bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic Models of Larval Zebrafish Behavior: Structure on Many Scales
Authors: Johnson Robert Evan , Linderman Scott , Panier Thomas , Wee Caroline Lei , Song Erin , Herrera Kristian Joseph , Miller Andrew , Engert Florian
Published: June 2019

Nervous systems have evolved to combine environmental information with internal state to select and generate adaptive behavioral sequences. To better understand these computations and their implementation in neural circuits, natural behavior must be carefully measured and quantified. Here, we collect high spatial resolution video of single zebrafish larvae swimming in a naturalistic environment and develop models of their action selection across exploration and hunting. Zebrafish larvae swim in punctuated bouts separated by longer periods of rest called interbout intervals. We take advantage of this structure by categorizing bouts into discrete types and representing their behavior as labeled sequences of bout-types emitted over time. We then construct probabilistic models – specifically, marked renewal processes – to evaluate how bout-types and interbout intervals are selected by the fish as a function of its internal hunger state, behavioral history, and the locations and properties of nearby prey. Finally, we evaluate the models by their predictive likelihood and their ability to generate realistic trajectories of virtual fish swimming through simulated environments. Our simulations capture multiple timescales of structure in larval zebrafish behavior and expose many ways in which hunger state influences their action selection to promote food seeking during hunger and safety during satiety.
Wide distribution of phage that infect freshwater SAR11 bacteria
Authors: Chen Lin-Xing , Zhao Yan-Lin , McMahon Katherine D. , Mori Jiro F. , Jessen Gerdhard L. , Nelson Tara Colenbrander , Warren Lesley A. , Banfield Jillian F.
Published: June 2019

Fonsibacter (LD12 subclade) are among the most abundant bacterioplankton in freshwater ecosystems. These bacteria belong to the order Pelagibacterales (SAR11) and are related to Pelagibacter (marine SAR11) that dominate many marine habitats. Although a handful of Pelagibacter phage (Pelagiphage) have been described, no phage that infect Fonsibacter have been reported. In this study, a complete Fonsibacter genome containing a prophage was reconstructed from metagenomic data. A circularized and complete genome related to the prophage, referred to as uv-Fonsiphage-EPL, shows high similarity to marine Pelagiphage HTVC025P. Additionally, we reconstructed three complete and one draft genome of phage related to marine Pelagiphage HTVC010P, and predicted a lytic strategy. The similarity in codon usage and co-occurrence patterns of HTVC010P-related phage and Fonsibacter suggested that these phage infect Fonsibacter. Similar phage were detected in Lake Mendota, Wisconsin, where Fonsibacter is also present. A search of related phage revealed the worldwide distribution of some genotypes in freshwater ecosystems, suggesting their substantial role in shaping indigenous microbial assemblages and influence on biogeochemical cycling. However, the uv-Fonsiphage-EPL and one lineage of HTVC010P-related phage have a more limited distribution in freshwater ecosystems. Based on this, and their close phylogenetic relatedness with Pelagiphage, we predict that they transitioned from saline into freshwater ecosystems comparatively recently. Overall, the findings provide insights into the genomic features of phage that infect Fonsibacter, and expand understanding of the ecology and evolution of these important bacteria.
Designing ecologically-optimised vaccines using population genomics
Authors: Colijn Caroline , Corander Jukka , Croucher Nicholas J.
Published: June 2019

Streptococcus pneumoniae (the pneumococcus) is a common nasopharyngeal commensal capable of infecting normally sterile anatomical sites, resulting in invasive pneumococcal disease (IPD). Effective vaccines preventing IPD exist, but each of the antigens they contain typically induces protective immunity against only one of the approximately 100 pneumococcal serotypes, which are differentiated by immunogenically-distinct polysaccharide capsules. Serotypes vary in their propensity to cause IPD, quantified as their invasiveness. Vaccines are designed to include serotypes commonly isolated from IPD, but the immunity they induce is sufficiently strong to also eliminate vaccine serotypes from carriage. This enables their replacement by non-vaccine serotypes in the nasopharynx. The emergence of invasive non-vaccine serotypes has undermined some vaccination programmes’ benefits. Recent advances in genomics and modeling have enabled forecasting of which non-vaccine serotypes will be successful post-vaccination. Here, we demonstrate that vaccines optimised using this framework can minimise IPD and antibiotic-resistant disease more effectively than existing formulations in the model, through mitigating the consequences of serotype replacement. The simulations also demonstrate that tailoring vaccines to the pre-vaccine bacterial population is likely to have a substantial impact on reducing IPD, highlighting the importance of epidemiological data, genomics and ecological models as tools for vaccine design and evaluation.
flexiMAP: A regression-based method for discovering differential alternative polyadenylation events in standard RNA-seq data
Authors: Szkop Krzysztof J. , Moss David S. , Nobeli Irene
Published: June 2019

We present flexiMAP (flexible Modeling of Alternative PolyAdenylation), a new beta-regression-based method implemented in R, for discovering differential alternative polyadenylation events in standard RNA-seq data. Importantly, flexiMAP allows modeling of multiple known covariates that often confound the results of RNA-seq data analysis. We show, using simulated data, that flexiMAP is very specific and outperforms in sensitivity existing methods, especially at low fold changes. In addition, the tests on simulated data reveal some hitherto unrecognised caveats of existing methods.

