bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol Reinforcement Elicits Novel Response Inhibition Behavior in a Rat Model of Ethanol Dependence
Authors: Somkuwar Sucharita S. , Quach Leon W. , Quigley Jacqueline A. , Purohit Dvijen C. , Fannon McKenzie J. , Koob George F. , Mandyam Chitra D.
Published: June 2018

Lower impulse control is a known risk factor for drug abuse vulnerability. Chronic experience with illicit drugs is suggested to enhance impulsivity and thereby perpetuate addiction. However, the nature of this relationship (directionality, causality) with regard to alcohol use disorder is unclear. The present study tested the hypothesis that higher impulsivity is observed during chronic intermittent ethanol vapor inhalation (CIE; a model of ethanol dependence) and subsequent abstinence from CIE in adult Wistar rats. Impulsivity was tested using a differential reinforcement of low rates 15 s (DRL15) schedule using either nondrug reward (palatable modified sucrose pellets) or sweetened ethanol. A decrease in the efficiency of earning reinforcers (expressed as % reinforcers/responses) is indicative of a decrease in response inhibition or an increase in impulsivity. The efficiency of reinforcement and amount of reinforcers earned were unaltered in CIE and control animals when the reinforcer was sucrose. When the reinforcer was sweetened ethanol, the efficiency of reinforcement increased in CIE rats compared with controls only during protracted abstinence. Responding for sweetened ethanol under a progressive-ratio schedule was more rapid in CIE rats during protracted abstinence. Contrary to the initial hypothesis, impulsivity did not increase in rats with a history of CIE; instead, it decreased when ethanol was used as the reinforcer. Furthermore, although the efficiency of ethanol reinforcement did not differ between CIE and control animals during CIE, CIE rats escalated the amount of sweetened ethanol consumed, suggesting that behavioral adaptations that are induced by CIE in rats that are tested under a DRL15 schedule appear to be targeted toward the maximization of ethanol intake and thus may contribute to escalation and relapse.
Rapid Evolution of Sperm Produces Diverse Centriole Structures that Reveal the Most Rudimentary Structure Needed for Function
Authors: Avidor-Reiss Tomer
Published: June 2018

Centrioles are ancient subcellular protein-based organelles that maintain a conserved number and structure across many groups of eukaryotes. Centriole number (two per cells) is tightly regulated; each pre-existing centriole nucleates only one centriole as the cell prepares for division. The structure of centrioles is barrel-shaped, with a nine-fold symmetry of microtubules. This organization of microtubules is essential for the ancestral function of centriole–cilium nucleation. In animal cells, centrioles have gained an additional role: recruiting pericentriolar material (PCM) to form a centrosome. Therefore, it is striking that in animal spermatozoa, the centrioles have a remarkable diversity of structures, where some are so anomalous that they are referred to as atypical centrioles and are barely recognizable. The atypical centriole maintains the ability to form a centrosome and nucleate a new centriole, and therefore reveals the most rudimentary structure that is needed for centriole function. However, the atypical centriole appears to be incapable of forming a cilium. Here, we propose that the diversity in sperm centriole structure is due to rapid evolution in the shape of the spermatozoa head and neck. The enhanced diversity may be driven by a combination of direct selection for novel centriole functions and pleiotropy, which eliminates centriole properties that are dispensable in the spermatozoa function.
Designing Secure Heterogeneous Multicore Systems from Untrusted Components
Authors: Kinsy Michel A. , Bu Lake , Isakov Mihailo , Mark Miguel
Published: June 2018

In current systems-on-chip (SoCs) designs, processing elements, i.e., intellectual property (IP) cores, may come from different providers, and executable code may have varying levels of trust, all executing on the same compute platform and sharing resources. This creates a very fertile attack ground and represents the Achilles’ heel of heterogeneous SoC architectures and distributed connected devices. The general consensus today is that conventional approaches and software-only add-on schemes fail to provide sufficient security protections and trustworthiness. In this paper, we develop a secure heterogeneous SoC architecture named Hermes. It represents a new architectural model that integrates multiple processing elements (called tenants) of secure and non-secure cores into the same chip design while: (a) maintaining individual tenant security; (b) preventing data leakage and corruption; (c) promoting collaboration among the tenants; and (d) tolerating untrusted tenants with potentially malicious purposes. The Hermes architecture is based on a programmable secure router interface and a trust-aware routing algorithm. Depending on the trust levels of computing nodes, it is able to virtually isolate them in different access modes to the memory blocks. With secure key management and join protocols, Hermes is also able to function properly when nodes request for, or allow, memory access in a dishonest manner. With 17% hardware overhead, it enables the implementation of processing-element-oblivious secure multicore systems with a programmable distributed group key management scheme. The Hermes architecture is meant to emblematize the design of secure heterogeneous multicore computing systems out of unsecured or untrusted components using user-defined security policies to create at the hardware-level virtual zones to enforce these security and trust policies.
Evaluation of Double-Sided Planetary Grinding Using Diamond Wheels for Sapphire Substrates
Authors: Wang Lijuan , Hu Zhongwei , Yu Yiqing , Xu Xipeng
Published: June 2018

