bluuebunny/crossref_metadata_2025 huggingface dataset:
Selecting Near-Native Protein Structures from Predicted Decoy Sets Using Ordered Graphlet Degree Similarity
Authors: Han Xu , Li Li , Lu Yonggang
Published: February 2019

Effective prediction of protein tertiary structure from sequence is an important and challenging problem in computational structural biology. Ab initio protein structure prediction is based on amino acid sequence alone, thus, it has a wide application area. With the ab initio method, a large number of candidate protein structures called decoy set can be predicted, however, it is a difficult problem to select a good near-native structure from the predicted decoy set. In this work we propose a new method for selecting the near-native structure from the decoy set based on both contact map overlap (CMO) and graphlets. By generalizing graphlets to ordered graphs, and using a dynamic programming to select the optimal alignment with an introduced gap penalty, a GR_score is defined for calculating the similarity between the three-dimensional (3D) decoy structures. The proposed method was applied to all 54 single-domain targets in CASP11 and all 43 targets in CASP10, and ensemble clustering was used to cluster the protein decoy structures based on the computed CR_scores. The most popular centroid structure was selected as the near-native structure. The experiments showed that compared to the SPICKER method, which is used in I-TASSER, the proposed method can usually select better near-native structures in terms of the similarity between the selected structure and the true native structure.
Improving Care Transitions for Hospitalized Veterans Discharged to Skilled Nursing Facilities: A Focus on Polypharmacy and Geriatric Syndromes
Authors: Mixon Amanda S. , Yeh Vivian M. , Simmons Sandra , Powers James , Ely Eugene Wesley , Schnelle John , Vasilevskis Eduard E.
Published: February 2019

Geriatric syndromes and polypharmacy are common in older patients discharged to skilled nursing facilities (SNFs) and increase 30-day readmission risk. In a U.S.A. Department of Veterans Affairs (VA)-funded Quality Improvement study to improve care transitions from the VA hospital to area SNFs, Veterans (N = 134) were assessed for geriatric syndromes using standardized instruments as well as polypharmacy, defined as five or more medications. Warm handoffs were used to facilitate the transfer of this information. This paper describes the prevalence of geriatric syndromes, polypharmacy, and readmission rates. Veterans were prescribed an average of 14.7 medications at hospital discharge. Moreover, 75% of Veterans had more than two geriatric syndromes, some of which began during hospitalization. While this effort did not reduce 30-day readmissions, the high prevalence of geriatric syndromes and polypharmacy suggests that future efforts targeting these issues may be necessary to reduce readmissions among Veterans discharged to SNF.
Analysis of Obesity among Malaysian University Students: A Combination Study with the Application of Bayesian Structural Equation Modelling and Pearson Correlation
Authors: Wan Mohamed Radzi Che Wan Jasimah , Salarzadeh Jenatabadi Hashem , Alanzi Ayed R. A. , Mokhtar Mohd Istajib , Mamat Mohd Zufri , Abdullah Nor Aishah
Published: February 2019

In obesity modelling studies, researchers have been seeking to identify the effective indicators of obesity by using appropriate statistical or mathematical techniques. The main objective of the present study is addressed in three stages. First, a new framework for modelling obesity in university students is introduced. The second stage involves data analysis based on Bayesian Structural Equation Modelling (BSEM) for estimating the Body Mass Index (BMI) (representative of the obesity level) of students at three university levels: Bachelor, Master and PhD. In the third stage, the highest significant correlation is determined between the BMI and other variables in the research model that were found significant through the second phase. The data for this study were collected from students at selected Malaysian universities. The results indicate that unhealthy food intake (fast food and soft drinks), social media use and stress exhibit the highest weightage contributing to overweight and obesity issues for Malaysian university students.
Understanding the Intrinsic and Extrinsic Motivations Associated with Community Gardening to Improve Environmental Public Health Prevention and Intervention
Authors: Ramirez-Andreotta Monica D. , Tapper Abigail , Clough Diamond , Carrera Jennifer S. , Sandhaus Shana
Published: February 2019

Considering that community members continue to garden in and near environments impacted by pollutants known to negatively impact human health, this paper seeks to characterize the intrinsic and extrinsic motivations of a gardener and elucidate their perception of soil quality and environmental responsibility, awareness of past land use, and gardening behavior. Via semi-structured interviews with community gardeners in the Boston area (N = 17), multifactorial motivations associated with gardening as well as ongoing environmental health challenges were reported. Gardeners are knowledgeable about their garden’s historical past and are concerned with soil quality, theft, trash maintenance, animal waste, and loss of produce from foraging animals. Study findings directly inform the field of environmental health exposure assessments by reporting gardening duration, activities that can lead to incidental soil ingestion, and consumption patterns of locally grown produce. This information combined with an understanding of a gardener’s intrinsic and extrinsic motivations can be used to develop urban agricultural infrastructure and management strategies, educational programming, and place-based environmental public health interventions.
Effect of Liming with Various Water Regimes on Both Immobilization of Cadmium and Improvement of Bacterial Communities in Contaminated Paddy: A Field Experiment
Authors: Shi Lei , Guo Zhaohui , Liang Fang , Xiao Xiyuan , Peng Chi , Zeng Peng , Feng Wenli , Ran Hongzhen
Published: February 2019