Availability

The flexiMAP R package is available at: https://github.com/kszkop/flexiMAP

Scripts and data to reproduce the analysis in this paper are available at: https://doi.org/10.5281/zenodo.3238619

Contact

Irene Nobeli, i.nobeli@bbk.ac.uk
Nature based measures increase freshwater biodiversity in agricultural catchments
Authors: Williams Penny , Biggs Jeremy , Stoate Chris , Szczur John , Brown Colin , Bonney Simon
Published: June 2019

This is the first study that describes the effect of adding mitigation measures on the freshwater biodiversity of all waterbody types in agricultural catchments. We measured alpha (site) and gamma (catchment) richness annually over a nine-year period in all the streams, ponds and ditches in three upper-catchments in the English lowlands, and investigated whether freshwater plant biodiversity could be increased by adding: (i) multi-functional ecosystem services measures to intercept pollutants, store water and promote biodiversity, and, (ii) biodiversity-only protection measures. In the absence of measures, all catchments saw a decline in macrophyte richness during the survey (mean species loss of 1% pa, rare species loss of 2% pa). Ponds were a key habitat with a disproportionate influence on catchment trends. Five years after introducing measures, natural colonisation of ecosystem services waterbodies (dammed streams and ditches, runoff ponds, flood storage ponds) largely cancelled-out the background loss of plant species but, importantly, did not restore the loss of rare plants. Adding clean water ponds as a biodiversity-only enhancement measure brought substantial benefits: increasing total-catchment richness by 26%, and the number of rare plant species by 181%. Populations of spatially restricted species also increased. Adding stream debris-dams as a biodiversity measure did not affect plant richness or rarity. The findings suggest that ecosystem services measures could bring some biodiversity benefits to agricultural catchments. However, creating clean-water ponds specifically targeted for biodiversity could hold considerable potential as a tool to help stem, and even reverse, ongoing declines in freshwater plant biodiversity across farming landscapes.
Reconstruction of in-vivo subthreshold activity of single neurons from large-scale spiking recordings
Authors: Papaioannou Stylianos , Marques Smith André , Eriksson David
Published: June 2019

Current developments in the manufacturing of silicon probes allow recording of spikes from large populations of neurons from several brain structures in freely moving animals. It is still, however, technically challenging to record the membrane potential from awake behaving animals. Routine access to the subthreshold activity of neurons would be of great value in order to understand the role of, for example, neuronal integration, oscillations, and excitability. Here we have developed a framework for reconstructing the subthreshold activity of single neurons using the spiking activity from large neuronal populations. The reconstruction accuracy and reliability have been evaluated with ground truth data provided from simultaneous patch clamp membrane potential recordings in-vivo. Given the abundance of large-scale spike recordings in the contemporary systems neuroscience society, this approach provides a general access to the subthreshold activity and hence could shed light on the intricate mechanisms of the genesis of spiking activity.
CRISPR-Cas immunity repressed by a biofilm-activating pathway inPseudomonas aeruginosa
Authors: Borges Adair L. , Castro Bardo , Govindarajan Sutharsan , Solvik Tina , Escalante Veronica , Bondy-Denomy Joseph
Published: June 2019

CRISPR-Cas systems are adaptive immune systems that protect bacteria from bacteriophage (phage) infection. To provide immunity, RNA-guided protein surveillance complexes recognize foreign nucleic acids, triggering their destruction by Cas nucleases. While the essential requirements for immune activity are well understood, the physiological cues that regulate CRISPR-Cas expression are not. Here, a forward genetic screen identifies a two-component system (KinB/AlgB), previously characterized in regulatingPseudomonas aeruginosavirulence and biofilm establishment, as a regulator of the biogenesis and activity of the Type I-F CRISPR-Cas system. Downstream of the KinB/AlgB system, activators of biofilm production AlgU (a σEorthologue) and AlgR, act as repressors of CRISPR-Cas activity during planktonic and surface-associated growth. AmrZ, another biofilm activator, functions as a surface-specific repressor of CRISPR-Cas immunity.Pseudomonasphages and plasmids have taken advantage of this regulatory scheme, and carry hijacked homologs of AmrZ, which are functional CRISPR-Cas repressors. This suggests that while CRISPR-Cas regulation may be important to limit self-toxicity, endogenous repressive pathways represent a vulnerability for parasite manipulation.
Immune cells lacking Y chromosome have widespread dysregulation of autosomal genes
Authors: Dumanski Jan P. , Halvardson Jonatan , Davies Hanna , Rychlicka-Buniowska Edyta , Mattisson Jonas , Moghadam Behrooz Torabi , Nagy Noemi , Węglarczyk Kazimierz , Bukowska-Strakova Karolina , Danielsson Marcus , Olszewski Paweł , Piotrowski Arkadiusz , Oerton Erin , Ambicka Aleksandra , Przewoźnik Marcin , Bełch Łukasz , Grodzicki Tomasz , Chłosta Piotr L. , Imreh Stefan , Giedraitis Vilmantas , Kilander Lena , Nordlund Jessica , Ameur Adam , Gyllensten Ulf , Johansson Åsa , Józkowicz Alicja , Siedlar Maciej , Klich-Rączka Alicja , Jaszczyński Janusz , Enroth Stefan , Baran Jarosław , Ingelsson Martin , Perry John R. B. , Ryś Janusz , Forsberg Lars A.
Published: June 2019

