bluuebunny/crossref_metadata_2025 huggingface dataset:
London Underground Deep Tube Upgrade Programme: System Function Definition Model Case Study
Authors: Everett Nathan , Coultharde-Steer Michael , Fischer Luke
Published: September 2019

On complex rail projects involving a step change in technology or capability, it is important to understand what functionality is required from the system, especially if such changes are new or novel. This paper details a case study (Deep Tube Upgrade Programme) where a structured functional breakdown approach was developed to provide stakeholders (including non‐Systems Engineering practitioners such as operators and maintainers) with an accessible means of checking their life‐cycle concepts and stakeholder requirements for completeness. The approach also enabled the decomposition of those needs into system design requirements for allocation to one or more of the 20 delivery projects, to ensure they will deliver the required emergent properties.
The Good, The Bad and The Ugly
Authors: Nolan Andy , Russell Jennifer L , Nolan Judy , Pruitt Timothy C
Published: September 2019

Many aspects of Systems Engineering rely on Judgement; that is the benefit of having experienced systems engineers in positions of influence. Judgement, as defined here, is the reliance on experience when making decisions. Making decisions based on Judgement can be risky because the accuracy of the Judgement is unknown. What if there a way to mitigate the risk of using Judgement as a basis for decisions?

This paper shows that it is possible to assess a person's Judgement Accuracy based on a simple test that takes less than ten minutes to complete. After testing over two hundred people from two companies and comparing their test results to the accuracy of their Judgements, the test is shown to be a reliable predictor of the a person's Judgement Accuracy.

Why is this important for Systems Engineering? If systems engineers are valued for their Judgement, it is important to know when Judgement is accurate and under what conditions. This paper provides a simple method for any organization to determine the Judgment Accuracy and what to do if is not.
Brownfield Systems Development: Moving from the Vee Model to the N Model for Legacy Systems
Authors: Walden David D.
Published: September 2019

Most systems engineering standards, references, and textbooks consider systems development from a “greenfield” (i.e., clean‐sheet, new development) perspective. There are several development (or life cycle) models used for greenfield developments, with the “Vee” model being a popular choice. Many development efforts are better considered from a “brownfield” perspective (i.e., improving upon or replacing legacy systems). This paper proposes an extension of the Vee model, called the N model, which adds a site survey and various reconstruction processes to help move from the as‐is system to the to‐be system for brownfield development efforts. Three examples are provided to demonstrate how the N model can be applied in different situations.
System Resilience: Application Domain Perspectives
Authors: Ferris Timothy L. J. , Jackson Scott , Willett Keith D. , Hailey Victoria A. , Specking Eric
Published: September 2019

Experts in many domains are studying the concept of resilience, that is, the ability of a system to maintain required capability in the face of an adversity. The purpose of the paper is to explore how resilience related considerations vary among different application domains. Domains examined include civil systems, military systems, cyber space, natural systems, and organizational systems. One factor in how domains differ is how the system reacts or adapts to an adversity, which may be natural or human‐made or internal to the system itself. Domains differ with respect to the timeframes in which the system engages the adversity. The system of systems context can either be a hindrance or a benefit to resilience. Recovery can be accomplished through architectural and design techniques suitable for the system and the scenario at hand. This paper concludes that resilience as described in all domains are contextually appropriate manifestations of resilience.
Interactive Knowledge Architecture An intuitive tool for effective knowledge sharing
Authors: Jensen Halvor Røed , Muller Gerrit , Balfour Adam
Published: September 2019

This paper focuses on sharing knowledge in early phases of system development. It introduces an interactive documentation tool called the Interactive Knowledge Architecture. The tool works as a knowledge base of the problem domain. We created the tool using Human‐Centered Design principles. The lack of an early common understanding of the problem domain can result in increased project costs. We have experienced that we need to focus on the human aspects of project execution to successfully achieve a common understanding among the project team members and customers.

This paper presents the results of implementing the Interactive Knowledge Architecture in three system development projects. To study the tool's ability to meet the human aspects, we used an action research approach. The results of this research imply that the Interactive Knowledge Architecture offers a usable, accessible, and desirable way to document and share knowledge.
The Drone System I: Context‐Level Architecture
Authors: MacCarthy John
Published: September 2019

This paper is the first of two papers that together provide an example of how to use the systems engineering processes outlined in the INCOSE Systems Engineering Handbook and ISO/IEC/IEEE 15288:2015 to develop a SysML system architecture from a user's statement of need and then to develop a mathematical system model for system reliability, availability, and maintainability that may be used to perform system design and cost‐effectiveness trade‐off analyses. This paper focuses on the development of a SysML architecture for a drone system that provides surveillance and delivery services.
An Integrated Quantitative Approach to Acceptance Testing and Related Decisions
Authors: MacCarthy John
Published: September 2019

