bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypothesis: Caco‐2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts
Authors: Zheng Gen , Kalinin Alexandr A. , Dinov Ivo D. , Meixner Walter , Zhu Shengtao , Wiley John W. 
Published: September 2018

AbstractColon crypts are recognized as a mechanical and biochemical Turing patterning model. Colon epithelial Caco‐2 cell monolayer demonstrated 2D Turing patterns via force analysis of apical tight junction live cell imaging which illuminated actomyosin meshwork linking the actomyosin network of individual cells. Actomyosin forces act in a mechanobiological manner that alters cell/nucleus/tissue morphology. We observed the rotational motion of the nucleus in Caco‐2 cells that appears to be driven by actomyosin during the formation of a differentiated confluent epithelium. Single‐ to multi‐cell ring/torus‐shaped genomes were observed prior to complex fractal Turing patterns extending from a rotating torus centre in a spiral pattern consistent with a gene morphogen motif. These features may contribute to the well‐described differentiation from stem cells at the crypt base to the luminal colon epithelium along the crypt axis. This observation may be useful to study the role of mechanogenomic processes and the underlying molecular mechanisms as determinants of cellular and tissue architecture in space and time, which is the focal point of the 4D nucleome initiative. Mathematical and bioengineer modelling of gene circuits and cell shapes may provide a powerful algorithm that will contribute to future precision medicine relevant to a number of common medical disorders.
Disseminated tumour cells in bone marrow are the source of cancer relapse after therapy
Authors: Sai Buqing , Xiang Juanjuan 
Published: September 2018

AbstractAccumulating evidence indicates that cancer cells spread much earlier than was previously believed. Recent technological advances have greatly improved the detection methods of circulating tumour cells (CTCs), suggesting that the dissemination of cancer cells into the circulation occurs randomly. Most CTCs die in circulation as a result of shear stress and/or anoikis. However, the persistence of disseminated tumour cells (DTCs) in the bone marrow is the result of interaction of DTCs with bone marrow microenvironment. DTCs in the bone marrow undergo successive clonal expansions and a parallel progression that leads to new variants. Compared to the CTCs, DTCs in the bone marrow have a unique signature, which displayed dormant, mesenchymal phenotype and osteoblast‐like or osteoclast‐like phenotype. The persistence of DTCs in the bone marrow is always related to minimal residual diseases (MRDs). This review outlines the difference between CTCs and DTCs in the bone marrow and describes how this difference affects the clinical values of CTCs and DTCs, such as metastasis and recurrence. We suggest that DTCs remaining in the bone marrow after therapy can be used as a superior marker in comparison with CTCs to define patients with an unfavourable prognosis and may therefore be a potential prognostic factor and therapeutic target for cancer therapy.
Increase of PRPP enhances chemosensitivity of PRPS1 mutant acute lymphoblastic leukemia cells to 5‐Fluorouracil
Authors: Wang Dan , Chen Yao , Fang Houshun , Zheng Liang , Li Ying , Yang Fan , Xu Yan , Du Lijuan , Zhou Bin‐Bing S. , Li Hui 
Published: September 2018

AbstractRelapse‐specific mutations in phosphoribosyl pyrophosphate synthetase 1 (PRPS1), a rate‐limiting purine biosynthesis enzyme, confer significant drug resistances to combination chemotherapy in acute lymphoblastic leukemia (ALL). It is of particular interest to identify drugs to overcome these resistances. In this study, we found that PRPS1 mutant ALL cells specifically showed more chemosensitivity to 5‐Fluorouracil (5‐FU) than control cells, attributed to increased apoptosis of PRPS1 mutant cells by 5‐FU. Mechanistically, PRPS1 mutants increase the level of intracellular phosphoribosyl pyrophosphate (PRPP), which causes the apt conversion of 5‐FU to FUMP and FUTP in Reh cells, to promote 5‐FU‐induced DNA damage and apoptosis. Our study not only provides mechanistic rationale for re‐targeting drug resistant cells in ALL, but also implicates that ALL patients who harbor relapse‐specific mutations of PRPS1 might benefit from 5‐FU‐based chemotherapy in clinical settings.
Longitudinal structural brain development and externalizing behavior in adolescence
Authors: Bos Marieke G.N. , Wierenga Lara M. , Blankenstein Neeltje E. , Schreuders Elisabeth , Tamnes Christian K. , Crone Eveline A. 
Published: September 2018