Cadmium (Cd) in paddy soil is one of the most harmful potentially toxic elements threatening human health. In order to study the effect of lime combined with intermittent and flooding conditions on the soil pH, Cd availability and its accumulation in tissues at the tillering, filling and maturity stages of rice, as well as enzyme activity and the microbial community in contaminated soil, a field experiment was conducted. The results showed that liming under flooding conditions is a more suitable strategy for in situ remediation of Cd-contaminated paddy soil than intermittent conditions. The availability of Cd in soils was closely related to the duration of flooding. Liming was an effective way at reducing available Cd in flooding soil because it promotes the transformation of Cd in soil from acid-extractable to reducible fraction or residual fraction during the reproductive growth period of rice. Compared with control, after liming, the concentration of Cd in brown rice was reduced by 34.9% under intermittent condition while reduced by 55.8% under flooding condition. Meanwhile, phosphatase, urease, and invertase activities in soil increased by 116.7%, 61.4% and 28.8%, and 41.3%, 46.5% and 20.8%, respectively. The high urease activity in tested soils could be used to assess soil recovery with liming for the remediation of contaminated soil. Soil microbial diversity was determined by the activities of soil acid phosphatase, urease and available Cd by redundancy analysis (RDA). The results indicated that the problem of Cd-contaminated paddy soil could achieve risk control of agricultural planting by chemical treatment such as lime, combined with various water regimes.
Interleukin-Mediated Pendrin Transcriptional Regulation in Airway and Esophageal Epithelia
Authors: Vanoni Simone , Scantamburlo Giada , Dossena Silvia , Paulmichl Markus , Nofziger Charity
Published: February 2019

Pendrin (SLC26A4), a Cl−/anion exchanger, is expressed at high levels in kidney, thyroid, and inner ear epithelia, where it has an essential role in bicarbonate secretion/chloride reabsorption, iodide accumulation, and endolymph ion balance, respectively. Pendrin is expressed at lower levels in other tissues, such as airways and esophageal epithelia, where it is transcriptionally regulated by the inflammatory cytokines interleukin (IL)-4 and IL-13 through a signal transducer and activator of transcription 6 (STAT6)-mediated pathway. In the airway epithelium, increased pendrin expression during inflammatory diseases leads to imbalances in airway surface liquid thickness and mucin release, while, in the esophageal epithelium, dysregulated pendrin expression is supposed to impact the intracellular pH regulation system. In this review, we discuss some of the recent findings on interleukin-mediated transcriptional regulation of pendrin and how this dysregulation impacts airway and esophagus epithelial homeostasis during inflammatory diseases.
An Altered Circadian Clock Coupled with a Higher Photosynthesis Efficiency Could Explain the Better Agronomic Performance of a New Coffee Clone When Compared with a Standard Variety
Authors: Toniutti Lucile , Breitler Jean-Christophe , Guittin Charlie , Doulbeau Sylvie , Etienne Hervé , Campa Claudine , Lambot Charles , Herrera Pinilla Juan-Carlos , Bertrand Benoît
Published: February 2019

In a context where climate change is threatening coffee productivity, the management of coffee leaf rust is a challenging issue. Major resistant genes, which have been used for many years, are systematically being overcome by pathogens. Developing healthy plants, able to defend themselves and be productive even when attacked by the pathogen, should be part of a more sustainable alternative approach. We compared one hybrid (GPFA124), selected for its good health in various environments including a reduced rust incidence, and the cv. ‘Caturra’, considered as a standard in terms of productivity and quality but highly susceptible to rust, for phenotypic variables and for the expression of genes involved in the circadian clock and in primary photosynthetic metabolism. The GPFA124 hybrid showed increased photosynthetic electron transport efficiency, better carbon partitioning, and higher chlorophyll content. A strong relationship exists between chlorophyll a fluorescence and the expression of genes related to the photosynthetic electron transport chain. We also showed an alteration of the amplitude of circadian clock genes in the clone. Our work also indicated that increased photosynthetic electron transport efficiency is related to the clone’s better performance. Chlorophyll a fluorescence measurement is a good indicator of the coffee tree’s physiological status for the breeder. We suggest a connection between the circadian clock and carbon metabolism in coffee tree.
Histamine N-Methyltransferase in the Brain
Authors: Yoshikawa Takeo , Nakamura Tadaho , Yanai Kazuhiko
Published: February 2019

Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood–brain barrier permeability have not been available until now. Recently, we have phenotyped Hnmt-deficient mice to elucidate the importance of HNMT in the central nervous system. Hnmt disruption resulted in a robust increase in brain histamine concentration, demonstrating the essential role of HNMT in the brain histamine system. Clinical studies have suggested that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as Parkinson’s disease and attention deficit hyperactivity disorder. Postmortem studies also have indicated that HNMT expression is altered in human brain diseases. These findings emphasise that an increase in brain histamine levels by novel HNMT inhibitors could contribute to the improvement of brain disorders.
Interaction among Calcium Diet Content, PTH (1-34) Treatment and Balance of Bone Homeostasis in Rat Model: The Trabecular Bone as Keystone
Authors: Ferretti Marzia , Cavani Francesco , Roli Laura , Checchi Marta , Magarò Maria Sara , Bertacchini Jessika , Palumbo Carla
Published: February 2019

