bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil Elastase Activates Macrophage MMPs, Promotes Cell Adhesion and Cytokine Production Via Integrin-Src Kinases Pathway
Authors: Krotova Karina , Khodayari Nazli , Oshins Regina , Aslanidi George , Brantly Mark L.
Published: December 2018

There are a number of diseases characterized by the presence of neutrophil elastase (NE) activity in tissues including cystic fibrosis and alpha-1-antitrypsin deficiency induced lung destruction. It is generally accepted that NE actively contributes to this pathological process, but the precise mechanisms has yet to be determined. We hypothesized that NE activates the macrophages (M□) pro-inflammatory program. We demonstrate that following NE exposure, monocyte-derived M□ release proteolytic activity composed of several matrix metalloproteinases (MMPs) which could contribute to extracellular matrix (ECM) degradation. NE upregulates expression of M□ derived pro-inflammatory cytokines including TNFα, IL-1β, and IL-8. Thus, NE-activated M□ can contribute to tissue destruction through the proteolytic activity of metalloproteinases and by supporting chronic inflammation through expression of pro-inflammatory cytokines. We also demonstrate that NE increases M□ adhesion that is attenuated by antibodies specific to integrin subunits. We show that the effects of NE on M□ can be mediated through an activation of integrin pathways. In support of integrin involvement, we demonstrate that NE activates the Src kinase family, a hallmark of integrin signaling activation. Moreover, pretreatment of macrophages with a specific Src kinase inhibitor, PP2, completely prevents NE-induced inflammatory cytokine production. Taken together these findings indicate that NE has effect on lung destruction that extends beyond direct proteolytic degradation of matrix proteins.
arcasHLA: high resolution HLA typing from RNA seq
Authors: Orenbuch Rose , Filip Ioan , Comito Devon , Shaman Jeffrey , Pe'er Itsik , Rabadan Raul
Published: December 2018

Human leukocyte antigen (HLA) locus makes up the major compatibility complex (MHC) and plays a critical role in host response to disease, including cancers and autoimmune disorders. In the clinical setting, HLA typing is necessary for determining tissue compatibility. Recent improvements in the quality and accessibility of next-generation sequencing have made HLA typing from standard short-read data practical. However, this task remains challenging given the high level of polymorphism and homology between the HLA genes. HLA typing from RNA sequencing is further complicated by post-transcriptional splicing and bias due to amplification. Here, we present arcasHLA: a fast and accurate in silico tool that infers HLA genotypes from RNA sequencing data. Our tool outperforms established tools on the gold-standard benchmark dataset for HLA typing in terms of both accuracy and speed, with an accuracy rate of 100% at two field precision for MHC class I genes, and over 99.7% for MHC class II. Importantly, arcasHLA takes as its input pre-aligned BAM files, and outputs three-field resolution for all HLA genes in less than 2 minutes. Finally, we discuss evaluate the performance of our tool on a new biological dataset of 447 single-end total RNA samples from nasopharyngeal swabs, and establish the applicability of arcasHLA in metatranscriptome studies. arcasHLA is available at https://github.com/RabadanLab/arcasHLA.
Engineering Brain Parasites for Intracellular Delivery of Therapeutic Proteins
Authors: Bracha Shahar , Hassi Karoliina , Ross Paul D. , Cobb Stuart , Sheiner Lilach , Rechavi Oded
Published: December 2018

Protein therapy has the potential to alleviate many neurological diseases; however, delivery mechanisms for the central nervous system (CNS) are limited, and intracellular delivery poses additional hurdles. To address these challenges, we harnessed the protist parasite Toxoplasma gondii, which can migrate into the CNS and secrete proteins into cells. Using a fusion protein approach, we engineered T. gondii to secrete therapeutic proteins for human neurological disorders. We tested two secretion systems, generated fusion proteins that localized to the secretory organelles of T. gondii and assessed their intracellular targeting in various mammalian cells including neurons. We show that T. gondii expressing GRA16 fused to the Rett syndrome protein MeCP2 deliver a fusion protein that mimics the endogenous MeCP2, binding heterochromatic DNA in neurons. This demonstrates the potential of T. gondii as a therapeutic protein vector, which could provide either transient or chronic, in situ synthesis and delivery of intracellular proteins to the CNS.
Transverse chromatic offsets with pupil displacements in the human eye: Sources of variability and methods for real-time correction
Authors: Boehm Alexandra E. , Privitera Claudio M. , Schmidt Brian P. , Roorda Austin
Published: December 2018

