bluuebunny/crossref_metadata_2025 huggingface dataset:
Bedding-scale geomodelling for effective permeability estimation in the Upper McMurray Formation, NE Alberta, Canada
Authors: Hao Chen , Longxin Mu , Jixin Huang , Guangfa Chang
Published: January 2019

The McMurray Formation is one of the most significant bitumen deposits in Canadian oil sands. Bitumen-bearing sand intervals deposited and reworked in fluvial, tidal or estuarine environments result in heterogeneous sediment distributions comprising clean sands and low-permeability muddy laminae or mud drapes. These interlayers increase the difficulty in estimating reservoir permeability, which is a critical geological parameter to predict the performance of
in situ
thermal processes of the oil sands projects. In this paper, we describe a bedding-scale geomodelling and simulation workflow using core images, core-plug and Vshale logs to estimate the effective permeability (
K
h
,
K
v
) in the Upper McMurray Formation. Details of five steps in this workflow are presented. To show the general applicability of this workflow, three pay-zone facies from tidal-channel infilled deposits of the Mackay River Project, CNPC, were selected to demonstrate this sedimentary process mimicking bedding-scale geomodelling strategy. The results of effective permeability estimation have the potential to improve history matching in flow simulations and performance forecasting.
Late Ordovician molluscs of the central and eastern Anti-Atlas, Morocco
Authors: Ebbestad Jan Ove R. , Polechová Marika , Kröger Björn , Gutiérrez-Marco Juan Carlos
Published: January 2019

More than 30 species of tergomyan, gastropod, bivalve and cephalopod molluscs are described from the Late Ordovician of central and eastern Anti-Atlas, Morocco. For the cephalopods this represents the first systematically known taxa of the region. Tergomyans and gastropods are most common in the more shaly part of the Lower Ktaoua Formation, while bivalves are more frequent in the sandy part of the Lower Second Bani Formation. A southern Gondwana aspect is evident for the tergomyan, gastropod and bivalve assemblages, sharing many taxa with Bohemia, while no clear signal is present for the cephalopods. The latter reflects insufficient knowledge of the fauna of large parts of these areas. The widely recognized
Holopea
?
antiquata
is transferred to the genus
Radvanospira
gen. nov.; other new gastropod taxa include
Allossospira
gen. nov.,
Tritonophon grandis
sp. nov.,
Radvanospira baniensis
sp. nov. and
Lophospira latilabra
sp. nov. Most of the diverse bivalve fauna and the few cephalopods are left in open nomenclature but new taxa include the bivalve
Praenucula pojetai
sp. nov. and the cephalopods
Wadema tattai
sp. nov. and
Tafadnatoceras tiouririnense
gen. et. sp. nov. The Late Ordovician bivalves from Morocco are dominated by pteriomorphs and protobranchs, inhabiting infaunal, semi-infaunal and epifaunal niches.
Vectorization of Line Drawings via Polyvector Fields
Authors: Bessmeltsev Mikhail , Solomon Justin
Published: January 2019

Image tracing is a foundational component of the workflow in graphic design, engineering, and computer animation, linking hand-drawn concept images to collections of smooth curves needed for geometry processing and editing. Even for clean line drawings, modern algorithms often fail to faithfully vectorize junctions, or points at which curves meet; this produces vector drawings with incorrect connectivity. This subtle issue undermines the practical application of vectorization tools and accounts for hesitance among artists and engineers to use automatic vectorization software. To address this issue, we propose a novel image vectorization method based on state-of-the-art mathematical algorithms for frame field processing. Our algorithm is tailored specifically to disambiguate junctions without sacrificing quality.
Interlinked SPH Pressure Solvers for Strong Fluid-Rigid Coupling
Authors: Gissler Christoph , Peer Andreas , Band Stefan , Bender Jan , Teschner Matthias
Published: January 2019

We present a strong fluid-rigid coupling for Smoothed Particle Hydrodynamics (SPH) fluids and rigid bodies with particle-sampled surfaces. The approach interlinks the iterative pressure update at fluid particles with a second SPH solver that computes artificial pressure at rigid-body particles. The introduced SPH rigid-body solver models rigid-rigid contacts as artificial density deviations at rigid-body particles. The corresponding pressure is iteratively computed by solving a global formulation that is particularly useful for large numbers of rigid-rigid contacts. Compared to previous SPH coupling methods, the proposed concept stabilizes the fluid-rigid interface handling. It significantly reduces the computation times of SPH fluid simulations by enabling larger time steps. Performance gain factors of up to 58 compared to previous methods are presented. We illustrate the flexibility of the presented fluid-rigid coupling by integrating it into DFSPH, IISPH, and a recent SPH solver for highly viscous fluids. We further show its applicability to a recent SPH solver for elastic objects. Large scenarios with up to 90
M
particles of various interacting materials and complex contact geometries with up to 90
k
rigid-rigid contacts are shown. We demonstrate the competitiveness of our proposed rigid-body solver by comparing it to Bullet.
Local Concurrency Detection in Business Process Event Logs
Authors: Armas-Cervantes Abel , Dumas Marlon , Rosa Marcello La , Maaradji Abderrahmane
Published: January 2019

