bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Lidocaine Gel on Pain Perception During Diagnostic Flexible Cystoscopy in Women: A Randomized Control Trial
Authors: Dougher Erin , Zoorob Dani , Thomas Diane , Hagan Joseph , Peacock Lisa
Published: February 2019

Objective

The objective of this study was to determine if there is a clinically meaningful variation in pain perception when using lidocaine gel versus plain lubricant prior to office-based diagnostic flexible cystoscopy.

Methods

This was a randomized, controlled, double-blind trial comparing lidocaine gel and water-based lubricant for the performance of diagnostic flexible cystoscopy. Women undergoing cystoscopy were randomized to either transurethral 2% lidocaine (Uro-Jet) or water-based lubricant prior to cystoscopy. Participants and physicians were blinded, and pain was assessed using an 11-point numeric rating scale (NRS). A priori sample size calculation indicated the need for 40 patients per group to achieve 90% power. Descriptive statistics and Student t test were utilized.

Results

The study included 116 patients, 61 in the lidocaine group and 55 in the plain lubricant group. Numeric rating scale in the lidocaine group (2.43 [SD, 1.95]) was significantly lower than that in the plain lubricant group (3.58 [SD, 2.73]) (P = 0.01). After controlling for age and ethnicity, separately as well as together, the procedural NRS scores were 1.37 points (P = 0.002), 0.97 points (P = 0.04), and 1.22 points (P = 0.01) lower in those receiving lidocaine. After the procedure, fewer patients in the lidocaine group (2/61 = 3.3%) requested pain medicine when compared with the plain lubricant group (11/55 = 20%) (P = 0.01). Although anticipated pain scored similarly between groups, actual pain compared with anticipated pain was significantly lower in the lidocaine group (P = 0.02).

Conclusions

Pain perception during flexible cystoscopy decreased when using 2% transurethral lidocaine gel. The use of 2% lidocaine gel is suggested for the reduction of pain at the time of diagnostic flexible cystoscopy in women.
Locating the source of large-scale outbreaks of foodborne disease
Authors: Horn Abigail L. , Friedrich Hanno
Published: February 2019

In today’s globally interconnected food system, outbreaks of foodborne disease can spread widely and cause considerable impact on public health. We study the problem of identifying the source of emerging large-scale outbreaks of foodborne disease; a crucial step in mitigating their proliferation. To solve the source identification problem, we formulate a probabilistic model of the contamination diffusion process as a random walk on a network and derive the maximum-likelihood estimator for the source location. By modelling the transmission process as a random walk, we are able to develop a novel, computationally tractable solution that accounts for all possible paths of travel through the network. This is in contrast to existing approaches to network source identification, which assume that the contamination travels along either the shortest or highest probability paths. We demonstrate the benefits of the multiple-paths approach through application to different network topologies, including stylized models of food supply network structure and real data from the 2011 Shiga toxin-producing
Escherichia coli
outbreak in Germany. We show significant improvements in accuracy and reliability compared with the relevant state-of-the-art approach to source identification. Beyond foodborne disease, these methods should find application in identifying the source of spread in network-based diffusion processes more generally, including in networks not well approximated by tree-like structure.
Drying of channels by evaporation through a permeable medium
Authors: Dollet Benjamin , Louf Jean-François , Alonzo Mathieu , Jensen Kaare H. , Marmottant Philippe
Published: February 2019

We study the drying of isolated channels initially filled with water moulded in a water-permeable polymer (polydimethylsiloxane, PDMS) by pervaporation, when placed in a dry atmosphere. Channel drying is monitored by tracking a meniscus, separating water from air, advancing within the channels. The role of two geometrical parameters, the channel width and the PDMS thickness, is investigated experimentally. All data show that drying displays a truncated exponential dynamics. A fully predictive analytical model, in excellent agreement with the data, is proposed to explain such a dynamics, by solving water diffusion both in the PDMS layer and in the gas inside the channel. This drying process is crucial in geological or biological systems, such as rock disintegration or the drying of plant leaves after cavitation and embolism formation.
Going with the flow: hydrodynamic cues trigger directed escapes from a stalking predator
Authors: Tuttle Lillian J. , Robinson H. Eve , Takagi Daisuke , Strickler J. Rudi , Lenz Petra H. , Hartline Daniel K.
Published: February 2019

In the coevolution of predator and prey, different and less well-understood rules for threat assessment apply to freely suspended organisms than to substrate-dwelling ones. Particularly vulnerable are small prey carried with the bulk movement of a surrounding fluid and thus deprived of sensory information within the bow waves of approaching predators. Some planktonic prey have solved this apparent problem, however. We quantified cues generated by the slow approach of larval clownfish (
Amphiprion ocellaris
) that triggered a calanoid copepod (
Bestiolina similis
) to escape before the fish could strike. To estimate water deformation around the copepod immediately preceding its jump, we represented the body of the fish as a rigid sphere in a hydrodynamic model that we parametrized with measurements of fish size, approach speed and distance to the copepod. Copepods of various developmental stages (CII–CVI) were sensitive to the water flow caused by the live predator, at deformation rates as low as 0.04 s
−1
. This rate is far lower than that predicted from experiments that used artificial predator-mimics. Additionally, copepods localized the source, with 87% of escapes directed away (greater than or equal to 90°) from the predator. Thus, copepods' survival in life-threatening situations relied on their detection of small nonlinear signals within an environment of locally linear deformation.
Simulation and inference algorithms for stochastic biochemical reaction networks: from basic concepts to state-of-the-art
Authors: Warne David J. , Baker Ruth E. , Simpson Matthew J.
Published: February 2019

