bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural language processing and recurrent network models for identifying genomic mutation-associated cancer treatment change from patient progress notes
Authors: Guan Meijian , Cho Samuel , Petro Robin , Zhang Wei , Pasche Boris , Topaloglu Umit
Published: January 2019

Objectives

Natural language processing (NLP) and machine learning approaches were used to build classifiers to identify genomic-related treatment changes in the free-text visit progress notes of cancer patients.

Methods

We obtained 5889 deidentified progress reports (2439 words on average) for 755 cancer patients who have undergone a clinical next generation sequencing (NGS) testing in Wake Forest Baptist Comprehensive Cancer Center for our data analyses. An NLP system was implemented to process the free-text data and extract NGS-related information. Three types of recurrent neural network (RNN) namely, gated recurrent unit, long short-term memory (LSTM), and bidirectional LSTM (LSTM_Bi) were applied to classify documents to the treatment-change and no-treatment-change groups. Further, we compared the performances of RNNs to 5 machine learning algorithms including Naive Bayes, K-nearest Neighbor, Support Vector Machine for classification, Random forest, and Logistic Regression.

Results

Our results suggested that, overall, RNNs outperformed traditional machine learning algorithms, and LSTM_Bi showed the best performance among the RNNs in terms of accuracy, precision, recall, and F1 score. In addition, pretrained word embedding can improve the accuracy of LSTM by 3.4% and reduce the training time by more than 60%.

Discussion and Conclusion

NLP and RNN-based text mining solutions have demonstrated advantages in information retrieval and document classification tasks for unstructured clinical progress notes.
10-MV SBRT FFF IRRADIATION TECHNIQUE IS ASSOCIATED TO THE LOWEST PERIPHERAL DOSE: THE OUTCOME OF 142 TREATMENT PLANS FOR THE 10 MOST COMMON TUMOUR LOCATIONS
Authors: Irazola L , Sánchez-Nieto B , García-Hernández M T , Terrón J A , Roselló J , Ortiz-Seidel M , Béjar M J , Linares R , Vélazquez S , Sánchez-Doblado F
Published: December 2018

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D‐CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.
Cryo-EM Structure of OSCA1.2 from Oryza sativa: Mechanical basis of hyperosmolality-gating in Plants
Authors: Maity Koustav , Heumann John , McGrath Aaron P , Kopcho Noah J , Hsu Po-Kai , Lee Chang-Wook , Mapes James H , Garza Denisse , Krishnan Srinivasan , Morgan Garry P , Medrano-Soto Arturo , Hendargo Kevin J , Klose Thomas , Rees Steven D , Saier Milton H. , Piñeros Miguel , Komives Elizabeth A , Schroeder Julian I , Chang Geoffrey , Stowell Michael H B
Published: December 2018

Sensing and responding to environmental water deficiencies is essential for the growth, development and survival of plants. Recently, an osmolality-sensing ion channel called OSCA1 was discovered that functions in sensing hyperosmolarity in Arabidopsis. Here, we report the cryo-EM structure and function of an ion channel from rice (Oryza stativa; OsOSCA1.2), showing how it mediates hyperosmolality sensing and ion permeability. The structure reveals a dimer, the molecular architecture of each subunit consists of eleven transmembrane helices and a cytosolic soluble domain that has homology to RNA recognition proteins. The transmembrane domain is structurally related to the TMEM16 family of calcium dependent ion channels and scramblases. The cytosolic soluble domain possesses a distinct structural feature in the form of extended intracellular helical arms parallel to the plasma membrane and well positioned to sense lateral tension on the inner leaflet of the lipid bilayer caused by changes in turgor pressure. Computational dynamic analysis suggests how this domain couples to the transmembrane domain to open the channel and HDX mass spectrometry experimentally confirmed the conformational dynamics of these coupled domains. The structure provides a framework to understand the structural basis of hyperosmolality sensing in crop plants, extending our knowledge of the anoctamin superfamily important for plants and fungi as well as structural mechanisms that can translate membrane stress to ion transporter regulation.
Neural ensemble dynamics in dorsal motor cortex during speech in people with paralysis
Authors: Stavisky Sergey D. , Willett Francis R. , Murphy Brian A , Rezaii Paymon , Avansino Donald T. , Memberg William D. , Miller Jonathan P. , Kirsch Robert F. , Hochberg Leigh R , Ajiboye A. Bolu , Shenoy Krishna V. , Henderson Jaimie M.
Published: December 2018