Mosaic loss of chromosome Y (LOY) in leukocytes has been associated with many diseases, yet it remains unclear whether this form of clonal mosaicism exerts a direct physiological effect. Here we perform single-cell and bulk RNA sequencing in leukocytes, observing considerable variation in the rate of LOY across individuals, cell types and disease state. Cells with LOY demonstrated a profound degree of transcriptional dysregulation impacting ∼500 autosomal genes. These genes are preferentially involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y challenging the view of it as a “genetic wasteland”. Furthermore, they support the hypothesis that altered immune function in leukocytes is a mechanism directly linking LOY to disease.
Maximizing the coding capacity of neuronal networks
Authors: Chowdhary Sandeep , Assisi Collins
Published: June 2019

Information in neuronal networks is encoded as spatiotemporal patterns of activity. The capacity of a network may thus be thought of as the number of stable spatiotemporal patterns it can generate. To understand what structural attributes of a network enable it to generate a profusion of stable patterns, we simulated an array of 9×9 neurons modelled as pulse-coupled oscillators. The structure of the network was inspired by the popular puzzle Sudoku such that its periodic responses mapped to solutions of the puzzle. Given that there are nearly a 109possible Sudokus, this networks could possibly generate 109spatiotemporal patterns. We show that the number of stable patterns were maximized when excitatory and inhibitory inputs to each neuron were balanced. When this balance was disrupted, only a subset of patterns with certain symmetries survived.
Kinetochore capture by spindle microtubules: why fission yeast may prefer pivoting to search-and-capture
Authors: Nayak Indrani , Das Dibyendu , Nandi Amitabha
Published: June 2019

The mechanism by which microtubules find kinetochores during spindle formation is a key question in cell biology. Previous experimental studies have shown that although search-and-capture of kinetochores by dynamic microtubules is a dominant mechanism in many organisms, several other capture mechanisms are also possible. One such mechanism reported in Schizosaccharomyces pombe shows that microtubules can exhibit a prolonged pause between growth and shrinkage. During the pause, the microtubules pivoted at the spindle pole body search for the kinetochores by performing an angular diffusion. Is the latter mechanism purely accidental, or could there be any physical advantage underlying its selection? To compare the efficiency of these two mechanisms, we numerically study distinct models and compute the timescales of kinetochore capture as a function of microtubule number N. We find that the capture timescales have non-trivial dependences on microtubule number, and one mechanism may be preferred over the other depending on this number. While for small N (as in fission yeast), the typical capture times due to rotational diffusion are lesser than those for search-and-capture, the situation is reversed beyond a certain N. The capture times for rotational diffusion tend to saturate due to geometrical constraints, while those for search-and-capture reduce monotonically with increasing N making it physically more efficient. The results provide a rationale for the common occurrence of classic search-and-capture process in many eukaryotes which have few hundreds of dynamic microtubules, as well as justify exceptions in cells with fewer microtubules.
Characterizing the innate and adaptive responses of immunized mice toBordetella pertussisinfection usingin vivoimaging and transcriptomic analysis
Authors: Boehm Dylan T. , Varney Melinda E. , Wong Ting Y. , Nowak Evan S. , Sen-Kilic Emel , Hall Jesse , Bradford Shelby D. , DeRoos Katherine , Bevere Justin , Epperly Matthew , Maynard Jennifer A. , Hewlett Erik L. , Barbier Mariette , Damron F. Heath
Published: June 2019

Bordetella pertussis(B. pertussis) is the causative agent of pertussis (whooping cough). Since the 1990s, pertussis has re-emerged in the United States despite an estimated 95% vaccine coverage. Our goal was to characterize neutrophil responses and gene expression profiles of murine lungs in the context of vaccination andB. pertussischallenge. We utilized a bioluminescent neutrophil mouse model (NECre luc) to track neutrophil recruitment. NECre luc mice were immunized with whole cell vaccine (WCV), acellular vaccine (ACV), or a truncated adenylate cyclase toxoid (RTX) vaccine. Neutrophil recruitment was measured in live mice across time and corroborated by flow cytometry and other data. WCV immunized mice showed signs of neutrophilia in response toB. pertussischallenge. Mice immunized with either ACV or WCV cleared the challenge infection; however immunization with RTX alone was not protective. RNA sequencing revealed distinctive gene expression profiles for each immunization group. We observed an increase in expression of genes associated with responses to infection, and changes in expression of distinct genes in each vaccine group, providing a complex view of the immune response toB. pertussisinfection in mice. This study suggests that combination of immunological analysis with transcriptomic profiling can facilitate discovery of pre-clinical correlates of protection for vaccine development.
Oligomeric state of the ZIKV E protein defines protective immune responses
Authors: Metz Stefan W. , Thomas Ashlie , Brackbill Alex , Forsberg John , Miley Michael J. , Lopez Cesar A. , Lazear Helen M. , Tian Shaomin , de Silva Aravinda M.
Published: June 2019