Double-sided planetary grinding as an efficient and precise machining method is used for the rapid thinning and flattening process of sapphire substrate. As an intermediate processing technology of sapphire substrate preparation procedure, many experiments are carried out to evaluate the lapping effect in the paper. Surface quality, processing efficiency, and surface dent depth, which all impact subsequent polishing processes, are evaluated. Firstly, the four stages of grinding process are analyzed to display the surface accuracy changing process of the sapphire substrates during grinding. Secondly, the effect of three main grinding parameters (grinding pressure, rotation speed of the grinding wheels, and the grain size of grinding wheels) on surface accuracy and processing efficiency are investigated. Finally, sapphire removal rate of about 10 µm/min is achieved easily at the optimized condition with a good surface quality by double-sided planetary grinding. The double-sided planetary grinding with the ceramic-bonded diamond wheel is suitable for the rapid thinning and flattening of the sapphire substrate.
The Control Scheme of the Multifunction Inverter for Power Factor Improvement
Authors: Reveles-Miranda María , Sánchez-Flórez Diego , Cruz-Chan José , Ordoñez-López Eduardo , Flota-Bañuelos Manuel , Pacheco-Catalán Daniella
Published: June 2018

Grid-connected photovoltaic (PV) systems require an inverter that allows an efficient integration between the panels and the grid; however, the operation of conventional inverters is limited to the periods of power generation by the panels. This paper proposes a control scheme based on the theory of passivity to provide additional functions to the inverter of a PV system. These additional functions improve the power quality; for example, when loads demand inductive currents be connected, the power factor is improved independently of the intermittency of the solar energy source. The performance of the system with the passivity-based control is verified by simulation and experimentation using MATLAB/Simulink® (2017a, MathWorks, Natick, MA, USA).
Climate Sensitive Tree Growth Functions and the Role of Transformations
Authors: Zell Jürgen
Published: June 2018

The aim of this study is to develop climate-sensitive single-tree growth models, to be used in stand based prediction systems of managed forest in Switzerland. Long-term observations from experimental forest management trials were used, together with retrospective climate information from 1904 up to 2012. A special focus is given to the role of transformation of modelling basal area increment, helping to normalize the random error distribution. A nonlinear model formulation was used to describe the basic relation between basal area increment and diameter at breast height. This formulation was widely expanded by groups of explanatory variables, describing competition, stand development, site, stand density, thinning, mixture, and climate. The models are species-specific and contain different explanatory variables per group, being able to explain a high amount of variance (on the original scale, up to 80% in the case of Quercus spec.). Different transformations of the nonlinear relation where tested and based on the mean squared error, the square root transformation performed best. Although the residuals were homoscedastic, they were still long-tailed and not normal distributed, making robust statistics the preferred method for statistical inference. Climate is included as a nonlinear and interacting effect of temperature, precipitation and moisture, with a biological meaningful interpretation per tree species, e.g., showing better growth for Abies alba in warm and wet climates and good growing conditions for Picea abies in colder and dryer climates, being less sensitive on temperature. Furthermore, a linear increase in growth was found to be present since the 1940s. Potentially this is an effect of the increased atmospheric CO2 concentration or changed management in terms of reduced nutrient subtractions from forest ground, since industrialization lowered the demand of residue and slash uptake.
Buying Optimal Payoffs in Bi-Matrix Games
Authors: Gupta Anshul , Schewe Sven
Published: June 2018

We consider non-zero sum bi-matrix games where one player presumes the role of a leader in the Stackelberg model, while the other player is her follower. We show that the leader can improve her reward if she can incentivise her follower by paying some of her own utility to the follower for assigning a particular strategy profile. Besides assuming that the follower is rational in that he tries to maximise his own payoff, we assume that he is also friendly towards his leader in that he chooses, ex aequo, the strategy suggested by her—at least as long as it does not affect his expected payoff. Assuming this friendliness is, however, disputable: one could also assume that, ex aequo, the follower acts adversarially towards his leader. We discuss these different follower behavioural models and their implications. We argue that the friendliness leads to an obligation for the leader to choose, ex aequo, an assignment that provides the highest follower return, resulting in ‘friendly incentive equilibria’. For the antagonistic assumption, the stability requirements for a strategy profile should be strengthened, comparable to the secure Nash equilibria. In general, no optimal incentive equilibrium for this condition exists, and therefore we introduce ε-optimal incentive equilibria for this case. We show that the construction of all of these incentive equilibria (and all the related leader equilibria) is tractable.
To Tender or Not to Tender? Deliberate and Exogenous Sunk Costs in a Public Good Game
Authors: Heine Florian , Sefton Martin
Published: June 2018

In an experimental study, we compare individual willingness to cooperate in a public good game after an initial team contest phase. While players in the treatment setup make a conscious decision on how much to invest in the contest, this decision is exogenously imposed on players in the control setup. As such, both groups of players incur sunk costs and enter the public good game with different wealth levels. Our results indicate that the way these sunk costs have been accrued matters especially for groups on the losing side of the contest: Given the same level of sunk costs, contributions to the public good are lower for groups which failed to be successful in the preceding between-group contest. Furthermore, this detrimental effect is more pronounced for individuals who play a contest with deliberate contributions before.
Gelation and Structural Formation of Amylose by In Situ Neutralization as Observed by Small-Angle X-ray Scattering
Authors: Yamamoto Kyoko , Suzuki Shiho , Kitamura Shinichi , Yuguchi Yoshiaki
Published: June 2018