Process mining techniques aim at analyzing records generated during the execution of a business process in order to provide insights on the actual performance of the process. Detecting concurrency relations between events is a fundamental primitive underpinning a range of process mining techniques. Existing approaches to this problem identify concurrency relations at the level of event types under a global interpretation. If two event types are declared to be concurrent, every occurrence of one event type is deemed to be concurrent to one occurrence of the other. In practice, this interpretation is too coarse-grained and leads to over-generalization. This article proposes a finer-grained approach, whereby two event types may be deemed to be in a concurrency relation relative to one state of the process, but not relative to other states. In other words, the detected concurrency relation holds locally, relative to a set of states. Experimental results both with artificial and real-life logs show that the proposed local concurrency detection approach improves the accuracy of existing concurrency detection techniques.
Emotional Energy, Relational Energy, and Organizational Energy: Toward a Multilevel Model
Authors: Baker Wayne E.
Published: January 2019

The concept of emotional energy generates increasing scholarly and popular interest. Research spans multiple disciplines (psychology, sociology, organization behavior, network science) and levels of analysis: micro (individual-level emotional energy), meso (dyadic or relational energy), and macro (group emotion, energy networks). I impose order on this sprawling and disparate literature by defining core concepts and conducting a broad but selective review with a focus on mechanisms. This review identifies key empirical findings but also reveals critical ambiguities and disagreements in the conceptualization (and therefore measurement) of energy. Theorizing has outpaced empirical testing. One implication is that practice may be unmoored from a solid empirical grounding. I offer a critique that points to several promising areas of empirical research. I conclude with practical implications for individuals and organizations, summary points, and future issues.
Reorganizing Organizational Politics Research: A Review of the Literature and Identification of Future Research Directions
Authors: Ferris Gerald R. , Ellen B. Parker , McAllister Charn P. , Maher Liam P.
Published: January 2019

Organizational politics has been an oft-studied phenomenon for nearly four decades. Prior reviews have described research in this stream as aligning with one of three categories: perceptions of organizational politics (POPs), political behavior, or political skill. We suggest that because these categories are at the construct level research on organizational politics has been artificially constrained. Thus, we suggest a new framework with higher-level categories within which to classify organizational politics research: political characteristics, political actions, and political outcomes. We then provide a broad review of the literature applicable to these new categories and discuss the possibilities for future research within each expanded category. Finally, we close with a discussion of future directions for organizational politics research across the categories.
Hong Kong Chinese Medicine Clinical Practice Guideline for Cancer Palliative Care: Pain, Constipation, and Insomnia
Authors: Lam Wai Ching , Zhong Linda , Liu Yuqi , Shi Nannan , Ng Bacon , Ziea Eric , Bian Zhaoxiang , Lu Aiping
Published: January 2019

It is common for patients with cancers in Hong Kong seeking Chinese Medicine (CM) therapies as supportive care during cancer treatment and to manage treatment-related side effects. This article provides clinical practice guideline (CPG) on the use of CM for specific clinical indications caused by cancer and during cancer treatment, including pain, constipation, and insomnia, and aims to guide local licensed CM practitioners and provide beneficial reference for social medical decision makers and patients. In this manuscript, we summarize the clinical manifestation, CM pattern classification, and CM intervention including herbal treatment, acupuncture treatment, regulating, and nursing based on pattern differentiation.
Nuclear Receptors in the Pathogenesis and Management of Inflammatory Bowel Disease
Authors: Ning Longgui , Lou Xinhe , Zhang Fenming , Xu Guoqiang
Published: January 2019

Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Previous epidemiological and genetic studies have documented the association of NRs with the risk of inflammatory bowel disease (IBD). Although the mechanisms of action of NRs in IBD have not been fully established, accumulating evidence has demonstrated that NRs play complicated roles in regulating intestinal immunity, mucosal barriers, and intestinal flora. As one of the first-line medications for the treatment of IBD, 5-aminosalicylic acid (5-ASA) activates peroxisome proliferator-activated receptor gamma (PPARγ) to attenuate colitis. The protective roles of rifaximin and rifampicin partly depend on promoting pregnane X receptor (PXR) expression. The aims of this review are to discuss the roles of several important NRs, such as PPARγ, PXR, vitamin D receptor (VDR), farnesoid X receptor (FXR), and RAR-related orphan receptor gammat (RORγt), in the pathogenesis of IBD and management strategies based on targeting these receptors.
A Real‐Time Reliable Condition Assessment System for 500kV Transmission Towers Based on Stress Measurement
Authors: Liu Zhi-xiong , Feng Xiao-bo
Published: January 2019

Transmission power towers play an important role in power delivery systems. In recent years, some important results on reliability of transmission towers have been obtained based on theoretical analysis, but there are very few practical application systems of real‐time condition monitoring. This paper proposes a new real‐time reliable condition assessment system for 500kV transmission power towers based on stress measurement. The necessity of such systems and the architecture of the online monitoring system will first be presented. Through calculating the stress distribution condition of different components of the transmission tower under typical working conditions, those positions with relatively high failure probability in the transmission tower can be identified monitored for installing the stress sensors on them. A new method is presented for calculating the reliability index of the transmission tower structure is also developed based on the mechanical structure of the tower. In particular, the tower structure is simplified to a series system, and the Ditlevsen’s bounds is used to estimate the reliability of the tower system. Finally, a designed example for the online reliable condition assessment procedure is given using a 500kV oxytropis tower as an illustration.
Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib
Authors: Böhm Michael J. , Marienfeld Ralf , Jäger Daniela , Mellert Kevin , von Witzleben Adrian , Brüderlein Silke , Wittau Mathias , von Baer Alexandra , Schultheiss Markus , Mayer-Steinacker Regine , Rücker Frank G. , Möller Peter , Bullinger Lars , Barth Thomas F. E.
Published: January 2019

Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.8%). It has been previously shown that the LMS cell line SK-LMS-1 has a defect in the p16 pathway and that this cell line can be inhibited by the CDK4 and CDK6 inhibitor palbociclib. For SK-LMS-1 we confirm and for SK-UT-1 we show that both LMS cell lines express CDK4 and that, in addition, strong CDK6 expression is seen in SK-LMS-1, whereas Rb was expressed in SK-LMS-1 but not in SK-UT-1. We confirm that inhibition of SK-LMS-1 with palbociclib led to a strong decrease in protein levels of Phospho-Rb (Ser780), a decreased cell proliferation, and G0/G1-phase arrest with decreased S/G2fractions. SK-UT-1 did not respond to palbociclib inhibition. To compare thesein vitrofindings with patient tissue samples, a p16, CDK4, CDK6, and p-Rb immunohistochemical staining assay of a large LMS cohort (n=99patients with 159 samples) was performed assigning a potential responder phenotype to each patient, which we identified in 29 out of 99 (29.3%) patients. Taken together, these data show that CDK4/6 inhibitors may offer a new option for targeted therapy in a subset of LMS patients.
Characterization of the Role of Squeeze Casting on the Microstructure and Mechanical Properties of the T6 Heat Treated 2017A Aluminum Alloy
Authors: Souissi S. , Souissi N. , Barhoumi H. , ben Amar M. , Bradai C. , Elhalouani F.
Published: January 2019

In this study, the effects of squeeze casting process and T6 heat treatment on the microstructure and mechanical properties of 2017A aluminum alloy were investigated with scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), differential scanning calorimetry (DSC), and microhardness and tensile tests. The results showed that this alloy contained α matrix, θ-Al2Cu, and other phases. Furthermore, the applied pressure and heat treatment refines the microstructure and improve the ultimate tensile strength (UTS) to 296 MPa and the microhardness to 106 HV with the pressure 90 MPa after ageing at 180°C for 6 h. With ageing temperature increasing to 320°C for 6 h, the strength of the alloy declines slightly to 27 MPa. Then, the yield strength drops quickly when temperature reaches over 320°C. The high strength of the alloy in peak-aged condition is caused by a considerable amount of θ′ precipitates. The growth of θ′ precipitates and the generation of θ phase lead to a rapid drop of the strength when temperature is over 180°C.
Internal Limiting Membrane Flap in the Management of Retinal Detachment due to Paracentral Retinal Breaks
Authors: Chen Yen-Chih , Yang Chung-May , Chen San-Ni
Published: January 2019

Purpose. To describe the technique and outcomes of using either inverted or free internal limiting membrane flap in the management of retinal detachment due to paracentral retinal breaks.Methods. This retrospective observational case series includes nine patients who received surgery for retinal detachment due to paracentral retinal breaks developed either from primary rhegmatogenous origin, or secondary iatrogenic retinal breaks after prior membrane peeling, or during surgery for tractional retinal detachment. Either inverted or free internal limiting membrane flaps were inserted in the identified breaks, followed by air fluid exchange and gas tamponade. Visual acuity and structural changes were evaluated.Results. Nine eyes were included. One had primary rhegmatogenous retinal detachment, one had highly myopic eye with peripapillary atrophic hole, three had secondary retinal detachment after membrane peeling for foveoschisis or macular pucker, one had recurrent retinal detachment due to proliferative vitreoretinopathy, one had combination of tractional and rhegmatogenous retinal detachment, and two had iatrogenic breaks during surgery. The retinal breaks of all eyes were sealed with retina attached postoperatively. Visual acuity in logarithm of minimal angle of resolution improved from 1.18 ± 0.55 preoperatively to 0.74 ± 0.47 postoperatively (p=0.04).Conclusion. Internal limiting membrane flap technique can be a surgical approach selectively for retinal detachment due to paracentral retinal breaks with difficulty for laser application. The retina can be attached successfully and achieve good visual outcome without major complication. This trial is registered withNCT03707015.
Topology: A Theory of a Pseudometric‐Based Clustering Model and Its Application in Content‐Based Image Retrieval
Authors: Osuna-Galán I. , Pérez-Pimentel Y. , Avilés-Cruz Carlos , Villegas-Cortez Juan
Published: January 2019

The clustering problem has been extensively studied over the last 50 years; however, it still has the attention of researchers. This paper presents a topological basis of a pseudometric‐based clustering model which takes into account the local and global topological properties of the data to be clustered, as per the definition of homogeneity measurement. The proposed approach takes into account the homogeneity effect produced when a new particle is added to a group. The additional element can be accumulated in the group if its local homogeneity is not altered and, therefore, it is not necessary to carry out tests in another group. A new group needs to be generated if the threshold of the local homogeneity of the group exceeds. Theoretical results, their implementation, and their application to the problem of Content Based Image Retrieval (CBIR) are presented. The tests were performed using three image databases widely used in the literature, which are “Vogel and Shiele,” “Oliva and Torralba,” and “L. Fei‐ Fei, R. Fergus and P. Perona.” The results are presented and compared with the most competitive methods available in the literature.
BCL6 Attenuates Proliferation and Oxidative Stress of Vascular Smooth Muscle Cells in Hypertension
Authors: Chen Dan , Zang Ying-Hao , Qiu Yun , Zhang Feng , Chen Ai-Dong , Wang Jue-Jin , Chen Qi , Li Yue-Hua , Kang Yu-Ming , Zhu Guo-Qing
Published: January 2019