Stochasticity is a key characteristic of intracellular processes such as gene regulation and chemical signalling. Therefore, characterizing stochastic effects in biochemical systems is essential to understand the complex dynamics of living things. Mathematical idealizations of biochemically reacting systems must be able to capture stochastic phenomena. While robust theory exists to describe such stochastic models, the computational challenges in exploring these models can be a significant burden in practice since realistic models are analytically intractable. Determining the expected behaviour and variability of a stochastic biochemical reaction network requires many probabilistic simulations of its evolution. Using a biochemical reaction network model to assist in the interpretation of time-course data from a biological experiment is an even greater challenge due to the intractability of the likelihood function for determining observation probabilities. These computational challenges have been subjects of active research for over four decades. In this review, we present an accessible discussion of the major historical developments and state-of-the-art computational techniques relevant to simulation and inference problems for stochastic biochemical reaction network models. Detailed algorithms for particularly important methods are described and complemented with Matlab®implementations. As a result, this review provides a practical and accessible introduction to computational methods for stochastic models within the life sciences community.
Screening analysis of RoHS directive hazardous substances (phthalate esters and bromodiphenyl ethers) by novel mass spectrometry using soft ionization
Authors: Ohgaki Masataka , Takeguchi Yuko , Okawa Shin , Namiki Kenji
Published: February 2019

In 2013, the European Union expanded the list of hazardous substances contained in the RoHS Directive. In addition, certain phthalate esters, such as dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and diisobutyl phthalate (DIBP), will be categorized as RoHS-prohibited substances starting from July 2019. Although pyrolysis–gas chromatography–mass spectrometry (Py-GC-MS) is a promising analytical method for the screening of phthalate esters, we have developed a novel soft-ionization MS method that is quantitative as well as faster and more convenient for this purpose. The sample was measured three times, after providing the calibration curve using a powdery standard material of SPEX. The data collection time is 5 min, and continuous measurements are completed within 8 min per sample. The mass spectrum was corrected by dividing the intensity by the sample weight. For the coefficient of variation, DBP was 2.9%, BBP was 3.4%, DEHP was 3.6%, and good reproducibility was observed. Precise analyses of phthalate esters using traditional methods can require solvent extraction times of up to 24 h as well as special techniques. Therefore, a screening method that can be easily carried out by anyone within ten minutes is very attractive.
Evolutionary and functional analysis of the plant-specific NADPH oxidase gene family in
Brassica rapa
L.
Authors: Li Dahui , Wu Di , Li Shizhou , Dai Yu , Cao Yunpeng
Published: February 2019

NADPH oxidases (NOXs) have been known as respiratory burst oxidase homologues (RBOHs) in plants. To characterize the evolutionary relationships and functions of RBOHs in
Brassica rapa
, 134
RBOH
homologues were identified from 13 plant species, including 14 members (namely
BrRBOH01
–
14
) from
B. rapa
. There presented 47 gene-pairs among 14
BrRBOH
s and other
RBOH
s, consisting of five pairs within
B. rapa
, and 15 pairs between
B. rapa
and
Arabidopsis thaliana
. Together with phylogenetic analysis, the results suggested that whole-genome duplication might have played an important role in
BrRBOH
gene expansion, and these duplication events occurred after the divergence of the eudicot and the monocot lineages examined. Furthermore, gene expression of
RBOH
s in both
A. thaliana
and
B. rapa
were assayed via qRT–PCR. An RBOH gene,
BrRBOH13
in
B. rapa
, was transformed into wild-type
Arabidopsis
plants. The transgenic lines with the overexpressed level of
BrRBOH13
conferred to be more tolerant to heavy metal lead (0.05 mM) than wild-type plants. Overall, this integrated analysis at genome-wide level has provided some information on the evolutionary relationships among plant-specific NOXs and the coordinated diversification of gene structure and function in
B. rapa
.
Acquisition of a phospho-acceptor site enhances HPV E6 PDZ-binding motif functional promiscuity
Authors: Sarabia-Vega Vanessa , Banks Lawrence
Published: February 2019

