of the cell. Nevertheless, the tiny cells of the yeastSaccharomyces cerevisiaereliably decode gradients of extracellular pheromones to find their mates. By imaging the behavior of polarity factors and pheromone receptors during mating encounters, we found that gradient decoding involves two steps. First, cells bias orientation of initial polarity up-gradient, even though they have unevenly distributed receptors. To achieve this, they measure the local fraction of occupied receptors, rather than absolute number. However, this process is error-prone, and subsequent exploratory behavior of the polarity factors corrects initial errors via communication between mating partners. The mobile polarity sites convert the difficult problem of spatial gradient decoding into the easier one of sensing temporal changes in local pheromone levels.
Optimization of the flash extraction of flavonoids from the leaves ofSalix babylonicausing the response surface method and an evaluation of the leaves’ high antioxidant activity
Authors: Chen Huijie , Diao Lei , Zhang Yue , Liu Haixin , Zhong Ming , Li Guangxing
Published: September 2018

Many biological activities ofSalix babylonicaleaves are attributed to the plants’ high total flavonoid content. Flash extraction has the advantages of high efficiency and maximum retention of the active ingredient. In this study, flash extraction was used to extract the total flavonoids, and a Box–Behnken design was used to optimize the extraction conditions for the first time. The effects of four independent variables, including ethanol concentration, extraction voltage, time, and ratio of liquid to material on flavonoid yield, was determined, and the optimal conditions for flavonoid extraction were evaluated using response surface methodology. Statistical analyses showed that the linear and quadratic terms of these four variables had significant effects. The fitted second-order model revealed that the optimal conditions consisted of an ethanol concentration of 67.91%, extraction time of 87 s, extraction voltage of 116 V and ratio of liquid to material of 42.79. Under the optimum conditions, the experimental value of 66.40±0.80% nearly coincided with that predicted by the model. In the ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) assays, the extracts showed significant antioxidant and scavenging capacity for free radicals, respectively. This study helps to better exploit the resources ofSalix babylonicaleaves and provides new insights for effective extraction of flavonoids.
Boundaries support specific long-distance interactions between enhancers and promoters inDrosophila Bithoraxcomplex
Authors: Postika Nikolay , Metzler Mario , Affolter Markus , Müller Martin , Schedl Paul , Georgiev Pavel , Kyrchanova Olga
Published: September 2018

Drosophilabithorax complex (BX-C) is one of the best model systems for studying the role of boundaries (insulators) in gene regulation. Expression of three homeotic genes,Ubx, abd-A,andAbd-B, is orchestrated by nine parasegment-specific regulatory domains. These domains are flanked by boundary elements, which function to block crosstalk between adjacent domains, ensuring that they can act autonomously. Paradoxically, seven of the BX-C regulatory domains are separated from their gene target by at least one boundary, and must “jump over” the intervening boundaries. To understand the jumping mechanism, theMcpboundary was replaced withFab-7andFab-8.Mcpis located between theiab-4andiab-5domains, and defines the border between the set of regulatory domains controllingabd-AandAbd-B. WhenMcpis replaced byFab-7orFab-8,they direct theiab-4domain (which regulatesabd-A) to inappropriately activateAbd-Bin abdominal segment A4. For theFab-8replacement, ectopic induction was only observed when it was inserted in the same orientation as the endogenousFab-8boundary. A similar orientation dependence for bypass activity was observed whenFab-7was replaced byFab-8. Thus, boundaries perform two opposite functions in the context of BX-C – they block crosstalk between neighboring regulatory domains, but at the same time actively facilitate long distance communication between the regulatory domains and their respective target genes.

Author Summary

Drosophilabithorax complex (BX-C) is one of a few examples demonstratingin vivorole of boundary/insulator elements in organization of independent chromatin domains. BX-C contains threeHOXgenes, whose parasegment-specific pattern is controlled bycis-regulatory domains flanked by boundary/insulator elements. Since the boundaries ensure autonomy of adjacent domains, the presence of these elements poses a paradox: how do the domains bypass the intervening boundaries and contact their proper regulatory targets? According to the textbook model, BX-C regulatory domains are able to bypass boundaries because they harbor special promoter targeting sequences. However, contrary to this model, we show here that the boundaries themselves play an active role in directing regulatory domains to their appropriateHOXgene promoter.
The effects of age at menarche and first sexual intercourse on reproductive and behavioural outcomes: a Mendelian randomization study
Authors: Lawn Rebecca B , Sallis Hannah M , Wootton Robyn E , Taylor Amy E , Demange Perline , Fraser Abigail , Penton-Voak Ian S , Munafò Marcus R
Published: September 2018