This paper provides an integrated, analytical framework (and associated tools) for determining the scope of an acceptance test, designing acceptance tests, and for making acceptance decisions. A decision tree model is developed that may be used to determine the value of different acceptance test designs. Hypothesis testing models are developed that may be used to determine the performance threshold for testing, given a desired confidence of failing a bad system (test “Power”), and the design margin required to have a given confidence of passing a good system (test “Confidence”). These two models are then integrated into a single model that may be used to establish a test design (in terms of an acceptance threshold and the number of measurements) that achieves a desired test Power and Confidence. Finally a decision tree model is developed for the system acceptance decision based on the results of a given acceptance test.
Genotoxic activity of 1,2,3‐triazolyl modified furocoumarins and 2,3‐dihydrofurocoumarins
Authors: Kremis Stepan A. , Baev Dmitry S. , Lipeeva Alla V. , Shults Elvira E. , Tolstikova Tatiana G. , Sinitsyna Olga I. , Kochetov Alexey V. , Frolova Tatiana S.
Published: September 2019

The furocoumarin backbone is a promising platform for chemical modifications aimed at creating new pharmaceutical agents. However, the high level of biological activity of furocoumarins is associated with a number of negative effects. For example, some of the naturally occurring ones and their derivatives can show genotoxic and mutagenic properties as a result of their forming crosslinks with DNA molecules. Therefore, a particularly important area for the chemical modification of natural furocoumarins is to reduce the negative aspects of their bioactivity. By studying a group of 21 compounds—1,2,3‐triazolyl modified derivatives of furocoumarin and peucedanin—using the SOS chromotest, the Ames test, and DNA‐comet assays, we revealed modifications that can neutralize the structure's genotoxic properties. Theoretical aspects of the interaction of the compound library were studied using molecular modeling and this identified the leading role of the polyaromatic molecular core that takes part in stacking‐interactions with the pi‐systems of the nitrogenous bases of DNA.
Religiosity and the psychological outcomes of trauma: A systematic review of quantitative studies
Authors: Kucharska Justyna
Published: September 2019

Objective

This is a broad review examining the relationships between religiosity and the psychological outcomes of trauma. Previous studies showed that some constructs of religiosity are associated with lower severity of symptoms of mental disorders, whereas others, for instance, negative religious coping, predict deteriorated mental health.

Method

A systematic review of peer‐reviewed quantitative studies was conducted to examine the patterns of relationships between religiosity and psychological outcomes of trauma, potential causal relationships, and specific effect of religiosity on the outcomes on trauma.

Results

A total of 79 quantitative studies were included. The majority focused on military trauma or various types of traumatic exposure in the general population. Most of the studies employed a cross‐sectional design.

Conclusions

The associations between religiosity and psychological outcomes of trauma depend on the concept of religion used in a study, type of trauma. There is not enough evidence to support the causal effect of religiosity.
When Sadness Comes Alive, Will It Be Less Painful? The Effects of Anthropomorphic Thinking on Sadness Regulation and Consumption
Authors: Chen Fangyuan , Chen Rocky Peng , Yang Li
Published: September 2019

Prior consumer research has studied the impact of anthropomorphism on product perception and evaluation. This research explores how anthropomorphic thinking influences people's experience of emotions and subsequent consumption behavior. Based on research on emotion regulation and the psychological process of detachment, we show that individuals instructed to anthropomorphize sadness (i.e., think of sadness as a person) report less experienced sadness afterward (Studies 1 and 2A). The same result is observed for its opposite, happiness, such that anthropomorphic thinking dilutes happiness (Study 2B). We argue that this reduction of emotion occurs because anthropomorphic thinking increases the perceived distance between the self and the anthropomorphized emotion, thereby creating a feeling of detachment. Evidence for a detachment process is found via measurement (Studies 3 and 4) and a theory‐guided moderation, with the effect lessening when sadness is seen as a dependent (vs. independent) person (Study 3). These findings have implications for consumer behavior. When sadness is ameliorated by anthropomorphic thinking, people tend to display better self‐control in subsequent consumption, as manifested by a greater likelihood of choosing a healthier or more practical product (Studies 4 and 5).
How individualism–collectivism influences consumer responses to the sharing economy: Consociality and promotional type
Authors: Mai Shirley , Ketron Seth , Yang Jun
Published: September 2019

With the explosion of online exchange of products, the sharing economy is experiencing ever‐increasing growth. Despite the increasing popularity of lateral exchange market platforms as part of the sharing economy, research has not yet adequately investigated cultural effects on how consumers’ intentions to purchase products on these platforms. Using two studies, this paper examines whether consumers high in individualism versus consumers high in collectivism respond differently to platforms with low versus high consociality and how individualistic and collectivistic consumers respond differently to two types of promotions that relate to self‐maximization. Findings in Study 1 indicated that consumers high in individualism (collectivism) have higher patronage intentions toward a platform low (high) in consociality. Findings in Study 2 suggested that in the presence of a promotion, collectivistic consumers respond comparably to promotional types across platforms, whereas individualistic consumers respond more positively to collective (individual) promotions when consociality is low (high). Further, felt commitment to others as a result of the consociality/promotional type relationship explains these effects. Theoretical and managerial implications are discussed.
Assessing the impact of curcumin on dual‐species biofilms formed by Streptococcus mutans and Candida albicans
Authors: Li Xinlong , Yin Luoping , Ramage Gordon , Li Bingchun , Tao Ye , Zhi Qinghui , Lin Huancai , Zhou Yan
Published: September 2019