Tracking SLO systems equipped to perform retinally targeted stimulus delivery typically use near-IR wavelengths for retinal imaging and eye tracking and visible wavelengths for stimulation. The lateral offsets between wavelengths caused by transverse chromatic aberration (TCA) must be carefully corrected in order to deliver targeted stimuli to the correct location on the retina. However, both the magnitude and direction of the TCA offset is dependent on the position of the eye’s pupil relative to the incoming beam, and thus can change dynamically within an experimental session without proper control of the pupil position. The goals of this study were twofold: 1) To assess sources of variability in TCA alignments as a function of pupil displacements in an SLO and 2) To demonstrate a novel method for real-time correction of chromatic offsets. To summarize, we found substantial between- and within-subject variability in TCA in the presence of monochromatic aberrations. When adaptive optics was used to fully correct for monochromatic aberrations, variability both within and between observers was minimized. In a second experiment, we demonstrate that pupil tracking can be used to update stimulus delivery in the SLO in real time to correct for variability in chromatic offsets with pupil displacements.
Characterizing smoking-induced transcriptional heterogeneity in the human bronchial epithelium at single-cell resolution
Authors: Duclos Grant E. , Teixeira Vitor H. , Autissier Patrick , Gesthalter Yaron B. , Reinders-Luinge Marjan A. , Terrano Robert , Dumas Yves M. , Liu Gang , Mazzilli Sarah A. , Brandsma Corry-Anke , van den Berge Maarten , Janes Sam M. , Timens Wim , Lenburg Marc E. , Spira Avrum , Campbell Joshua D. , Beane Jennifer
Published: December 2018

The human bronchial epithelium is composed of multiple, distinct cell types that cooperate to perform functions, such as mucociliary clearance, that defend against environmental insults. While studies have shown that smoking alters bronchial epithelial function and morphology, the precise effects of this exposure on specific cell types are not well-understood. We used single-cell RNA sequencing to profile bronchial epithelial cells from six never- and six current smokers. Unsupervised analyses identified thirteen cell clusters defined by unique combinations of nineteen distinct gene sets. Expression of a set of toxin metabolism genes localized to ciliated cells from smokers. Smoking-induced airway remodeling was characterized by a loss of club cells and extensive goblet cell hyperplasia. Finally, we identified a novel peri-goblet epithelial subpopulation in smokers that expressed a marker of bronchial premalignant lesions. Our data demonstrates that smoke exposure drives a complex landscape of cellular and molecular alterations in the human bronchial epithelium that may contribute to the onset of smoking-associated lung diseases.
Ccube: A fast and robust method for estimating cancer cell fractions
Authors: Yuan Ke , Macintyre Geoff , Liu Wei ,   PCAWG-11 working group, Markowetz Florian
Published: December 2018

Estimating and clustering cancer cell fractions of genomic alterations are central tasks for studying intratumour heterogeneity. We present Ccube, a probabilistic framework for inferring the cancer cell fraction of somatic point mutations and the subclonal composition from whole-genome sequencing data. We develop a variational inference method for model fitting, which allows us to handle samples with large number of the variants (more than 2 million) while quantifying uncertainty in a Bayesian fashion. Ccube is available at https://github.com/keyuan/ccube.
Precocious neuronal differentiation and disrupted oxygen responses in Kabuki syndrome
Authors: Carosso Giovanni A. , Boukas Leandros , Augustin Jonathan J. , Nguyen Ha Nam , Winer Briana L. , Cannon Gabrielle H. , Robertson Johanna D. , Zhang Li , Hansen Kasper D. , Goff Loyal A. , Bjornsson Hans T.
Published: December 2018

Chromatin modifiers act to coordinate gene expression changes critical to neuronal differentiation from neural stem/progenitor cells (NSPCs). Lysine-specific methyltransferase 2D (KMT2D) encodes a histone methyltransferase that promotes transcriptional activation, and is frequently mutated in cancers and in the majority (>70%) of patients diagnosed with the congenital, multisystem intellectual disability (ID) disorder Kabuki syndrome 1 (KS1). Critical roles for KMT2D are established in various non-neural tissues, but the effects of KMT2D loss in brain cell development have not been described. We conducted parallel studies of proliferation, differentiation, transcription, and chromatin profiling in KMT2D-deficient human and mouse models to define KMT2D-regulated functions in neurodevelopmental contexts, including adult-born hippocampal NSPCs in vivo and in vitro. We report cell-autonomous defects in proliferation, cell cycle, and survival, accompanied by early NSPC maturation in several KMT2D-deficient model systems. Transcriptional suppression in KMT2D-deficient cells indicated strong perturbation of hypoxia-responsive metabolism pathways. Functional experiments confirmed abnormalities of cellular hypoxia responses in KMT2D-deficient neural cells, and accelerated NSPC maturation in vivo. Together, our findings support a model in which loss of KMT2D function suppresses expression of oxygen-responsive gene programs important to neural progenitor maintenance, resulting in precocious neuronal differentiation in a mouse model of KS1.