Speaking is a sensorimotor behavior whose neural basis is difficult to study at the resolution of single neurons due to the scarcity of human intracortical measurements and the lack of animal models. We recorded from electrode arrays in the ‘hand knob’ area of motor cortex in people with tetraplegia. Neurons in this area, which have not previously been implicated in speech, modulated during speaking and during non-speaking movement of the tongue, lips, and jaw. This challenges whether the conventional model of a ‘motor homunculus’ division by major body regions extends to the single-neuron scale. Spoken words and syllables could be decoded from single trials, demonstrating the potential utility of intracortical recordings for brain-computer interfaces (BCIs) to restore speech. Two neural population dynamics features previously reported for arm movements were also present during speaking: a large initial condition-invariant signal, followed by rotatory dynamics. This suggests that common neural dynamical motifs may underlie movement of arm and speech articulators.
Multi-plane Imaging of Neural Activity From the Mammalian Brain Using a Fast-switching Liquid Crystal Spatial Light Modulator
Authors: Liu Rui , Ball Neil , Brockill James , Kuan Leonard , Millman Daniel , White Cassandra , Leon Arielle , Williams Derric , Nishiwaki Shig , de Vries Saskia , Larkin Josh , Sullivan David , Slaughterbeck Cliff , Farrell Colin , Saggau Peter
Published: December 2018

We report a novel two-photon fluorescence microscope based on a fast-switching liquid crystal spatial light modulator and a pair of galvo-resonant scanners for large-scale recording of neural activity from the mammalian brain. The utilized imaging technique is capable of monitoring large populations of neurons spread across different layers of the neocortex in awake and behaving mice. During each imaging session, all visual stimulus driven somatic activity could be recorded in the same behavior state. We observed heterogeneous response to different types of visual stimuli from ~ 3,300 excitatory neurons reaching from layer II/III to V of the striate cortex.
Human RAD51 paralogue, SWSAP1, fosters RAD51 filament by regulating the anti-recombinase, FIGNL1 AAA+ ATPase
Authors: Matsuzaki Kenichiro , Kondo Shizuka , Ishikawa Tatsuya , Shinohara Akira
Published: December 2018

RAD51 assembly on single-stranded (ss)DNAs is a crucial step in the homology-dependent repair of DNA damage for genomic stability. The formation of the RAD51 filament is tightly regulated by various RAD51-interacting proteins. The familial breast cancer gene, BRCA2, as well as RAD52 and six RAD51 paralogues (SWSAP1, RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) promote RAD51 assembly on ssDNAs in humans. However, the mechanisms underlying the differential control of RAD51 filament dynamics by these factors remain largely unknown. Here, we report a role for the human RAD51 paralogue, SWSAP1, as a novel regulator of RAD51 assembly. Swsap1-deficient cells show defects in DNA damage-induced RAD51 assembly during both mitosis and meiosis. Defective RAD51 assembly in SWSAP1-depleted cells is suppressed by the depletion of FIGNL1, an AAA+ ATPase, which binds to RAD51 as well as SWSAP1. Purified FIGNL1 promotes the dissociation of RAD51 from ssDNAs. The in vitro dismantling activity of FIGNL1 does not require its ATPase but depends on RAD51-binding, suggesting a novel mechanism of RAD51 filament remodelling. Purified SWSAP1 inhibits the RAD51-dismantling activity of FIGNL1. Taken together, our data suggest that SWSAP1 protects RAD51 filaments by antagonizing the anti-recombinase, FIGNL1.
Cation binding to SERCA
Authors: Sun Bin , Stewart Bradley D , Kucharski Amir N , Kekenes-Huskey Peter M
Published: December 2018

Sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) is a transmembrane pump that plays an important role in transporting calcium into the sarcoplasmic reticulum (SR). While Ca2+ binds SERCA with micromolar affinity, Mg2+ and K+ compete with Ca2+ binding, yet the molecular bases for these competing ions' influence on SERCA function has not been established. We therefore used three in silico methods to resolve molecular determinants of cation binding in the canonical site I and II Ca2+ binding sites: 1) triplicate molecular dynamic (MD) simulations of Mg2+, Ca2+ and K+-bound SERCA. 2) mean spherical approximation (MSA) theory to determine the affinity and selectivity of cation binding to the MD-resolved structures and 3) state models of SERCA turnover informed from MSA-derived affinity data. Our key findings are that a) coordination at sites I and II are optimized for Ca2+ and to a lesser extent for Mg2+ and K+, as determined by MD-derived cation-amino acid oxygen and bound water configurations, b) the impaired coordination and high desolvation cost for Mg2+ precludes favorable Mg2+ binding relative to Ca2+, while K+ has limited capacity to bind site I, c) Mg2+ most likely acts as inhibitor and K+ as intermediate in SERCA's reaction cycle, based on a state model of SERCA turnover. These findings provide a quantitative basis for SERCA function that leverages molecular-scale thermodynamic data and rationalize enzyme activity across broad range of K+, Ca2+ and Mg2+ concentrations.
Glia-neuron interactions underlie state transitions to generalized seizures
Authors: Verdugo Carmen Diaz , Myren-Svelstad Sverre , Deneubourg Celine , Pelgrims Robbrecht , Muto Akira , Kawakami Koichi , Jurisch-Yaksi Nathalie , Yaksi Emre
Published: January 2019