The gelation and structural formation of two types of amylose in alkaline solution by in situ neutralization was monitored with time-resolved small-angle X-ray scattering (tr-SAXS). Sharp increases of SAXS profile in lower angle region were observed after gelation. The results showed that aggregation of amylose chains led to a gel point with crystal growth. The aggregation appeared to function as a junction zone, and the aggregate structure depended on the molecular weight of amylose. A high-molecular-weight sample was fitted using a Debye-Bueche function, and a low-molecular-weight sample was fitted using a stretched exponential function.
Geotourism: A Systematic Literature Review
Authors: Ólafsdóttir Rannveig , Tverijonaite Edita
Published: June 2018

Geotourism is one of the newest concepts within tourism studies today. The popularity of geotourism has likewise grown rapidly over the past few decades. This rapidly growing popularity and the growing body of research on geotourism create the need for a comprehensive review of existing literature on the subject. The present study aims to systematically review scientific literature on geotourism published over the past two decades by identifying what knowledge has been produced on geotourism in the scientific literature and by analyzing the evolving research trends in geotourism during the same time period. The results reveal that researchers are placing an increasing focus on geotourism. A geographical analysis of the study areas indicates a true global distribution, encompassing studies of 53 countries altogether. Most of the research focusses on identifying, describing, and assessing the geoheritage of the areas in question together with their geotourism potential. The volume of research on these topics is growing at a rapid pace. Other common research topics as regards geotourism include management of geotourism and geoheritage, new geosite/geomorphosite assessment models, together with other methodological approaches. The results further indicate that researchers are less interested in geotourism stakeholders such as tourists and local communities, and that only a very small number of studies examine geotourism in the context of sustainable development. The vast majority of the studies utilize empirical data as the basis of the research or for the testing of proposed models and methodology. The present review identifies a need for a larger body of empirical research focusing on (i) sustainability of geotourism, including actual impacts of geotourism on the geoheritage and on the ecosystems of geotourism areas, (ii) knowledge on effective management of the main challenges of geotourism, as well as (iii) on stakeholders and their complex interrelations, including the effects of geotourism on local communities and their well-being.
Animal Voices: Catherine Louisa Pirkis’ The Experiences of Loveday Brooke, Lady Detective and the Crimes of Animality
Authors: Pittard Christopher
Published: June 2018

While previous readings of Catherine Louisa Pirkis’ series The Experiences of Loveday Brooke, Lady Detective (1894) have focused on Brooke’s status as New Woman detective, this article considers the series in the context of Pirkis’ own engagement with animal rights and anti-vivisection campaigns in the late nineteenth century. The discussion focuses on one Loveday Brooke story in particular, “The Murder at Troyte’s Hill,” arguing that Pirkis dramatises contemporary anti-vivisectionist rhetoric (that animal experimentation was not only scientifically flawed, but morally damaging, leading to human experimentation). Pirkis’ fiction instead presents a number of contact zones in which human and animal identities are renegotiated, most significantly in the figure of Loveday Brooke herself. The article considers the representation of comparative philology in the story, as an emerging linguistic science which raised anxieties of cultural dissolution and which was often associated with the image of the vivisector. It concludes that the Pirkis stories demonstrate, anticipating Derrida, that to write of the animal in the nineteenth century is inevitably to write about crime, and vice versa; the animal is a perpetual presence in Victorian detective fiction.
Glocal Participatory System for the Recording, Documentation and Promotion of Cultural Heritage: A Greek Case-Study
Authors: Psychogyios Dimitris , Poulakis Nick
Published: June 2018

The recording, documentation and promotion of local cultural heritage has been the subject of significant research from scientists from various fields such as architecture, anthropology, history, folklore, ethnomusicology, and museology. This paper argues that digital technologies could have a catalytic role concerning the operational part of a holistic–interdisciplinary approach to the maintenance of cultural heritage. Simultaneous and bidirectional recording, documentation and promotion of human histories, material elements of space, personal and collective memories, music, dance, singing and other performances, customs, traditions etc. has the effect of improving the understanding of each place and, therefore, contributing to the establishment of sustainable living conditions and environmental balance. At the same time, it facilitates the process of presenting the place’s local identity as well as its tangible and intangible cultural heritage. The paper proposes the design, the creation and the pilot operation of a glocal hybrid (physical and digital) participatory system for monitoring cultural heritage, which consists of (a) spatial recording and projection constructions (open micro-labs); (b) research and documentation centers; and (c) digital databases and mobile applications for interconnection and diffusion of digital content. The system’s implementation domain is considered to be “historic urban landscapes”, i.e., geographical areas with particular cultural features such as traditional settlements, monuments and historical centers, regarded as exceptional universal heritage. In particular, the project’s prime exemplary pilot setup is considered to be operated in specific Greek areas of cultural importance.
Time Spent in Sedentary Behaviour as Discriminant Criterion for Frailty in Older Adults
Authors: Da Silva Venicius Dantas , Tribess Sheilla , Meneguci Joilson , Sasaki Jeffer Eidi , Santos Douglas de Assis Teles , Carneiro José Ailton Oliveira , Virtuoso Júnior Jair Sindra
Published: June 2018