All cancer-causing human papillomavirus (HPV) E6 oncoproteins have a C-terminal PDZ-binding motif (PBM), which correlates with oncogenic potential. Nonetheless, several HPVs with little or no oncogenic potential also have an E6 PBM, with minor sequence differences affecting PDZ protein selectivity. Furthermore, certain HPV types have a phospho-acceptor site embedded within the PBM. We therefore compared HPV-18, HPV-66 and HPV-40 E6 proteins to examine the possible link between the ability to target multiple PDZ proteins and the acquisition of a phospho-acceptor site. The mutation of essential residues in HPV-18E6 reduces its phosphorylation, and fewer PDZ substrates are bound. In contrast, the generation of consensus phospho-acceptor sites in HPV-66 and HPV-40 E6 PBMs increases the PDZ proteins recognized. Thus, although phosphorylation of the E6 PBM and PDZ protein recognition are mutually exclusive, they are closely linked, with the acquisition of a phospho-acceptor site also contributing to an expansion in the number of PDZ proteins bound.
Gene Expression Modulation by the Linker of Nucleoskeleton and Cytoskeleton Complex Contributes to Proteostasis
Authors: Levine Amir , Grushko Danielle , Cohen Ehud
Published: February 2019

Cellular mechanisms that act in concert to maintain protein homeostasis (proteostasis) are vital for survival. Nevertheless, subsets of aggregation-prone proteins form toxic aggregates (proteotoxicity) that sometimes underlie the development of neurodegenerative diseases. Proteotoxic aggregates are often deposited in the vicinity of the nucleus, a process that is cytoskeleton-dependent. Accordingly, cytoskeletal dysfunction contributes to pathological hallmarks of various neurodegenerative diseases. Thus, we asked whether the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, which bridges these filaments across the nuclear envelope, is needed for the maintenance of proteostasis. Employing model nematodes, we discovered that knocking down LINC components impairs the ability of the worm to cope with proteotoxicity. Knocking down anc-1, which encodes a key component of the LINC complex, modulates the expression of transcription factors and E3 ubiquitin ligases, thereby changing the rates of protein ubiquitination and degradation. Our results establish a link between the LINC complex and aging-associated proteotoxicity.
Understanding the Athena SWAN award scheme for gender equality as a complex social intervention in a complex system: analysis of Silver award action plans in a comparative European perspective
Authors: Schmidt Evanthia Kalpazidou , Ovseiko Pavel V. , Henderson Lorna R , Kiparoglou Vasiliki
Published: February 2019

Background

Given that the complex mix of structural, cultural, and institutional factors has produced barriers for women in science, an equally complex intervention is required to understand and address them. The Athena SWAN award scheme for gender equality has become a widespread means to address barriers for women’s advancement and leadership in the United Kingdom, Ireland, Australia, the United States of America, and Canada, while he European Commission is exploring the introduction of a similar award scheme across Europe.

Methods

This study analyses the design and implementation of 16 departmental Athena SWAN Silver action plans in Medical Sciences at one of the world’s leading universities in Oxford, United Kingdom. Data pertaining to the design and implementation of gender equality interventions were extracted from the action plans, analysed thematically, coded using categories from the 2015 Athena SWAN Charter Awards Handbook, and synthesised against a typology of gender equality interventions in the European Research Area. The results were further analysed against the complexity research literature framework, where research organisations are perceived as dynamic systems that adapt, interact and co-evolve with other systems.

Results

Athena SWAN is a complex contextually-embedded system of action planning within the context of universities. It depends on a multitude of contextual variables that relate in complex, non-linear ways, and dynamically adapt to constantly moving targets and new emergent conditions. Athena SWAN Silver action plans conform to the key considerations of complexity: 1) multiple actions and areas of intervention with a focus on the complex system embedded in and the local dynamics, 2) the non-linearity of interventions and the constantly emerging conditions, 3) impact in terms of contribution to change, improved conditions to foster change, and the increased probability that change can occur.

Conclusions

To enact effective sustainable gender equality structural and cultural change, it is necessary to acknowledge and operationalize complexity as a frame of reference. Athena SWAN is the single most comprehensive and systemic gender equality scheme in Europe and can be strengthened further by promoting the integration of sex and gender analysis in research and education. Gender equality policies in the wider European Research Area can benefit from exploring Athena SWAN’s contextually-embedded systemic approach to dynamic action planning and inclusive focus on all genders and categories of staff and students.
LUXendins reveal endogenous glucagon-like peptide-1 receptor distribution and dynamics
Authors: Ast Julia , Arvaniti Anastasia , Fine Nicholas H.F. , Nasteska Daniela , Ashford Fiona B. , Stamataki Zania , Koszegi Zsombor , Bacon Andrea , Trapp Stefan , Jones Ben J. , Hastoy Benoit , Tomas Alejandra , Reissaus Christopher A. , Linnemann Amelia K. , D’Este Elisa , Calebiro Davide , Johnsson Kai , Podewin Tom , Broichhagen Johannes , Hodson David J.
Published: February 2019