Streptococcus mutans and Candida albicans are often isolated from plaques associated with early childhood caries. However, there are limited studies examining how these microorganisms interact with one another and how best to manage them. Recent studies have shown that curcumin (CUR), a natural compound, has the potential to independently control both of these microorganisms. The purpose of this study was to investigate how S. mutans and C. albicans respond in mono‐ and dual‐species biofilms challenged with CUR. Quantitative biofilm biomass and viability were first evaluated and supported by live–dead PCR to assess biofilm composition. Confocal laser scanning microscopy (CLSM) was used to evaluate the exopolysaccharide (EPS) content and thickness of the biofilms, and the structure of the biofilms and morphology of the cells were observed by scanning electron microscopy (SEM). Quantitative real‐time PCR (qRT‐PCR) was applied to assess relative gene expression. The 50% minimum biofilm eradication concentration (MBEC50) of CUR against S. mutans and C. albicans was 0.5 mM. The biomass and viability decreased after treatment with CUR both in dual‐species biofilms and in mono‐species biofilm. CUR inhibited S. mutans and C. albicans in both mono‐ and dual‐species biofilms. Streptococcus mutans was more sensitive to CUR in dual‐species biofilm than in mono‐species biofilms, whereas C. albicans was less sensitive in dual‐species biofilms. EPS production was decreased by CUR in both mono‐ and dual‐species biofilms, which coincided with the downregulation of glucosyltransferase and quorum sensing‐related gene expression of S. mutans. In C. albicans, the agglutinin‐like sequence family of C. albicans was also downregulated in dual‐species biofilms. Collectively, these data show the potential benefit of using a natural antimicrobial, CUR, to control caries‐related dual‐species plaque biofilms.
Clinical and genetic analysis of ZTTK syndrome caused by SON heterozygous mutation c.394C>T
Authors: Yang Yu , Xu Lei , Yu Zhen , Huang Hui , Yang Li
Published: September 2019

Background

The present study aims to summarize the clinical and genetic characteristics of ZTTK syndrome.

Methods

The clinical and genetic data of a Chinese girl with severe growth and development delay, intellectual disability, and facial features were analyzed. Original articles on ZTTK syndrome published up to November 20l8 were identified from PubMed, Human Gene Mutation Database, Online Mendelian Inheritance in Man, China National Knowledge Infrastructure, and WanFang databases using the keywords “ZTTK syndrome” and “SON”.

Results

The patient was born small for gestational age, and had poor academic performance, delayed language development, and motor retardation. The patient's height was 113 cm (less than −3 SD), and had moles on the back skin and possessed facial features. A novel heterozygous mutation c.394C>T (p.Q132X) of SON was found in this patient, but the parents were normal.

Conclusion

The patient's clinical phenotype was consistent with ZTTK syndrome. The novel heterozygous mutation c.394C>T (p.Q132X) of SON was its pathogenic mutation, which has not been reported at home and abroad.
Optimizing natural gas pipeline transmission with nonuniform elevation: A new initialization approach
Authors: Xue Mengying , Deng Tianhu , Max Shen Zuo‐Jun
Published: September 2019

In this paper, we develop an iterative piecewise linear approximation approach with a novel initialization method to solve natural gas pipeline transmission problems with the nonuniform network elevation. Previous approaches, such as energy minimization methods, cannot be applied to solve problems with the nonuniform network elevation because they exclude pressure range constraints, and thus provide solutions far from optimum. We propose a new initialization model that considers pressure range constraints and improves the optimality of the solutions and the computational efficiency. Furthermore, we extend the energy minimization methods and provide the necessary conditions under which the extended methods operate in networks with the nonuniform elevation. We test the performances of the methods with previously reported pipeline networks from the literature, with the open data set GasLib, and with our industrial collaborator. The initialization approach is shown to be more efficient than the method with fixed initial breakpoints. The newly proposed initialization approach generates solutions with a higher accuracy than the extended energy minimization methods, especially in large‐size networks. The proposed method has been applied to natural gas transmission planning by the China National Petroleum Corporation and has brought a direct profit increase of 330 million U.S. dollars in 2015‐2017.
A cover based competitive facility location model with continuous demand
Authors: Drezner Tammy , Drezner Zvi , Suzuki Atsuo
Published: September 2019

In this paper we propose and solve a competitive facility location model when demand is continuously distributed in an area and each facility attracts customers within a given distance. This distance is a measure of the facility's attractiveness level which may be different for different facilities. The market share captured by each facility is calculated by two numerical integration methods. These approaches can be used for evaluating functional values in other operations research models as well. The single facility location problem is optimally solved by the big triangle small triangle global optimization algorithm and the multiple facility problem is heuristically solved by the Nelder‐Mead algorithm. Extensive computational experiments demonstrate the effectiveness of the solution approaches.
Single‐machine scheduling with deadlines to minimize the total weighted late work
Authors: Chen Rubing , Yuan Jinjiang , Ng C.T. , Cheng T.C.E.
Published: September 2019

We consider scheduling a set of jobs with deadlines to minimize the total weighted late work on a single machine, where the late work of a job is the amount of processing of the job that is scheduled after its due date and before its deadline. This is the first study on scheduling with the late work criterion under the deadline restriction. In this paper, we show that (i) the problem is unary NP‐hard even if all the jobs have a unit weight, (ii) the problem is binary NP‐hard and admits a pseudo‐polynomial‐time algorithm and a fully polynomial‐time approximation scheme if all the jobs have a common due date, and (iii) some special cases of the problem are polynomially solvable.
Increasing self‐efficacy and knowledge in carer training: Hispanic versus Caucasian
Authors: Easom Leisa , Wang Ke , Alston Gayle
Published: September 2019

Aim

Nurses are teachers to their patients and need to know best practices for diverse families living with dementia. Little is known about Hispanic beliefs around dementia knowledge and self‐efficacy that may have an impact on the learning situation.