This paper aims to analyse whether time spent in sedentary behaviour was a discriminant criterion for frailty in older adults. This was a cross-sectional study conducted in a sample of 457 elderly individuals aged ≥60 years. Frailty was defined as the presence of three or more of the following criteria: Unintentional weight loss, low walking speed at a 4.57 m course, reduced manual grip strength, exhaustion and insufficient physical activity level. Participants were classified into two groups: Non-frail or frail. Exposure to sedentary behaviour was assessed by the time spent sitting during a typical week, according to the adapted version of the International Physical Activity Questionnaire. Descriptive (mean, frequency) and inferential statistics (Poisson regression, Pearson’s Chi-square, Receiver Operating Characteristic Curve) were used to analyse the data, comparing them to the time-related areas exposed to sedentary behaviour by gender and the presence of fragility. The prevalence of frailty was 22.1% (n = 101). The most accurate cut-off points of sitting time for predicting frailty were >495 min/day (men) or >536 min/day (women). Time spent in sedentary behaviour can be used to indicate fragility in the elderly of both sexes.
Indoor Radon Gas (222Rn) Levels in Homes in Aldama, Chihuahua, Mexico and the Risk of Lung Cancer
Authors: Lerma-Treviño Carolina , Rubio-Arias Hector , Colmenero-Sujo Luis Humberto , De Lourdes Villalba Maria , Ochoa-Rivero Jesus Manuel
Published: June 2018

Radon (222Rn) is an odorless and tasteless gas that is known to cause lung cancer. The objective of this research was to quantify the levels of exposure to radon among people living in an environment rich in uranium (U). Radon concentrations were measured for 3 days in 12 homes in Aldama, Mexico. Homeowners agreed to participate in the study; hence, the sample was non-probabilistic. Radon was measured with a portable AlphaGuard Radon Monitor (Genicron Instruments GmbH), which was placed in a bedroom of each home at a height of 0.74 m. Gas levels were registered in Becquerels (Bq m−3), with readings taken every 10 min along with readings of ambient temperature (AT), air pressure (AP), and relative humidity (RH). We found that radon gas levels in Aldama exceed the maximum permissible limits (USA: 148 Bq m−3). Levels were higher at night, and were above the maximum permissible level recommended by the International Atomic Energy Agency of the United Nations (<200 Bq m−3). Most residents in the area have family histories of lung problems, but it was difficult to establish a strong correlation between 222Rn and lung cancer. Federal, state, and municipal governments should take stronger action to reduce the effects of radon gas on communities.
Lessons and Guidance from the Special Issue on Electronic Cigarette Use and Public Health
Authors: Sumner Walton , Farsalinos Konstantinos
Published: June 2018

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Modifiable Risk Factors for Common Ragweed (Ambrosia artemisiifolia) Allergy and Disease in Children: A Case-Control Study
Authors: Agnew Maureen , Banic Ivana , Lake Iain R. , Goodess Clare , Grossi Carlota M. , Jones Natalia R. , Plavec Davor , Epstein Michelle , Turkalj Mirjana
Published: June 2018

Ragweed allergy is a major public health concern. Within Europe, ragweed is an introduced species and research has indicated that the amounts of ragweed pollen are likely to increase over Europe due to climate change, with corresponding increases in ragweed allergy. To address this threat, improving our understanding of predisposing factors for allergic sensitisation to ragweed and disease is necessary, specifically focusing upon factors that are potentially modifiable (i.e., environmental). In this study, a total of 4013 children aged 2–13 years were recruited across Croatia to undergo skin prick tests to determine sensitisation to ragweed and other aeroallergens. A parental questionnaire collected home environment, lifestyle, family and personal medical history, and socioeconomic information. Environmental variables were obtained using Geographical Information Systems and data from nearby pollen, weather, and air pollution stations. Logistic regression was performed (clustered on school) focusing on risk factors for allergic sensitisation and disease. Ragweed sensitisation was strongly associated with ragweed pollen at levels over 5000 grains m–3 year−1 and, above these levels, the risk of sensitisation was 12–16 times greater than in low pollen areas with about 400 grains m–3 year−1. Genetic factors were strongly associated with sensitisation but nearly all potentially modifiable factors were insignificant. This included measures of local land use and proximity to potential sources of ragweed pollen. Rural residence was protective (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55–0.98), but the factors underlying this association were unclear. Being sensitised to ragweed doubled (OR 2.17, 95% CI 1.59–2.96) the risk of rhinoconjunctivitis. No other potentially modifiable risk factors were associated with rhinoconjunctivitis. Ragweed sensitisation was strongly associated with ragweed pollen, and sensitisation was significantly associated with rhinoconjunctivitis. Apart from ragweed pollen levels, few other potentially modifiable factors were significantly associated with ragweed sensitisation. Hence, strategies to lower the risk of sensitisation should focus upon ragweed control.
Predictors of Urinary Arsenic Levels among Postmenopausal Danish Women
Authors: Roswall Nina , Hvidtfeldt Ulla A. , Harrington James , Levine Keith E. , Sørensen Mette , Tjønneland Anne , Meliker Jaymie R. , Raaschou-Nielsen Ole
Published: June 2018