BackgroundCross‐sectional studies report relations between externalizing behavior and structural abnormalities in cortical thickness of prefrontal regions and volume reductions in subcortical regions. To understand how these associations emerge and develop, longitudinal designs are pivotal.MethodIn the current longitudinal study, a community sample of children, adolescents and young adults (N = 271) underwent magnetic resonance imaging (MRI) in three biennial waves (680 scans). At each wave, aspects of externalizing behavior were assessed with parent‐reported aggression and rule‐breaking scores (Child Behavior Checklist), and self‐reported aggression scores (Buss‐Perry Aggression Questionnaire). Regions of interest (ROIs) were selected based on prior research: dorsolateral prefrontal (dlPFC), orbitofrontal (OFC), anterior cingulate cortex (ACC), insula, and parahippocampal cortex, as well as subcortical regions. Linear mixed models were used to assess the longitudinal relation between externalizing behavior and structural brain development. Structural covariance analyses were employed to identify whether longitudinal relations between ROIs (maturational coupling) were associated with externalizing behavior.ResultsLinear mixed model analyses showed a negative relation between parent‐reported aggression and right hippocampal volume. Moreover, this longitudinal relation was driven by change in hippocampal volume and not initial volume of hippocampus at time point 1. Exploratory analyses showed that stronger maturational coupling between prefrontal regions, the limbic system, and striatum was associated with both low and high externalizing behavior.ConclusionsTogether, these findings reinforce the hypothesis that altered structural brain development coincides with development of more externalizing behavior. These findings may guide future research on normative and deviant development of externalizing behavior.
Wholesale price discrimination: Innovation incentives and upstream competition
Authors: Akgün Uğur , Chioveanu Ioana 
Published: September 2018

AbstractIn intermediate good markets where there are alternative supply sources, wholesale price discrimination may enhance innovation incentives downstream. We consider a vertical chain where a dominant firm and a competitive fringe supply imperfect substitutes to duopoly retailers which carry both varieties. We show that a ban on price discrimination by the dominant supplier makes uniform pricing credible and reduces retailers’ incentives to decrease the cost of acquiring the competitively supplied variety, leading to higher upstream profits and lower downstream welfare. Our analysis complements existing results by identifying a novel channel through which wholesale price discrimination can improve dynamic market efficiency.
Ultrasound assisted enzymolysis of sunflower meal protein: Kinetics and thermodynamics modeling
Authors: Dabbour Mokhtar , He Ronghai , Mintah Benjamin , Tang Yingxiu , Ma Haile 
Published: September 2018

AbstractThis study examined the effect of dual‐frequency ultrasound (DFU) pretreatment on thermodynamics and kinetics of sunflower‐meal protein (SMP) using alcalase to improve efficiency in enzymolysis process. The concentration of hydrolyzed protein and kinetic parameters after traditional pretreatment (control) were investigated and compared with DFU‐assisted enzymolysis. The results indicated that DFU‐pretreatment enhanced SMP‐enzymolysis efficiency at different substrate and enzyme concentrations, temperature, and pH. Kinetics analysis showed DFU‐pretreatment reduced the Michaelis constant by 11.29%, while the apparent breakdown rate constant increased by 1.96%, indicating DFU‐pretreatment improved the affinity among substrate and enzyme. The rate constants for DFU‐pretreatment were increased by 45.96, 26.92, 21.14, and 27.89% at 293, 303, 313, and 323 K, respectively (p < .05). On Arrhenius kinetics, DFU reduced the activation energy, enthalpy and entropy by 24.28, 26.13, and 9.10%, respectively (p < .05). DFU had slight influence on Gibbs‐free energy when temperature increased from 293 to 323 K.Practical applicationsThe positive impact of DFU pretreatment of sunflower meal protein on enzymatic hydrolysis kinetics makes this method suitable for use in the pharmaceutical and food process industries to yield peptides from residues of oil industry.
Nonthermal pasteurization of onion juice by continuous UV‐C reactor
Authors: Demir Hande , Oral Mehmet Onur 
Published: September 2018