The glucagon-like peptide-1 receptor (GLP1R) is a class B G protein-coupled receptor (GPCR) involved in metabolism. Presently, its visualization is limited to genetic manipulation, antibody detection or the use of probes that stimulate receptor activation. Herein, we present LUXendin645, a far-red fluorescent GLP1R antagonistic peptide label. LUXendin645 produces intense and specific membrane labeling throughout live and fixed tissue. GLP1R signaling can additionally be evoked when the receptor is allosterically modulated in the presence of LUXendin645. Using LUXendin645 and STED-compatible LUXendin651 we describe islet GLP1R expression patterns, reveal higher-order GLP1R organization including the existence of membrane nanodomains, and track single receptor subpopulations. We furthermore show that different fluorophores can confer agonistic behavior on the LUXendin backbone, with implications for the design of stabilized incretin-mimetics. Thus, our labeling probes possess divergent activation modes, allow visualization of endogenous GLP1R, and provide new insight into class B GPCR distribution and dynamics.
A re-interpretation of the experimental data of Shinder and Taube “Three-dimensional Tuning of Head Direction Cells in Rats”, Journal of Neurophysiology 121(1), 2019
Authors: Laurens Jean , Angelaki Dora E.
Published: February 2019

In a recent study, Shinder and Taube (2019) concluded that head direction cells in the anterior thalamus of rats are tuned to one-dimensional (1D, yaw-only) motion exclusively, in contrast to recent findings in bats (Finkelstein et al. 2015), mice (Angelaki et al. 2016; Cham et al. 2017; Laurens et al. 2017), and rats (Page et al. 2017). Here we re-interpret the author’s experimental results using model comparison and demonstrate that, contrary to their conclusions, their data actually supports the dual-axis rule (Page et al. 2017) and tilted azimuth model (Laurens and Angelaki 2018), where head direction cells use gravity to integrate 3D rotation signals about all cardinal axes of the head. We further show that this study is inconclusive regarding the presence of vertical orientation tuning; i.e. whether head direction cells encode 3D orientation in the horizontal and vertical planes conjunctively. Using model simulations, we demonstrate that, even if 3D tuning existed, the experimental protocol and data analyses used by Shinder and Taube (2019) would not have revealed it. We conclude that the actual experimental data of Shinder and Taube (2019) are compatible with the 3D properties of head direction cells discovered by other groups, yet incorrect conclusions were reached because of incomplete and qualitative analyses.
Endothelial specific PER2 at the crossroads of light elicited circadian amplitude enhancement as novel cardioprotective strategy and transcriptional regulation of HIF1A-dependent metabolic adaptation to myocardial ischemia
Authors: Oyama Yoshimasa , Bartman Colleen M. , Bonney Stephanie , Lee J. Scott , Walker Lori A. , Han Jun , Borchers Christoph H. , Buttrick Peter M. , Clendenen Nathan , Colgan Sean P. , Eckle Tobias
Published: February 2019

Consistent daylight oscillations and abundant oxygen availability are fundamental to human health. While both are connected from an evolutionary and cellular perspective, only oxygen is an established therapy in cardiovascular medicine. Here, we probe the mechanistic intersection between light-(Period 2, PER2) and oxygen-(hypoxia inducible factor, HIF1A) sensing pathways in cellular adaptation to low oxygen conditions with respect to myocardial ischemia.

Using a whole genome array from daylight exposed wildtype orPer2−/−mice, an affinity purification-mass spectrometry-based proteomics screen for PER2 targets in hypoxic human endothelial cells, and targeted metabolomics from human healthy volunteers after daylight therapy, we investigated the intersection of light and hypoxia elicited pathways. Housing mice under daylight conditions prior to myocardial ischemia and reperfusion (IR)-injury, uncovered circadian PER2 amplitude enhancement as novel cardioprotective strategy, mimicking HIF1A metabolic adaptation to myocardial ischemia in a PER2 regulated manner. Whole genome array analysis from daylight exposed wildtype andPer2−/−mice or myocardial IR-injury in endothelial specific PER2 deficient mice (Per2loxP/loxP-VE-Cadherin -Cre) revealed a critical role for light elicited PER2 in maintaining the endothelial barrier function during myocardial ischemia. Mechanistic studies in human endothelia pointed towards a master transcriptional regulatory role for endothelial PER2 in metabolic reprograming to hypoxia via HIF1A, which was mimicked during normoxic PER2 stabilization. Translational investigation of light elicited pathways in human healthy volunteers found similar increases of PER2 or mimicking of HIF1A dependent metabolism. These studies identify light elicited circadian amplitude enhancement of endothelial PER2 as a novel cardioprotective strategy. Furthermore, these studies identify PER2 as critical control point of endothelial metabolic reprograming to maintain vascular integrity during myocardial IR-injury and implicate the use of daylight therapy to increase endothelial PER2 signaling as a strategy for the treatment of coronary artery disease.
Src-dependent DBL family members drive resistance to vemurafenib in human melanoma
Authors: Feddersen Charlotte R. , Schillo Jacob L. , Varzavand Afshin , Vaughn Hayley R. , Wadsworth Lexy S. , Voigt Andrew P. , Zhu Eliot Y. , Jennings Brooke M. , Mullen Sarah A. , Bobera Jeremy , Riordan Jesse D. , Stipp Christopher S. , Dupuy Adam J.
Published: February 2019