Brain activity and connectivity alter drastically during epileptic seizures. Throughout this transition, brain networks shift from a balanced resting state to a hyperactive and hypersynchronous state, spreading across the brain. It is, however, less clear which mechanisms underlie these state transitions. By studying neuronal and glial activity across the zebrafish brain, we observed striking differences between these networks. During the preictal period, neurons displayed a small increase in synchronous activity only locally, while the entire glial network was highly active and strongly synchronized across large distances. We observed that the transition from a preictal state to a generalized seizure leads to an abrupt increase in neuronal activity and connectivity, which is accompanied by a strong functional coupling between glial and neuronal networks. Optogenetic activation of glia induced strong and transient burst of neuronal activity, emphasizing a potential role for glia-neuron connections in the generation of epileptic seizures.
Enjoy The Violence: Is appreciation for extreme music the result of cognitive control over the threat response system?
Authors: Ollivier Rosalie , Goupil Louise , Liuni Marco , Aucouturier Jean-Julien
Published: January 2019

Traditional neurobiological theories of musical emotions explain well why extreme music such as punk, hardcore or metal, whose vocal and instrumental characteristics share much similarity with acoustic threat signals, should evoke unpleasant feelings for a large proportion of listeners. Why it doesn’t for metal music fans, however, remains a theoretical challenge: metal fans may differ from non-fans in how they process acoustic threat signals at the sub-cortical level, showing deactivated or reconditioned responses that differ from controls. Alternatively, it is also possible that appreciation for metal depends on the inhibition by cortical circuits of a normal low-order response to auditory threat. In a series of three experiments, we show here that, at a sensory level, metal fans actually react equally negatively, equally fast and even more accurately to cues of auditory threat in vocal and instrumental contexts than non-fans. Conversely, cognitive load somewhat appears to reduce fans’ appreciation of metal to the level reported by non-fans. Taken together, these results are not compatible with the idea that extreme music lovers do so because of a different low-level response to threat, but rather, highlight a critical contribution of higher-order cognition to the aesthetic experience. These results are discussed in the light of recent higher-order theories of emotional consciousness, which we argue should be generalized to the emotional experience of music across musical genres.
Kinetics of Xist-induced gene silencing can be predicted from combinations of epigenetic and genomic features
Authors: Andrade e Sousa Lisa Barros de , Jonkers Iris , Syx Laurène , Chaumeil Julie , Picard Christel , Foret Benjamin , Chen Chong-Jian , Lis John T. , Heard Edith , Schulz Edda G. , Marsico Annalisa
Published: January 2019

To initiate X-chromosome inactivation (XCI), the long non-coding RNA Xist mediates chromosome-wide gene silencing of one X chromosome in female mammals to equalize gene dosage between the sexes. The efficiency of gene silencing, however is highly variable across genes, with some genes even escaping XCI in somatic cells. A genes susceptibility to Xist-mediated silencing appears to be determined by a complex interplay of epigenetic and genomic features; however, the underlying rules remain poorly understood. We have quantified chromosome-wide gene silencing kinetics at the level of the nascent transcriptome using allele-specific Precision nuclear Run-On sequencing (PRO-seq). We have developed a Random Forest machine learning model that can predict the measured silencing dynamics based on a large set of epigenetic and genomic features and tested its predictive power experimentally. While the genomic distance to the Xist locus is the prime determinant of the speed of gene silencing, we find that also pre-marking of gene promoters with polycomb complexes is associated with fast silencing. Moreover, a series of features associated with active transcription and the O-GlcNAc transferase Ogt are enriched at rapidly silenced genes. Our machine learning approach can thus uncover the complex combinatorial rules underlying gene silencing during X inactivation.
Evidence of a Functionally Segregated Pathway from Lateral Superior Olive to Inferior Colliculus
Authors: Greene Nathaniel T. , Davis Kevin A.
Published: January 2019

Neurons in the central nucleus of the inferior colliculus (ICC) of decerebrate cats show three major response patterns when tones of different frequencies and levels are presented to the contralateral ear. The frequency response maps of type I units uniquely exhibit a narrowly tuned I-shaped area of excitation around best frequency (the most sensitive frequency) and flanking regions of inhibition at lower and higher frequencies. Type I units receive ipsilateral inhibition, and show binaural excitatory/inhibitory interactions. Lateral superior olive (LSO) principal cells display a similar receptive field organization and sensitivity to interaural level differences (ILDs) and project directly to the ICC, therefore are supposed to be the dominant source of excitatory input for type I units. To test this hypothesis, the responses of ICC units were compared before and after reversible inactivation of the LSO by injection of the non-specific excitatory amino-acid antagonist kynurenic acid. When excitatory activity within the LSO was blocked, many ICC type I units (~50%) were silenced or showed substantially decreased activitycomparable. By contrast, the responses of the other two ICC unit types were largely unaffected. With regard to the origins of unaffected ICC type I units, evidence indicates that the LSO was inactivated in an incomplete, anisotropic manner, and the monaural and binaural responses of such units are similar to those of affected type I units. Taken together, these results support the interpretation that most type I units are the midbrain components of a functionally segregated ILD processing pathway initiated by the LSO.
Embryonic signals perpetuate polar-like trophoblast stem cells and pattern the blastocyst axis
Authors: Frias-Aldeguer Javier , Kip Maarten , Vivié Judith , Li Linfeng , Alemany Anna , Korving Jeroen , Darmis Frank , van Oudenaarden Alexander , Geijsen Niels , Rivron Nicolas C.
Published: January 2019