Design

A pre‐/postresearch design was used in this intervention study with a baseline assessment of dementia knowledge and caregiver self‐efficacy and a reassessment at training completion.

Methods

Investigation of education training with two caregiver groups caring for persons with dementia: Caucasian and Hispanic. Convenience sample consisted of 567 Caucasians and 104 Hispanic dementia caregivers. Groups received training in their primary language accompanied by a training book (Dealing with Dementia Guide) also in the primary language.

Results

Dementia knowledge and caregiver self‐efficacy increased in both groups with the Hispanic group demonstrating significantly greater increase in self‐efficacy. The Caucasian group had a significantly greater increase in the dementia knowledge compared with the Hispanic group.
Validation of the instrument “Complexity of Nursing Care”—A mixed‐methods study
Authors: Huber Evelyn , Kleinknecht‐Dolf Michael , Kugler Christiane , Müller Marianne , Spirig Rebecca
Published: September 2019

Aims

This study aimed to psychometrically test the instrument “Complexity of Nursing Care” and to broaden the understanding of the instrument's psychometrics and applicability.

Design

Embedded mixed‐methods design.

Methods

We performed a cross‐sectional study assessing all stationary patients of five Swiss hospitals daily for up to 5 days with the instrument “Complexity of Nursing Care” over a 1–month period in 2015. The scale's psychometrics were analysed using partial least square structural equation modelling. In the qualitative study section, we completed 12 case studies and analysed them case‐wise and across cases. Quantitative and qualitative results were synthesized in tables.

Results

Structural equation modelling confirmed a reflective‐formative second‐order model of the instrument with good psychometric properties leading to a formula for the calculation of a complexity score. Qualitative results evolved descriptions of low and high extent of complexity. Narrative considerations of two raters deepened the understanding of the inter‐rater reliability.
Do Machines Replicate Humans? Toward a Unified Understanding of Radicalizing Content on the Open Social Web
Authors: Hall Margeret , Logan Michael , Ligon Gina S. , Derrick Douglas C.
Published: September 2019

The advent of the Internet inadvertently augmented the functioning and success of violent extremist organizations. Terrorist organizations like the Islamic State in Iraq and Syria (ISIS) use the Internet to project their message to a global audience. The majority of research and practice on web‐based terrorist propaganda uses human coders to classify content, raising serious concerns such as burnout, mental stress, and reliability of the coded data. More recently, technology platforms and researchers have started to examine the online content using automated classification procedures. However, there are questions about the robustness of automated procedures, given insufficient research comparing and contextualizing the difference between human and machine coding. This article compares output of three text analytics packages with that of human coders on a sample of one hundred nonindexed web pages associated with ISIS. We find that prevalent topics (e.g., holy war) are accurately detected by the three packages whereas nuanced concepts (Lone Wolf attacks) are generally missed. Our findings suggest that naïve approaches of standard applications do not approximate human understanding, and therefore consumption, of radicalizing content. Before radicalizing content can be automatically detected, we need a closer approximation to human understanding.
Cationic Vacancy Mediated Conductivity and Charge Transport in Non‐Stoichiometric Epitaxial BaTi0.75Nb0.25O3 Films
Authors: Gao Dong , Guo Min , Li Qiang , Zhang Aihua , Feng Jiajun , Qin Minghui , Fan Zhen , Chen Deyang , Zeng Min , Zhou Guofu , Lu Xubing , Liu J.-M.
Published: September 2019

High‐quality epitaxial BaTi0.75Nb0.25O3 (BNTO) films with controllable Ba/(Nb + Ti) ratio are fabricated by pulsed laser deposition, and a systematic investigation on their conductivity and charge transport behaviors is carried out. The Ba/(Nb + Ti) ratio can be significantly regulated from 0.96 to 0.53 when the laser fluence varies from 0.5 to 2.0 J cm−2. Resistivity–temperature measurements indicate that all the BNTO films exhibit semiconductor transport behaviors at temperatures from 50 to 400 K. Their conductivity increases monotonically with the decrease in the Ba/(Nb + Ti) ratio. For films with a high Ba/(Nb + Ti) ratio of 0.96, the small polaron (SP) hopping dominates in the temperature range from 200 to 400 K. Nevertheless, the SP hopping can only be observed at temperatures ranging from 285 to 400 K for the films with a Ba/(Nb + Ti) ratio of 0.53, implying that the reduction of Ba vacancy is favorable for SP hopping transport in BNTO films, especially at low temperature. Hall effect measurements indicate a higher carrier mobility observed in the films with lower Ba/(Nb + Ti) ratio, revealing the promotion of carrier mobility by Ba vacancy. The work reveals that cationic vacancy plays an important role in the conductivity and charge transport mechanisms in perovskite oxide materials, such as BNTO films.
Biopolymer Microparticles Prepared by Microfluidics for Biomedical Applications
Authors: Jo Yun Kee , Lee Daeyeon
Published: September 2019