The use of selective BRAF inhibitors (BRAFi) has produced remarkable outcomes for patients with advanced cutaneous melanoma harboring a BRAFV600E mutation. Unfortunately, the majority of patients eventually develop drug-resistant disease. We employed a genetic screening approach to identify gain-of-function mechanisms of BRAFi resistance in two independent melanoma cell lines. Our screens identified both known and unappreciated drivers of BRAFi resistance, including multiple members of the DBL family. Mechanistic studies identified a DBL/Rac1/Pak signaling axis capable of driving resistance to both current and next-generation BRAF inhibitors. However, we show that the Src inhibitor, saracatinib, can block the DBL-driven resistance. Our work highlights the utility of our straightforward genetic screening method in identifying new drug combinations to combat acquired BRAFi resistance.
RumimiR: a detailed microRNA database focused on ruminant species
Authors: Céline Bourdon , Philippe Bardou , Etienne Aujean , Sandrine Le Guillou , Gwenola Tosser-Klopp , Fabienne Le Provost
Published: February 2019

In recent years, the increasing use of Next Generation Sequencing technologies to explore the genome has generated large quantities of data. For microRNAs, more and more publications have described several thousand sequences, all species included. In order to obtain a detailed description of microRNAs from the literature for three ruminant species (bovine, caprine and ovine), a new database has been created: RumimiR. To date, 2,887, 2,733 and 5,095 unique microRNAs of bovine, caprine and ovine species, respectively, have been included. In addition to the most recent reference genomic position and sequence of each microRNA, this database contains details on the animals, tissue origins and experimental conditions available from the publications. Identity with human or mouse microRNA is mentioned. The RumimiR database enables data filtering, the selection of microRNAs being based on defined criteria such as animal status or tissue origin. For ruminant studies, RumimiR supplements the widely used miRBase database by browsing and filtering using complementary criteria, and the integration of all published sequences described as novel. The principal goal of this database is to provide easy access to all ruminant microRNAs described in the literature.
The pseudogene SURFIN 4.1 is vital for merozoite formation in blood stage P. falciparum
Authors: Macedo-Silva Tatiane , Araujo Rosana Beatriz Duque , Wunderlich Gerhard
Published: February 2019

The surf gene family of the human malaria parasite Plasmodium falciparum encodes for antigens with largely unknown functions. Three of the ten surf genes found in the P. falciparum 3D7 genome are annotated as pseudogenes, and one of these – surf4.1 (PF3D7_0402200) - was continuously transcribed in P. falciparum 3D7 blood stage forms. GFP-tagging revealed that despite several stop codons a full-length protein was expressed, which localized to developing merozoites. Analysis of cDNAs showed that no specific editing occurred pointing to readthrough of stop codons during translation. Intriguingly, attempts to generate parasite lines containing an additional artificial stop codon failed. Transcript knockdown revealed that surf4.1 is essential for merozoite formation in late trophozoite/schizont stages while DNA replication seemed not to be influenced. SURFIN4.1 is the first example of a plasmodial multigene family member of which a knockout is deleterious and may pose as a novel target for anti-malarial therapy.
Structural disconnections explain brain network dysfunction after stroke
Authors: Griffis Joseph C. , Metcalf Nicholas V. , Corbetta Maurizio , Shulman Gordon L.
Published: February 2019

Functional connectivity (FC) studies have identified physiological signatures of stroke that correlate with behavior. Using structural and functional MRI data from 114 stroke patients, 24 matched controls, and the Human Connectome Project, we tested the hypothesis that structural disconnection, not damage to critical regions, underlies FC disruptions. Disconnection severity outperformed damage to putative FC connector nodes for explaining reductions in system modularity, and multivariate models based on disconnection outperformed damage models for explaining FC disruptions within and between systems. Across patients, disconnection and FC patterns exhibited a low-dimensional covariance dominated by a single axis linking interhemispheric disconnections to reductions in FC measures of interhemispheric system integration, ipsilesional system segregation, and system modularity, and that correlated with multiple behavioral deficits. These findings clarify the structural basis of FC disruptions in stroke patients and demonstrate a low-dimensional link between perturbations of the structural connectome, disruptions of the functional connectome, and behavioral deficits.
Enzyme kinetics of tobacco Rubisco expressed in Escherichia coli varies depending on the small subunit composition
Authors: Lin Myat T. , Stone William D. , Chaudhari Vishal , Hanson Maureen R.
Published: February 2019

Abstract

Rubisco catalyzes the first step in carbon fixation and has been a strategic target to improve photosynthetic efficiency. In plants, Rubisco is a complex made up of eight large subunits encoded by a chloroplast gene, rbcL, and eight small subunits expressed from a nuclear gene family and targeted to chloroplast stroma. Biogenesis of Rubisco in plants requires a chaperonin system composed of Cpn60α, Cpn60β and Cpn20, which helps fold the large subunit, and multiple chaperones including RbcX, Raf1, Raf2 and BSD2, which help the dimerization of the folded large subunits and subsequent assembly with the small subunits into L8S8 holoenzymes. A recent study successfully assembled functional Arabidopsis Rubisco in Escherichia coli by co-expressing the two subunits with Arabidopsis chaperonins and chaperones (Aigner et al., 2017). In this study, we modified the expression vectors used in that study and adapted them to express tobacco Rubisco by replacing the Arabidopsis genes with tobacco ones. Next, we surveyed the small subunits present in tobacco, co-expressed each with the large subunit and successfully produced active tobacco enzymes composed of different small subunits in E. coli. These enzymes produced in E. coli have carboxylation kinetics very similar to that of the native tobacco Rubisco. We also produced tobacco Rubisco with a recently discovered trichome small subunit in E. coli and found that it has a higher catalytic rate and a lower CO2 affinity compared to the enzymes with other small subunits. Our improvements in the E. coli Rubisco expression system will allow us to probe features of both the chloroplast and nuclear-encoded subunits of Rubisco that affect its catalytic rate and CO2 specificity.
Efficient mesoscale phenotypic screening in cultured primary neuron culture
Authors: Nedrud David , He Yungui , Schmidt Daniel
Published: February 2019