Graphical Abstract
Decoding functional regulatory maps via genomic evolutionary footprints in 63 green plants
Authors: Tian Feng , Yang De-Chang , Meng Yu-Qi , Jin Jinpu , Gao Ge
Published: December 2018

Systematic identification of functional transcriptional regulatory interactions is essential for understanding regulatory systems. Here, we firstly established genome-wide conservation landscapes for 63 green plants of seven lineages and then developed an algorithm FunTFBS to screen for functional regulatory elements and interactions by coupling base-varied binding affinities of transcription factors with the evolutionary footprints on their binding sites. Using the FunTFBS and the conservation landscapes, we further identified over two million functional interactions for 21,346 TFs, charting functional regulatory maps of these 63 plants. Our work provides plant community with valuable resources to decode plant transcriptional regulatory system and genome sequences.
Bilateral spontaneous otoacoustic emissions show coupling between active oscillators in the two ears
Authors: Roongthumskul Yuttana , O Maoileidigh Daibhid , Hudspeth Albert
Published: December 2018

Spontaneous otoacoustic emissions (SOAEs) are weak sounds that emanate from the ears of tetrapods in the absence of acoustic stimulation. These emissions are an epiphenomenon of the active process of the inner ear, which enhances the sensitivity of the auditory system to weak sounds, but their mechanism of production remains a matter of debate. To understand the relationship between SOAEs that we recorded simultaneously from the two ears of the tokay gecko, we developed a mathematical model of the eardrums as noisy nonlinear oscillators coupled by the air within the mouth of a lizard. We found that binaural emissions could be strongly correlated: some emissions occurred at the same frequency in both ears and were highly synchronized. Suppression of the emissions in one ear often changed the amplitude or shifted the frequency of emissions in the other. Decreasing the frequency of emissions from one ear by lowering its temperature usually reduced the frequency of the contralateral emissions. By according with the model, the results indicate that some SOAEs are generated bilaterally through acoustic coupling across the oral cavity. The model predicts that sound localization through the acoustic coupling between ears is influenced by the active processes of both ears.
A cross-cancer metastasis signature in the microRNA-mRNA axis of paired tissue samples
Authors: Lee Samuel C. , Quinn Alistair , Nguyen Thin , Venkatesh Svetha , Quinn Thomas P.
Published: December 2018

In the progression of cancer, cells acquire genetic mutations that cause uncontrolled growth. Over time, the primary tumour may undergo additional mutations that allow for the cancerous cells to spread throughout the body as metastases. Since metastatic development typically results in markedly worse patient outcomes, research into the identity and function of metastasisassociated biomarkers could eventually translate into clinical diagnostics or novel therapeutics. Although the general processes underpinning metastatic progression are understood, no consistent nor clear cross-cancer biomarker profile has yet emerged. However, the literature suggests that some microRNAs (miRNAs) may play an important role in the metastatic progression of several cancer types. Using a subset of The Cancer Genome Atlas (TCGA) data, we performed an integrated analysis of mRNA and miRNA expression with paired metastatic and primary tumour samples to interrogate how the miRNA-mRNA regulatory axis influences metastatic progression. From this, we successfully built mRNAand miRNA-specific classifiers that can discriminate pairs of metastatic and primary samples across 11 cancer types. In addition, we identified a number of miRNAs whose metastasis-associated dysregulation could predict mRNA metastasis-associated dysregulation. Among the most predictive miRNAs, we found several previously implicated in cancer progression, including miR-301b, miR-1296, and miR-423. Taken together, our results suggest that cross-cancer metastatic samples have unique biomarker signatures when compared with paired primary tumours, and that these miRNA biomarkers can be used to predict both metastatic status and mRNA expression.
Protein stability engineering insights revealed by domain-wide comprehensive mutagenesis
Authors: Nisthal Alex , Wang Connie Y. , Ary Marie L. , Mayo Stephen L.
Published: December 2018

The accurate prediction of protein stability upon sequence mutation is an important but unsolved challenge in protein engineering. Large mutational datasets are required to train computational predictors, but traditional methods for collecting stability data are either low-throughput or measure protein stability indirectly. Here, we develop an automated method to generate thermodynamic stability data for nearly every single mutant in a small 56-residue protein. Analysis reveals that most single mutants have a neutral effect on stability, mutational sensitivity is largely governed by residue burial, and unexpectedly, hydrophobics are the best tolerated amino acid type. Correlating the output of various stability prediction algorithms against our data shows that nearly all perform better on boundary and surface positions than for those in the core, and are better at predicting large to small mutations than small to large ones. We show that the most stable variants in the single mutant landscape are better identified using combinations of two prediction algorithms, and that including more algorithms can provide diminishing returns. In most cases, poor in silico predictions were tied to compositional differences between the data being analyzed and the datasets used to train the algorithm. Finally, we find that strategies to extract stabilities from high-throughput fitness data such as deep mutational scanning are promising and that data produced by these methods may be applicable toward training future stability prediction tools.