There is substantial variation in the timing of significant reproductive life events such as menarche and first sexual intercourse. Life history theory explains this variation as an adaptive response to the developmental environment. In environments characterized by harsh conditions, adopting a fast life history strategy may increase fitness. In line with this, there is evidence demonstrating that greater childhood adversity is associated with earlier age at menarche. Here we applied Mendelian randomization (MR) methods to investigate whether there is a causal effect of variation in age at menarche and age at first sexual intercourse on outcomes related to reproduction, education and risky behaviour in UK Biobank (N = 114883–181,255). Our results suggest that earlier age at menarche affects some traits that characterize life history strategies including earlier age at first and last birth, decreased educational attainment, and decreased age at leaving education (for example, we found evidence for a 0.26 year decrease in age at first birth per year decrease in age at menarche, 95% confidence interval: −0.34 to −0.17; p < 0.0001). We find no clear evidence of effects of age at menarche on other outcomes, such as risk taking behaviour. Age at first sexual intercourse was also related to many life history outcomes, although there was evidence of horizontal pleiotropy which violates an assumption of MR and results should be treated with caution. Taken together, these results highlight how MR can be applied to test predictions of life history theory and to better understand determinants of health and social behaviour.
Effects of multiple scattering encountered for various small-angle scattering model functions
Authors: Jensen Grethe Vestergaard , Barker John George
Published: September 2018

In small-angle scattering theory and data modeling, it is generally assumed that each scattered ray – photon or neutron – is only scattered once on its path through the sample. This assumption greatly simplifies the interpretation of the data and is valid in many cases. However, it breaks down under conditions of high scattering power, increasing with sample concentration, scattering contrast, sample path length and ray wavelength. For samples with a significant scattering power, disregarding multiple scattering effects can lead to erroneous conclusions on the structure of the investigated sample. In this paper, the impact of multiple scattering effects on different types of scattering pattern are determined, and methods for assessing and addressing them are discussed, including the general implementation of multiple scattering effects in structural model fits. The modification of scattering patterns by multiple scattering is determined for the sphere scattering function and the Gaussian function, as well as for different Sabine-type functions, including the Debye–Andersen–Brumberger (DAB) model and the Lorentzian scattering function. The calculations are performed using the semi-analytical convolution method developed by Schelten & Schmatz [J. Appl. Cryst. (1980). 13, 385–390], facilitated by analytical expressions for intermediate functions, and checked with Monte Carlo simulations. The results show how a difference in the shape of the scattering function plotted versus momentum transfer q results in different multiple scattering effects at low q, where information on the particle mass and radius of gyration is contained.
Structure of crystallized particles in sputter-deposited amorphous germanium films
Authors: Okugawa Masayuki , Nakamura Ryusuke , Hirata Akihiko , Ishimaru Manabu , Yasuda Hidehiro , Numakura Hiroshi
Published: September 2018

Pristine thin films of amorphous Ge prepared by sputtering are unstable and form coarse crystalline particles of 100 nm in size upon crystallization by electron irradiation. These crystalline particles exhibit unusual diffraction patterns that cannot be understood from the diamond cubic structure. The structure has previously been assumed to be a metastable hexagonal form. In the present work, the structure of the coarse crystalline particles has been analysed in detail by transmission electron microscopy, considering the possibility that those diffraction patterns might occur with the diamond cubic structure if the particle consists of thin twin layers. By high-resolution lattice imaging the particles have been shown to be of the diamond cubic structure containing a high density of twins and stacking faults parallel to {111}. With such defects, diffraction patterns can be complex because of the following effects: superposition of two or more diffraction patterns of the same structure but of different orientations, double diffraction through twin crystals, and streaks parallel to the thin crystal which give rise to extra diffraction spots. It is found that diffraction patterns taken from various orientations can be explained in terms of these effects.
xINTERPDF: a graphical user interface for analyzing intermolecular pair distribution functions of organic compounds from X-ray total scattering data
Authors: Shi Chenyang
Published: September 2018

A new software program, xINTERPDF, that analyzes the intermolecular correlations in organic compounds via measured X-ray total scattering data is described.
Effect of temperature and pressure on mechanical, surface and electrochemical properties of Al-1.5Cu-5.5Zn-2.5Mg (Alumix-431)
Authors: Acar Ayşe Nur , Mutlu Rasiha Nefise , Ekşi Abdul Kadir , Ekicibil Ahmet , Yazıcı Birgül
Published: September 2018

Purpose

The purpose of this paper is to examine new alloys created from Alumix 431 powder and investigate their mechanical and electrochemical properties.