Proliferation and oxidative stress of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling in hypertension and several major vascular diseases. B-cell lymphoma 6 (BCL6) functions as a transcriptional repressor. The present study is designed to determine the roles of BCL6 in VSMC proliferation and oxidative stress and underlying mechanism. Angiotensin (Ang) II was used to induce VSMC proliferation and oxidative stress in human VSMCs. Effects of BCL6 overexpression and knockdown were, respectively, investigated in Ang II-treated human VSMCs. Therapeutical effects of BCL6 overexpression on vascular remodeling, oxidative stress, and proliferation were determined in the aorta of spontaneously hypertensive rats (SHR). Ang II reduced BCL6 expression in human VSMCs. BCL6 overexpression attenuated while BCL6 knockdown enhanced the Ang II-induced upregulation of NADPH oxidase 4 (NOX4), production of reactive oxygen species (ROS), and proliferation of VSMCs. BCL6 expression was downregulated in SHR. BCL6 overexpression in SHR reduced NOX4 expression, ROS production, and proliferation of the aortic media of SHR. Moreover, BCL6 overexpression attenuated vascular remodeling and hypertension in SHR. However, BCL6 overexpression had no significant effects on NOX2 expression in human VSMCs or in SHR. We conclude that BCL6 attenuates proliferation and oxidative stress of VSMCs in hypertension.
Use of Mastectomy for Overdiagnosed Breast Cancer in the United States: Analysis of the SEER 9 Cancer Registries
Authors: Harding C. , Pompei F. , Burmistrov D. , Wilson R.
Published: January 2019

Aim. We investigated use of mastectomy as treatment for early breast cancer in the US and applied the resulting information to estimate the minimum and maximum rates at which mastectomy could plausibly be undergone by patients with overdiagnosed breast cancer. Little is currently known about overtreatments undergone by overdiagnosed patients. Methods. In the US, screening is often recommended at ages ≥40. The study population was women age ≥40 diagnosed with breast cancer in the US SEER 9 cancer registries during 2013 (n=26,017). We evaluated first-course surgical treatments and their associations with case characteristics. Additionally, a model was developed to estimate probability of mastectomy conditional on observed case characteristics. The model was then applied to evaluate possible rates of mastectomy in overdiagnosed patients. To obtain minimum and maximum plausible rates of this overtreatment, we respectively assumed the cases that were least and most likely to be treated by mastectomy had been overdiagnosed. Results. Of women diagnosed with breast cancer at age ≥40 in 2013, 33.8% received mastectomy. Mastectomy was common for most investigated breast cancer types, including for the early breast cancers among which overdiagnosis is thought to be most widespread: mastectomy was undergone in 26.4% of in situ and 28.0% of AJCC stage-I cases. These rates are substantively higher than in many European nations. The probability-based model indicated that between >0% and <18% of the study population could plausibly have undergone mastectomy for overdiagnosed cancer. This range reduced depending on the overdiagnosis rate, shrinking to >0% and <7% if 10% of breast cancers were overdiagnosed and >3% and <15% if 30% were overdiagnosed. Conclusions. Screening-associated overtreatment by mastectomy is considerably less common than overdiagnosis itself but should not be assumed to be negligible. Screening can prompt or prevent mastectomy, and the balance of this harm-benefit tradeoff is currently unclear.
Clinicopathological Factors Influencing Lymph Node Yield in Colorectal Cancer: A Retrospective Study
Authors: Orsenigo Elena , Gasparini Giulia , Carlucci Michele
Published: January 2019

Many colorectal resections do not meet the minimum of 12 lymph nodes (LNs) recommended by the American Joint Committee on Cancer for accurate staging of colorectal cancer. The aim of this study was to investigate factors affecting the number of the adequate nodal yield in colorectal specimens subject to routine pathological assessment. We have retrospectively analysed the data of 2319 curatively resected colorectal cancer patients in San Raffaele Scientific Institute, Milan, between 1993 and 2017 (1259 colon cancer patients and 675 rectal cancer patients plus 385 rectal cancer patients who underwent neoadjuvant therapy). The factors influencing lymph node retrieval were subjected to uni- and multivariate analyses. Moreover, a survival analysis was carried out to verify the prognostic implications of nodal counts. The mean number of evaluated nodes was 24.08±11.4, 20.34±11.8, and 15.33±9.64 in surgically treated right-sided colon cancer, left-sided colon cancer, and rectal tumors, respectively. More than 12 lymph nodes were reported in surgical specimens in 1094 (86.9%) cases in the colon cohort and in 425 (63%) cases in the rectal cohort, and patients who underwent neoadjuvant chemoradiation were analysed separately. On univariate analysis of the colon cancer group, higher LNs counts were associated with female sex, right colon cancer, emergency surgery, pT3-T4 diseases, higher tumor size, and resected specimen length. On multivariate analysis right colon tumors, larger mean size of tumor, length of specimen, pT3-T4 disease, and female sex were found to significantly affect lymph node retrieval. Colon cancer patients with 12 or more lymph nodes removed had a significantly better long-term survival than those with 11 or fewer nodes (P=0.002, log-rank test). Rectal cancer patients with 12 or more lymph nodes removed approached but did not reach a statistically different survival (P=0.055, log-rank test). Multiple tumor and patients’ factors are associated with lymph node yield, but only the removal of at least 12 lymph nodes will reliably determine lymph node status.
Quadratic Programming Method for Cooperative Games with Coalition Values Expressed by Triangular Fuzzy Numbers and Its Application in the Profit Distribution of Logistics Coalition
Authors: Liu Jia-Cai , Zhu Yuan-Fei , Zhao Wen-Jian
Published: January 2019