A longstanding question in neuroscience is how the activity of ion channels shapes neuronal activity and, as a result, computation in circuits and networks. Optogenetic reagents are tools to answer this question by enabling precise and dynamic perturbation of cellular states. However, development of these reagents can be hampered by low-throughput assays in non-physiological contexts. Here, we develop an all optical phenotypic screen in cultured primary hippocampal neurons that enables the functional assessment of large libraries of genetically encoded optogenetic actuators. Combining real-time analysis and data reduction methods allows for continuous observation of several thousand neurons for several days without onerous data storage overhead. This screening system may be useful in a diversity of research questions that can be coupled to optical perturbation and sensing.
Fluorescence intensity monitors as intensity and beam-position diagnostics for X-ray free-electron lasers
Authors: Heimann Philip , Reid Alexander , Feng Yiping , Fritz David
Published: February 2019

For LCLS-II, a fluorescence intensity monitor for the non-invasive, pulse-by-pulse normalization of experiments has been developed. A prototype diagnostic was constructed with a microchannel plate assembly and two photodiodes. The diagnostic was then installed in the LCLS SXR instrument Kirkpatrick–Baez mirror chamber with the detectors located above the vertically reflecting mirror. The linearity, noise and position sensitivity of the detectors have been characterized. The photodiode responsivity is suitable for high pulse energies. The microchannel plate detector shows sufficient responsivity over a wide range of pulse energies. The relative signal from the two photodiodes provides a sensitive measure of the X-ray beam position. The fluorescence intensity monitor provides intensity normalization while being compatible with high incident power, a 0.93 MHz repetition rate and ultra-high vacuum.
A comparison of absorption and phase contrast for X-ray imaging of biological cells. Erratum
Authors: Nave Colin
Published: February 2019

An error in the calculation for X-ray absorption imaging has been identified in the paper by Nave (2018) [J. Synchrotron Rad.
25, 1490–1504]. The required fluence and dose in the paper are a factor of ten too low for this mode of imaging.
Cyber threats confronting the digital built environment
Authors: Parn Erika A. , Edwards David
Published: February 2019

Purpose

Smart cities provide fully integrated and networked connectivity between virtual/digital assets and physical building/infrastructure assets to form digital economies. However, industrial espionage, cyber-crime and deplorable politically driven cyber-interventions threaten to disrupt and/or physically damage the critical infrastructure that supports national wealth generation and preserves the health, safety and welfare of the populous. The purpose of this paper is to present a comprehensive review of cyber-threats confronting critical infrastructure asset management reliant upon a common data environment to augment building information modelling (BIM) implementation.

Design/methodology/approach

An interpretivist, methodological approach to reviewing pertinent literature (that contained elements of positivism) was adopted. The ensuing mixed methods analysis: reports upon case studies of cyber-physical attacks; reveals distinct categories of hackers; identifies and reports upon the various motivations for the perpetrators/actors; and explains the varied reconnaissance techniques adopted.

Findings

The paper concludes with direction for future research work and a recommendation to utilize innovative block chain technology as a potential risk mitigation measure for digital built environment vulnerabilities.

Originality/value

While cyber security and digitization of the built environment have been widely covered within the extant literature in isolation, scant research has hitherto conducted an holistic review of the perceived threats, deterrence applications and future developments in a digitized Architecture, Engineering, Construction and Operations (AECO) sector. This review presents concise and lucid reference guidance that will intellectually challenge, and better inform, both practitioners and researchers in the AECO field of enquiry.
Marie Unna hereditary hypotrichosis accompanied by multiple familial trichoepithelioma in a Chinese family
Authors: Huang Ye , Cai Chuan , Ren Li , Cui Caijuan , Zhang Xue , Liu Wei
Published: February 2019