Arsenic is a risk factor for several noncommunicable diseases, even at low doses. Urinary arsenic (UAs) concentration is a good biomarker for internal dose, and demographic, dietary, and lifestyle factors are proposed predictors in nonoccupationally exposed populations. However, most predictor studies are limited in terms of size and number of predictors. We investigated demographic, dietary, and lifestyle determinants of UAs concentrations in 744 postmenopausal Danish women who had UAs measurements and questionnaire data on potential predictors. UAs concentrations were determined using mass spectrometry (ICP-MS), and determinants of the concentration were investigated using univariate and multivariate regression models. We used a forward selection procedure for model optimization. In all models, fish, alcohol, and poultry intake were associated with higher UAs concentration, and tap water, fruit, potato, and dairy intake with lower concentration. A forward regression model explained 35% (R2) of the variation in concentrations. Age, smoking, education, and area of residence did not predict concentration. The results were relatively robust across sensitivity analyses. The study suggested that UAs concentration in postmenopausal women was primarily determined by dietary factors, with fish consumption showing the strongest direct association. However, the majority of variation in UAs concentration in this study population is still unexplained.
Integrating Qualitative and Quantitative Data in the Development of Outcome Measures: The Case of the Recovering Quality of Life (ReQoL) Measures in Mental Health Populations
Authors: Keetharuth Anju Devianee , Taylor Buck Elizabeth , Acquadro Catherine , Conway Katrin , Connell Janice , Barkham Michael , Carlton Jill , Ricketts Thomas , Barber Rosemary , Brazier John
Published: June 2018

While it is important to treat symptoms, there is growing recognition that in order to help people with mental health problems lead meaningful and fulfilling lives, it is crucial to capture the impact of their conditions on wider aspects of their social lives. We constructed two versions of the Recovering Quality of Life (ReQoL) measure—ReQoL-10 and ReQoL-20—for use in routine settings and clinical trials from a larger pool of items by combining qualitative and quantitative evidence covering six domains. Qualitative evidence was gathered through interviews and focus groups with over 76 service users, clinicians, and a translatability assessment. Psychometric evidence generated from data from over 6200 service users was obtained from confirmatory factor models and item response theory analyses. In this paper we present an approach based on a traffic light pictorial format that was developed to present qualitative and quantitative evidence to a group of service users, clinicians, and researchers to help to make the final selection. This work provides a pragmatic yet rigorous approach to combining qualitative and quantitative evidence to ensure that ReQoL is psychometrically robust and has high relevance to service users and clinicians. This approach can be extended to the development of patient reported outcome measures in general.
Effect of Social Media on Child Obesity: Application of Structural Equation Modeling with the Taguchi Method
Authors: Khajeheian Datis , Colabi Amir , Ahmad Kharman Shah Nordiana , Bt Wan Mohamed Radzi Che , Jenatabadi Hashem
Published: June 2018

Through public health studies, specifically on child obesity modeling, research scholars have been attempting to identify the factors affecting obesity using suitable statistical techniques. In recent years, regression, structural equation modeling (SEM) and partial least squares (PLS) regression have been the most widely employed statistical modeling techniques in public health studies. The main objective of this study to apply the Taguchi method to introduce a new pattern rather than a model for analyzing the body mass index (BMI) of children as a representative of childhood obesity levels mainly related to social media use. The data analysis includes two main parts. The first part entails selecting significant indicators for the proposed framework by applying SEM for primary and high school students separately. The second part introduces the Taguchi method as a realistic and reliable approach to exploring which combination of significant variables leads to high obesity levels in children. AMOS software (IBM, Armonk, NY, USA) was applied in the first part of data analysis and MINITAB software (Minitab Inc., State College, PA, USA) was utilized for the Taguchi experimental analysis (second data analysis part). This study will help research scholars view the data and a pattern rather than a model, as a combination of different factor levels for target factor optimization.
LncRNA ITGB2-AS1 Could Promote the Migration and Invasion of Breast Cancer Cells through Up-Regulating ITGB2
Authors: Liu Mengyao , Gou Liyao , Xia Jing , Wan Qun , Jiang Yayun , Sun Shilei , Tang Min , He Tongchuan , Zhang Yan
Published: June 2018