AbstractThe objective of this study is to investigate the continuous pasteurization of onion (Allium cepa L.) juice by ultraviolet (UV‐C) irradiation by a designed coiled‐tube type UV‐C reactor. System is composed of four vertical low‐pressure mercury lamps (20 W/lamp, 254 nm) coiled using a PTFE tube. A secondary eddy flow effect was achieved with a Dean number of 0.073. The Escherichia coli K‐12 count in onion juice was reduced by 4.83 log after exposure to UV‐C light for 8.13 min at an estimated UV‐C dosage of 38.1 J/mL with the flow rate of 1.26 L/min. After UV‐C treatment, the total color change (ΔE) of the onion juice was recorded as 1.15 which can be referred as slightly noticeable. Total aerobic mesophilic count of UV‐C irradiated samples was below acceptable limits after 6 weeks of storage. Meat marination in UV‐C‐treated onion juice reduced the hardness of meat by 78%.Practical applicationsCurrently, many of the large‐scale processed meat producers prefer to marinate the meat directly in the onion juice or in a sauce formulation including onion juice. Therefore, they are the major end‐users of this product. In addition, onion juice has a large potential to be used by the catering industry providing food service for relatively large number of people. If the storage space for onions, the preparation, and service time for the meals are taken into consideration, catering services may highly benefit from the pasteurized onion juice products. Conventional heat treatment is the most common method to extend shelf‐life of vegetable juices. The results of this study indicated that continuous UV‐C irradiation can successfully be used to pasteurize onion juice. The outcomes will also serve the basis to technical knowledge for designing the pilot‐scale production of onion juice processed by nonthermal treatments.
Unspanned stochastic volatility in the multifactor CIR model
Authors: Filipović Damir , Larsson Martin , Statti Francesco 
Published: September 2018

AbstractEmpirical evidence suggests that fixed‐income markets exhibit unspanned stochastic volatility (USV), that is, that one cannot fully hedge volatility risk solely using a portfolio of bonds. While Collin‐Dufresne and Goldstein (2002, Journal of Finance, 57, 1685–1730) showed that no two‐factor Cox–Ingersoll–Ross (CIR) model can exhibit USV, it has been unknown to date whether CIR models with more than two factors can exhibit USV or not. We formally review USV and relate it to bond market incompleteness. We provide necessary and sufficient conditions for a multifactor CIR model to exhibit USV. We then construct a class of three‐factor CIR models that exhibit USV. This answers in the affirmative the above previously open question. We also show that multifactor CIR models with diagonal drift matrix cannot exhibit USV.
A Multivariate Computational Framework to Characterize and Rate Virtual Portland Cements
Authors: Tao Chengcheng , Watts Benjamin , Ferraro Christopher C. , Masters Forrest J. 
Published: September 2018

AbstractThis article presents a novel application of metaheuristic optimization and rating techniques to virtual test results for cement and mortar, and presents objective computational methods for the evaluation and selection of cementitious materials based on simulated material testing. A scalable approach based on particle swarm optimization of the National Institute of Standards and Technology Virtual Cement and Concrete Testing Laboratory (VCCTL) is successfully demonstrated using ∼150,000 combinations of cement phase distributions and water‐to‐cement ratios, with as few as 10% of the VCCTL runs required to obtain the optimal solutions. The application of Pareto front analysis reveals an inherent trade‐off between the modulus of elasticity, time of set, and kiln temperature (using alite:belite as a proxy) at the performance limits. This study also provides a means to objectively characterize cements in these contexts using a maximum likelihood estimator to calculate a score from the cumulative distribution function, using a random subset of the 150,000 simulated cement pastes. The proposed approach provides a new pathway to optimally proportion raw materials (and eventually waste by‐products) to reduce production costs, extend the life of a quarry, or reduce the carbon footprint of cement plants.
Influences of immunostimulants on phagocytes in cultured fish: a mini review
Authors: Abarike Emmanuel D. , Kuebutornye Felix K.A. , Jian Jichang , Tang Jufen , Lu Yishan , Cai Jia 
Published: September 2018