A quadratic programming model is constructed for solving the fuzzy cooperative games with coalition values expressed by triangular fuzzy numbers, which will be abbreviated to TFN‐typed cooperative games from now on. Based on the concept of α‐cut set and the representation theorem for the fuzzy set, the least square distance solution for solving TFN‐typed cooperative games is proposed. The least square distance solution successfully avoids the subtraction operation of TFNs, which may inevitably lead to the amplification of uncertainty and the distortion of decision information. A calculating example related to the profit distribution of logistics coalition is illustrated to show the advantages, validity, and applicability of the proposed method. Besides, the least square distance solution for solving TFN‐typed cooperative games satisfies many important properties of cooperative games, such as uniqueness, additivity, symmetry, and uniqueness.
Analysis of TGFBI Gene Mutations in Three Chinese Families with Corneal Dystrophy
Authors: Zhao Feng , Liu Yuan , Guan Tao
Published: January 2019

Objective. To identify the types of TGFBI (transforming growth factor, beta-induced) gene mutations in three Chinese families with Reis–Bücklers corneal dystrophy (RBCD), lattice corneal dystrophy type I (LCDI), or Avellino corneal dystrophy (ACD) and to investigate the relationship between the phenotypes and genotypes of corneal dystrophy. Methods. Peripheral blood was collected from 24 patients and 76 phenotypically normal members in three Chinese families as well as from 100 healthy controls. Genomic DNA was extracted. All 17 exons of the TGFBI gene, and the exon-intron junctions were examined by polymerase chain reaction (PCR) and direct DNA sequencing to identify and analyse gene mutations. In addition, all members of the three families were subjected to detailed clinical examinations. Results. The heterozygous c.371G > T (p.R124L) mutation was detected in exon 4 of the TGFBI gene in nine patients from the family with RBCD. In contrast, this mutation was not found in the phenotypically normal members of the family. The heterozygous c.370C > T (p.R124C) mutation was found in exon 4 of the TGFBI gene in 11 patients from the family with LCDI. This mutation was not found in the phenotypically normal members of the family. The heterozygous c.371G > A (p.R124H) mutation was detected in exon 4 of the TGFBI gene in four patients from the family with ACD. Again, this mutation was not found in the phenotypically normal members of the family. The TGFBI gene mutations cosegregated with the disease phenotypes in the three families and exhibited an autosomal dominant mode of inheritance. No TGFBI gene mutations were detected in the 100 healthy controls. Conclusion. There is a high degree of correlation between the phenotypes and genotypes of TGFBI-linked corneal dystrophies. R124 represents a mutational hotspot in the TGFBI gene. Gene mutation analysis provides a reliable basis for the definitive diagnosis of corneal dystrophy.
In Vitro Assessment of Antiplasmodial Activity and Cytotoxicity of Polyalthia longifolia Leaf Extracts on Plasmodium falciparum Strain NF54
Authors: Kwansa-Bentum Bethel , Agyeman Kojo , Larbi-Akor Jeffrey , Anyigba Claudia , Appiah-Opong Regina
Published: January 2019

Background. Malaria is one of the most important life-threatening infectious diseases in the tropics. In spite of the effectiveness of artemisinin-based combination therapy, reports on reduced sensitivity of the parasite to artemisinin in Cambodia and Thailand warrants screening for new potential antimalarial drugs for future use. Ghanaian herbalists claim that Polyalthia longifolia has antimalarial activity. Therefore, antiplasmodial activity, cytotoxic effects, and antioxidant and phytochemical properties of P. longifolia leaf extract were investigated in this study. Methodology/Principal Findings. Aqueous, 70% hydroethanolic and ethyl acetate leaf extracts were prepared using standard procedures. Antiplasmodial activity was assessed in vitro by using chloroquine-sensitive malaria parasite strain NF54. The SYBR® Green and tetrazolium-based calorimetric assays were used to measure parasite growth inhibition and cytotoxicity, respectively, after extract treatment. Total antioxidant activity was evaluated using a free radical scavenging assay. Results obtained showed that extracts protected red blood cells against Plasmodium falciparum mediated damage. Fifty percent inhibitory concentration (IC50) values were 24.0±1.08 μg/ml, 22.5±0.12 μg/ml, and 9.5±0.69 μg/ml for aqueous, hydroethanolic, and ethyl acetate extracts, respectively. Flavonoids, tannins, and saponins were present in the hydroethanolic extract, whereas only the latter was observed in the aqueous extract. Aqueous and hydroethanolic extracts showed stronger antioxidant activities compared to the ethyl acetate extract. Conclusions/Significance. The extracts of P. longifolia have antiplasmodial properties and low toxicities to human red blood cells. The extracts could be developed as useful alternatives to antimalarial drugs. These results support claims of the herbalists that decoctions of P. longifolia are useful antimalarial agents.
Effects on Parental Stress of Early Home-Based CareToy Intervention in Low-Risk Preterm Infants
Authors: Sgandurra Giuseppina , Beani Elena , Inguaggiato Emanuela , Lorentzen Jakob , Nielsen Jens Bo , Cioni Giovanni
Published: January 2019