The early mammalian conceptus (blastocyst) comprises an outer trophoblast globe that forms an axis originating from the inner embryonic cells. From the mouse conceptus, Trophoblast stem cells (TSCs) are derived, which are in vitro analogues of early trophoblasts. Here, we show that TSCs contain plastic subpopulations reflecting developmental states ranging from pre- to post-implantation trophoblasts. However, upon exposure to a specific combination of embryonic inductive signals, TSCs globally acquire properties of pre-implantation polar trophoblasts (gene expression, self-renewal) juxtaposing the inner embryonic cells, and an enhanced, homogeneous epithelial phenotype. These lines of polar-like TSCs (pTSCs) represent a transcriptionally earlier state that more efficiently forms blastoids, whose inner embryonic cells then induce the patterning of gene expression along the embryonic-abembryonic axis. Altogether, delineating the requirements and properties of polar trophoblasts and blastocyst axis formation in vitro provides a foundation for the precise description and dissection of early development.
Differential expression of BMP antagonists,gremlinandnogginin hydra: antagonism between Wnt and BMP pathways
Authors: Surekha Krishnapati Lakshmi , Khade Samiksha , Trimbake Diptee , Patwardhan Rohan , Nadimpalli Siva Kumar , Ghaskadbi Surendra
Published: January 2019

Mechanisms regulating BMP and Wnt signaling pathways have been widely studied in many organisms. One of the mechanisms by which these pathways are regulated is by binding of extracellular ligands. In the present study, we report studies with two BMP antagonists,gremlinandnogginfromHydra vulgarisInd-Pune and demonstrate antagonistic relationship between BMP and Wnt pathways.Gremlinwas ubiquitously expressed from the body column to head region except in the basal disc and hypostome. During budding,gremlinwas expressed predominantly in the budding region suggesting a possible role in budding; this was confirmed in polyps with different stages of buds.Noggin, on the other hand, was predominantly expressed in the endoderm of hypostome, base of the tentacles, lower body column and at the basal disc in whole polyps. During budding,nogginwas expressed at the sites of emergence of tentacles suggesting a role in tentacle formation. This was confirmed in alsterpaullone-treated polyps, which showednogginexpression as distinct spots where ectopic organizers and ectopic tentacles eventually formed. Using RT-PCR, we found that up-regulation ofWntis accompanied with down-regulation ofBMP5-8bdemonstrating antagonism between the two pathways. Down-regulation ofnogginandgremlin, however, occurred only after 24 h recovery. The data suggest that inhibition of BMP pathway by Wnt signaling in hydra does not directly involvenogginandgremlin. Our findings indicate that the BMP/Noggin antagonism evolved early for setting up and/or maintaining the head organizer while involvement of these BMP antagonists during vertebrate axial patterning are recent evolutionary acquisitions.

Summary statement

We show that setting up of the Organizer by BMP/Noggin antagonism and role of BMP inhibitors in tissue patterning are evolutionarily ancient, probably arising for the first time in hydra
Optimization of the experimental parameters of the ligase cycling reaction
Authors: Schlichting Niels , Reinhardt Felix , Jager Sven , Schmidt Michael , Kabisch Johannes
Published: January 2019

The ligase cycling reaction (LCR) is a scarless and efficient method to assemble plasmids from fragments of DNA. This assembly method is based on the hybridization of DNA fragments with complementary oligonucleotides, so-called bridging oligos (BOs), and an experimental procedure of thermal denaturation, annealing and ligation. In this study, we explore the effect of molecular crosstalk of BOs and various experimental parameters on the LCR by utilizing a fluorescence-based screening system. The results indicate an impact of the melting temperatures of BOs on the overall success of the LCR assembly. Secondary structure inhibitors, such as DMSO and betaine, are shown to negatively impact the number of correctly assembled plasmids. Adjustments of the annealing, ligation and BO-melting temperature further improved the LCR. The optimized LCR was confirmed by validation experiments. Based on these findings, a step-by-step protocol is offered within this study to ensure a routine for high efficient LCR assemblies.
Doubled haploid based parental lines are most suitable in predicting heterosis using microsatellites and in development of highly heterotic F1hybrids inBrassica oleracea
Authors: Singh Saurabh , Dey S.S. , Bhatia Reeta , Kumar Raj , Sharma Kanika , Behera T.K.
Published: January 2019