Design/methodology/approach

In this study; Alumix-431 alloy samples were prepared using the powder metallurgy (P/M) method applying cold (RT) and warm (50°C and 80°C) compaction methods under pressures of 200 and 250 MPa and were sintered at 600°C in N2(g) atmosphere. Hardness and density of the samples were measured, and corrosion properties were determined by electrochemical impedance spectroscopy charting polarization curves. Surface characterization was determined by contact angle, scanning electron microscopy/mapping, energy dispersive X-ray spectrometry and X-ray diffractometry images.

Findings

Alumix-431 alloys obtained upon compaction at 250 MPa/50 °C had the highest mechanical properties and corrosion resistance and good surface properties. On the surfaces of Alumix-431 alloys, α-Al, MgZn2, Al2,CuMg, Al2,O3, Al2MgO4 phases were recorded.

Originality/value

This study aimed to construct a correlation between mechanical and electrochemical properties of the newly created alloys (prepared under special conditions).
Continuous process improvement implementation framework using multi-objective genetic algorithms and discrete event simulation
Authors: Kang Parminder Singh , Bhatti Rajbir Singh
Published: September 2018

Purpose

Continuous process improvement is a hard problem, especially in high variety/low volume environments due to the complex interrelationships between processes. The purpose of this paper is to address the process improvement issues by simultaneously investigating the job sequencing and buffer size optimization problems.

Design/methodology/approach

This paper proposes a continuous process improvement implementation framework using a modified genetic algorithm (GA) and discrete event simulation to achieve multi-objective optimization. The proposed combinatorial optimization module combines the problem of job sequencing and buffer size optimization under a generic process improvement framework, where lead time and total inventory holding cost are used as two combinatorial optimization objectives. The proposed approach uses the discrete event simulation to mimic the manufacturing environment, the constraints imposed by the real environment and the different levels of variability associated with the resources.

Findings

Compared to existing evolutionary algorithm-based methods, the proposed framework considers the interrelationship between succeeding and preceding processes and the variability induced by both job sequence and buffer size problems on each other. A computational analysis shows significant improvement by applying the proposed framework.

Originality/value

Significant body of work exists in the area of continuous process improvement, discrete event simulation and GAs, a little work has been found where GAs and discrete event simulation are used together to implement continuous process improvement as an iterative approach. Also, a modified GA simultaneously addresses the job sequencing and buffer size optimization problems by considering the interrelationships and the effect of variability due to both on each other.
Stakeholder management: a systematic literature review
Authors: Pedrini Matteo , Ferri Laura Maria
Published: September 2018

Purpose

The stakeholder theory is a prominent management approach that has primarily been adopted in the past few years. Despite the increase in the theory’s use, a limited number of studies have discussed ways to develop, execute and measure the results of using this strategic approach with stakeholders. This study aims to address this gap in the literature by conducting a systematic review of the stakeholder management process.

Design/methodology/approach

Five databases were selected to search articles published from 1985 to 2015. The keywords used were stakeholder management, stakeholder relationship and stakeholder engagement. Starting from 2,457 articles identified using a keyword search, 33 key journal articles were systematically reviewed using both bibliometric and qualitative methods for analysis.

Findings

The results highlight that stakeholder management is increasingly embedded in corporate activities, and that the coming of the internet, social networking and Big Data have put more pressure on companies to develop new tools and techniques to manage stakeholders online. In conclusion, synthesizing the findings and developed framework allows the understanding of different streams of research and identifies future steps for research.

Originality/value

While literature reviews are a widespread practice in business studies, only a few more recent reviews use the systematic review methodology that aggregates knowledge using clearly defined processes and criteria. This is the first review on stakeholder management in which the structure is existing knowledge on strategy development, execution and the measurement of performance.
Voltage distribution in the windings of high temperature inverter-fed motors
Authors: Roger Daniel , Napieralska-Juszczak Ewa
Published: September 2018

Purpose

High-temperature (HT°) motors are made with inorganic coils wound with a ceramic-coated wire. They must be carefully designed because the HT° insulating materials have a lower breakdown voltages than the polymers used for insulating standard machines.