Significance Statement

Using liquid-handling automation, we constructed and measured the thermodynamic stability of almost every single mutant of protein G (Gβ1), a small domain. This self-consistent dataset is the largest of its kind and offers unique opportunities on two fronts: (i) insight into protein domain properties such as positional sensitivity and incorporated amino acid tolerance, and (ii) service as a validation set for future efforts in protein stability prediction. As Gβ1 is a model system for protein folding and design, and its single mutant landscape has been measured by deep mutational scanning, we expect our dataset to serve as a reference for studies aimed at extracting stability information from fitness data or developing novel high-throughput stability assays.
Deciphering the molecular pathways of apoptosis using leaf extract of Basella alba against Ehrlichs Ascites Carcinoma (EAC) cell line in Swiss albino mice model
Authors: Islam Md. Shihabul , Rahi Md. Sifat , Jahangir Chowdhury Arif , Hasan Md. Mahmudul , Sajib Salek Ahmed , Haque Ariful , Kabir Syed Rashel , Hoque Kazi Md. Faisal , Moni Mohammad Ali , Reza Md. Abu
Published: December 2018

A series of programmed cell death that plays a vital role in the exclusion of abnormal cells without any ruin into the surrounding neighboring cells is called Apoptosis. Generally, it occurs in multi-cellular organisms through an orderly and autonomously processes that is controlled by proper function of various genes. In the current studies, cell apoptosis in EAC cells treated with different fractions (BLP-01, BLP-02 and BLP-03) of leaf ex- tract of B. alba was detected by conducting several bio-assays such as cell growth inhibition, fluorescence and optical microscopy, DNA fragmentation and PCR amplification etc. The results of these experiments indicate that the plant extracts are able to inhibit cell growth significantly where morphological features of apoptosis were appeared under both fluorescence and optical microscope. The PCR amplification results showed that the leaf ex- tracts of B. alba were able to cause EAC cell apoptosis in both the extrinsic and intrinsic pathway. An excellent figure of fragmented DNA was found in DNA fragmentation assay when the gel was observed under UV light which confirms the cell apoptosis. The current findings suggest that the samples of this experiment occupy fascinating competence to conduct cell apoptosis and become an ideal resource for cancer research as well as drugs development for cancer treatment.
Neuroblast-specific chromatin landscapes allow integration of spatial and temporal cues to generate neuronal diversity in Drosophila
Authors: Sen Sonia Q , Chanchani Sachin , Southall Tony D , Doe Chris Q
Published: December 2018

During early neurogenesis in flies and mice, spatial and temporal cues interact to specify neuronal diversity, yet in no organism is it known how spatial and temporal cues are integrated. We used Targeted DamID (TaDa) to identify the genomic binding sites of the temporal transcription factor Hunchback in two adjacent Drosophila neuroblasts (NB5-6 and NB7-4). Hunchback targets were different in each neuroblast. Profiling chromatin accessibility showed that each neuroblast had a distinct chromatin landscape: Hunchback-bound loci in NB5-6 were in open chromatin, but the same loci in NB7-4 were in closed chromatin. Moreover, binding of the spatial factor Gsb/Pax3, essential for NB5-6 specification, was correlated with open chromatin and Hunchback-enriched loci in NB5-6, but not NB7-4. We propose early-acting spatial factors establish a unique chromatin landscape in each neuroblast, thereby restricting temporal factor binding to different loci in each neuroblast, resulting in different neurons in each neuroblast lineage.

Impact statement

Integration of spatial and temporal identity during Drosophila neurogenesis is due to spatial factors generating neuroblast-specific chromatin thereby biasing subsequent temporal transcription factor binding and producing neuroblast-specific neurons.
Which author is which? Gender Authorship Position in Aquaculture Literature
Authors: Chow Morgan , Egna Hillary , West Jevin
Published: December 2018

Examining authorship position in aquaculture facilitates an improved understanding of status of women in the discipline, as authorship is a critical factor in professional success. In a review of more than eight million papers in the JSTOR Corpus across disciplines, West et al. 2013 found that men predominate in the first and last author positions and women are underrepresented in single-authored papers. Other studies have assessed women authorship, and found that a gender gap in published literature persists. This study applies the large sample size and methodology of West et al. 2013 to the broad discipline of aquaculture, and compares these results to gender authorship in the International Aquaculture Curated Database (IACD) – a compilation of 543 peer-reviewed publications supported by four international aquaculture programs headquartered at Oregon State University -- and two curated databases in the JSTOR in the Web of Science.
Results reveal that the percentage of women authors (13.8%) was similar for the JSTOR aquaculture subsample and the IACD (15.7%), yet significantly lower for that of the Web of Science database (3.7%). Women are not well represented any of the databases, and remain underrepresented as authors in any position in aquaculture journals. To contextualize our findings, we examined the number of women graduates in agricultural, biological, natural, and social sciences who earned degrees in the U.S. from 1991-2015. Results from the U.S. Department of Education's National Center for Education Statistics and the percent of female graduates in the IACD show that the percent of women graduates each year has increased with women representing more than 50% of graduates, providing contextualization for the proportion of women in the discipline. Learning how authorship has changed in the aquaculture discipline over the recent decades is critical for promoting gender equity for future aquaculture scholarship and the sustainability of the professional discipline.
Wind drives drought responses of green roof vegetation in two substrates
Authors: Przybysz Arkadiusz , Sonkin Konstantin , Sæbø Arne , Hanslin Hans Martin ,   Konstantin Sonkin, Arne Sæbø, Hans Martin Hanslin
Published: December 2018