The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies. We hypothesized that Zika Envelope (E) protein subunit vaccines have performed poorly because the antigens tested have been recombinant E monomers that do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. To test this hypothesis, we engineered and produced stable recombinant E protein homodimers. Unlike the E monomer, the dimer was recognized by strongly neutralizing monoclonal antibodies isolated from Zika-immune individuals. In a mouse model of vaccination, the dimeric antigen stimulated strongly neutralizing antibodies that targeted epitopes that were similar to epitopes recognized by human antibodies following natural Zika virus infection. In contrast, the monomer antigen stimulated lower levels of neutralizing antibodies directed to simple epitopes on domain III of E protein. In a mouse model of ZIKV challenge, only E dimer antigen stimulated protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines. The flavivirus field has a long history of using E monomers as vaccine antigens with limited success. These results are applicable to developing second generation subunit vaccines against Zika as well as other medically important flaviviruses such as dengue and yellow fever viruses.
A large-scale comparison shows that genetic changes causing antibiotic resistance in experimentally evolvedPseudomonas aeruginosapredict those in naturally evolved bacteria
Authors: Wardell Samuel J. T. , Rehman Attika , Martin Lois W. , Winstanley Craig , Patrick Wayne M. , Lamont Iain L.
Published: June 2019

Pseudomonas aeruginosais an opportunistic pathogen that causes a wide range of acute and chronic infections. An increasing number of isolates have acquired mutations that make them antibiotic resistant, making treatment more difficult. To identify resistance-associated mutations we experimentally evolved the antibiotic sensitive strainP. aeruginosaPAO1 to become resistant to three widely used anti-pseudomonal antibiotics, ciprofloxacin, meropenem and tobramycin. Mutants were able to tolerate up to 2048-fold higher concentrations of antibiotic than strain PAO1. Genome sequences were determined for thirteen mutants for each antibiotic. Each mutant had between 2 and 8 mutations. There were at least 8 genes mutated in more than one mutant per antibiotic, demonstrating the complexity of the genetic basis of resistance. Additionally, large deletions of up to 479kb arose in multiple meropenem resistant mutants. For all three antibiotics mutations arose in genes known to be associated with resistance, but also in genes not previously associated with resistance. To determine the clinical relevance of mutations uncovered in experimentally-evolved mutants we analysed the corresponding genes in 457 isolates ofP. aeruginosafrom patients with cystic fibrosis or bronchiectasis as well as 172 isolates from the general environment. Many of the genes identified through experimental evolution had changes predicted to be function-altering in clinical isolates but not in isolates from the general environment, showing that mutated genes in experimentally evolved bacteria can predict those that undergo mutation during infection. These findings expand understanding of the genetic basis of antibiotic resistance inP. aeruginosaas well as demonstrating the validity of experimental evolution in identifying clinically-relevant resistance-associated mutations.

Importance

The rise in antibiotic resistant bacteria represents an impending global health crisis. As such, understanding the genetic mechanisms underpinning this resistance can be a crucial piece of the puzzle to combatting it. The importance of this research is that by experimentally evolvingP. aeruginosato three clinically relevant antibiotics, we have generated a catalogue of genes that can contribute to resistancein vitro. We show that many (but not all) of these genes are clinically relevant, by identifying variants in clinical isolates ofP. aeruginosa. This research furthers our understanding of the genetics leading to resistance inP. aeruginosaand provides tangible evidence that these genes can play a role clinically, potentially leading to new druggable targets or inform therapies.
Exploratory Data Analysis in a Six-Year Longitudinal Study in Healthy Brain Aging
Authors: Gómez-Ramírez Jaime , Ávila Villanueva Marina , Frades Payo Belén , del Ser Quijano Teodoro , Valentí Soler Meritxell , Zea Sevilla María Ascensión , Fernández-Blázquez Miguel Ángel
Published: June 2019

Abstract

Alzheimer’s Disease (AD) is a complex, multifactorial and comorbid condition. The asymptomatic behavior in early stages of the disease is a paramount obstacle to formulate a preclinical and predictive model of AD. Not surprisingly, the AD drug approval rate is one of the lowest in the industry, an exiguous 0.4%. The identification of risk factors, preferably obtained by the subject herself, is sorely needed given that the incidence of Alzheimer’s disease grows exponentially with age [Ferri et al., 2005], [Ganguli and Rodriguez, 2011].

During the last 7 years, researchers at Proyecto Vallecas have collected information about the project’s volunteers, aged 70 or more. The Proyecto Vallecas dataset includes information about a wide range of factors including magnetic resonance imaging, genetic, demographic, socioeconomic, cognitive performance, subjective memory complaints, neuropsychiatric disorders, cardiovascular, sleep, diet, physical exercise and self assessed quality of life. The subjects in each visit were diagnosed as healthy, mild cognitive impairment (MCI) or dementia.