Parenting a preterm infant is more challenging than a full-term one. Parent involvement in early intervention programs seems to have positive psychosocial effects on both the child and parent. CareToy is an innovative smart system that provides an intensive individualized home-based family-centred EI in preterm infants between 3 and 9 age-corrected months. A RCT study, preceded by a pilot study, has been recently carried out to evaluate the effects of CareToy intervention on neurodevelopmental outcomes with respect to Standard Care. This study aims at evaluating the effects of CareToy early intervention on parenting stress in preterm infants. Parents (mother and father) of a subgroup of infants enrolled in the RCT filled out a self-report questionnaire on parenting stress (Parenting Stress Index-Short Form (PSI-SF)) before (T0) and after (T1) the CareToy or Standard Care period (4 weeks), according to the allocation of their preterm infant. For twins, an individual questionnaire for each one was filled out. Results obtained from mothers and fathers were separately analysed with nonparametric tests. 44 mothers and 44 fathers of 44 infants (24 CareToy/20 Standard Care) filled out the PSI-SF at T0 and at T1. CareToy intervention was mainly managed by mothers. A significant (p<0.05) reduction in Parental Distress subscale in the CareToy group versus Standard Care was found in the mothers. No differences were found among the fathers. CareToy training seems to be effective in reducing parental distress in mothers, who spent more time on CareToy intervention. These findings confirm the importance of parental involvement in early intervention programs. This trial is registered with Clinical Trial.gov NCT01990183.
Mixed Convection Magnetohydrodynamics Flow of a Nanofluid with Heat Transfer: A Numerical Study
Authors: Khan Abdul Quayam , Rasheed Amer
Published: January 2019

In this paper we have studied the magnetohydrodynamic (MHD) mixed convection Maxwell flow of an incompressible nanofluid with magnetic field and heat transfer over a moving plate aligned horizontally. Thermal radiation has also been applied in order to investigate its effects on velocity and temperature variations in the fluid. The Caputo time derivative has been employed to derive the mathematical model. A numerical solution has been obtained using finite difference discretization along with L1‐algorithm. Fractional and other pertinent physical fluid parameters like magnetic field parameter, thermal radiation, effect on velocity, and temperature distribution are analyzed and demonstrated through graphs.
Multi‐Swarm Multi‐Objective Optimizer Based on p‐Optimality Criteria for Multi‐Objective Portfolio Management
Authors: Hu Yabao , Chen Hanning , He Maowei , Sun Liling , Liu Rui , Shen Hai
Published: January 2019

Portfolio management is an important technology for reasonable investment, fund management, optimal asset allocation, and effective investment. Portfolio optimization problem (POP) has been recognized as an NP‐hard problem involving numerous objectives as well as constraints. Applications of evolutionary algorithms and swarm intelligence optimizers for resolving multi‐objective POP (MOPOP) have attracted considerable attention of researchers, yet their solutions usually convert MOPOP to POP by means of weighted coefficient method. In this paper, a multi‐swarm multi‐objective optimizer based on p‐optimality criteria called p‐MSMOEAs is proposed that tries to find all the Pareto optimal solutions by optimizing all objectives at the same time, rather than through the above transforming method. The proposed p‐MSMOEAs extended original multiple objective evolutionary algorithms (MOEAs) to cooperative mode through combining p‐optimality criteria and multi‐swarm strategy. Comparative experiments of p‐MSMOEAs and several MOEAs have been performed on six mathematical benchmark functions and two portfolio instances. Simulation results indicate that p‐MSMOEAs are superior for portfolio optimization problem to MOEAs when it comes to optimization accuracy as well as computation robustness.
Optimum Design of Ship Cabin Equipment Layout Based on SLP Method and Genetic Algorithm
Authors: Li Jinghua , Guo Hui , Zhang Shichao , Wu Xiaoyuan , Shi Liuling
Published: January 2019