InBrassica oleracea, heterosis is one of the most efficient tools giving impetus to hybrid vegetable industry. In this context, we presented the first report on identifying superior heterotic crosses for yield and commercial traits in cauliflower involving cytoplasmic male sterile (CMS) and doubled haploid (DH) lines as parents. We studied the suitability of SSR and EST-SSRs based genetic distance (GD) and morphological markers based phenotypic distance (PD) in prediction of heterosis when DH based genotypes are used as parents in developing F1hybrids. Overall 120 F1hybrids derived from twentyOguracybrid CMS lines and six DH based testers were evaluated for 16 phenotypic traits along with their 26 parental lines and 4 commercial standard checks, in 10 × 15 alpha lattice design. The genomic SSR and EST-SSRs based genetic structure analysis grouped 26 parental lines into 4 distinct clusters. The CMS lines Ogu118-6A, Ogu33A, Ogu34-1A were good general combiner for developing short duration hybrids. The SCA effects were significantly associated with heterosis suggesting non-additive gene effects for heterotic response of hybrids. Less than unity value of σ2A/D coupled with σ2gca/σ2scaindicated the predominance of non-additive gene action in the expression of studied traits. The genetic distance estimates among 26 parents ranged from 0.44 to 0.98 and were significantly associated with heterosis for important commercial traits, suggesting the utility of microsatellite based genetic distance in prediction of heterosis inB. oleracea.
Computational modeling of anthocyanin pathway evolution
Authors: Wheeler Lucas C. , Smith Stacey D.
Published: January 2019

Alteration of metabolic pathways is a key component of the evolution of new phenotypes. Flower color is a striking example of the importance of metabolic evolution in a complex phenotype, wherein shifts in the activity of the underlying pathway lead to a wide range of pigments. Although experimental work has identified common classes of mutations responsible for transitions among colors, we lack a unifying model that relates pathway function and activity to the evolution of distinct pigment phenotypes. One challenge in creating such a model is the branching structure of pigment pathways, which may lead to evolutionary trade-offs due to competition for shared substrates. In order to predict the effects of shifts in enzyme function and activity on pigment production, we created a simple kinetic model of a major plant pigmentaion pathway: the anthocyanin pathway. This model describes the production of the three classes of blue, purple and red anthocyanin pigments, and accordingly, includes multiple branches and substrate competition. We first studied the general behavior of this model using a realistic, functional set of parameters. We then stochastically evolved the pathway toward a defined optimum and and analyzed the patterns of fixed mutations. This approach allowed us to quantify the probability density of trajectories through pathway state space and identify the types and number of changes. Finally, we examine whether the observed trajectories and constraints help to explain experimental observations, i.e., the predominance of mutations which change color by altering the function of branching genes in the pathway. These analyses provide a theoretical framework which can be used to predict the consequences of new mutations in terms of both pigment phenotypes and pleiotropic effects.
Dissection and validation of minor quantitative trait loci (QTLs) conferring grain size and weight in rice
Authors: Sun Ping , Zheng Yuanyuan , Li Pingbo , Ye Hong , Zhou Hao , Gao Guanjun , He Yuqing
Published: January 2019

Grain size and weight contribute greatly to the grain yield of rice. In order to identify minor QTLs conferring grain size and weight, an F2population derived from a cross between twoindicarice lines showing small difference on grain size, Guangzhan 63-4S (GZ63-4S) and Dodda, and its derived F2:3population were developed and used for QTL analysis. Totally, 36 QTLs for grain size and weight were detected, and 7 were repeatedly detected, of which the number of beneficial alleles was contributed roughly equally by the two parents. In order to further validate effects of QTLs detected, a BC1F2population derived from a backcross of a mixture of F2lines with GZ63-4S was developed and subjected to QTL selection. Heterozygous regions of 3 QTLs,qGS3,qTGW6.2andqGT7were identified, and corresponding near-isogenic lines (NILs) of each QTL were constructed with three rounds of self-crosses. In the background of NILs,qGS3was responsible for GL, LWR, GT and TGW,qTGW6.2was for GL and TGW, andqGT7was for GT and TGW. These results have laid the foundation of further fine mapping and cloning of underlying genes, and could be of great use in breeding and improvement of rice lines with desirable size and yield.
Differential expression feature extraction (DEFE) and its application in RNA-seq data analysis
Authors: Pan Youlian , Li Yifeng , Liu Ziying , Surendra Anuradha , Wang Lipu , Foroud Nora A. , Goyal Ravinder K. , Ouellet Thérèse , Fobert Pierre R.
Published: January 2019

In differential gene expression data analysis, one objective is to identify groups of co-expressed genes from a large dataset to detect the association between such a group of genes and a phenotypic trait. This is often done through a clustering approach, such as k-means or bipartition hierarchical clustering, based on particular similarity measures in the grouping process. In such a dataset, the gene differential expression itself is an innate attribute that can be used in the feature extraction process. For example, in a dataset consisting of multiple treatments versus their controls, the expression of a gene in each treatment would have three possible behaviors, up-, down- regulated, or unchanged. We propose here a differential expression feature extraction (DEFE) method by using a string consisting of three numerical values at each character to denote such behavior, i.e. 1=up, 2=down, and 0=unchanged, which results in up to 3B differential expression patterns across all B comparisons. This approach has been successfully applied in many datasets, of which we present in this study two sets of RNA-sequencing (RNA-seq) data on wheat challenged with stress related phytohormones or Fusarium graminearum, the causal agent of fusarium head blight (FHB), a devastating wheat disease to illustrate the algorithm. Combinations of multiple schemes of DEFE patterns revealed groups of genes putatively associated with resistance or susceptibility to FHB. DEFE enabled discovery of genes closely associated with defense related signaling molecules such as JAZ10, shikimate and chorismate biosynthesis pathway and groups of wheat genes with differential effects between more or less virulent strains of Fusarium graminearum.
A general decrease of normalized ncDNA in evolution
Authors: Lobo-Cabrera Francisco Javier
Published: January 2019