AbstractLower vertebrates like fish mostly depend on innate immunity as the first line of defence against invading pathogens. One of the defence mechanisms in innate immunity for fish is the use of phagocytic cells such as monocytes, macrophages, neutrophils, mast cells and dendritic cells in fighting pathogens. These cellular cells employ a variety of mechanisms in protecting fish including but not limited to; the use of pattern recognition receptors and antigen presenting cells to detect the presence of pathogens in host, neutralising them using measures including; inflammation, production of lysosomal enzymes released into the phagosome to neutralising pathogens and prevention of systemic autoimmunity by apoptosis. Some phagocytic cells play the extra role of serving as a bridge between innate and adaptive immunity in fish. Recent accumulating data showed that phagocyte cell activity in fish could be enhanced by a natural or chemical substance (immunostimulants) that stimulates the immune system in fish principally meant to enhance the immune response mechanisms. In this review, the main focus is on elucidating the distinct phagocytic mechanisms played by monocytes, macrophages, neutrophils, mast cells and dendritic cells as principal phagocytes in immune defence and how their activities are influenced by immunostimulants in cultured fish.
Numbers in regulatory intermediation: Exploring the role of performance measurement between legitimacy and compliance
Authors: Mehrpouya Afshin , Samiolo Rita 
Published: September 2018

AbstractMuch regulatory intermediation has come to entail forms of calculation and performance measurement. In this paper we analyze the role of performance measurement in regulatory intermediation in a transnational multistakeholder setting where intermediation lacks an official mandate. We do this through a study of the Access to Medicine Index, which ranks pharmaceutical companies in terms of their access to medicine policies and practices in developing countries. We conceptualize multistakeholder intermediaries as “second order rulemakers” reconciling diverse and often competing implicit and explicit rules across the governance field. We then detail various intermediation roles of performance measurement between attaining input and output legitimacy and enticing compliance among targets. Our case demonstrates how the selective formalization of measurement processes and the related ability to move back and forth from the role of intermediary to that of “ad hoc rulemaker” are important conditions for achieving and maintaining legitimacy. Furthermore, it shows that for multistakeholder intermediaries that rely on performance measurement, compliance by targets depends on the uptake of performance information by powerful constituencies. This illustrates how addressing legitimacy concerns and enticing compliance through performance measurement should be examined as co‐emerging processes.
Residential segregation and educational attainment of children from regional migrant families in China
Authors: Ma Xiangjun , Zhou Yean 
Published: September 2018

AbstractThis paper studies the residential segregation effects on educational attainment of children from regional migrant families in China. We find that if migrant families live in segregated communities with fewer local residents, the school dropout rate of the children living with their parents in the host cities is higher and their high school enrollment rate is lower. We employ a unique set of nationwide survey data of regional migrants in China in 2012 and 2013 that comprises more than 150,000 individuals in each year. We first use the ratio of migrants over the total population residing in a community to measure segregation. When the ratio increases by 10%, the school dropout rate of migrant children increases by 4.7% from the mean value. Secondly, we identify segregation from the housing type of the migrant family. When they reside in the dorms provided by their employers or in the workplace, they will also be surrounded by many migrant colleagues. We find that living in such places increases the “not‐going‐to‐high‐school rate” of migrant children by 35% from the mean value. Our subsample analysis indicates that the segregation effects only exist in the samples of male migrant children and rural hukou families.
Assessment of the common carotid artery wall stiffness by Shear Wave Elastography in Behcet’s disease
Authors: Alis Deniz , Durmaz Emine Sebnem Memis , Civcik Ceren , Tutuncu Melih , Saip Sabahattin , Kocer Naci , Islak Civan , Kizilkilic Osman 
Published: September 2018

Aim: To evaluate endothelial dysfunction and subclinical atherosclerosis in Behcet’s disease (BD) by measuring the common carotid artery (CCA) wall stiffness and carotid intima-media thickness (CIMT).Materials and methods: We prospectively evaluated CIMT and the CCA wall stiffness of 34 BD patients and 28 age/sex-matched controls. CIMT measurements were performed from the posterior wall of the carotid artery approximately 10 mm proximal to the initiation of the carotid bulb using B-mode ultrasound. The stiffness of the CCA was measured from the superficial wall of the CCA using shear wave elastography (SWE). SWE measurements were recorded as shear wave velocity (SWV) using m/s as a unit.Results: The mean right (0.5±0.11 mm) and left (0.5±0.14 mm) CIMT of the patients were significantly higher compared to the mean right (0.41±0.07 mm) and left (0.41±0.11 mm) CIMT of the healthy controls (p=0.001 and p= 0.003 respectively). The mean right (3.72±0.94 m/s) and left (3.57±0.72 m/s) CCA wall stiffness of the patients were significantly higher compared to the mean right (2.42±0.49 m/s) and left (2.56±0.49 m/s) CCA wall stiffness of the controls (p<0.001 for both).Conclusions: SWE seems to be a promising modality to evaluate endothelial dysfunction in BD by interpreting the arterial stiffness, and SWE might be an important adjunct to clinical and laboratory findings, and imaging modalities to assess cardiovascular risk in BD. Moreover, SWE evaluation of the arterial stiffness might assist us to understand pathophysiological aspects of BD.
Electroacupuncture Ameliorates Cognitive Impairment through Inhibition of Ca2+-Mediated Neurotoxicity in a Rat Model of Cerebral Ischaemia–reperfusion Injury
Authors: Zhang Yun , Mao Xiang , Lin Ruhui , Li Zuanfang , Lin Jing 
Published: September 2018