In this study we perform Exploratory Data Analysis to summarize the main characteristics of this unique longitudinal dataset. The objective is to characterize the evolution of the collected features over time and most importantly, how their dynamics are related to cognitive decline. We show that the longitudinal dataset of Proyecto Vallecas, if conveniently exploited, holds promise to identifying either factors promoting healthy aging and risk factors related to cognitive decline.
Interkingdom Signal Indole Inhibits Pseudomonas aeruginosa Persister Cell Waking
Authors: Zhang Weiwei , Yamasaki Ryota , Wood Thomas K.
Published: June 2019

Aims

Persister cells are stressed cells that have transient tolerance to antibiotics; these cells undergo no genetic change, but instead, their tolerance is due to reduced metabolism. Unfortunately, little is known about how persisters resuscitate, so we explored the waking of a cells in the presence of the interkingdom signal indole.

Methods and Results

To generate a large population of persister cells, we induced the persister phenotype in the opportunistic pathogen Pseudomonas aeruginosa by pre-treating cells with carbonyl cyanide m-chlorophenylhydrazone to reduce translation by depleting ATP levels, and found, via single cell observations, that proline is sufficient to wake the persister cells. P. aeruginosa is often present in the gastrointestinal tract, and indole from commensal bacteria such as Escherichia coli has been shown to inhibit P. aeruginosa quorum sensing and pathogenicity without influencing growth. Furthermore, indole is not toxic to P. aeruginosa persister cells. However, we find here that physiological concentrations of indole inhibit P. aeruginosa persister cell resuscitation with an efficiency of higher than 95%. Critically, when contacted with E. coli stationary phase cultures, the indole produced by E. coli completely inhibits persister cell resuscitation of P. aeruginosa.

Conclusions

Therefore, E. col has devised a method to outcompete its competitors by preventing their resuscitation with indole.

Significance

This work provides insight into why indole is produced by commensal bacteria.
Dose assessment in dental cone beam computed tomography: comparison of optically stimulated luminescence dosimetry with the Monte Carlo method
Authors: Lee Chena , Yoon Jeongmin , Han Sang-Sun , Na Ji Yeon , Lee Jeong-Hee , Kim Young Hyun , Hwang Jae Joon
Published: June 2019

The usage and the model variety of CBCT machine has been rapidly increasing, the dose evaluation of individual devices became an important issue. Patient dose from CBCT was assessed with two different methods, optically stimulated luminescence dosimeter (OSLD) measured and monte carlo (MC) simulation, in four different examination modes. Through the measurement process and obtained value, more practical and efficient method in acquiring CBCT effective dose would be suggested. Twenty-five OSLD were calibrated and equipped in human phantom of head and neck organs. This was exposed on 2 CBCT units, CS9300 (Carestream Dental LLC, Atlanta, Georgia) and RAYSCAN α+ (Ray Co. Ltd, Hwaseong-si, Korea) with 2 different examination modes. Dose recorded in dosimetry was obtained and organ dose as well as an effective dose were obtained in each units of examination modes. Those values were also calculated using MC software, PCXMC (STUK, Helsinki, Finland). The organ doses and effective doses from both methods were compared by each examination mode of individual unit. OSLD measured effective dose value was higher than that obtained with MC method in each examination mode, except dual jaw mode of CS9300. The percent difference of effective dose between the two methods were ranged from 4.0 to 14.3 %. The dose difference between the methods was decreased as the examination FOV decreased. Organ dose values were varied according to the method, while overall trend was similar in both methods. The organs showing high dose were mostly consistent in both methods. In this study, the effective dose obtained by OSLD measurement and MC simulation were compared and both methods were described in detail. Consequently, as relatively efficient and easy-handling method, we carefully suggest MC simulation for further dose evaluation.
Practical considerations in the use of a porcine model (Sus scrofa domesticus) to assess prevention of postoperative peritubal adhesions
Authors: Crispi Claudio Peixoto , Crispi Claudio Peixoto , Fernandes Mendes Fernando Luis , de Andrade Claudio Moura , Cardeman Leon , de Nadai Filho Nilton , Portari Elyzabeth Avvad , de Freitas Fonseca Marlon
Published: June 2019