Complexity is often associated with increasing non-coding DNA (ncDNA). For example, the human genome is in its vast majority ncDNA. Here, it is hypothesized that normalized ncDNA (nncDNA) has in fact diminished in evolution. This definition of ncDNA content takes into consideration total proteomic content. It is shown that by reducing their normalized ncDNA, organisms may have obtained more complexity in evolution. Also, a potential connection between ncDNA, proteome information and chromatin interactions in mice and humans is presented.
Reachable domain of spacecraft with a single normal impulse
Authors: Zhang Junhua , Yuan Jianping , Wang Wei , Wang Jiao
Published: January 2019

Purpose

The purpose of this paper is to obtain the reachable domain (RD) for spacecraft with a single normal impulse while considering both time and impulse constraints.

Design/methodology/approach

The problem of RD is addressed in an analytical approach by analyzing for either the initial maneuver point or the impulse magnitude being arbitrary. The trajectories are considered lying in the intersection of a plane and an ellipsoid of revolution, whose family can be determined analytically. Moreover, the impulse and time constraints are considered while formulating the problem. The upper bound of impulse magnitude, “high consumption areas” and the change of semi-major axis and eccentricity are discussed.

Findings

The equations of RD with a single normal impulse are analytically obtained. The equations of three scenarios are obtained. If normal impulse is too large, the RD cannot be obtained. The change of the semi-major axis and eccentricity with large normal impulse is more obvious. For long-term missions, the change of semi-major axis and eccentricity leaded by multiple normal impulses should be considered.

Practical implications

The RD gives the pre-defined region (all positions accessible) for a spacecraft under a given initial orbit and a normal impulse with certain magnitude.

Originality/value

The RD for spacecraft with normal impulse can be used for non-coplanar orbital transfers, emergency evacuation after failure of rendezvous and docking and collision avoidance.
Effect of non-uniform asymmetric heating on the thermal and entropy generation characteristics for flow of Al2O3-water nanofluid in a micro-channel
Authors: Boruah Manash Protim , Randive Pitambar R. , Pati Sukumar
Published: January 2019

Purpose

The purpose of this study is to numerically analyze the thermal and entropy generation characteristics on two-dimensional, incompressible, laminar single-phase flow of Al2O3-water nanofluid in a micro-channel subjected to asymmetric sinusoidal wall heating with varying amplitude, length of fluctuation period and phase difference of applied heat flux for Reynolds number in the range of 25-1000.

Design/methodology/approach

The numerical computation is based on the Finite Element Method and the Lagrange finite element technique is used for approximating the flow variables within the computational domain.

Findings

The average Nusselt number increases with increasing Reynolds number (Re) for all the volume fractions of nanofluid. However, the total entropy generation decreases up to a critical value of Re and increases thereafter. Increase in volume fraction shifts the critical Re towards the lower Re regime. The average Nusselt number and total entropy generation increase with amplitude and length of fluctuation period of heat flux. The optimal choice of volume fraction for lesser entropy generation and higher heat transfer is found to be 3 per cent independent of the value of amplitude, length of fluctuation period and phase difference of the heat flux.

Originality/value

To the best of authors’ knowledge, the interplay of various parameters concerning non-uniform heating in achieving the maximum heat transfer with minimum irreversibility has not been investigated. Focusing on this agenda, the results of this study would benefit the industrial sector in achieving the maximum heat transfer at the cost of minimum irreversibilities with an optimal choice of inlet Reynolds number, volume fraction of nanofluid, amplitude, length of the period of fluctuation of heat flux and phase difference of applied heat flux.
The socioeconomic effects of small-scale women businesses in broom production and marketing industry
Authors: Nwosu Ijeoma Ikejiofor , Onoyima Rita Oluchi , Madu Ignatius Ani , Nwokocha Victor Chukwunweike
Published: January 2019

Purpose

Broom production and marketing is a local business industry operated by women in Nigeria. This activity serves not only as a source of livelihood to women but also has created job opportunities for the teeming unemployed persons in the rural areas. This paper aims to examine socioeconomic effects of small-scale women businesses in broom production and marketing industry in Nigeria with a view to analyze small-scale women businesses in Igbo Eze North District of Nigeria.

Design/methodology/approach

New economic theory was used to guide the study. The study adopted a quantitative research design comprising of semi-structured interviews, field observations, reference to relevant literature and a questionnaire survey of 340 female households engaged in broom production and marketing from fifteen villages. This sample size was selected using purposive sampling technique and Yamane formula. Frequencies and Spearman rank correlation were used to analyze the data.

Findings

The study found that broom production and marketing have an effect on the socioeconomic development of the people. The study found a positive relationship between broom production and marketing and income generated, education and occupation in the study area. This study concluded by suggesting that broom production in the study area should be mechanized to improve the quality and quantity of broom produced in the area.