In the previous study, we screened a novel lncRNA-ITGB2-AS1, which was down-regulated by bone morphogenetic protein 9 (BMP9) in breast cancer cell. Studying ITGB2-AS1 will lay the foundation for the exploring mechanism of the BMP9 inhibitory effect on breast cancer. The expression analysis related to ITGB2-AS1 in clinical samples was conducted on online websites. The overexpression plasmid or siRNA fragment was transfected into breast cancer cells to alter its gene expression. The MTT assay and flow cytometry were used to measure cell viability and cell cycle. Additionally, cell migration and invasion were detected by wound healing and transwell assay. The results of biological function experiments showed that ITGB2-AS1 could promote the migration and invasion of breast cancer. Furthermore, ITGB2-AS1 increased the mRNA and protein expression of ITGB2. Consistent with ITGB2-AS1, ITGB2 exerted the promotion effect on the migration and invasion of breast cancer and activated integrin-related FAK signaling. The OL plasmid expressing the truncation of ITGB2-AS1, which was complementary to ITGB2, was essential for activation of FAK signaling. In conclusion, LncRNA ITGB2-AS1 could promote the migration and invasion of breast cancer cells by up-regulating ITGB2.
Donor Site Location Is Critical for Proliferation, Stem Cell Capacity, and Osteogenic Differentiation of Adipose Mesenchymal Stem/Stromal Cells: Implications for Bone Tissue Engineering
Authors: Reumann Marie K. , Linnemann Caren , Aspera-Werz Romina H. , Arnold Sigrid , Held Manuel , Seeliger Claudine , Nussler Andreas K. , Ehnert Sabrina
Published: June 2018

Human adipose mesenchymal stem/stromal cells (Ad-MSCs) have been proposed as a suitable option for bone tissue engineering. However, donor age, weight, and gender might affect the outcome. There is still a lack of knowledge of the effects the donor tissue site might have on Ad-MSCs function. Thus, this study investigated proliferation, stem cell, and osteogenic differentiation capacity of human Ad-MSCs obtained from subcutaneous fat tissue acquired from different locations (abdomen, hip, thigh, knee, and limb). Ad-MSCs from limb and knee showed strong proliferation despite the presence of osteogenic stimuli, resulting in limited osteogenic characteristics. The less proliferative Ad-MSCs from hip and thigh showed the highest alkaline phosphatase (AP) activity and matrix mineralization. Ad-MSCs from the abdomen showed good proliferation and osteogenic characteristics. Interestingly, the observed differences were not dependent on donor age, weight, or gender, but correlated with the expression of Sox2, Lin28A, Oct4α, and Nanog. Especially, low basal Sox2 levels seemed to be pivotal for osteogenic differentiation. Our data clearly show that the donor tissue site affects the proliferation and osteogenic differentiation of Ad-MSCs significantly. Thus, for bone tissue engineering, the donor site of the adipose tissue from which the Ad-MSCs are derived should be adapted depending on the requirements, e.g., cell number and differentiation state.
The Effect of GPRC5a on the Proliferation, Migration Ability, Chemotherapy Resistance, and Phosphorylation of GSK-3β in Pancreatic Cancer
Authors: Liu Bin , Yang Hai , Pilarsky Christian , Weber Georg F.
Published: June 2018

Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related death, and personalized targeted cancer therapy is becoming a promising treatment strategy for PaCa. The central approach of targeted therapy is to find a targetable key and an effective targeting method. In this study, the importance of GPRC5a (the G-protein-coupled receptor family C, member 5, group A) was identified using data mining methods based on published datasets. After analysis of the basic expression of GPRC5a in normal pancreas tissue and various PaCa cell lines, gene editing of GPRC5a in the human PaCa cell line MIA PaCa-2 and the mouse PaCa cell line TB32047 was performed using CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated proteins 9) to investigate the influence of GPRC5a on the proliferation and migration of PaCa cells as well as its effects on chemotherapy drug resistance. The results showed that GPRC5a was upregulated in PaCa tissues and various PaCa cell lines. Knockout of GPRC5a reduced the proliferation and migration ability of PaCa cell lines and suppressed the chemotherapy drug resistance of gemcitabine, oxaliplatin, and fluorouracil in PaCa cells. The phosphorylation of GSK-3β (Glycogen synthase kinase-3β) was found to be upregulated in the MIA PaCa-2 and TB32047 cells after GPRC5a knockout. In conclusion, GPRC5a was upregulated in PaCa leading to an enhanced drug resistance in PaCa cells. These results provide for the first time a theoretical basis for the development of an improved PaCa targeted therapy.
PPARγ Expression Is Diminished in Macrophages of Recurrent Miscarriage Placentas
Authors: Kolben Theresa Maria , Rogatsch Elisabeth , Vattai Aurelia , Hester Anna , Kuhn Christina , Schmoeckel Elisa , Mahner Sven , Jeschke Udo , Kolben Thomas
Published: June 2018

PPARγ belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARγ is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPARγ under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion and 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPARγ. Expression changes were evaluated by immunohistochemistry and real time PCR (RT-PCR) in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using cluster of differentiation 68 (CD68) as marker for macrophages and further characterized regarding their M1/M2 polarization status. The intermediate villous trophoblast revealed a significantly lower PPARγ expression in spontaneous and recurrent abortion. Maternal macrophages express PPARγ. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPARγ only in very few cases. PPARγ is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPARγ in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus.
FGF Family: From Drug Development to Clinical Application
Authors: Hui Qi , Jin Zi , Li Xiaokun , Liu Changxiao , Wang Xiaojie
Published: June 2018