The present study is the second step (concerning normal diet restoration) of the our previous study (concerning the calcium-free diet) to determine whether normal diet restoration, with/without concomitant PTH (1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in the rat model. The final goals are (i) to define timing and manners of bone mass changes when calcium is restored to the diet, (ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e., trabecular versus cortical bone), and (iii) to verify the eventual role of PTH (1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical bone, in response to different levels of calcium content in the diet, and the effect of PTH, mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are (i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone’s response to dietary/metabolic alterations and (ii) the evidence that the more involved bony architecture is the trabecular bone, the most susceptible to the dynamical balance of the two homeostases.
Protective Effect of Koumine, an Alkaloid from Gelsemium Sempervirens, on Injury Induced by H2O2 in IPEC-J2 Cells
Authors: Yuan Zhihang , Liang Zengenni , Yi Jine , Chen Xiaojun , Li Rongfang , Wu Yong , Wu Jing , Sun Zhiliang
Published: February 2019

Medicinal herbal plants have been commonly used for intervention in different diseases and improvement of health worldwide. Koumine, an alkaloid monomer found abundantly in Gelsemium plants, can be effectively used as an antioxidant. The purpose of this study was to evaluate the potential protective effect of koumine against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in porcine intestinal epithelial cell line (IPEC-J2 cells). MTT assays showed that koumine significantly increased cell viability in H2O2-mediated IPEC-J2 cells. Preincubation with koumine ameliorated H2O2-medicated apoptosis by decreasing reactive oxygen species (ROS) production, and efficiently suppressed the lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production. Moreover, a loss of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) activities was restored to normal level in H2O2-induced IPEC-J2 cells upon koumine exposure. Furthermore, pretreatment with koumine suppressed H2O2-mediated loss of mitochondrial membrane potential, caspase-9 and caspase-3 activation, decrease of Bcl-2 expression and elevation of Bax expressions. Collectively, the results of this study indicated that koumine possesses the cytoprotective effects in IPEC-J2 cells during exposure to H2O2 by suppressing production of ROS, inhibiting the caspase-3 activity and influencing the expression of Bax and Bcl-2. Koumine could potentially serve as a protective effect against H2O2-induced apoptosis.
Fluoxetine Induces Apoptosis through Extrinsic/Intrinsic Pathways and Inhibits ERK/NF-κB-Modulated Anti-Apoptotic and Invasive Potential in Hepatocellular Carcinoma Cells In Vitro
Authors: Chen Wei-Ting , Hsu Fei-Ting , Liu Yu-Chang , Chen Cheng-Hsien , Hsu Li-Cho , Lin Song-Shei
Published: February 2019

The aim of the present study was to verify the effects of fluoxetine on dysregulation of apoptosis and invasive potential in human hepatocellular carcinoma (HCC) SK-Hep1 and Hep3B cells. Cells were treated with different concentrations of fluoxetine for different times. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assays were used for testing the effects of fluoxetine on cell viability. The regulation of apoptosis signaling, and anti-apoptotic, proliferation, and metastasis-associated proteins after fluoxetine treatment were assayed by flow cytometry and Western blotting assay. The detection of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation after fluoxetine treatment was performed by NF-κB reporter gene assay. The results demonstrated that fluoxetine significantly reduced cell viability, cell migration/invasion, NF-κB, extracellular signal-regulated kinases (ERK) activation, and expression of anti-apoptotic (Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (C-FLIP), Myeloid cell leukemia-1 (MCL-1), X-Linked inhibitor of apoptosis protein (XAIP), and Survivin), proliferation (Cyclin-D1), angiogenesis (vascular endothelial growth factor (VEGF)), and metastasis-associated proteins (matrix metalloproteinase-9 (MMP-9)). Fluoxetine also significantly induced apoptosis, unregulated extrinsic (activation of first apoptosis signal protein and ligand (Fas/FasL), and caspase-8) and intrinsic (loss of mitochondrial membrane potential (ΔΨm) pathways and increased Bcl-2 homologous antagonist killer (BAK) apoptosis signaling. Taken together, these results demonstrated that fluoxetine induced apoptosis through extrinsic/intrinsic pathways and diminished ERK/NF-κB-modulated anti-apoptotic and invasive potential in HCC cells in vitro.
Is Retinal Metabolic Dysfunction at the Center of the Pathogenesis of Age-related Macular Degeneration?
Authors: Léveillard Thierry , Philp Nancy J. , Sennlaub Florian
Published: February 2019