Practical implications

This study has shown that Nigerian women have good potentials for entrepreneurship. Both the society and the government authorities should work together in supporting female ventures in Nigeria.

Originality/value

The paper empirically has shown the socioeconomic effects of small-scale women businesses in broom production and marketing on local household of Igbo Eze North District of Nigeria. This study stands as the first in Nigeria to consider the effects of broom production and marketing and how women in this part of Nigeria have used it to create job opportunities and opportunities of income for themselves and their families.
Corporate governance, European bank performance and the financial crisis
Authors: Ayadi Mohamed A. , Ayadi Nesrine , Trabelsi Samir
Published: January 2019

Purpose

This paper aims to analyze the effects of internal and external governance mechanisms on the performance and risk taking of banks from the Euro zone before and after the 2008 financial crisis.

Design/methodology/approach

To avoid macroeconomic problems and shocks and because of data availability, the authors select some countries of the Euro zone, namely, France, Belgium, Germany and Finland, during the 2004-2009 period. These countries share similar macroeconomic environments (unemployment, inflation and economic growth rates). All the data relating to the banks are manually drawn from the supervising reports submitted to banks and are available on the banks’ websites and/or on that of the AMF website. The banks included in our sample are drawn from the list of European central banks onwww.ecb.int

Findings

The empirical results show that banks undertake tradeoffs between different governance mechanisms to alleviate the intensity of the agency conflicts between the shareholders and managers. The findings also confirm that internal mechanisms and capital regulations are complementary and significantly impact bank performance.

Research limitations/implications

This analysis can be extended through studying the interaction between bondholders’ governance and shareholders’ governance and their impact on the 2008 financial crisis.

Practical implications

The changes in banking governance help banks find a useful and necessary way to avoid ill-considered risks that can cause a systemic risk. Therefore, some conditions should be met so that banking governance can contribute to the economic development.

Social implications

Culture and mentality of good banking governance must grow as much as possible through awareness-raising, training, promotion, recognition of performance, enhancing procedure transparency and stability of good banking governance and regulations, strengthening the national capacity to fight against corruption, and preventive mechanisms.

Originality/value

This paper complements previous studies, mainly those of Andres and Vallelado (2008) who examine the impact of the components of the board on banking performance and of Laeven and Levine (2009) who estimate the combined effect of regulatory and ownership structure on the risk-taking of each bank.
Optimisation of pre‐operative anaemia in patients before elective major surgery – why, who, when and how?
Authors: Munting K. E. , Klein A. A.
Published: January 2019

Anaemia in surgical patients is a common and serious problem; around 40% of patients presenting for major surgery are anaemic. Patients with pre‐operative anaemia have significantly higher rates of morbidity and mortality and are likely to be transfused red cells. In addition, red cell transfusions are independently associated with worse outcomes. Pre‐optimisation of anaemia in surgical patients leads to higher pre‐operative haemoglobin concentrations and less need for transfusion. Patients undergoing major surgery (defined as blood loss > 500 ml expected or possible) should be optimised if their haemoglobin concentration is less than 130 g.l−1 on screening. Detection of anaemia should follow listing for surgery as soon as possible to allow enough time for optimisation. The most common cause of pre‐operative anaemia is iron deficiency, which can be treated with iron therapy. Iron clinics should be set up in either primary or secondary care to allow for optimal treatment. In this review, we present literature supporting the optimisation of pre‐operative anaemia and propose a treatment algorithm.
Improving inverse docking target identification with Z‐score selection
Authors: Kim Stephanie S. , Aprahamian Melanie L. , Lindert Steffen
Published: January 2019

The utilization of inverse docking methods for target identification has been driven by an increasing demand for efficient tools for detecting potential drug side‐effects. Despite impressive achievements in the field of inverse docking, identifying true positives from a pool of potential targets still remains challenging. Notably, most of the developed techniques have low accuracies, limit the pool of possible targets that can be investigated or are not easy to use for non‐experts due to a lack of available scripts or webserver. Guided by our finding that the absolute docking score was a poor indication of a ligand's protein target, we developed a novel “combined Z‐score” method that used a weighted fraction of ligand and receptor‐based Z‐scores to identify the most likely binding target of a ligand. With our combined Z‐score method, an additional 14%, 3.6%, and 6.3% of all ligand–protein pairs of the Astex, DUD, and DUD‐E databases, respectively, were correctly predicted compared to a docking score‐based selection. The combined Z‐score had the highest area under the curve in a ROC curve analysis of all three datasets and the enrichment factor for the top 1% predictions using the combined Z‐score analysis was the highest for the Astex and DUD‐E datasets. Additionally, we developed a user‐friendly python script (compatible with both Python2 and Python3) that enables users to employ the combined Z‐score analysis for target identification using a user‐defined list of ligands and targets. We are providing this python script and a user tutorial as part of the supplemental information.
Variable effects of an invasive species on the reproduction and distribution of native species in pond networks
Authors: Bélouard Nadège , Petit Eric J. , Paillisson Jean‐Marc
Published: January 2019

The arrival of non‐native species in a community can be deleterious for native species. The joint investigation of several descriptors of native populations susceptible to invaders, under different invasion contexts, may help in predicting the outcome of their co‐occurrence with invasive species. Moreover, empirical studies seldom document the relative importance of the effects of invasive species on native species compared with other factors.