Infertility has been a common postoperative problem caused by peritoneal adhesions. Since several prophylactic agents have recently shown promising preliminary results, more complete studies comparing their real efficacy and safety are needed urgently. The aim of this study was to investigate and describe practical considerations of a porcine model that can be used to assess such prophylactic agents. First, 10 healthy 5½ months old female pigs (24.3 – 31.3 Kg) underwent a standardized laparoscopy to provoke peritubal adhesion formation without prophylactic agents. After 30 days, a second-look laparoscopy was performed to evaluate adhesions and perform adnexectomy for histopathological evaluation. Adhesions at different sites were classified by grade, for which the scores range from 0 (no adhesion) to 3 (very strong vascularized adhesions), and also by area, with scores ranging from 0 (no adhesion) to 4 (>75% of the injured area). The histopathological evaluation of the distal uterine horns, oviducts and ovaries were compared withthose from a control group of six healthy pigs with no previous surgery. Biological samples were collected to assess vitality, inflammation and renal, hepatic and hematopoietic systems. There were small (but significant) changes in serum albumin (P=0.07), globulin (P=0.07), C-reactive protein (P=0.011), fibrinogen (P=0.023) and bilirubin (P<0.01) after 30 days, but all values were within the normal range. No inflammation or abscess formation was observed, but different degrees of adhesion were identified. The estimated occurrence of adhesion (scores >0) and of strong / very strong adhesion (scores >1) was 75% (95% CI: 55 – 94.9) and 65% (95% CI: 45 – 85), respectively. The porcine model represents a useful animal platform that can be used to test the efficacy and safety of candidate prophylactic agents intended to prevent postoperative peritubal adhesions formation. We present several practical considerations and measures that can help to minimize animal suffering and avoid problems during such experiments.
NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype in a novel zebrafish model for Dravet Syndrome
Authors: Weuring Wout J. , Singh Sakshi , Volkers Linda , Rook Martin , van ‘t Slot Ruben H. , Bosma Marjolein , Inserra Marco , Vetter Irina , Verhoeven-Duif Nanda M. , Braun Kees P.J. , Rivara Mirko , Koeleman Bobby P. C.
Published: June 2019

Dravet syndrome is caused by dominant loss-of-function mutations in SCN1A which cause reduced activity of Nav1.1 leading to lack of neuronal inhibition. On the other hand, gain-of-function mutations in SCN8A can lead to a severe epileptic encephalopathy subtype by over activating NaV1.6 channels. These observations suggest that Nav1.1 and Nav1.6 represent two opposing sides of the neuronal balance between inhibition and activation. Here, we hypothesize that Dravet syndrome may be treated by either enhancing Nav1.1 or reducing Nav1.6 activity. To test this hypothesis we generated and characterized a novel DS zebrafish model and tested new compounds that selectively activate or inhibit the human NaV1.1 or NaV1.6 channel respectively. We used CRISPR/Cas9 to generate two separate Scn1Lab knockout lines as an alternative to previous knock-down models. Using an optimized locomotor assay, spontaneous burst movements were detected that were unique to Scn1Lab knockouts and disappear when introducing human SCN1A mRNA. Besides the behavioral phenotype, Scn1Lab knockouts show sudden, electrical discharges in the brain that indicate epileptic seizures in zebrafish. Scn1Lab knockouts showed increased sensitivity to the convulsant pentylenetetrazole and a reduction in whole organism GABA levels. Drug screenings further validated a Dravet syndrome phenotype. We tested the NaV1.1 activator AA43279 and our newly synthesized NaV1.6 inhibitors MV1369 and MV1312 in the Scn1Lab knockouts. Both type of compounds significantly reduced the number of burst movements. Our results show that selective inhibition of NaV1.6 could be just as efficient as selective activation of NaV1.1 and these approaches could prove to be novel potential treatment strategies for Dravet syndrome and other (genetic) epilepsies. Compounds tested in zebrafish however, should always be further validated in other model systems, preferably human derived.
The role of critical moments in young offenders’ drug-using trajectories
Authors: Beccaria Franca , Rolando Sara
Published: June 2019

Purpose

The purpose of this paper is to explore the relationship between drug use and offending by using the concept of critical moments as an analytical tool.

Design/methodology/approach

In total, 41 semi-structured individual interviews with young people (15–25 years) using drugs and in touch with the criminal justice system (CJS) were conducted.

Findings

Analysing critical moments in young people’s drug use contributes to explaining some of the multiple, possible links between drug use and offending. Institutional factors emerged as important, as well as social and economic inequality. This was in particular clear when comparing students’ and immigrants’ trajectories.

Research limitations/implications

Limitations are due to the difficulties in getting access to prisoners and young people in touch with the CJS and the possibility to meet them only once with time limits due to the setting.

Practical implications

Prevention intervention addressed to this target group could take young people’s social contexts and everyday life situation into consideration.

Social implications

To decrease both offending and drug use, structural measures aimed at decreasing social inequalities would be more effective than punishment.

Originality/value

The study proposes a practical way to analyse narratives of young people who have experienced both drug use and offending and to show the importance of socially structured patterns without reducing the complexity of the topic.
A comparison investigation of the contact models for contact and vibration features of cylindrical roller bearings
Authors: Liu Jing , Wang Linfeng , Shi Zhifeng , Yu Wennian , Xiao Huifang
Published: June 2019

Purpose

The purpose of this study is to investigate the contact models for contact and vibration features of cylindrical roller bearings (CRBs). CRBs are important parts of rotating machinery. The contact deformation between the roller and the raceway is an essential research topic for the CRBs. The contact deformation between the roller and the raceway can greatly affect vibration characteristics and fatigue life of the CRBs. In this investigation, six different methods are adopted to calculate the contact deformation, contact area width and contact stress between the roller and raceways of a CRB.

