bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractPseudomonas 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.ImportanceThe 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

AbstractAlzheimer’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

ABSTRACTAimsPersister 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 ResultsTo 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.ConclusionsTherefore, E. col has devised a method to outcompete its competitors by preventing their resuscitation with indole.SignificanceThis 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

AbstractThe 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

ABSTRACTInfertility 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

AbstractDravet 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

PurposeThe 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/approachIn 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.FindingsThe 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/valueThis 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.