Fibroblast growth factor (FGF) belongs to a large family of growth factors. FGFs use paracrine or endocrine signaling to mediate a myriad of biological and pathophysiological process, including angiogenesis, wound healing, embryonic development, and metabolism regulation. FGF drugs for the treatment of burn and ulcer wounds are now available. The recent discovery of the crucial roles of the endocrine-acting FGF19 subfamily in maintaining homeostasis of bile acid, glucose, and phosphate further extended the activity profile of this family. Here, the applications of recombinant FGFs for the treatment of wounds, diabetes, hypophosphatemia, the development of FGF receptor inhibitors as anti-neoplastic drugs, and the achievements of basic research and applications of FGFs in China are reviewed.
Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update
Authors: Evangelisti Camilla , Chiarini Francesca , McCubrey James , Martelli Alberto
Published: June 2018

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood malignancy that arises from the clonal expansion of transformed T-cell precursors. Although T-ALL prognosis has significantly improved due to the development of intensive chemotherapeutic protocols, primary drug-resistant and relapsed patients still display a dismal outcome. In addition, lifelong irreversible late effects from conventional therapy are a growing problem for leukemia survivors. Therefore, novel targeted therapies are required to improve the prognosis of high-risk patients. The mechanistic target of rapamycin (mTOR) is the kinase subunit of two structurally and functionally distinct multiprotein complexes, which are referred to as mTOR complex 1 (mTORC1) and mTORC2. These two complexes regulate a variety of physiological cellular processes including protein, lipid, and nucleotide synthesis, as well as autophagy in response to external cues. However, mTOR activity is frequently deregulated in cancer, where it plays a key oncogenetic role driving tumor cell proliferation, survival, metabolic transformation, and metastatic potential. Promising preclinical studies using mTOR inhibitors have demonstrated efficacy in many human cancer types, including T-ALL. Here, we highlight our current knowledge of mTOR signaling and inhibitors in T-ALL, with an emphasis on emerging evidence of the superior efficacy of combinations consisting of mTOR inhibitors and either traditional or targeted therapeutics.
Ethanolic Extracts from Azadirachta indica Leaves Modulate Transcriptional Levels of Hormone Receptor Variant in Breast Cancer Cell Lines
Authors: Braga Deisi L. , Mota Sara T. S. , Zóia Mariana A. P. , Lima Paula M. A. P. , Orsolin Priscila C. , Vecchi Lara , Nepomuceno Júlio C. , Fürstenau Cristina R. , Maia Yara C. P. , Goulart Luiz Ricardo , Araújo Thaise G.
Published: June 2018

Breast Cancer (BC) encompasses numerous entities with different biological and behavioral characteristics, favored by tumor molecular complexity. Azadirachta indica (neem) presents phenolic compounds, indicating its potential as an antineoplastic compound. The present study aimed to evaluate the cellular response of MCF10, MCF7, and MDA-MB-231 breast cell lines to ethanolic extracts of neem leaves (EENL) obtained by dichloromethane (DCM) and ethyl acetate (EA) solvent. Extracts’ antiproliferative activities were evaluated against MCF 10A, MCF7, and MDA-MB-231 for 24 and 48 h using MTT assay. ESR1, ESR2, AR, AR-V1, AR-V4, and AR-V7 transcripts were quantified through qPCR for 0.03125 μg/mL of DCM and 1.0 μg/mL for EA for 48 h. The EENL was tested on Drosophila melanogaster as a sole treatment and then also together with doxorubicin. Antiproliferative effect on tumor cell lines without affecting MCF 10A were 1.0 µg/mL (P < 0.001) for EA, and 0.03125 µg/mL (P < 0.0001) for DCM, both after 48 h. Transcriptional levels of AR-V7 increased after treatment. In vivo assays demonstrated that EENL induced fewer tumors at a higher concentration with doxorubicin (DXR). The behavior of AR-V7 in the MDA-MB-231 tumor lineage indicates new pathways involved in tumor biology and this may have therapeutic value for cancer.
Glutathione in Ovarian Cancer: A Double-Edged Sword
Authors: Nunes Sofia C. , Serpa Jacinta
Published: June 2018

Glutathione (GSH) has several roles in a cell, such as a reactive oxygen species (ROS) scavenger, an intervenient in xenobiotics metabolism and a reservoir of cysteine. All of these activities are important in the maintenance of normal cells homeostasis but can also constitute an advantage for cancer cells, allowing disease progression and resistance to therapy. Ovarian cancer is the major cause of death from gynaecologic disease and the second most common gynaecologic malignancy worldwide. In over 50 years, the overall survival of patients diagnosed with epithelial ovarian cancer has not changed, regardless of the efforts concerning early detection, radical surgery and new therapeutic approaches. Late diagnosis and resistance to therapy are the main causes of this outcome, and GSH is profoundly associated with chemoresistance to platinum salts, which, together with taxane-based chemotherapy and surgery, are the main therapy strategies in ovarian cancer treatment. Herein, we present some insights into the role of GSH in the poor prognosis of ovarian cancer, and also point out how some strategies underlying the dependence of ovarian cancer cells on GSH can be further used to improve the effectiveness of therapy.
An Evolutionary Algorithm for an Optimization Model of Edge Bundling
Authors: Ferreira Joelma , Do Nascimento Hugo , Foulds Les
Published: June 2018