The retinal pigment epithelium (RPE) forms the outer blood–retina barrier and facilitates the transepithelial transport of glucose into the outer retina via GLUT1. Glucose is metabolized in photoreceptors via the tricarboxylic acid cycle (TCA) and oxidative phosphorylation (OXPHOS) but also by aerobic glycolysis to generate glycerol for the synthesis of phospholipids for the renewal of their outer segments. Aerobic glycolysis in the photoreceptors also leads to a high rate of production of lactate which is transported out of the subretinal space to the choroidal circulation by the RPE. Lactate taken up by the RPE is converted to pyruvate and metabolized via OXPHOS. Excess lactate in the RPE is transported across the basolateral membrane to the choroid. The uptake of glucose by cone photoreceptor cells is enhanced by rod-derived cone viability factor (RdCVF) secreted by rods and by insulin signaling. Together, the three cells act as symbiotes: the RPE supplies the glucose from the choroidal circulation to the photoreceptors, the rods help the cones, and both produce lactate to feed the RPE. In age-related macular degeneration this delicate ménage à trois is disturbed by the chronic infiltration of inflammatory macrophages. These immune cells also rely on aerobic glycolysis and compete for glucose and produce lactate. We here review the glucose metabolism in the homeostasis of the outer retina and in macrophages and hypothesize what happens when the metabolism of photoreceptors and the RPE is disturbed by chronic inflammation.
Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin
Authors: Favero Gaia , Bonomini Francesca , Franco Caterina , Rezzani Rita
Published: February 2019

Fibromyalgia syndrome (FMS) is considered a musculoskeletal disorder associated to other symptoms including chronic pain. Since the hypothesis of FMS etiogenesis is consistent with mitochondrial dysfunction and oxidative stress, we evaluated the pathophysiological correlation among these factors studying some proteins involved in the mitochondrial homeostasis. We focused our attention on the roles of peroxisome proliferator activated receptor gamma coactivator-1alpha (PGC-1α), mitofusin2 (Mfn2), and coenzyme Q10 (CoQ10) in reserpine-induced myalgic (RIM) rats that manifest fibromyalgia-like chronic pain symptoms. First, we underlined that RIM rats are a good model for studying the pathophysiology of FMS and moreover, we found that PGC-1α, Mfn2, and CoQ10 are involved in FMS. In fact, their expressions were reduced in gastrocnemius muscle determining an incorrect mitochondrial homeostasis. Today, none of the currently available drugs are fully effective against the symptoms of this disease and they, often, induce several adverse events; hence, many scientists have taken on the challenge of searching for non-pharmacological treatments. Another goal of this study was therefore the evaluation of the potential benefits of melatonin, an endogenous indoleamine having several functions including its potent capacity to induce antioxidant enzymes and to determine the protective or reparative mechanisms in the cells. We observed that melatonin supplementation significantly preserved all the studied parameters, counteracting oxidative stress in RIM rats and confirming that this indoleamine should be taken in consideration for improving health and/or counteract mitochondrial related diseases.
The Adaptation of a Model of an Artifact-Centric Business Process Instance and Its Validation
Authors: Zhang Junbao , Liu Guohua
Published: February 2019

The adaptability of an in-progress business process is an essential requirement for any business process management system in dynamic business process environments. Over the last two decades, the artifact-centric approach for business process management has been evidenced to have higher level of flexibility. However, the adaptation of a model of an artifact-centric business process instance is still inevitable and pervasive due to the complex and ever-changing business environments. Almost all works of artifact-centric business process neglect this issue. To fill this gap, we propose a special business rule called adaptation rule to address the dynamic adaptation problem and describe the adaptation by a global adaptation model. Moreover, we provide a validation mechanism over our proposed adaptation rule of the global adaptation model to guarantee the behavior correctness of the adaptation. Through this validation approach, computing the lifecycle of the global adaptation model can be avoided.
KIFC1 Inhibitor CW069 Induces Apoptosis and Reverses Resistance to Docetaxel in Prostate Cancer
Authors: Sekino Yohei , Oue Naohide , Koike Yuki , Shigematsu Yoshinori , Sakamoto Naoya , Sentani Kazuhiro , Teishima Jun , Shiota Masaki , Matsubara Akio , Yasui Wataru
Published: February 2019

Kinesin family member C1 (KIFC1) is a minus end-directed motor protein that plays an essential role in centrosome clustering. Previously, we reported that KIFC1 is involved in cancer progression in prostate cancer (PCa). We designed this study to assess the involvement of KIFC1 in docetaxel (DTX) resistance in PCa and examined the effect of KIFC1 on DTX resistance. We also analyzed the possible role of a KIFC1 inhibitor (CW069) in PCa. We used DTX-resistant PCa cell lines in DU145 and C4-2 cells to analyze the effect of KIFC1 on DTX resistance in PCa. Western blotting showed that KIFC1 expression was higher in the DTX-resistant cell lines than in the parental cell lines. Downregulation of KIFC1 re-sensitized the DTX-resistant cell lines to DTX treatment. CW069 treatment suppressed cell viability in both parental and DTX-resistant cell lines. DTX alone had little effect on cell viability in the DTX-resistant cells. However, the combination of DTX and CW069 significantly reduced cell viability in the DTX-resistant cells, indicating that CW069 re-sensitized the DTX-resistant cell lines to DTX treatment. These results suggest that a combination of CW069 and DTX could be a potential strategy to overcome DTX resistance.
A Personalized CYP2C19 Phenotype-Guided Dosing Regimen of Voriconazole Using a Population Pharmacokinetic Analysis
Authors: Kim Yun , Rhee Su-jin , Park Wan Beom , Yu Kyung-Sang , Jang In-Jin , Lee SeungHwan
Published: February 2019