Biopolymers are macromolecules that are derived from natural sources and have attractive properties for a plethora of biomedical applications due to their biocompatibility, biodegradability, low antigenicity, and high bioactivity. Microfluidics has emerged as a powerful approach for fabricating polymeric microparticles (MPs) with designed structures and compositions through precise manipulation of multiphasic flows at the microscale. The synergistic combination of materials chemistry afforded by biopolymers and precision provided by microfluidic capabilities make it possible to design engineered biopolymer‐based MPs with well‐defined physicochemical properties that are capable of enabling an efficient delivery of therapeutics, 3D culture of cells, and sensing of biomolecules. Here, an overview of microfluidic approaches is provided for the design and fabrication of functional MPs from three classes of biopolymers including polysaccharides, proteins, and microbial polymers, and their advances for biomedical applications are highlighted. An outlook into the future research on microfluidically‐produced biopolymer MPs for biomedical applications is also provided.
Oxygen Vacancy–Rich In‐Doped CoO/CoP Heterostructure as an Effective Air Cathode for Rechargeable Zn–Air Batteries
Authors: Jin Wei , Chen Jianping , Liu Bing , Hu Jiugang , Wu Zexing , Cai Weiquan , Fu Gengtao
Published: September 2019

An efficient and low‐cost electrocatalyst for reversible oxygen electrocatalysis is crucial for improving the performance of rechargeable metal−air batteries. Herein, a novel oxygen vacancy–rich 2D porous In‐doped CoO/CoP heterostructure (In‐CoO/CoP FNS) is designed and developed by a facile free radicals–induced strategy as an effective bifunctional electrocatalyst for rechargeable Zn–air batteries. The electron spin resonance and X‐ray absorption near edge spectroscopy provide clear evidence that abundant oxygen vacancies are formed in the interface of In‐CoO/CoP FNS. Owing to abundant oxygen vacancies, porous heterostructure, and multiple components, In‐CoO/CoP FNS exhibits excellent oxygen reduction reaction activity with a positive half‐wave potential of 0.81 V and superior oxygen evolution reaction activity with a low overpotential of 365 mV at 10 mA cm−2. Moreover, a home‐made Zn–air battery with In‐CoO/CoP FNS as an air cathode delivers a large power density of 139.4 mW cm−2, a high energy density of 938 Wh kgZn−1, and can be steadily cycled over 130 h at 10 mA cm−2, demonstrating great application potential in rechargeable metal–air batteries.
Ratio of fetal choroid plexus to head size: simple sonographic marker of open spina bifida at 11–13 weeks' gestation
Authors: Chaoui R. , Benoit B. , Entezami M. , Frenzel W. , Heling K. S. , Ladendorf B. , Pietzsch V. , Sarut Lopez A. , Karl K.
Published: September 2019

Objectives

To measure the ratio of choroid plexus (CP) size to head size in normal fetuses and to compare it to that in fetuses with open spina bifida (OSB) and quantify the subjective sign of a ‘dry brain’.

Methods

This was a retrospective study of ultrasound images, obtained during first‐trimester screening between 11 and 13 weeks of gestation, from 34 fetuses with OSB and 160 normal fetuses. From the hospital databases, we retrieved images of the fetal head in the transventricular axial plane. We measured the areas of both CPs and the head and calculated the ratio between them. We also measured the longest diameter of each CP and calculated their mean (CP length), and measured the occipitofrontal diameter (OFD) and calculated the ratio of CP length to OFD. Measurements from the OSB fetuses were plotted on crown–rump length (CRL) reference ranges constructed using data from the normal fetuses, and Z‐scores were calculated.

Results

In the normal fetuses, the CP area increased, while the ratios of CP area to head area and CP length to OFD decreased, with increasing CRL. In 30 of the 34 (88%) fetuses with OSB, both ratios were increased significantly and the CPs filled the entirety of the head, giving the impression of a dry brain. In these cases, the borders of the lateral ventricles could not be identified.

Conclusions

At 11–13 weeks, the majority of fetuses with OSB have reduced fluid in the lateral ventricles such that the CPs fill the head. The dry brain sign is easily visualized during routine first‐trimester ultrasound examination while measuring the biparietal diameter, and can be quantified by comparing the size of the CPs to the head size. Until prospective data confirm the usefulness of this sign in screening for OSB, it should be considered as a hint to prompt the examiner to assess thoroughly the posterior fossa and spine. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Hospital wastewater treatment reduces NDM‐positive bacteria being discharged into water bodies
Authors: Divyashree Mithoor , Mani Madhu K. , Shama Prakash Kabekkodu , Vijaya Kumar Deekshit , Veena Shetty Alandur , Shetty Avinash K. , Karunasagar Indrani
Published: September 2019

New Delhi metallo‐β‐lactamase‐1 (NDM‐1) is a novel type of metallo‐β‐lactamase (MBL) associated with Enterobacteriaceae constitutes an important growing public health threat. The present study aims to characterize the NDM‐1 producing Gram‐negative bacteria (GNB) from the effluents of two tertiary care hospitals in Mangalore, South India and to profile their antibiotic resistance pattern. A total of 134 GNB were isolated from 30 hospital wastewater samples (treated and untreated) and analyzed. High‐level resistance among untreated effluent sample was found toward nalidixic acid (74.52%), followed by cefotaxime (72.64%) and ampicillin (66.03%). Among the treated effluent isolates, the high resistance was found toward ampicillin (85.71%) followed by cefotaxime (85.71%) and piperacillin–tazobactam (53.57%). From untreated effluent isolates, 9 were NDM‐1 positive by PCR; no isolates from treated effluent samples harbored blaNDM‐1. Untreated hospital wastewater is found to be important reservoirs of antibiotic‐resistant bacteria carrying blaNDM‐1, and the presence of such bacteria in the effluents is a matter of great concern because they can contribute the antibiotic resistance to the natural environment. However, the absence of NDM in treated effluents emphasizes the importance of effluent treatment in reducing the dissemination of antibiotic‐resistant bacteria.