The multifunctionality and delivery of ecosystem services from green roofs is improved by biological diversity of the roof vegetation. However, the frequency and intensity of drought episodes on extensive green roofs may limit the use of non-succulent species and the potential functional and phylogenetic diversity of the vegetation. Wind accelerates water use by plants and desiccation of the green roof substrate, and may be a key factor in selection of non-succulent plant species for green roofs. In this study, we tested wind interactions with green roof substrate composition and the effects on plant and substrate water balance, overall plant performance, and wilting and survival of three non-succulent species (Plantago maritima L., Hieracium pilosella L., and Festuca rubra L.) under realistic prolonged water deficit conditions. We found that, regardless of species or substrate tested, wind accelerated drought response. Drought-stressed plants exposed to wind wilted and died earlier, mostly due to more rapid desiccation of the growth substrate (critical substrate moisture content was 6-8%). The moderate wind levels applied did not affect plant performance when not combined with drought. Species with contrasting growth forms showed similar responses to treatments, but there were some species-specific responses. This highlights the importance of including wind to increase realism when evaluating drought exposure in non-succulent green roof vegetation.
Cerebral amyloid angiopathy and comparative analysis of amyloid-β protein in birds
Authors: Une Yumi , Yamazaki Mutsumi , Morimoto Maho , Kametani Fuyuki , Parker Dennilyn , Karawita Anjana , Scott Steven James ,   Yamazaki, Morimoto, Kametani, Scott, Parker, Karawita, Une
Published: December 2018

Senile plaques and cerebral amyloid angiopathy (CAA)?are well-documented in various mammals, and several species even exhibit neurofibrillary tangle (NFT). However, we know far less about whether such symptoms are present in birds. Therefore, here we clarified the occurrence and pathogenesis of avian aβ-related lesions, analyzing the aβ amino-acid sequence across 28 birds at multiple life stages, representing 15 species, 14 genera, and 9 nine families.?We also determined the expected aβ amino-acid sequence after comparing data from the brains of nine birds (seven species) with publicly available NCBI data. We observed CAA and senile plaque-like deposition only in a female Amazon parrot, estimated to be around 30–40 years old. We identified two Aβ depositions (40 and 42) in the same location that correspond to Aβ 6-42. Additionally, we observed severe Aβ deposition, accompanied by severe hemorrhaging, in blood vessels of the superficial and deep portions of the brain. These lesions were directly related to the cause of death. Of 40 bird species, 36 exhibited type 1 Aβ amino-acid sequences, similar to humans. Given that all of these birds were old, our results suggest that Aβ is deposited primarily as CAA as the animals age. This report is the first clinically based description of CAA in birds. Interspecific variation likely exists because we identified species that did not exhibit Aβ deposition even when the birds are old enough. However, even birds of the same taxonomic status differed in whether they possessed or lacked Aβ deposition. Thus, other factors besides Aβ amino-acid sequence could influence this symptom.
Reconstruction of Escherichia coli ancient diversification by layered phylogenomics and polymorphism fingerprinting
Authors: González-Alba Jose M , Baquero Fernando , Cantón Rafael , Galán Juan Carlos
Published: December 2018

The rapidly increasing availability of whole genomes provides the opportunity to reach an updated comprehensive view of bacterial evolution. The staggered diversification of evolutionary processes, based on the combined strategy of layered phylogenomics and polymorphism fingerprinting, give a new perspective in phylogenetic reconstructions. Layered phylogenomics is based on the assignation of genes according to five different evolutionary layers: minimal genome, genus-core genome, species-core genome, phylogroup-core genome and phylogroup-flexible genome. Polymorphism fingerprinting is based on the detection of conserved positions in each phylogenetic group but differing from those of their hypothetical ancestors. This approach was applied to Escherichia coli because there are unresolved evolutionary questions, although has been highly studied. Phylogenetic analysis based on 6,220 full genomes, identified three E. coli root lineages, defined as D, EB1A and FGB2. A new phylogroup, called G was detected near to phylogroup B2. The closest phylogroup to ancestral E. coli was phylogroup D, whereas E and F were the closest ones in their respective lineages; moreover, A and B2 were the most distant phylogroups in EB1A and FGB2 respectively. We suspect that EB1A and FGB2 lineages represent different adaptive strategies. In the deepest branch of EB1A lineage, the number of accumulated mutations was lower than in recent branches, whereas in FGB2 lineage the opposite occurred. The FGB2 lineage was enriched in genes related to host colonization-pathogenicity and toxin-antitoxin systems (such as hipA), whereas B1A sub-lineage acquired functions related to uptake and metabolism of carbohydrates (such as bgl, mng or xlyE). This new combined strategy shows a detailed staggered evolutionary reconstruction, which help us to understand the deepest events and the selection forces have driven E. coli diversification. This approach could add resolution in the reconstruction of the evolutionary trajectories of other microorganisms.
In Vitro Screen to Identify Silent but Activatable (S/A) Integration Sites for a Tetracycline-Inducible Transgene in Mice
Authors: Behringer Richard , Gertsenstein Marina , Nagy Kristina Vintersten , Nagy Andras
Published: December 2018