Marie Unna hereditary hypotrichosis (MUHH) and multiple familial trichoepithelioma (MFT) are both autosomal dominant disorders. Recently, certain genes (HR and EPS8L3) have been found to be responsible for MUHH, while CYLD has been demonstrated to be the main pathogenic gene in MFT patients. However, there exist a number of CYLD mutation‐negative MFT cases, for which the causative gene has been unknown. Here, we identified a large, five‐generation Han Chinese family with several patients presenting with MUHH and MFT. Sanger sequencing of three genes in 13 family members was performed. We found that the c.1A>G mutation in an inhibitory upstream open‐reading frame of HR (U2HR) was present in all MUHH patients, while no pathogenic variants were found in the 3ʹ‐ or 5ʹ‐untranslated regions, exons or flanking intronic sequences of EPS8L3 or CYLD in any family members. Subsequently, whole‐genome sequencing was performed for five affected and one unaffected family member. We found no CYLD variants but identified an FABP12 variant (rs536105592 G>A) in the patients with both MUHH and MFT. These results suggest that the U2HR mutation was responsible for MUHH and the FABP12 variant may be coincidental in the accompanying MFT in this unique pedigree. This report deepens our understanding of the genetic basis of hair follicle diseases.
In‐transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab
Authors: Kiyohara Takahiro , Shijimaya Takako , Miyamoto Mari , Nagano Naoko , Nakamaru Sei , Makimura Kaoru , Tanimura Hirotsugu
Published: February 2019

A 65‐year‐old Japanese man presented with a dome‐shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin–eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier‐like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in‐transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in‐transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in‐transit recurrence of Merkel cell carcinoma.
Seismic receiver coupling to the seafloor
Authors: Landschulze Marcus
Published: February 2019

The presence of geophysical receivers on the seafloor changes the local wave field due to the receiver seafloor interaction. The resulting PP‐ and PS‐wave distortion of the wave field is often referred to as receiver coupling to the seafloor and can make data processing challenging and sometimes impossible. This paper provides an overview of the mathematical approaches to describe receiver coupling, how to estimate receiver coupling and what the difficulties and possible solutions are. The first section shows how the mathematical approach developed from a simple model considering only the vertical receiver component to include all three receiver components and their interactions with the seafloor. In the second section, I show how receiver coupling can be measured and how it can be improved using mathematical and data‐driven approaches.
Effect of hippotherapy on gait symmetry in children with cerebral palsy: A pilot study
Authors: Mutoh Tomoko , Mutoh Tatsushi , Tsubone Hirokazu , Takada Makoto , Doumura Misato , Ihara Masayo , Shimomura Hideo , Taki Yasuyuki , Ihara Masahiro
Published: February 2019

We aimed to investigate the effect of hippotherapy on gait symmetry in children with cerebral palsy (CP). Twelve children with Gross Motor Function Classification System (GMFCS) levels II−IV received weekly hippotherapy lesson for 1 year. Gait analyses were performed during a 5‐m walking test, using a portable, tri‐axial accelerometer‐based motion recorder. The baseline symmetry index derived from the Lissajous index (LI) figure before hippotherapy was greater than the LI in age‐matched normal subjects (P < 0.01). Hippotherapy was associated with a decreased LI (−10.4 ± 4.9%, P = 0.018) and an improved GMFCS score (−0.6 ± 0.7, P = 0.02). These data suggest that hippotherapy has a beneficial effect on symmetry of the trunk movement in children with CP.
The Proliferation of Dan Graham's Pavilions
Authors: Roberts Bill
Published: February 2019

This essay revisits American artist Dan Graham's original motivations for the development of his long‐running series of pavilion sculptures. It explores their relationship to minimalist art of the 1960s and to the postmodern architecture of the 1970s and 1980s, before considering the implications of their large number and global spread for their current critical purchase. It is argued that the proliferation of Graham's pavilions across innumerable sites since the early 1980s augments their mimicry of corporate architecture, lending additional credence to existing claims made for his work as a critical parallel to wider architectural trends. This is especially the case in so far as contemporary corporate architecture itself, as a key expression of today's ruling logic of finance capitalism, is programmed to proliferate as a ‘spatial fix’ for capital's periodic crises of over‐accumulation, as a means to absorb surplus capital.
Strategies for integrating farmers into modern vegetable supply chains in Vietnam: farmer attitudes and willingness to accept
Authors: Pham Hung Duy , Crase Lin , Burton Michael , Cooper Bethany
Published: February 2019

In Vietnam, the development of so‐called ‘modern’ vegetable supply chains is receiving considerable interest amongst researchers and governments. This interest partly stems from the view that enhancements in food safety can be achieved if farmers are willing to adopt supply chains that are often associated with ‘western’ forms of retailing. Our study investigates farmers’ willingness to change to two ‘modern’ alternatives – a supply model based on cooperatives and another based on investors facilitating the change. Using discrete choice data drawn from 412 farmers, mixed logit models in willingness to pay space are developed that reveal the relative importance of different drivers of change. The paper offers insights that can inform governments about the incentives required to bring about change. In addition, the paper illustrates the novel application of a choice experiment to enumerating the perceived costs of changes in vegetable supply chains.
Component skills of reading and their structural relations: evidence from three sub‐Saharan African languages with transparent orthographies
Authors: Kim Young‐Suk Grace , Piper Benjamin
Published: February 2019

Background

We examined the component skills of reading comprehension (i.e., letter sound knowledge, syllable reading fluency, decoding fluency, text or oral reading fluency and listening comprehension) and their structural relations using data from three sub‐Saharan African languages with transparent orthographies in a multilingual context.