Highly variable and non-linear pharmacokinetics of voriconazole are mainly caused by CYP2C19 polymorphisms. This study aimed to develop a mechanistic population pharmacokinetic model including the CYP2C19 phenotype, and to assess the appropriateness of various dosing regimens based on the therapeutic target. A total of 1,828 concentrations from 193 subjects were included in the population pharmacokinetic analysis. A three-compartment model with an inhibition compartment appropriately described the voriconazole pharmacokinetics reflecting auto-inhibition. Voriconazole clearance in the CYP2C19 intermediate metabolizers (IMs) and poor metabolizers (PMs) decreased by 17% and 53% compared to that in the extensive metabolizers (EMs). There was a time-dependent inhibition of clearance to 16.2% of its original value in the CYP2C19 EMs, and the extent of inhibition differed according to the CYP2C19 phenotypes. The proposed CYP2C19 phenotype-guided initial dosing regimens are 400 mg twice daily (bid) for EMs, 200 mg bid for IMs, and 100 mg bid for PMs. This CYP2C19 phenotype-guided initial dosing regimen will provide a rationale for individualizing the optimal voriconazole therapy.
Frequent Alteration of Annexin A9 and A10 in HPV-Negative Head and Neck Squamous Cell Carcinomas: Correlation with the Histopathological Differentiation Grade
Authors: Salom Cecilia , Álvarez-Teijeiro Saúl , Fernández M. Pilar , Morgan Reginald O. , Allonca Eva , Vallina Aitana , Lorz Corina , de Villalaín Lucas , Fernández-García M. Soledad , Rodrigo Juan P. , García-Pedrero Juana M.
Published: February 2019

The annexin protein superfamily has been implicated in multiple physiological and pathological processes, including carcinogenesis. Altered expression of various annexins has frequently been observed and linked to the development and progression of various human malignancies. However, information is lacking on the expression and clinical significance of annexin A9 (ANXA9) and A10 (ANXA10) in head and neck squamous cell carcinomas (HNSCC). ANXA9 and ANXA10 expression was evaluated in a large cohort of 372 surgically treated HPV-negative HNSCC patients and correlated with the clinicopathologic parameters and disease outcomes. Down-regulation of ANXA9 expression was found in 42% of HNSCC tissue samples, compared to normal epithelia. ANXA9 expression in tumors was significantly associated with oropharyngeal location and histological differentiation grade (p < 0.001). In marked contrast, ANXA10 expression was absent in normal epithelium, but variably detected in the cytoplasm of cancer cells. Positive ANXA10 expression was found in 64% of tumors, and was significantly associated with differentiation grade (p < 0.001), being also more frequent in oropharyngeal tumors (p = 0.019). These results reveal that the expression of both ANXA9 and ANXA10 is frequently altered in HNSCC and associated to the tumor differentiation grade, suggesting that they could be implicated in the pathogenesis of these cancers.
In Silico Study Probes Potential Inhibitors of Human Dihydrofolate Reductase for Cancer Therapeutics
Authors: Rana Rabia , Rampogu Shailima , Zeb Amir , Son Minky , Park Chanin , Lee Gihwan , Yoon Sanghwa , Baek Ayoung , Parameswaran Sarvanan , Park Seok , Lee Keun
Published: February 2019

Dihydrofolate reductase (DHFR) is an essential cellular enzyme and thereby catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF). In cancer medication, inhibition of human DHFR (hDHFR) remains a promising strategy, as it depletes THF and slows DNA synthesis and cell proliferation. In the current study, ligand-based pharmacophore modeling identified and evaluated the critical chemical features of hDHFR inhibitors. A pharmacophore model (Hypo1) was generated from known inhibitors of DHFR with a correlation coefficient (0.94), root mean square (RMS) deviation (0.99), and total cost value (125.28). Hypo1 was comprised of four chemical features, including two hydrogen bond donors (HDB), one hydrogen bond acceptor (HBA), and one hydrophobic (HYP). Hypo1 was validated using Fischer’s randomization, test set, and decoy set validations, employed as a 3D query in a virtual screening at Maybridge, Chembridge, Asinex, National Cancer Institute (NCI), and Zinc databases. Hypo1-retrieved compounds were filtered by an absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment test and Lipinski’s rule of five, where the drug-like hit compounds were identified. The hit compounds were docked in the active site of hDHFR and compounds with Goldfitness score was greater than 44.67 (docking score for the reference compound), clustering analysis, and hydrogen bond interactions were identified. Furthermore, molecular dynamics (MD) simulation identified three compounds as the best inhibitors of hDHFR with the lowest root mean square deviation (1.2 Å to 1.8 Å), hydrogen bond interactions with hDHFR, and low binding free energy (−127 kJ/mol to −178 kJ/mol). Finally, the toxicity prediction by computer (TOPKAT) affirmed the safety of the novel inhibitors of hDHFR in human body. Overall, we recommend novel hit compounds of hDHFR for cancer and rheumatoid arthritis chemotherapeutics.
Sensors for Lung Cancer Diagnosis
Authors: Capuano Rosamaria , Catini Alexandro , Paolesse Roberto , Di Natale Corrado
Published: February 2019