To obtain ubiquitous or simply widespread transgene expression from a single stable integrant transgene is quite challenging because the random genomic integration sites of transgenes may create expression variation or frequent silencing. The tetracycline (Tet)-inducible system requires two reliable working transgenes, one for the tetracycline transactivators (tTA or rtTA) and one for the responder transgene driven by the tet-O promoter. Therefore, the challenge of getting this system working properly is a serious prospect. In this protocol, we describe how to identify a silent but highly activatable genomic site by taking advantage of transgenic lines reliably expressing the tetracycline transactivators from the Rosa-26 locus. These lines provide optimal Tet-inducible expression: There is minimal leakiness at the “off” state and a high level of induction in the presence of the inducer, doxycycline. The procedure requires (1) an embryonic stem (ES) cell line (germline competent) expressing rtTA from the Rosa-26 locus and (2) construction of a Tet-inducible transgene. The transgene contains the tet-O promoter followed by the gene of interest linked to a βgeo gene (a fusion between lacZ and neo) through an internal ribosomal entry site (IRES) sequence, which allows the initiation of translation in a cap-independent manner.
Crystal structure of poly[bis(μ-2-bromopyrazine)tetra-μ2-cyanido-dicopper(I)iron(II)]: a bimetallic metal-organic framework
Authors: Kucheriv Olesia I. , Tokmenko Inna I. , Matushko Igor P. , Tsapyuk Galyna G. , Gural'skiy Il'ya A.
Published: November 2018

In the title metal-organic framework, [Fe(C4H3BrN2)2{Cu(CN)2}2]n, the FeIIcation is located on an inversion center and has a slightly elongated octahedral coordination environment [FeN6], ligated by two pyrazine N atoms of symmetry-related bridging 2-bromopyrazine molecules in the axial positions and by four N atoms of pairs of symmetry-related cyanido groups in the equatorial positions. The CuIcenter has a fourfold coordination environment [CuC3N], with an almost perfect trigonal–pyramidal geometry, formed by three cyanido C atoms and an N atom of a bridging 2-bromopyrazine molecule. Copper(I) centers related by a twofold rotation axis are bridged by two carbon atoms from a pair of μ-CN groups, resulting in Cu2(CN)2units. Each Cu2(CN)2unit is linked to six FeIIcations via a pair of linear CN units, the pair of μ-CN groups and two bridging 2-bromopyrazine ligands, resulting in the formation of a metal–organic framework, which is additionally stabilized by the short Cu...Cu contacts of 2.4450 (7) Å.
Structure of voltage-dependent anion channel-tethered bilayer lipid membranes determined using neutron reflectivity
Authors: Hoogerheide David P. , Noskov Sergei Yu. , Kuszak Adam J. , Buchanan Susan K. , Rostovtseva Tatiana K. , Nanda Hirsh
Published: November 2018

Neutron reflectivity (NR) has emerged as a powerful technique to study the structure and behavior of membrane proteins at planar lipid interfaces. Integral membrane proteins (IMPs) remain a significant challenge for NR owing to the difficulty of forming complete bilayers with sufficient protein density for scattering techniques. One strategy to achieve high protein density on a solid substrate is the capture of detergent-stabilized, affinity-tagged IMPs on a nitrilotriacetic acid (NTA)-functionalized self-assembled monolayer (SAM), followed by reconstitution into the lipids of interest. Such protein-tethered bilayer lipid membranes (ptBLMs) have the notable advantage of a uniform IMP orientation on the substrate. Here, NR is used to provide a structural characterization of the ptBLM process from formation of the SAM to capture of the detergent-stabilized IMP and lipid reconstitution. The mitochondrial outer-membrane voltage-dependent anion channel (VDAC), which controls the exchange of bioenergetic metabolites between mitochondria and the cytosol, was used as a model β-barrel IMP. Molecular dynamics simulations were used for comparison with the experimental results and to inform the parameters of the physical models describing the NR data. The detailed structure of the SAM is shown to depend on the density of the NTA chelating groups. The relative content of detergent and protein in surface-immobilized, detergent-stabilized VDAC is measured, while the reconstituted lipid bilayer is shown to be complete to within a few percent, using the known atomic structure of VDAC. Finally, excess lipid above the reconstituted bilayer, which is of consequence for more indirect structural and functional studies, is shown to be present.
BP's Procurement and Supply Chain Management
Authors: Narayanan Arunachalam , Natarajarathinam Malini , Winn Brandon
Published: December 2018

BP has interest in both upstream and downstream segments in over 100 countries worldwide. The United States subsidiary of BP is the nation's largest producer of oil and gas. This case focuses on the upstream procurement activities in the Gulf of Mexico.
INCOTERMs: International Logistics Negotiation Game
Authors: García-Dastugue Sebastián
Published: December 2018

In this case, teams can compete in the real-life situation produced by Tommasso-Southwest Sport Machines. Teams will act as the buyer or the seller and will need to consider the cost implications, risk and responsibility, and price negotiation.
Value creation and value maintenance
Authors: Chen Jiawen , Yao Xiaotao , Liu Linlin
Published: November 2018

Purpose

This paper aims to examine how a firm’s capability affects its political networking in emerging economies and how the institutional environment influences the relationship between a firm’s capability and its political networking.