Design/methodology/approach

In this paper, the contact deformations and the contact stiffnesses between the roller and the raceway of a CRB obtained by various well-known empirical methods (Lundberg’s, Palmgren’s, Houpert’s, Cheng’s and Hertzian methods) are directly compared with those by the finite element (FE) method. A two degree-of-freedom (2 DOF) dynamic model of the CRB is applied to investigate the effects of the contact stiffness obtained by different line contact deformation calculation methods on the vibration characteristics, such as the root mean square (RMS), the peak to peak (PTP), the crest factor and the kurtosis of the displacement, velocity and acceleration of the inner raceway.

Findings

The computational results show that different calculation methods for the contact deformations between rollers and raceways have significant effects on the vibrations of the CRB. It is found that that the differences of computational results obtained by Palmgren’s and Lundberg’s models with respect to the FE method are smaller than those by the other three methods, i.e. Houpert’s, Cheng’s and Hertzain models. The amplitude and peak frequency of the frequency response functions from Palmgren’s method are much more similar to those from the finite element method. The above results indicate that Palmgren’s method is a better calculation method for predicting the contact deformations and dynamics of the CRBs.

Originality/value

This work adopts six different methods to calculate the contact deformation, contact area width and contact stress between the roller and raceways of a CRB. Moreover, a vibration model of a CRB is used to investigate the effect of contact stiffness obtained by the above methods on the vibrations of the CRB. The works can give some guidance for the accurate analytical method for calculating the contact deformations between rollers and raceways and the vibrations of the CRB.
Development of low-cost mobile laser scanning for 3D construction indoor mapping by using inertial measurement unit, ultra-wide band and 2D laser scanner
Authors: Chen Chao , Tang Llewellyn , Hancock Craig Matthew , Zhang Penghe
Published: June 2019

Purpose

The purpose of this paper is to introduce the development of an innovative mobile laser scanning (MLS) method for 3D indoor mapping. The generally accepted and used procedure for this type of mapping is usually performed using static terrestrial laser scanning (TLS) which is high-cost and time-consuming. Compared with conventional TLS, the developed method proposes a new idea with advantages of low-cost, high mobility and time saving on the implementation of a 3D indoor mapping.

Design/methodology/approach

This method integrates a low-cost 2D laser scanner with two indoor positioning techniques – ultra-wide band (UWB) and an inertial measurement unit (IMU), to implement a 3D MLS for reality captures from an experimental indoor environment through developed programming algorithms. In addition, a reference experiment by using conventional TLS was also conducted under the same conditions for scan result comparison to validate the feasibility of the developed method.

Findings

The findings include: preset UWB system integrated with a low-cost IMU can provide a reliable positioning method for indoor environment; scan results from a portable 2D laser scanner integrated with a motion trajectory from the IMU/UWB positioning approach is able to generate a 3D point cloud based in an indoor environment; and the limitations on hardware, accuracy, automation and the positioning approach are also summarized in this study.

Research limitations/implications

As the main advantage of the developed method is low-cost, it may limit the automation of the method due to the consideration of the cost control. Robotic carriers and higher-performance 2D laser scanners can be applied to realize panoramic and higher-quality scan results for improvements of the method.

Practical implications

Moreover, during the practical application, the UWB system can be disturbed by variances of the indoor environment, which can affect the positioning accuracy in practice. More advanced algorithms are also needed to optimize the automatic data processing for reducing errors caused by manual operations.

Originality/value

The development of this MLS method provides a novel idea that integrates data from heterogeneous systems or sensors to realize a practical aim of indoor mapping, and meanwhile promote the current laser scanning technology to a lower-cost, more flexible, more portable and less time-consuming trend.
Financing method for real estate and infrastructure development using Markowitz’s portfolio selection model and the Monte Carlo simulation
Authors: Lee Chijoo
Published: June 2019

Purpose

Special purpose companies issue stocks to raise money to finance development of real estate and infrastructure. The advantage of a stock issue is that it does not entail financial cost such as interest on a loan. However, financing obtained in this way has been insufficient due to low interest by investors because of the large variability of the stocks’ earnings rates. The purpose of this paper is to propose methods to improve investment earnings rate for financing.

Design/methodology/approach

The proposed methods are Markowitz’s model and a combination of Markowitz’s model and Monte Carlo simulation. The proposed methods were verified by comparison with actual earnings rate.

Findings

The earnings rate was increased by as much as 23 percent over the actual value. Then, earnings rate compared with risk was analyzed using the Sharpe ratio which is a method to measure investment performance. The performance was also increased by as much as 23 percent over the actual value. The proposed method can help activate investment by increasing investors’ interest in the stock issue.

Originality/value

This study verified that Markowitz’s portfolio model, which is used for econometrics, could be applied for financing of construction project. It is valuable because the previous studies did not propose the method for financing.
Adaptivity of pattern making methods to garments for varying body dimensions
Authors: Kim KyoungOk , Fujii Chinami , Takatera Masayuki
Published: June 2019

Purpose

To suggest a garment for a wider market, the purpose of this paper is to assess the appearance of garments manufactured by a combination of four methods of flat pattern making and four dress forms from different countries. The paper also compares Japanese and British women’s evaluations of these garments’ appearances.