The positive outcome of lung cancer treatment is strongly related to the earliness of the diagnosis. Thus, there is a strong requirement for technologies that could provide an early detection of cancer. The concept of early diagnosis is immediately extended to large population screening, and then, it is strongly related to non-invasiveness and low cost. Sensor technology takes advantage of the microelectronics revolution, and then, it promises to develop devices sufficiently sensitive to detect lung cancer biomarkers. A number of biosensors for the detection of cancer-related proteins have been demonstrated in recent years. At the same time, the interest is growing towards the analysis of volatile metabolites that could be measured directly from the breath. In this paper, a review of the state-of-the-art of biosensors and volatile compound sensors is presented.
Modeling Tidal Datums and Spatially Varying Uncertainty in the Texas and Western Louisiana Coastal Waters
Authors: Wu Wei , Myers Edward , Shi Lei , Hess Kurt , Michalski Michael , White Stephen
Published: February 2019

Tidal datums are key components in NOAA’s Vertical Datum transformation project (VDatum), which enables effective vertical transformation of the water level between tidal, orthometric, and ellipsoid -based three-dimensional reference systems. An initial application of modeling tidal datums was developed for the coastal waters of Texas and western Louisiana in 2013. The goals of the current work include: (1) updating the tidal model by using the best available shoreline, bathymetry, and tide station data; (2) implementing a recently developed statistical interpolation method for interpolating modeled tidal datums and computing tidal datum uncertainties; and (3) using modeled tidal datums to upgrade non-tidal polygons for enhancing the quality of the VDatum marine grid population. The updated tidal model outperformed the previous tidal model in most cases. The statistical interpolation method is able to limit the interpolated tidal datums to within a user-defined model error (0.01 m in this work) and produce a spatially varying uncertainty field for each interpolated tidal datum field. The upgraded non-tidal polygons enhanced the quality of the VDatum marine grid population. This paper will introduce the detailed procedures of this modeling work, present and discuss the obtained results, share the effective methods used for improving model performance and lessons learned in the model assessments, and analyze the improvement of the current tidal model in comparison with the previous tidal model.
Invasive Aspergillosis in Pediatric Leukemia Patients: Prevention and Treatment
Authors: Papachristou Savvas , Iosifidis Elias , Roilides Emmanuel
Published: February 2019

The purpose of this article is to review and update the strategies for prevention and treatment of invasive aspergillosis (IA) in pediatric patients with leukemia and in patients with hematopoietic stem cell transplantation. The major risk factors associated with IA will be described since their recognition constitutes the first step of prevention. The latter is further analyzed into chemoprophylaxis and non-pharmacologic approaches. Triazoles are the mainstay of anti-fungal prophylaxis while the other measures revolve around reducing exposure to mold spores. Three levels of treatment have been identified: (a) empiric, (b) pre-emptive, and (c) targeted treatment. Empiric is initiated in febrile neutropenic patients and uses mainly caspofungin and liposomal amphotericin B (LAMB). Pre-emptive is a diagnostic driven approach attempting to reduce unnecessary use of anti-fungals. Treatment targeted at proven or probable IA is age-dependent, with voriconazole and LAMB being the cornerstones in >2yrs and <2yrs age groups, respectively.
Multivariate Student versus Multivariate Gaussian Regression Models with Application to Finance
Authors: Nguyen Thi Huong An , Ruiz-Gazen Anne , Thomas-Agnan Christine , Laurent Thibault
Published: February 2019

To model multivariate, possibly heavy-tailed data, we compare the multivariate normal model (N) with two versions of the multivariate Student model: the independent multivariate Student (IT) and the uncorrelated multivariate Student (UT). After recalling some facts about these distributions and models, known but scattered in the literature, we prove that the maximum likelihood estimator of the covariance matrix in the UT model is asymptotically biased and propose an unbiased version. We provide implementation details for an iterative reweighted algorithm to compute the maximum likelihood estimators of the parameters of the IT model. We present a simulation study to compare the bias and root mean squared error of the ensuing estimators of the regression coefficients and covariance matrix under several scenarios of the potential data-generating process, misspecified or not. We propose a graphical tool and a test based on the Mahalanobis distance to guide the choice between the competing models. We also present an application to model vectors of financial assets returns.
The Determinants of Sovereign Risk Premium in African Countries
Authors: Mpapalika Jane , Malikane Christopher
Published: February 2019

This paper investigates the determinants of the sovereign risk premium in African countries. We employ the dynamic fixed effects model to determine the key drivers of sovereign bond spreads. Country-specific effects are fixed and the inclusion of dummy variables using the Bai–Perron multiple structural break test is significant at a 5% level. For robustness, the time-series generalized method of moments (GMM) is used where the null hypothesis of the Sargan Test of over-identifying restrictions (OIR) and the Arellano–Bond Test of no autocorrelation are not rejected. This implies that the instruments used are valid and relevant. In addition, there is no autocorrelation in the error terms. Our results show that the exchange rate, Money supply/GDP (M2/GDP) ratio, and trade are insignificant. Furthermore, our findings indicate that public debt/GDP ratio, GDP growth, inflation rate, foreign exchange reserves, commodity price, and market sentiment are significant at a 5% and 10% level.
Predicting Micro-Enterprise Failures Using Data Mining Techniques
Authors: Ptak-Chmielewska Aneta
Published: February 2019