Methods

Data from Kiswahili (N = 946), Kikamba (N = 444) and Lubukusu (N = 499) reading assessments at the end of Grade 2 in Kenya were analysed using path analyses.

Results

The magnitudes of the relations were similar across the three languages with some differences amongst the languages. Total effects (regression weights), accounting for direct and indirect effects, varied across the component skills: text reading fluency (0.73 to 0.77), decoding fluency (0.49 to 0.82), letter sound knowledge (0.44 to 0.45), syllable reading fluency (−0.12 to 0.16) and listening comprehension (0.08 to 0.23).

Conclusions

The results indicate similar reading mechanisms across the three sub‐Saharan languages.
Getting along with danger? Place attachment, employment relationship, and protective behaviour responses
Authors: Hou Guanghui , Chen Tong , Zhang Qin , Wang Ying , Yuan Ying
Published: February 2019

This study aims to explain a commonly overlooked risk phenomenon where a community living around a hazardous facility adapts itself to the dangers posed by the facility. A survey of 434 residents was administered in the community around the Botian chemical plant in Tianjin, China. Hierarchical regression analyses indicate that place attachment negatively predicts intention to move away and positively predicts intention to protest. Moreover, it negatively moderates the relationship between risk perception and intention to move away. Employment relationship negatively affects intention to move and protest, and it negatively (positively) moderates the relationship between risk perception and intention to move (intention to protest). The total effects of place attachment and employment relationship weaken the positive effect of risk perception on protective responses.
Workplace wellbeing in an urban emergency department in Aotearoa New Zealand
Authors: Kumar Rishi , Pio Fofoa , Brewer Julianne , Frampton Christopher , Nicholls Mike
Published: February 2019

Objectives

Staff wellbeing is important for individuals and considered integral to the development and maintenance of high performing health systems. Unless baseline parameters of wellbeing are known, the effects of any interventions to improve staff wellbeing will remain uncertain. By clarifying staff perceptions and objective measures of important factors related to wellbeing, our primary goal was to assess the baseline wellbeing of staff in our central city ED.

Methods

A survey template, the WoWe@AED (Workplace Wellbeing at the Adult Emergency Department) was developed from several sources. Burnout was measured using the Copenhagen Burnout Inventory. Inclusion in the survey required that participants worked in our ED, all staff groups were eligible. The electronic survey was conducted between 22 January and 5 February 2018. Quantitative and qualitative data were analysed.

Results

Two hundred and seventy (71.1%) of 380 potential participants participated. All staff groups were represented. About 72.4% agreed/strongly agreed that Adult Emergency Department was an excellent place to work, 80.7% found their work meaningful. About 42.0% felt well informed regarding important decisions. One hundred and eighty‐three (48.2%) out of 380 completed the Copenhagen Burnout Inventory. Overall, personal burnout was 42.1% (n = 77), work‐related burnout was 35% (n = 64) and client‐related burnout was 27.9% (n = 51). Females were significantly (<0.05) more likely to have burnout in some or all domains. Four key themes were identified: supportive teamwork and relationships; providing high quality patient care; resourcing; and workload issues.

Conclusions

Baseline indices of wellbeing of the frontline staff in a central city ED have been documented. These have informed wellbeing interventions. Future measures can be compared against these data.
Save Palm Oil, Save the Nation: Palm Oil Companies and the Shaping of Indonesia’s National Interest
Authors: Choiruzzad Shofwan Al Banna
Published: February 2019

This article argues that rather than being an automatic consequence of the rising importance of palm oil in Indonesia’s economy, the inclusion of palm oil in Indonesia’s set of national interest priorities in its international relations was a result of an intentional campaign run by palm oil companies. Taking the subjectivist assumption on national interest as the starting point and drawing on the narrative policy analysis literature, this study investigates the process of inclusion by unpacking the discursive framework that enables such a process to be successful. It finds that palm oil companies employed “objectification” to frame the growth of the palm oil industry as a shared interest of the public and “delegitimization” to frame opposing voices as the manifestations of foreign interests. Such discursive frameworks provided unambiguous and straightforward foreign policy direction, but at the same time prevented a more comprehensive understanding of the complex issue of palm oil.
Territory, Class, and Kinship: A Case Study of an Indonesian Regional Election
Authors: Haryanto  , Sukmajati Mada , Lay Cornelis
Published: February 2019

This article examines electoral strategies used by candidates in regional elections in new Indonesian jurisdictions. It uses the 2017 regional election in Maybrat, West Papua as a case study. It explores the candidates’ strategies and motivations in context, as well as their results. Research indicates that similar election strategies were used by candidates, such as exploiting elements of territory, class, and kinship. However, their emphases differed: the losing candidate had positioned class solidarity centrally in their campaigns, while the victorious candidate had emphasized spatial solidarity. This research also observed the exploitation of latent tensions over the location of the regional capital in the new jurisdiction of Maybrat, where the creation of new resources, services, and public offices intensified long‐standing contestations. Ultimately, distancing themselves from electoral logics that target individual voters, the candidates in Maybrat targeted specific groups, a strategy representative of Papuan society’s communal tendencies.