Background The hippocampus is vulnerable to severe damage after cerebral ischaemia–reperfusion (I/R) injury. This study aimed to explore the effect of electroacupuncture (EA) on cognitive impairment and its relationship with Ca2+neurotoxicity in a rat model of I/R injury induced by middle cerebral artery occlusion (MCAO). Methods 60 adult male Sprague-Dawley rats were randomly divided into three groups: control (sham surgery) group, untreated MCAO group and EA-treated MCAO+EA group. Rats in the MCAO and MCAO+EA groups underwent modelling of poststroke cognitive impairment by MCAO surgery. EA was performed for 30 min daily at GV20 and GV24 (1–20 Hz) for 1 week. The Morris water maze experiment was used to assess cognitive function. 2,3,5-triphenyl tetrazolium chloride staining was used to measure infarct volume. The intracellular Ca2+content in the Cornu Ammonis (CA)1 area of the hippocampus was assessed by laser confocal scanning microscopy. ELISA was performed to evaluate the concentration of glutamate (Glu) in the hippocampus, and the protein expression of two Glu receptors (N-methyl-D-aspartic acid receptor (NMDAR) 2A and NMDAR2B) were analysed by Western blotting. Results Compared with the untreated MCAO group, EA effectively ameliorated cognitive impairment (P=0.01) and shrunk the infarct volume (P=0.032). The content of intracellular Ca2+, Glu and NMDAR2B in the hippocampus was significantly raised by MCAO (P=0.031-0.043), while EA abrogated these effects. NMDAR2A was decreased by MCAO (P=0.015) but increased by EA (P=0.033). Conclusions EA had a beneficial effect on cognitive repair after cerebral I/R, and its mechanism of action likely involves a reduction of Ca2+influx via inhibition of Glu neurotoxicity and downregulation of NMDAR2B expression.
Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis
Authors: Seid Mohammed Assen , Ayalew Mohammed Biset , Muche Esileman Abdela , Gebreyohannes Eyob Alemayehu , Abegaz Tadesse Melaku 
Published: September 2018

ObjectivesThe main aim of this study was to assess the overall tuberculosis (TB) treatment success in Ethiopia and to identify potential factors for poor TB treatment outcome.DesignA systematic review and meta-analysis of published literature was conducted. Original studies were identified through a computerised systematic search using PubMed, Google Scholar and Science Direct databases. Heterogeneity across studies was assessed using Cochran’s Q test and I2statistic. Pooled estimates of treatment success were computed using the random-effects model with 95% CI using Stata V.14 software.ResultsA total of 230 articles were identified in the systematic search. Of these 34 observational studies were eligible for systematic review and meta-analysis. It was found that 117 750 patients reported treatment outcomes. Treatment outcomes were assessed by World Health Organization (WHO) standard definitions of TB treatment outcome. The overall pooled TB treatment success rate in Ethiopia was 86% (with 95% CI 83%_88%). TB treatment success rate for each region showed that, Addis Ababa (93%), Oromia (84%), Amhara (86%), Southern Nations (83%), Tigray (85%) and Afar (86%). Mainly old age, HIV co-infection, retreatment cases and rural residence were the most frequently identified factors associated with poor TB treatment outcome.ConclusionThe result of this study revealed that the overall TB treatment success rate in Ethiopia was below the threshold suggested by WHO (90%). There was also a discrepancy in TB treatment success rate among different regions of Ethiopia. In addition to these, HIV co-infection, older age, retreatment cases and rural residence were associated with poor treatment outcome. In order to further improve the treatment success rate, it is strategic to give special consideration for regions which had low TB treatment success and patients with TB with HIV co-infection, older age, rural residence and retreatment cases.