The engine room is the heart of a ship, and almost all of the main electromechanical equipment that supports the work on board can be found here. Finding a way to arrange the equipment in a small cabin space is an essential factor in the design and construction of a ship. However, in existing research, when an intelligent algorithm is used to optimize the design of a cabin, the established mathematical model is not comprehensive and the solution has not been evaluated. The optimal solution obtained is not feasible for the actual design of a ship. This can lead to unnecessary redesign work, which seriously affects design efficiency and increases design costs. In order to solve the above problems, this paper innovatively refers to a Systematic Layout Planning (SLP) method (normally applied to the layout of plant equipment) to the cabin equipment layout issue. The SLP method is used to quantitatively analyze the adjacency and logistics relationship between devices, and the mutual integration relationship between devices is obtained so that a preliminary layout scheme can be retrieved. The problem model is constructed by considering various factors such as the comprehensive relationship between the equipment and the stability of the cabin, and the corresponding objective function and constraint function are established to further design the variables, operators, and steps of the genetic algorithm. The initial solution obtained from the SLP method is used as part of an initial solution to the genetic algorithm, and the genetic algorithm is used to optimize the problem. Finally, the Analytic Hierarchy Process (AHP) is used to evaluate and optimize several groups of better schemes obtained by running multiple genetic algorithms and select the better schemes. The experimental design proves that the integrated design method has certain feasibility and superiority.
Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment
Authors: Tulotta Claudia , Lefley Diane V. , Freeman Katy , Gregory Walter M. , Hanby Andrew M. , Heath Paul R. , Nutter Faith , Wilkinson J. Mark , Spicer-Hadlington Amy R. , Liu Xinming , Bradbury Steven M.J. , Hambley Lisa , Cookson Victoria , Allocca Gloria , Kruithof de Julio Marianna , Coleman Robert E. , Brown Janet E. , Holen Ingunn , Ottewell Penelope D.
Published: January 2019

Purpose:

Breast cancer bone metastases are incurable, highlighting the need for new therapeutic targets. After colonizing bone, breast cancer cells remain dormant, until signals from the microenvironment stimulate outgrowth into overt metastases. Here we show that endogenous production of IL1B by tumor cells drives metastasis and growth in bone.

Experimental Design:

Tumor/stromal IL1B and IL1 receptor 1 (IL1R1) expression was assessed in patient samples and effects of the IL1R antagonist, Anakinra, or the IL1B antibody canakinumab on tumor growth and spontaneous metastasis were measured in a humanized mouse model of breast cancer bone metastasis. Effects of tumor cell–derived IL1B on bone colonization and parameters associated with metastasis were measured in MDA-MB-231, MCF7, and T47D cells transfected with IL1B/control.

Results:

In tissue samples from >1,300 patients with stage II/III breast cancer, IL1B in tumor cells correlated with relapse in bone (HR = 1.85; 95% CI, 1.05–3.26; P = 0.02) and other sites (HR = 2.09; 95% CI, 1.26–3.48; P = 0.0016). In a humanized model of spontaneous breast cancer metastasis to bone, Anakinra or canakinumab reduced metastasis and reduced the number of tumor cells shed into the circulation. Production of IL1B by tumor cells promoted epithelial-to-mesenchymal transition (altered E-Cadherin, N-Cadherin, and G-Catenin), invasion, migration, and bone colonization. Contact between tumor and osteoblasts or bone marrow cells increased IL1B secretion from all three cell types. IL1B alone did not stimulate tumor cell proliferation. Instead, IL1B caused expansion of the bone metastatic niche leading to tumor proliferation.

Conclusions:

Pharmacologic inhibition of IL1B has potential as a novel treatment for breast cancer metastasis.
L-Carnitine–Mediated Tumor Cell Protection and Poor Patient Survival Associated with OCTN2 Overexpression in Glioblastoma Multiforme
Authors: Fink Matthias A. , Paland Heiko , Herzog Susann , Grube Markus , Vogelgesang Silke , Weitmann Kerstin , Bialke Angela , Hoffmann Wolfgang , Rauch Bernhard H. , Schroeder Henry W.S. , Bien-Möller Sandra
Published: January 2019

Purpose:

Apoptotic dysregulation, redox adaptive mechanisms, and resilience to hypoxia are major causes of glioblastoma (GBM) resistance to therapy. Commonly known as crucial factors in energy metabolism, OCTN2 (SLC22A5) and its substrate L-carnitine (LC) are increasingly recognized as actors in cytoprotection. This study provides a comprehensive expression and survival analysis of the OCTN2/LC system in GBM and clarifies the system's impact on GBM progression.

Experimental Design:

OCTN2 expression and LC content were measured in 121 resected human GBM specimens and 10 healthy brain samples and analyzed for prognostic significance. Depending on LC administration, the effects of hypoxic, metabolic, and cytotoxic stress on survival and migration of LN18 GBM cells were further studied in vitro. Finally, an orthotopic mouse model was employed to investigate inhibition of the OCTN2/LC system on in vivo GBM growth.

Results:

Compared with healthy brain, OCTN2 expression was increased in primary and even more so in recurrent GBM on mRNA and protein level. High OCTN2 expression was associated with a poor overall patient survival; the unadjusted HR for death was 2.7 (95% CI, 1.47–4.91; P < 0.001). LC administration to GBM cells increased their tolerance toward cytotoxicity, whereas siRNA-mediated OCTN2 silencing led to a loss of tumor cell viability. In line herewith, OCTN2/LC inhibition by meldonium resulted in reduced tumor growth in an orthotopic GBM mouse model.