Research analysis of small enterprises are still rare, due to lack of individual level data. Small enterprise failures are connected not only with their financial situation abut also with non-financial factors. In recent research we tend to apply more and more complex models. However, it is not so obvious that increasing complexity increases the effectiveness. In this paper the sample of 806 small enterprises were analyzed. Qualitative factors were used in modeling. Some simple and more complex models were estimated, such as logistic regression, decision trees, neural networks, gradient boosting, and support vector machines. Two hypothesis were verified: (i) not only financial ratios but also non-financial factors matter for small enterprise survival, and (ii) advanced statistical models and data mining techniques only insignificantly increase the prediction accuracy of small enterprise failures. Results show that simple models are as good as more complex model. Data mining models tend to be overfitted. Most important financial ratios in predicting small enterprise failures were: operating profitability of assets, current assets turnover, capital ratio, coverage of short-term liabilities by equity, coverage of fixed assets by equity, and the share of net financial surplus in total liabilities. Among non-financial factors only two of them were important: the sector of activity and employment.
Temporary Inhibition of the Corrosion of AZ31B Magnesium Alloy by Formation of Bacillus subtilis Biofilm in Artificial Seawater
Authors: Kang Yaxin , Li Lei , Li Shunling , Zhou Xin , Xia Ke , Liu Chang , Qu Qing
Published: February 2019

It is well known that microorganisms tend to form biofilms on metal surfaces to accelerate/decelerate corrosion and affect their service life. Bacillus subtilis was used to produce a dense biofilm on an AZ31B magnesium alloy surface. Corrosion behavior of the alloy with the B. subtilis biofilm was evaluated in artificial seawater. The results revealed that the biofilm hampered extracellular electron transfer significantly, which resulted in a decrease of icorr and increase of Rt clearly compared to the control group. Moreover, an ennoblement of Ecorr was detected under the condition of B. subtilis biofilm covering. Significant reduction of the corrosion was observed by using the cyclic polarization method. All of these prove that the existence of the B. subtilis biofilm effectively enhances the anti-corrosion performance of the AZ31B magnesium alloy. This result may enhance the usage of bio-interfaces for temporary corrosion control. In addition, a possible corrosion inhibition mechanism of B. subtilis on AZ31B magnesium alloy was proposed.
Electron Transport in Carbon Nanotubes with Adsorbed Chromium Impurities
Authors: Repetsky Stanislav , Vyshyvana Iryna , Nakazawa Yasuhiro , Kruchinin Sergei , Bellucci Stefano
Published: February 2019

We employ Green’s function method for describing multiband models with magnetic impurities and apply the formalism to the problem of chromium impurities adsorbed onto a carbon nanotube. Density functional theory is used to determine the bandstructure, which is then fit to a tight-binding model to allow for the subsequent Green’s function description. Electron–electron interactions, electron–phonon coupling, and disorder scattering are all taken into account (perturbatively) with a theory that involves a cluster extension of the coherent potential approximation. We show how increasing the cluster size produces more accurate results and how the final calculations converge as a function of the cluster size. We examine the spin-polarized electrical current on the nanotube generated by the magnetic impurities adsorbed onto the nanotube surface. The spin polarization increases with both increasing concentration of chromium impurities and with increasing magnetic field. Its origin arises from the strong electron correlations generated by the Cr impurities.
Application of Crumb Rubber in Cement-Matrix Composite
Authors: Chen Chi-Yao , Lee Maw-Tien
Published: February 2019

Many studies have used rubber as an additive to form a cement-matrix composite (rubcrete). However, rubcrete has a lower mechanical strength than standard concrete. To improve the properties of rubcrete, this study performed surface modifications on crumb rubber through a partial oxidization reaction. The optimal ratio of air to nitrogen was determined by experiments to be 1:4. Fourier transform infrared spectroscopy (FT-IR) was used to identify the functional groups on the surface of the crumb rubber. A colloidal probe of calcium silicate hydrate (C–S–H) was prepared, and the intermolecular interactions between the rubber and the C–S–H were measured using an atomic force microscope (AFM). The experimental results showed that the partially oxidized crumb rubber contained more hydrophilic S–O bonds. The intermolecular force between C–S–H and treated rubber increased by 23% compared to the force between the original rubber and C–S–H. The compressive strength of the hardened cement paste (56 days) with the treated crumb rubber increased 50% in comparison with that of the hardened cement paste with the as-received crumb rubber.
The Penetration Ability of Calcium Silicate Root Canal Sealers into Dentinal Tubules Compared to Conventional Resin-Based Sealer: A Confocal Laser Scanning Microscopy Study
Authors: Kim Yemi , Kim Ban-Suk , Kim Yong-Min , Lee Donghee , Kim Sin-Young
Published: February 2019