Design/methodology/approach

The authors test the theoretical model by analyzing a database from a World Bank survey in China.

Findings

The results show a nonlinear (U-shaped) relationship between a firm’s capability and its efforts in political networking. The relationship between a firm’s capability and political networking is contingent on the institutional environment, as reflected in institutional development and industry regulation.

Originality/value

This study elucidates political networking in emerging economies and contributes to research on corporate political strategy.
Ontology-based heuristic patent search
Authors: Phan Cong-Phuoc , Nguyen Hong-Quang , Nguyen Tan-Tai
Published: December 2018

Purpose

Large collections of patent documents disclosing novel, non-obvious technologies are publicly available and beneficial to academia and industries. To maximally exploit its potential, searching these patent documents has increasingly become an important topic. Although much research has processed a large size of collections, a few studies have attempted to integrate both patent classifications and specifications for analyzing user queries. Consequently, the queries are often insufficiently analyzed for improving the accuracy of search results. This paper aims to address such limitation by exploiting semantic relationships between patent contents and their classification.

Design/methodology/approach

The contributions are fourfold. First, the authors enhance similarity measurement between two short sentences and make it 20 per cent more accurate. Second, the Graph-embedded Tree ontology is enriched by integrating both patent documents and classification scheme. Third, the ontology does not rely on rule-based method or text matching; instead, an heuristic meaning comparison to extract semantic relationships between concepts is applied. Finally, the patent search approach uses the ontology effectively with the results sorted based on their most common order.

Findings

The experiment on searching for 600 patent documents in the field of Logistics brings better 15 per cent in terms of F-Measure when compared with traditional approaches.

Research limitations/implications

The research, however, still requires improvement in which the terms and phrases extracted by Noun and Noun phrases making less sense in some aspect and thus might not result in high accuracy. The large collection of extracted relationships could be further optimized for its conciseness. In addition, parallel processing such as Map-Reduce could be further used to improve the search processing performance.

Practical implications

The experimental results could be used for scientists and technologists to search for novel, non-obvious technologies in the patents.

Social implications

High quality of patent search results will reduce the patent infringement.

Originality/value

The proposed ontology is semantically enriched by integrating both patent documents and their classification. This ontology facilitates the analysis of the user queries for enhancing the accuracy of the patent search results.
“It’s not black and white”
Authors: Crawford Sharinne , Hokke Stacey , Nicholson Jan M. , Zion Lawrie , Lucke Jayne , Keyzer Patrick , Hackworth Naomi
Published: December 2018

Purpose

The internet offers an opportunity for researchers to engage participants in research in a cost-effective and timely manner. Yet the use of the internet as a research tool (internet research) comes with a range of ethical concerns, and the rapidly changing online environment poses challenges for both researchers and ethics committees. The purpose of this paper is to highlight the key ethical issues of using the internet to recruit, retain and trace participants in public health research, from the perspectives of researchers and human research ethics committee (HREC) members.

Design/methodology/approach

This study employed a qualitative design using semi-structured interviews with eight public health researchers and seven HREC members in Australia to explore the key ethical issues of using the internet to engage research participants.

Findings

The study identified commonalities between researchers and HREC members regarding the utility and ethical complexity of using the internet to recruit, retain and trace research participants. The need for guidance and support regarding internet research, for both groups, was highlighted, as well as the need for flexibility and responsiveness in formal ethical processes.

Originality/value

This research contributes to the understanding of how the internet is used to engage participants in public health research and the ethical context in which that occurs. Supporting the ethical conduct of internet research will benefit those involved in research, including researchers, HRECs, organisations and research participants.
Online product category and pricing strategies of land-based retailers
Authors: Wu Jin-Feng , Chang Ya Ping , Yan Jun , Hou De-Lin
Published: December 2018

Purpose

The purpose of this paper is to understand how two online marketing orientations of land-based retailers in product category and price could change retail brand attitude when retail brand familiarities differ.

Design/methodology/approach

This paper proposes a research model with two orientations in product category and price as antecedents of retail brand attitude change and retail brand familiarity as a moderator. Empirical data were collected from 684 shoppers across three land-based retailers to test the research hypotheses.

Findings

Both orientations in product category and price can improve customers’ retail brand attitudes. Retail brand familiarity plays a significant moderator in some of the situations. Online-offline product category congruence and online-prototypical price congruence have significantly positive effects on retail brand attitude change whether retail brand familiarity is high or low. The effect of online-offline price congruence is significant only among high-familiarity customers, while the effect of online-prototypical product category congruence is found to be significant only among low-familiarity customers.

Research limitations/implications

The study identifies the moderating effects of retail brand familiarity on the relationships between two online marketing orientations in product category and price and retail brand attitude change. Based on the moderating effects, this study will help researchers to better understand the effectiveness of two online marketing orientations subject to varying degrees of retail brand familiarity in a multichannel retailing context.