Using survey data, we evaluated whether reproduction (larval density) and distribution of breeding sites of three amphibian species (Rana dalmatina, Lissotriton helveticus, and Triturus marmoratus) were related to the presence of invasive red swamp crayfish Procambarus clarkii, compared to other native predators, habitat, and landscape features, in two pond networks that differed in invasion intensity.

The red swamp crayfish was only negatively associated with the larval density of one amphibian species studied. Its effect size was similar to that of some native predators, and much smaller than that of the canopy cover of ponds. Amphibians were widespread in the two pond networks. The occupancy of only one species in each network was negatively related to crayfish presence, while the occupancy of all species was negatively related to fish presence. The distribution of amphibian breeding sites was positively associated with aquatic vegetation cover.

Negative associations between amphibians and red swamp crayfish were detected only in a few cases, even in the most invaded area, and thus results were less alarming than in previous studies. Differences in ecological traits of native amphibians and interactions with other environmental factors may explain the variable effects of red swamp crayfish on native amphibian populations.
The 1st WFH Gene Therapy Round Table: Understanding the landscape and challenges of gene therapy for haemophilia around the world
Authors: Pierce Glenn F. , Coffin Donna ,   Members of the WFH Gene Therapy Round Table Program Committee and Organizing Committee
Published: January 2019

In this first in a series of round table meetings, the 1st World Federation of Hemophilia Gene Therapy Round Table was convened to initiate a global dialogue on the expected challenges and opportunities that a disruptive therapy, such as gene therapy, will bring to the haemophilia community. Perspectives from key stakeholder groups, including healthcare professionals, regulators, payors, people with hemophilia and pharmaceutical industry representatives, were sought in the identification of the key issues we expect to face. Didactic presentations and open discussion covered the clinical development of gene therapy in haemophilia; regulatory perspectives of gene therapy; making informed decisions; accessibility, affordability and pricing of gene therapy; and ethical issues of gene therapy clinical trials. These were followed by small group work. This manuscript outlines the key issues identified and the path forward.
A realist evaluation of a regional Dementia Health Literacy Project
Authors: Grace Sandra , Horstmanshof Louise
Published: January 2019

Background

A Dementia Health Literacy Project was undertaken in the north coast region of NSW, Australia, after it was identified as having a high prevalence of dementia. A Dementia Support Kit was produced with service user engagement to provide useful information to people with dementia and their families.

Objective

To evaluate the Dementia Health Literacy Project using a realist evaluation framework.

Setting and participants

The setting was the region of the north coast of New South Wales. Eight people diagnosed with dementia and their carers, 13 members of social groups of older people in the local area, and 22 local GPs and other health‐care and service providers participated in this study.

Results

Two context‐mechanism‐outcome configurations were identified: (a) co‐design workshops where the stakeholders’ opinions were equally valued (context) led service users to feel listened to and prompted them to provide feedback (mechanism) to develop a practical resource that they would use (outcome); and (b) use of health professionals to distribute the resources (context) that they consider useful and valuable (mechanism) resulted in the target audience receiving the resources (outcome).

Discussion and conclusions

The Dementia Health Literacy Project produced a Dementia Support Kit that is likely to provide locally relevant and useful information for people with dementia and their carers. The results highlight the value of the co‐design approach in producing and disseminating dementia health literacy resources. Further evaluation is required to confirm the impact of the Kit over time on service users’ behaviour and consequently on their health outcomes.
Pyoderma gangrenosum and tumour necrosis factor alpha inhibitors: A semi‐systematic review
Authors: Ben Abdallah Hakim , Fogh Karsten , Bech Rikke
Published: January 2019

Pyoderma gangrenosum (PG) is a rare ulcerative skin disease that presents a therapeutic challenge. Tumour necrosis factor alpha (TNFα) inhibitors have been reported to successfully control PG. Our aim was to systematically evaluate and compare the clinical effectiveness of TNFα inhibitors in adults with PG. A literature search including databases such as PubMed, Embase, Scopus, and Web of Science was conducted, using search terms related to PG and TNFα inhibitors. Studies and case reports were included if patients were diagnosed with PG, over the age of 18 and administered TNFα inhibitor. A total of 3212 unique citations were identified resulting in 222 articles describing 356 patients being included in our study. The study we report found an 87% (95% CI: 83%‐90%) response rate and a 67% (95% CI: 62%‐72%) complete response rate to TNFα inhibitors. No statistically significant differences in the response rates (P = 0.6159) or complete response rates (P = 0.0773) to infliximab, adalimumab, and etanercept were found. In our study TNFα inhibitors demonstrated significant effectiveness with response and complete response rates supporting the use of TNFα inhibitors to treat PG in adults. Our study suggests that there is no significant difference in effectiveness among infliximab, adalimumab, and etanercept.