Conclusions:

Our data indicate a potential role of the OCTN2/LC system in GBM progression and resistance to therapy, and suggests OCTN2 as a prognostic marker in patients with primary GBM.
Comprehensive Assessment of Genotype Imputation Performance
Authors: Shi Shuo , Yuan Na , Yang Ming , Du Zhenglin , Wang Jinyue , Sheng Xin , Wu Jiayan , Xiao Jingfa
Published: January 2019

Genotype imputation is a process of estimating missing ge­notypes from the haplotype or genotype reference panel. It can effectively boost the power of detecting single nucleotide polymorphisms (SNPs) in genome-wide association studies, integrate multi-studies for meta-analysis, and be applied in fine-mapping studies. The performance of genotype imputation is affected by many factors, including software, reference selection, sample size, and SNP density/sequencing coverage. A systematical evaluation of the imputation performance of current popular software will benefit future studies. Here, we evaluate imputation performances of Beagle4.1, IMPUTE2, MACH+Minimac3, and SHAPEIT2+ IM­PUTE2 using test samples of East Asian ancestry and references of the 1000 Genomes Project. The result indicated the accuracy of IMPUTE2 (99.18%) is slightly higher than that of the others (Beagle4.1: 98.94%, MACH+Minimac3: 98.51%, and SHAPEIT2+IMPUTE2: 99.08%). To achieve good and stable imputation quality, the minimum requirement of SNP density needs to be > 200/Mb. The imputation accuracies of IMPUTE2 and Beagle4.1 were under the minor influence of the study sample size. The contribution extent of reference to genotype imputation performance relied on software selection. We assessed the imputation performance on SNPs generated by next-generation whole genome sequencing and found that SNP sets detected by sequencing with 15× depth could be mostly got by imputing from the haplotype reference panel of the 1000 Genomes Project based on SNP data detected by sequencing with 4× depth. All of the imputation software had a weaker performance in low minor allele frequency SNP regions because of the bias of reference or software. In the future, more comprehensive reference panels or new algorithm developments may rise up to this challenge.
Inferring Gene-Disease Association by an Integrative Analysis of eQTL Genome-Wide Association Study and Protein-Protein Interaction Data
Authors: Wang Jun , Zheng Jiashun , Wang Zengmiao , Li Hao , Deng Minghua
Published: January 2019

Objectives: Genome-wide association studies (GWASs) have revealed many candidate SNPs, but the mechanisms by which these SNPs influence diseases are largely unknown. In order to decipher the underlying mechanisms, several methods have been developed to predict disease-associated genes based on the integration of GWAS and eQTL data (e.g., Sherlock and COLOC). A number of studies have also incorporated information from gene networks into GWAS analysis to reprioritize candidate genes. Methods: Motivated by these two different approaches, we have developed a statistical framework to integrate information from GWAS, eQTL, and protein-protein interaction (PPI) data to predict disease-associated genes. Our approach is based on a hidden Markov random field (HMRF) model, and we called the resulting computational algorithm GeP-HMRF (a GWAS-eQTL-PPI-based HMRF). Results: We compared the performance of GeP-HMRF with Sherlock, COLOC, and NetWAS methods on 9 GWAS datasets, using the disease-related genes in the MalaCards database as the standard, and found that GeP-HMRF significantly improves the prediction accuracy. We also applied GeP-HMRF to an age-related macular degeneration disease (AMD) dataset. Among the top 50 genes predicted by GeP-HMRF, 7 are reported by the MalaCards database to be AMD-related with an enrichment p value of 3.61 × 10–119. Among the top 20 genes predicted by GeP-HMRF, CFHR1, CGHR3, HTRA1, and CFH are AMD-related in the MalaCards database, and another 9 genes are supported by the literature. Conclusions: We built a unified statistical model to predict disease-related genes by integrating GWAS, eQTL, and PPI data. Our approach outperforms Sherlock, COLOC, and NetWAS in simulation studies and 9 GWAS datasets. Our approach can be generalized to incorporate other molecular trait data beyond eQTL and other interaction data beyond PPI.
Genetic-Epigenetic Interactions in Asthma Revealed by a Genome-Wide Gene-Centric Search
Authors: Kogan Vladimir , Millstein Joshua , London Stephanie J. , Ober Carole , White Steven R. , Naureckas Edward T. , Gauderman W. James  , Jackson Daniel J. , Barraza-Villarreal Albino , Romieu Isabelle , Raby Benjamin A.  , Breton Carrie V.
Published: January 2019

Objectives: There is evidence to suggest that asthma pathogenesis is affected by both genetic and epigenetic variation independently, and there is some evidence to suggest that genetic-epigenetic interactions affect risk of asthma. However, little research has been done to identify such interactions on a genome-wide scale. The aim of this studies was to identify genes with genetic-epigenetic interactions associated with asthma. Methods: Using asthma case-control data, we applied a novel nonparametric gene-centric approach to test for interactions between multiple SNPs and CpG sites simultaneously in the vicinities of 18,178 genes across the genome. Results: Twelve genes, PF4, ATF3, TPRA1, HOPX, SCARNA18, STC1, OR10K1, UPK1B, LOC101928523, LHX6, CHMP4B, and LANCL1, exhibited statistically significant SNP-CpG interactions (false discovery rate = 0.05). Of these, three have previously been implicated in asthma risk (PF4, ATF3, and TPRA1). Follow-up analysis revealed statistically significant pairwise SNP-CpG interactions for several of these genes, including SCARNA18, LHX6, and LOC101928523 (p = 1.33E–04, 8.21E–04, 1.11E–03, respectively). Conclusions: Joint effects of genetic and epigenetic variation may play an important role in asthma pathogenesis. Statistical methods that simultaneously account for multiple variations across chromosomal regions may be needed to detect these types of effects on a genome-wide scale.