Practitioner points

Hospital wastewater is the important reservoir of antibiotic‐resistant bacteria especially metallo‐β‐lactamase producers (NDM‐1).

Wastewater treatment procedures in hospitals reduce the NDM isolates in the treated effluent.

Thereby reduces the risk of resistance spread in the environment.
Fbxl17 is rearranged in breast cancer and loss of its activity leads to increased global O-GlcNAcylation
Authors: Mason Bethany , Flach Susanne , Teixeira Felipe R. , Manzano Garcia Raquel , Rueda Oscar M. , Abraham Jean E. , Caldas Carlos , Edwards Paul A. W. , Laman Heike
Published: September 2019

In cancer, many genes are mutated by genome rearrangement, but our understanding of the functional consequences of this remains rudimentary. Here we report the F-box protein encoded byFBXL17is disrupted in the region of the gene that encodes its substrate-binding leucine rich repeat (LRR) domain. Truncating Fbxl17 LRRs impaired its association with the other SCF holoenzyme subunits Skp1, Cul1 and Rbx1, and decreased ubiquitination activity. Loss of the LRRs also differentially affected Fbxl17 binding to its targets. Thus, genomic rearrangements inFBXL17are likely to disrupt SCFFbxl17-regulated networks in cancer cells. To investigate the functional effect of these rearrangements, we performed a yeast two-hybrid screen to identify Fbxl17-interacting proteins. Among the 37 binding partners Uap1, an enzyme involved inO-GlcNAcylation of proteins was identified most frequently. We demonstrate that Fbxl17 binds to UAP1 directly and inhibits its phosphorylation, which we propose regulates UAP1 activity. Knockdown of Fbxl17 expression elevatedO-GlcNAcylation in breast cancer cells, arguing for a functional role for Fbxl17 in this metabolic pathway.
Chain length of dietary fatty acids determines gastrointestinal motility and visceromotor function in mice in a fatty acid binding protein 4-dependent manner
Authors: Mosińska Paula , Szczepaniak Adrian , Wojciechowicz Tatiana , Skrzypski Marek , Nowak Krzysztof , Fichna Jakub
Published: September 2019

Purpose

We hypothesize that different types of dietary fatty acids (FAs) affect gastrointestinal (GI) motility and visceromotor function and that this effect can be regulated by the fatty acid binding protein 4 (FABP4).

Methods

Mice were fed for 60 days with standard diet (STD), STD with 7% (by weight) coconut oil, rich in medium-chain FAs (MCFAs) (COCO), or with 7% evening primrose oil, rich in long-chain FAs (LCFAs) (EPO). In each group, half of the mice received FABP4 inhibitor, BMS309403 (1 mg/kg; i.p.) twice a week. Body weight (BW) and food intake were measured; well-established tests were performed to characterize the changes in GI motility and visceral pain. White adipose tissue and colonic samples were collected for cell culturing and molecular studies.

Results

COCO significantly increased GI transit, but not colonic motility. COCO and EPO delayed the onset of diarrhea, but none affected the effect of loperamide. EPO reduced BW and increased the visceromotor response (VMR) to colorectal distension (CRD). COCO and EPO reduced differentiation of preadipocytes. Treatment with BMS309403: (1) reversed the effects induced by COCO in physiological conditions and in mouse models of diarrhea; (2) prevented the effects of EPO on BW, VMR to CRD and castor oil-induced diarrhea; (3) affected proliferation of preadipocytes; (4) changed the expression of Fabp4 in colonic and adipocyte samples from COCO and EPO.

Conclusion

Modifying dietary intake of MCFAs and LCFAs may be used to control GI motility or visceral pain and thus modulate the symptoms of functional GI disorders. The effect is dependent on the expression of FABP4.
Generalised free energy and active inference
Authors: Parr Thomas , Friston Karl J.
Published: September 2019