Design/methodology/approach

The authors made 16 garments by combining 4 pattern making methods with measurements from 4 dress forms and evaluated their appearance. The four dress forms were from Japan (Kiiya, called “Kii”), France (Siegel & Stockman, called “St”), the UK (Kennett & Lindsell, called “KL”) and the USA (Wolf Form, called “Wo”), and the four pattern making methods were from Japan (Bunka), Italy (Secoli), France (ESMOD) and the USA (Fashion Institute of Technology, called “FIT”). The authors captured 64 sets of pictures of the 16 garments with the 4 dress forms from the front and the side. The authors then showed images of the four garments made using the same pattern making method with measurements from the four dress forms to subjects for assessment. The subjects – 15 Japanese and 11 British women in their 20s – ranked the pictures in descending order of appearance.

Findings

Subjects from both countries rated garments manufactured using the Bunka and Secoli pattern making methods with the Kii and KL dress forms, and those made using ESMOD and FIT with St and Wo as the highest, even though the dress forms used for pattern making and those for wearing were not coincident. On the contrary, many garments made using Bunka and Secoli with St and Wo, and those made using ESMOD and FIT with Kii and KL were rated lowest in terms of appearance, even though the target dress form and wearing dress form were coincident. Therefore, there are appropriate body measurements for each pattern making method that can render the relevant garment more attractive, likely because these measurements are derived from assumed body proportions in the pattern making method of each country.

Originality/value

Although the evaluation of the appearance of garments is an important factor in garment manufacture, scant research has addressed this issue. Moreover, the comparison between Japanese and British women provided here will help manufacturers make garments that are more attractive to people in both countries.
The mediating effect of intellectual capital, management accounting information systems, internal process performance, and customer performance
Authors: Hariyati Hariyati , Tjahjadi Bambang , Soewarno Noorlailie
Published: June 2019

Purpose

The purpose of this paper is to examine the mediating effect of intellectual capital (IC), management accounting information systems, internal process performance and customer performance (CP) on the relationship of strategies with financial performance (FP).

Design/methodology/approach

The population in this research was medium and large manufacturing company business units in Java. The business unit as the unit of analysis in this research is part of the organization that: is responsible for the production and marketing of a product or set of products; is formed by product type; has its own competitors which are different from competitors of other business units or divisions within a parent company; and has a manager who is responsible and has authority over the planning and implementation of strategies to achieve the specified profit target.

Findings

An innovation strategy that includes product innovation, process innovation and technology has an impact on FP if there is a good internal process performance, reliable management accounting information system and good CP. The internal process performance, which includes operations management processes, customer management processes, innovation processes and regulatory and social processes, optimizes the relationship of the strategy with FP. In this study, IC does not affect CP and internal process performance, nor does the management accounting information system affect FP. However, information systems affect FP through internal process performance and CP.

Originality/value

The originalities of this study are: the use of the continuous innovation strategy in an integrated manner between product innovation and process and information technology – this has never been conducted by other researchers, especially in Indonesia; the use of IC, management accounting information systems, internal process performance and CP as mediating variables; the use of an integrative approach by including variables of IC, management accounting information systems and non-FP as contextual variables related to contingency approaches that have never been conducted in previous research; the modeling of new related concepts with the one developed in the balanced scorecard; and using single mediating and multiple mediating on the influence of sustainable innovation strategies on FP.
Lean-excellence business management for manufacturing SMEs focusing on KRI
Authors: Mohammad Ibrahim Salih , Oduoza Chike F.
Published: June 2019

Purpose

The purpose of this paper is to develop an effective framework for implementing Lean strategies in small- and medium-sized enterprises (SMEs) in the Kurdistan Region of Iraq (KRI).

Design/methodology/approach

Based on the integration of LM tools and techniques with the Malcolm Baldrige National Quality Award (MBNQA) criteria a systematic Lean implementation framework for manufacturing SMEs has been proposed. The core values, drivers and tools of the proposed framework were further developed based on case studies in three SMEs in the KRI.

Findings

Proposed framework is able to provide a simple pathway for SMEs to systematically implement Lean techniques in seven functional areas in order to create Lean culture in the organisation. Business performance measurement in terms of profitability, customer satisfaction, employee’s satisfaction, competitiveness growth and ergonomic improvement is presented in favour of evaluating Lean outcomes appropriately. It also presents the experience of small firms in implementing Lean programmes to show that Lean is valid in SMEs.

Research limitations/implications

The framework concentrates only on the internal issues of the organisation, while external variables such as national culture and external support are excluded.

Practical implications

The framework assists improvements in SMEs that either initially attempt to start Lean journey or those that are at more advanced levels towards excellent-Lean manufacturing. The framework can also be used as a self-assessment model to determine the degree of Lean readiness.

Originality/value

To the best knowledge of the author, it is the first framework that integrates Lean techniques with MBNQA criteria to support Lean implementation in SMEs. It is also the first study regarding Lean-excellence in the KRI.