Design/methodology/approach

The voltage distribution between stator coils is computed with high-frequency (HF) equivalent circuits that consider the magnetic couplings and the stray capacitances. Two time scales are used for getting a fast computation of very short voltage spikes. For the first step, a medium time scale analysis is performed considering a simplified equivalent circuit made without any stray capacitance but with the full PWM pattern and the magnetic couplings. For the second step, a more detailed HF equivalent circuit computes voltage spikes during short critical time windows.

Findings

The computation made during the first step provides the critical time windows and the initial values of the state variables to the second one. The rise and fall time of the electronic switches have a minor influence on the maximum voltage stress. Conversely, the connection cable length and the common-mode capacitances have a large influence.

Research limitations/implications

HF equivalent circuits cannot be used with random windings but only to formed coils that have a deterministic position of turns.

Practical implications

The proposed method can be used designing of HT° machine windings fed by PWM inverter and for improving the coils of standard machine used in aircraft’s low-pressure environments.

Originality/value

The influence of grounding system of the DC link is considered for computing the voltage spikes in the motor windings.
Finding a place for genealogy and family history in the digital humanities
Authors: Hoeve Casey Daniel
Published: September 2018

Purpose

Despite its growing popularity, there is a noticeable absence of references to the inclusion of genealogy and family history studies within the field of digital humanities. New forms of inclusiveness, particularly in production-coding and cultural analysis, closely align genealogy and family history with the core tenants practiced among humanities computing and digital humanities. This paper aims to prove that genealogy as family history should be formally recognized within this cohort, as it can serve as a valuable and innovative partner for advocacy and technological advancement of the field.

Design/methodology/approach

By examining the literature, genealogy will be defined according to its use in the digital humanities, as well as its use in family history studies. The core tenants of humanities computing and digital humanities will be identified and compared against the research methodology and technological tools used in genealogy and family history research. The comparison will determine how closely the fields align, and if genealogy defined as family history should be used, and included within the field of digital humanities.

Findings

The progression of genealogy and family history from production to cultural analysis corresponds with the transition of production and coding (influenced by humanities computing) to the inclusion of experimental cultural research adopted by the digital humanities. Genealogy’s use of technological tools, such as databases, text encoding, data-text mining, graphic information systems and DNA mapping, demonstrates the use of coding and production. Cultural analysis through demographic study, crowdsourcing and establishing cultural connections illustrates new methods of scholarship, and connects coding and cultural criticism, serving as a bridge between digital humanities and the humanities at large. As genealogy continues to create new partnerships of a collaborative nature, it can, and will, continue to contribute to new areas of study within the field. As these practices continue to converge with the digital humanities, genealogy should be recognized as a partner and member in the digital humanities cohort.

Originality/value

Despite its growing popularity, there is a noticeable absence of references to the inclusion of genealogy and family history studies within the field of the digital humanities. The term genealogy resonates differently within the digital humanities, primarily articulating the history of the field over the study and research of family lineage. This study seeks to demonstrate how genealogy and family history can fit within the digital humanities, providing a new perspective that has not yet been articulated in the scholarly literature.
3D investigation of natural convection of nanofluids in a curved boundary enclosure applying lattice Boltzmann method
Authors: Hosseini Abadshapoori Mehdi , Saidi Mohammad Hassan
Published: September 2018

Purpose

The purpose of this paper is to investigate the natural convection behavior of nanofluids in an enclosure. The enclosure is a 3D capsule with curved boundaries filled with TiO2-water nanofluid.

Design/methodology/approach

In this paper, a multiple relaxation times lattice Boltzmann method (MRT-LBM) has been used. Two-component LBM has been conducted to consider the interaction forces between nanoparticles and the base fluid.

Findings

Results show that the enhanced Nusselt number (Nu*) increases with the increase in volume fraction of nanoparticles (ϕ) and Ra number and decrease of nanoparticle size (λ). Additionally, the findings indicate that increasing volume fraction beyond a certain value decreases Nu*.

Originality/value

This paper presents a MRT model of lattice Boltzmann in a 3D curved enclosure. A correlation is also presented based on the current results for Nu* depending on Ra number, volume fraction and size of nanoparticles. Furthermore, a comparison for the convergence rate and accuracy of this model and the SIMPLE algorithm is presented.