Active inference is an approach to understanding behaviour that rests upon the idea that the brain uses an internal generative model to predict incoming sensory data. The fit between this model and data may be improved in two ways. The brain could optimise probabilistic beliefs about the variables in the generative model (i.e. perceptual inference). Alternatively, by acting on the world, it could change the sensory data, such that they are more consistent with the model. This implies a common objective function (variational free energy) for action and perception that scores the fit between an internal model and the world. We compare two free energy functionals for active inference in the framework of Markov decision processes. One of these is a functional of beliefs (i.e. probability distributions) about states and policies, but a function of observations, while the second is a functional of beliefs about all three. In the former (expected free energy), prior beliefs about outcomes are not part of the generative model (because they are absorbed into the prior over policies). Conversely, in the second (generalised free energy), priors over outcomes become an explicit component of the generative model. When using the free energy function, which is blind to future observations, we equip the generative model with a prior over policies that ensure preferred (i.e. priors over) outcomes are realised. In other words, if we expect to encounter a particular kind of outcome, this lends plausibility to those policies for which this outcome is a consequence. In addition, this formulation ensures that selected policies minimise uncertainty about future outcomes by minimising the free energy expected in the future. When using the free energy functional—that effectively treats future observations as hidden states—we show that policies are inferred or selected that realise prior preferences by minimising the free energy of future expectations. Interestingly, the form of posterior beliefs about policies (and associated belief updating) turns out to be identical under both formulations, but the quantities used to compute them are not.
Tumor-infiltrating lymphocytes and CD8+ T cells predict survival of triple-negative breast cancer
Authors: Vihervuori H. , Autere T. A. , Repo H. , Kurki S. , Kallio L. , Lintunen M. M. , Talvinen K. , Kronqvist P.
Published: September 2019

Purpose

Tumor inflammatory response was evaluated as a prognostic feature in triple-negative breast cancer (TNBC) and compared with the clinical prognosticators of breast cancer and selected biomarkers of cancer cell proliferation.

Methods

TNBC patients (n = 179) with complete clinical data and up to 18-year follow-up were obtained from Auria biobank, Turku University Hospital, Turku, Finland. Tumor-infiltrating lymphocytes (TILs) and several subtypes of inflammatory cells detected with immunohistochemistry were evaluated in different tumor compartments in full tissue sections and tissue microarrays.

Results

Deficiency of stromal TILs and low number of CD8+ T cells independently predicted mortality in TNBC (HR 2.4, p 0.02 and HR 2.1, p 0.02, respectively). Each 10% decrease in stromal TILs resulted in 20% increased risk of mortality. An average of 13.2-year survival difference was observed between the majority (> 75%) of patients with low (< 14% of TILs) vs high (≥ 14% of TILs) frequency of CD8+ T cells. The prognostic value of TILs and CD8+ T cells varied when evaluated in different tumor compartments. TILs and CD8+ T cells were significantly associated with Securin and Separase, essential regulators of metaphase–anaphase transition of the cell cycle.

Discussion

TILs and CD8+ T cells provide additional prognostic value to the established clinical prognostic markers in TNBC. However, possible clinical applications would still benefit from systematic guidelines for evaluating tumor inflammatory response. Increasing understanding on the interactions between the regulation of cancer cell proliferation and inflammatory response may in future advance treatment of TNBC.
Selegiline: a molecule with innovative potential
Authors: Tábi Tamás , Vécsei László , Youdim Moussa B. , Riederer Peter , Szökő Éva
Published: September 2019

Monoamine oxidase B (MAO-B) inhibitors have an established role in the treatment of Parkinson’s disease as monotherapy or adjuvant to levodopa. Two major recognitions were required for their introduction into this therapeutic field. The first was the elucidation of the novel pharmacological properties of selegiline as a selective MAO-B inhibitor by Knoll and Magyar and the original idea of Riederer and Youdim, supported by Birkmayer, to explore its effect in parkinsonian patients with on–off phases. In the 1960s, MAO inhibitors were mainly studied as potential antidepressants, but Birkmayer found that combined use of levodopa and various MAO inhibitors improved akinesia in Parkinson’s disease. However, the serious side effects of the first non-selective MAO inhibitors prevented their further use. Later studies demonstrated that MAO-B, mainly located in glial cells, is important for dopamine metabolism in the brain. Recently, cell and molecular studies revealed interesting properties of selegiline opening new possibilities for neuroprotective mechanisms and a disease-modifying effect of MAO-B inhibitors.
Contributions to the stereochemistry of zirconium oxysalts—part III: syntheses and crystal structures of M2+Zr(SO4)3 with M = Mg, Mn, Co, Ni, Zn and Cd, and a note on (Fe3+,2+,Zr)2(SO4)3 and Fe2(SO4)3
Authors: Giester Gerald , Talla Dominik , Wildner Manfred
Published: September 2019

The novel compoundsM2+Zr(SO4)3withM = Mg, Mn, Co, Ni, Zn, and Cd as well as (Fe3+,2+,Zr)2(SO4)3were synthesized at mild hydrothermal conditions (Teflon-lined stainless steel vessels, 220 °C) from the mixtures of Zr2O2(CO3)(OH)2, the respectiveM2+(SO4)·nH2O hydrated salts, H2SO4and a minor amount of water. Crystals up to several tenths of a mm in size were obtained within a few days and studied at 200 K by single-crystal X-ray diffraction techniques. All these compounds belong to the structure type of monoclinic Fe2(SO4)3; they are either isotypic in space groupP21/n(No. 14),Z = 4, i.e.M2+Zr(SO4)3withM = Mn, Co, Ni, Zn, and Cd as well as the mixed valence sulfate (Fe3+,2+,Zr)2(SO4)3or in the case of MgZr(SO4)3, closely related but with a larger unit cell, in space groupPcandZ = 8. The framework of the monoclinic Fe2(SO4)3structure is characterized by two types of isolated Fe3+O6octahedra, corner-linked with three types of sulfate groups. In the isotypicM2+Zr(SO4)3series, the Fe3+atom on the Fe(1) position is substituted by Zr4+whileM2+ions occupy the Fe(2) site in the ferric sulfate structure type. Mean cation-oxygen bond lengths (S[4]: 1.462–1.472 Å; Zr[6]: 2.053–2.060 Å as well asM2+–O distances) are generally rather short, but still within the range reported in literature.