This paper discusses three edge bundling optimization problems that aim to minimize the total number of bundles of a graph drawing, in conjunction with other aspects, as the main goal. A novel evolutionary algorithm for edge bundling for these problems is described. The algorithm was successfully tested by solving the related problems applied to real-world instances in reasonable computational time. The development and analysis of optimization models have received little attention in the area of edge bundling. However, the reported experimental results demonstrate the effectiveness and the applicability of the proposed evolutionary algorithm to help resolve edge bundling problems by formally defining them as optimization models.
Good Things in Small Packages? Evaluating an Economy of Scale Approach to Behavioral Health Promotion in Rural America
Authors: Bartkowski John , Xu Xiaohe , Avery Jerri , Ferguson Debbie , Johnson Frankie
Published: June 2018

Rural American youth exhibit pronounced health disparities. This study enlists insights from an economy of scale paradigm to determine the relative effects of serving smaller versus larger client groups in an assembly-style school-based behavioral health promotion program. Evaluation results are reported from a three-year intervention delivered to eighth-grade and tenth-grade rural Mississippi students from 2012 to 2015. The program, I Got U: Healthy Life Choices for Teens, coupled a day-long intensive immersion in youth risk prevention and mental health promotion with school-based information dissemination. Results reveal robust effectiveness in program years 1 and 2, during which caps of 175 attendees per event were imposed. Salutary results were no longer evident during year 3, when larger venues were used to serve over three times the number of students per event. This program teaches valuable lessons about the potential for diminishing returns yielded by an economy of scale approach to implementation.
Forced Expression of Foxg1 in the Cortical Hem Leads to the Transformation of Cajal-Retzius Cells into Dentate Granule Neurons
Authors: Liu Bin , Xiao Hongmei , Zhao Chunjie
Published: June 2018

The Wnt- and BMP-rich cortical hem has been demonstrated to be critical for the pattern formation of the telencephalon, and it is particularly important for the induction of the hippocampus. Meanwhile, the cortical hem is one of the sources of Cajal-Retzius cells. Many Cajal-Retzius cells are produced in the hem and populated to the media-caudal surface of the telencephalon. However, the mechanism of the maintenance of the hem remain unclear. In this study, we generated a transgenic mouse line CAG-loxp-stop-loxp-Foxg1-IRES-EGFP. By crossing Fzd10CreERTM with this line, combined with tamoxifen induction, Foxg1 was ectopically expressed in the hem from embryonic day 10.5 (E10.5) onwards. We have found the hem-derived Cajal-Retzius cells were transformed into dentate granule neurons accompanied with ectopic expression of Lhx2. However, the morphology of the hem displayed no obvious changes. The hem specific markers, Wnt3a and Wnt2b, were slightly downregulated. Our results indicate that Foxg1 is sufficient to induce the expression of Lhx2 in the dorsal part of the hem. The ectopic Lhx2 and decreased Wnt signals may both contribute to the cell fate switch. Our study provides new insight into the mechanism underlying the maintenance of the hem.
A Survey of Comics Research in Computer Science
Authors: Augereau Olivier , Iwata Motoi , Kise Koichi
Published: June 2018

Graphic novels such as comic books and mangas are well known all over the world. The digital transition started to change the way people are reading comics: more and more on smartphones and tablets, and less and less on paper. In recent years, a wide variety of research about comics has been proposed and might change the way comics are created, distributed and read in the future. Early work focuses on low level document image analysis. Comic books are complex; they contains text, drawings, balloons, panels, onomatopoeia, etc. Different fields of computer science covered research about user interaction and content generation such as multimedia, artificial intelligence, human–computer interaction, etc. with different sets of values. We review the previous research about comics in computer science to state what has been done and give some insights about the main outlooks.
Study on Electrolytic Magnetic Abrasive Finishing for Finishing Stainless Steel SUS304 Plane with a Special Compound Machining Tool
Authors: Sun Xu , Zou Yanhua
Published: June 2018

In order to improve the finishing efficiency of traditional plane magnetic abrasive finishing (MAF), we have previously proposed an effective plane MAF process combined with an electrolytic process and developed a special compound machining tool for the electrolytic magnetic abrasive finishing (EMAF). In this research, the EMAF process is divided into two finishing steps. The first finishing step is the EMAF step, and a single MAF step constitutes the second finishing step. The machinability of SUS304 material can be improved through the formation of passive films from the electrolytic process in the EMAF step. Meanwhile, the passive films can be rapidly and easily removed by friction between the magnetic particles and the workpiece-generated mechanical machining force. Thus, the surface finishing efficiency can be greatly improved. Compared with a dedicated MAF machining tool or a dedicated electrolytic machining tool, this special compound machining tool can synchronously achieve MAF and electrolytic processes to make the processing more convenient. This study focuses on exploring mechanical finishing characteristics of the special compound machining tool through MAF experiments. Additionally, EMAF experiments are conducted under the optimal mechanical finishing conditions. The experimental results of the EMAF process show that the surface roughness Ra can be reduced to less than 30 nm at the 4-min EMAF step, and it can be further reduced to 20 nm at the 10-min MAF step.