Practical implications

The findings of this study can guide land-based retailers to focus on the right orientations in product category and price to improve customers’ attitudes toward the retail brand when existing or new customers are targeted.

Originality/value

This study provides a first study to empirically assess the change in retail brand attitude prompted by homogenous and prototypical orientations in product category and price and subject to varying degrees of retail brand familiarity. Overall, the results offer insights of how land-based retailers could manage their overall performance by designing more effective online product category and pricing strategies for existing or new customers.
The impact of GST implementation on the Malaysian stock market index volatility
Authors: Haron Razali , Ayojimi Salami Mansurat
Published: December 2018

Purpose

The purpose of this paper is to examine the impact of the Goods and Service Tax (GST) implementation on Malaysian stock market index.

Design/methodology/approach

This study used daily closing prices of the Malaysian stock index and futures markets for the period ranging from June 2009 to November 2016. Empirical estimation is based on the generalised autoregressive conditional heteroscedasticity (1, 1) model for pre- and post-announcement of the GST.

Findings

Result shows that volatility of Malaysian stock market index increases in the post-announcement than in the pre-announcement of the GST which indicates that educative programs employed by the government before the GST announcement did not yield meaningful result. The volatility of the Malaysian stock market index is persistent during the GST announcement and highly persistent after the implementation. Noticeable increase in post-announcement is in support with the expectation of the market about GST policy in Malaysia.

Practical implications

The finding of this study is consistent with expectation of the market that GST policy will increase the price of the goods and services and might reduce standard of living. This is supported by a noticeable increase in the volatility of the Malaysian stock market index in the post-announcement of GST which is empirically shown during the announcement and after the implementation of GST. Although the GST announcement could be classified as a scheduled announcement, unwillingness to accept the policy prevails in the market as shown by the increase in the market volatility.

Originality/value

Past studies on Malaysian stock market index volatility focus on the impact of Asian and global financial crisis whereas this study examines the impact of the GST announcement and implementation on the volatility of the Malaysian stock market index.
A new weighted fuzzy information axiom method in production research
Authors: Cebi Selcuk , Kahraman Cengiz
Published: December 2018

Purpose

The purpose of this paper is to propose a novel weighting algorithm for fuzzy information axiom (IA) and to apply it to the evaluation process of 3D printers.

Design/methodology/approach

As a decision-making tool, IA method is presented to evaluate the performance of any design. Then, weighted IA methods are investigated and a new weighting procedure is introduced to the literature. Then, the existing axiomatic design methods and the proposed new method are classified into two groups: weighting based on information content and weighting based on design ranges. The weighting based on information content approach consists of four methods including pessimistic and optimistic approaches. The philosophy of the weighting based on design ranges is to narrow design ranges in order to decrease fuzziness in the model. To prove the robustness and the performance of the proposed weighting method, the results are compared with the existing methods in the literature. Then, the new approach is applied to evaluate 3D printers.

Findings

The results of the proposed study show that the proposed weighting algorithm has better performance than the old ones for IA. Therefore, the proposed weighting algorithm should be used for the weighting tool of IA thereafter.

Originality/value

An effective weighting method compatible with the philosophy of IA method has been proposed. Furthermore, the performances of 3D printers are compared by using the proposed method.
Facing disruptive technologies: aligning purchasing maturity to contingencies
Authors: Søgaard Britta , Skipworth Heather Dawn , Bourlakis Michael , Mena Carlos , Wilding Richard
Published: December 2018

Purpose

This paper aims to explore how purchasing could respond to disruptive technologies by examining the assumptions underlying purchasing strategic alignment and purchasing maturity through a contingency lens.

Design/methodology/approach

This study uses a systematic review across purchasing maturity and purchasing strategic alignment literature. This is supplemented with exploratory case studies to include practitioners’ views.

Findings

This research demonstrates that neither purchasing maturity nor purchasing strategic alignment are suitable approaches to respond to disruptive technologies. Purchasing maturity does not allow purchasing managers to select relevant practices. It also shows no consideration of any contingencies, which practitioners highlight as important for the selection of practices. Purchasing strategic alignment includes the company strategy as a contingency but does not provide any practices to choose from. It does not include any other contextual contingencies considered important by practitioners. The findings indicate that linking the two research streams may provide a more suitable approach to responding to disruptive technologies.

Research limitations/implications

This research demonstrates the requirement to develop a new approach to responding to disruptive technologies, by linking purchasing maturity and purchasing strategic alignment to contextual contingencies. This is a currently unexplored approach in academic literature, which refutes the generally accepted premise that higher maturity unilaterally supports a better positioning towards technological disruption. This research also highlights a requirement for practitioners to shift their approach to “best practices”.

Originality/value

This is the first research to systematically review the relationships between purchasing maturity and purchasing strategic alignment. It adds to contingency theory by suggesting that purchasing maturity models can support the achievement of strategic alignment. Also, future research directions are suggested to explore these relationships.