Graphic abstract
Semi-automatic segmentation from intrinsically-registered 18F-FDG–PET/MRI for treatment response assessment in a breast cancer cohort: comparison to manual DCE–MRI
Authors: Andreassen Maren Marie Sjaastad , Goa Pål Erik , Sjøbakk Torill Eidhammer , Hedayati Roja , Eikesdal Hans Petter , Deng Callie , Østlie Agnes , Lundgren Steinar , Bathen Tone Frost , Jerome Neil Peter
Published: September 2019

Objectives

To investigate the reliability of simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI)-derived biomarkers using semi-automated Gaussian mixture model (GMM) segmentation on PET images, against conventional manual tumor segmentation on dynamic contrast-enhanced (DCE) images.

Materials and methods

Twenty-four breast cancer patients underwent PET/MRI (following 18F-fluorodeoxyglucose (18F-FDG) injection) at baseline and during neoadjuvant treatment, yielding 53 data sets (24 untreated, 29 treated). Two-dimensional tumor segmentation was performed manually on DCE–MRI images (manual DCE) and using GMM with corresponding PET images (GMM–PET). Tumor area and mean apparent diffusion coefficient (ADC) derived from both segmentation methods were compared, and spatial overlap between the segmentations was assessed with Dice similarity coefficient and center-of-gravity displacement.

Results

No significant differences were observed between mean ADC and tumor area derived from manual DCE segmentation and GMM–PET. There were strong positive correlations for tumor area and ADC derived from manual DCE and GMM–PET for untreated and treated lesions. The mean Dice score for GMM–PET was 0.770 and 0.649 for untreated and treated lesions, respectively.

Discussion

Using PET/MRI, tumor area and mean ADC value estimated with a GMM–PET can replicate manual DCE tumor definition from MRI for monitoring neoadjuvant treatment response in breast cancer.
Stand growth and structure of mixed-species and monospecific stands of Scots pine (Pinus sylvestris L.) and oak (Q. robur L., Quercus petraea (Matt.) Liebl.) analysed along a productivity gradient through Europe
Authors: Pretzsch H. , Steckel M. , Heym M. , Biber P. , Ammer C. , Ehbrecht M. , Bielak K. , Bravo F. , Ordóñez C. , Collet C. , Vast F. , Drössler L. , Brazaitis G. , Godvod K. , Jansons A. , de-Dios-García J. , Löf M. , Aldea J. , Korboulewsky N. , Reventlow D. O. J. , Nothdurft A. , Engel M. , Pach M. , Skrzyszewski J. , Pardos M. , Ponette Q. , Sitko R. , Fabrika M. , Svoboda M. , Černý J. , Wolff B. , Ruíz-Peinado R. , del Río M.
Published: September 2019

Past failures of monocultures, caused by wind-throw or insect damages, and ongoing climate change currently strongly stimulate research into mixed-species stands. So far, the focus has mainly been on combinations of species with obvious complementary functional traits. However, for any generalization, a broad overview of the mixing reactions of functionally different tree species in different mixing proportions, patterns and under different site conditions is needed, including assemblages of species with rather similar demands on resources such as light. Here, we studied the growth of Scots pine and oak in mixed versus monospecific stands on 36 triplets located along a productivity gradient across Europe, reaching from Sweden to Spain and from France to Georgia. The set-up represents a wide variation in precipitation (456–1250 mm year−1), mean annual temperature (6.7–11.5 °C) and drought index by de Martonne (21–63 mm °C−1). Stand inventories and increment cores of trees stemming from 40- to 132-year-old, fully stocked stands on 0.04–0.94-ha-sized plots provided insight into how species mixing modifies stand growth and structure compared with neighbouring monospecific stands. On average, the standing stem volume was 436 and 360 m3 ha−1in the monocultures of Scots pine and oak, respectively, and 418 m3 ha−1in the mixed stands. The corresponding periodical annual volume increment amounted to 10.5 and 9.1 m3 ha−1 year−1in the monocultures and 10.5 m3 ha−1 year−1in the mixed stands. Scots pine showed a 10% larger quadratic mean diameter (p < 0.05), a 7% larger dominant diameter (p < 0.01) and a 9% higher growth of basal area and volume in mixed stands compared with neighbouring monocultures. For Scots pine, the productivity advantages of growing in mixture increased with site index (p < 0.01) and water supply (p < 0.01), while for oak they decreased with site index (p < 0.01). In total, the superior productivity of mixed stands compared to monocultures increased with water supply (p < 0.10). Based on 7843 measured crowns, we found that in mixture both species, but especially oak, had significantly wider crowns (p < 0.001) than in monocultures. On average, we found relatively small effects of species mixing on stand growth and structure. Scots pine benefiting on rich, and oak on poor sites, allows for a mixture that is productive and most likely climate resistant all along a wide ecological gradient. We discuss the potential of this mixture in view of climate change.