The purpose of this study was to compare the penetration ability of calcium silicate root canal sealers and conventional resin-based sealer using confocal laser scanning microscopy (CLSM). A total of 60 recently extracted single-rooted human premolars were used in this study. The root canals were prepared to a size 40/0.06 taper with ProFile rotary instruments and irrigated with NaOCl and EDTA. After drying all canals, the specimens were randomly divided into three experimental groups (n = 20): Group 1, gutta-percha (GP)/AH Plus with continuous wave compaction; group 2, GP/BioRoot RCS with a single-cone technique; and group 3, GP/Endoseal MTA with a single-cone technique. All experimental samples were sectioned perpendicular to their long axis using a low-speed diamond wheel at the apical, middle, and coronal third levels. The penetration abilities of all samples were evaluated using CLSM. A Kruskal–Wallis analysis and a series of Mann–Whitney U post hoc tests were performed. A higher intensity level was found in the coronal area and a lower intensity level in the apical area in all the experimental groups. The AH Plus group showed higher sum fluorescence intensity in the apical and coronal thirds compared with the BioRoot RCS and Endoseal MTA groups, whereas the BioRoot RCS group showed a higher intensity level in the middle third, similar to the AH Plus group. The maximum sealer penetration depth was low in the apical area and high in the coronal area in the AH Plus and Endoseal MTA groups. In the BioRoot RCS group, maximum sealer penetration was observed in the middle third. In conclusion, there were significant differences in sealer penetration pattern and distance according to the root level and sealer type.
Influence of Torsion on Matteucci Effect Signal Parameters in Co-Based Bistable Amorphous Wire
Authors: Charubin Tomasz , Nowicki Michał , Szewczyk Roman
Published: February 2019

The Matteucci effect (ME) is one of the lesser-known magnetomechanical effects and is most prominent in bistable amorphous wires. It has some experimental applications—Matteucci effect-based magnetic field sensors are very easy to produce and have inherently linear, hybrid analog/digital output signal. The effect is still poorly understood, however, and although it relies on torsion of the wire to manifest, there is no available model, or much experimental data, which would quantitatively connect the ME with the sample twist. In this paper, experimental characteristics of ME signal parameters dependence on torsion in Co-based amorphous bistable wire are presented. The results hint at possible applications, such as rotation or critical current sensors, as well as the necessity of torsion control in the development of ME magnetic field sensors.
Analysis of General Humoral Immunity HIV Dynamics Model with HAART and Distributed Delays
Authors: Elaiw A. , Elnahary E.
Published: February 2019

This paper deals with the study of an HIV dynamics model with two target cells, macrophages and CD4 + T cells and three categories of infected cells, short-lived, long-lived and latent in order to get better insights into HIV infection within the body. The model incorporates therapeutic modalities such as reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). The model is incorporated with distributed time delays to characterize the time between an HIV contact of an uninfected target cell and the creation of mature HIV. The effect of antibody on HIV infection is analyzed. The production and removal rates of the ten compartments of the model are given by general nonlinear functions which satisfy reasonable conditions. Nonnegativity and ultimately boundedness of the solutions are proven. Using the Lyapunov method, the global stability of the equilibria of the model is proven. Numerical simulations of the system are provided to confirm the theoretical results. We have shown that the antibodies can play a significant role in controlling the HIV infection, but it cannot clear the HIV particles from the plasma. Moreover, we have demonstrated that the intracellular time delay plays a similar role as the Highly Active Antiretroviral Therapies (HAAT) drugs in eliminating the HIV particles.
Dynamic Horizontal Union Algorithm for Multiple Interval Concept Lattices
Authors: Yang Yafeng , Zhang Ru , Liu Baoxiang
Published: February 2019

In the era of big data, the data is updating in real-time. How to prepare the data accurately and efficiently is the key to mining association rules. In view of the above questions, this paper proposes a dynamic horizontal union algorithm of multiple interval concept lattices under the same background of the different attribute set and object set. First, in order to ensure the integrity of the lattice structure, the interval concept lattice incremental generation algorithm was improved, and then interval concept was divided into existing concept, redundancy concept and empty concept. Secondly, combining the characteristics of the interval concept lattice, the concept of consistency of interval concept lattice was defined and it is necessary and sufficient for the horizontal union of the lattice structure. Further, the interval concepts united were discussed, and the principle of horizontal unions was given. Finally, the sequence was scanned by the traversal method. This method increased the efficiency of horizontal union. A case study shows the feasibility and efficiency of the proposed algorithm.
Convergence Theorems for Generalized Viscosity Explicit Methods for Nonexpansive Mappings in Banach Spaces and Some Applications
Authors: Sunthrayuth Pongsakorn , Pakkaranang Nuttapol , Kumam Poom , Thounthong Phatiphat , Cholamjiak Prasit
Published: February 2019

In this paper, we introduce a generalized viscosity explicit method (GVEM) for nonexpansive mappings in the setting of Banach spaces and, under some new techniques and mild assumptions on the control conditions, prove some strong convergence theorems for the proposed method, which converge to a fixed point of the given mapping and a solution of the variational inequality. As applications, we apply our main results to show the existence of fixed points of strict pseudo-contractions and periodic solutions of nonlinear evolution equations and Fredholm integral equations. Finally, we give some numerical examples to illustrate the efficiency and implementation of our method.