bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Effect of Natural Fractures on Multiple Shale-Gas Well Performance Using Non-Intrusive EDFM Technology
Authors: Yu Wei , Hu Xiaohu , Liu Malin , Wang Weihong
Published: March 2019

The influence of complex natural fractures on multiple shale-gas well performance with varying well spacing is poorly understood. It is difficult to apply the traditional local grid refinement with structured or unstructured gridding techniques to accurately and efficiently handle complex natural fractures. In this study, we introduced a powerful non-intrusive embedded discrete fracture model (EDFM) technology to overcome the limitations of exiting methods. Through this unique technology, complex fracture configurations can be easily and explicitly embedded into structured matrix blocks. We set up a field-scale two-phase reservoir model to history match field production data and predict long-term recovery from Marcellus. The effective fracture properties were determined thorough history matching. In addition, we extended the single-well model to include two horizontal wells with and without including natural fractures. The effects of different numbers of natural fractures on two-well performance with varying well spacing of 200 m, 300 m, and 400 m were examined. The simulation results illustrate that gas productivity almost linearly increases with the number of two-set natural fractures. Furthermore, the difference of well performance between different well spacing increases with an increase in natural fracture density. A larger well spacing is preferred for economically developing the shale-gas reservoirs with a larger natural fracture density. The findings of this study provide key insights into understanding the effect of natural fractures on well performance and well spacing optimization.
An Investigation of a Root Zone Heating System and Its Effects on the Morphology of Winter-Grown Green Peppers
Authors: Ameen Muhammad , Zhang Zhuo , Wang Xiaochan , Yaseen Muhammad , Umair Muhammad , Noor Rana Shahzad , Lu Wei , Yousaf Khurram , Ullah Fahim , Memon Muhammad Sohail
Published: March 2019

The winter season in Nanjing is from December to February, with extremely low temperature and high humidity due to seasonal snowfall. During these extreme cold climatic conditions, plants have to survive severe heat stress conditions, even if they are being kept in greenhouses. The objective of this study was to investigate a heating system that can provide heat directly to the root zone instead of heating the entire greenhouse, which is a viable option to reduce energy consumption. Root zone heating could be an effective alternative for the sustainable development of plants during the winter. A novel type of root zone heating system was applied to evaluate the energy consumption during different greenhouse ambient temperature conditions, the effects of root zone heating systems on pepper plant morphology, and heat transfer rates to plant canopy in the greenhouse. The temperature treatments in root zone heating system were T-15, T-20, T-25, T-30, and a control treatment (TC) at 15 °C, 20 °C, 25 °C, and 30 °C, respectively, while TC received no heat. A simulation study was carried out to validate the root zone temperature. The results of the current investigation revealed that energy consumption has an inverse relationship to the ambient temperature of the greenhouse, while temperature gradients to the plant canopy observed from the lower to the upper part of the plant and the upper canopy experienced less temperature fluctuation as compared to the lower part of the plant. The results also showed that treatment T-20 had the maximum in terms of the leaf dry weight, stem diameter, and the number of leaves, while T-25 showed the maximum root dry weight and stem dry weight; T-30 and T-15 had minimum dry weights of plant segments among all treatments. Control treatment (TC) showed a minimum dry mass of plant. The root zone heating with optimal root zone temperature was found to be a viable and adaptable option as this leads to improved energy consumption patterns for the sustainable growth and development of plants in greenhouses during extremely low temperatures.
Fuzzy Rule-Based and Particle Swarm Optimisation MPPT Techniques for a Fuel Cell Stack
Authors: Luta Doudou N. , Raji Atanda K.
Published: March 2019

The negative environmental impact and the rapidly declining reserve of fossil fuel-based energy sources for electricity generation is a big challenge to finding sustainable alternatives. This scenario is complicated by the ever-increasing world population growth demanding a higher standard of living. A fuel cell system is able to generate electricity and water with higher energy efficiency while producing near-zero emissions. A common fuel cell stack displays a nonlinear power characteristic as a result of internal limitations and operating parameters such as temperature, hydrogen and oxygen partial pressures and humidity levels, leading to a reduced overall system performance. It is therefore important to extract as much power as possible from the stack, thus hindering excessive fuel use. This study considers and compares two Maximum Power Point Tracking (MPPT) approaches; one based on the Mamdani Fuzzy Inference System and the other on the Particle Swarm Optimisation (PSO) algorithm to maintain the output power of a fuel cell stack extremely close to its maximum. To ensure that, the power converter interfaced to the fuel cell unit must be able to continuously self-modify its parameters, hence changing its voltage and current depending upon the Maximum Power Point position. While various methods exist for Maximum Power Point tracker design, this paper analyses the response characteristics of a Mamdani Fuzzy Inference Engine and the Particle Swarm Optimisation technique. The investigation was conducted on a 53 kW Proton Exchange Membrane Fuel Cell interfaced to a DC-to-DC boost converter supplying 1.2 kV from a 625 V input DC voltage. The modelling was accomplished using a Matlab/Simulink environment. The results showed that the MPPT controller based on the PSO algorithm presented better tracking efficiency as compared to the Mamdani controller. Furthermore, the rise time of the PSO controller was slightly shorter than the Mamdani controller and the overshoot of the PSO controller was 2% lower than that of the Mamdani controller.
Quantifying the Benefits of a Solar Home System-Based DC Microgrid for Rural Electrification
Authors: Narayan Nishant , Chamseddine Ali , Vega-Garita Victor , Qin Zian , Popovic-Gerber Jelena , Bauer Pavol , Zeman Miroslav
Published: March 2019

Off-grid solar home systems (SHSs) currently constitute a major source of providing basic electricity needs in un(der)-electrified regions of the world, with around 73 million households having benefited from off-grid solar solutions by 2017. However, in and of itself, state-of-the-art SHSs can only provide electricity access with adequate power supply availability up to tier 2, and to some extent, tier 3 levels of the Multi-tier Framework (MTF) for measuring household electricity access. When considering system metrics of loss of load probability (LLP) and battery size, meeting the electricity needs of tiers 4 and 5 is untenable through SHSs alone. Alternatively, a bottom-up microgrid composed of interconnected SHSs is proposed. Such an approach can enable the so-called climb up the rural electrification ladder. The impact of the microgrid size on the system metrics like LLP and energy deficit is evaluated. Finally, it is found that the interconnected SHS-based microgrid can provide more than 40% and 30% gains in battery sizing for the same LLP level as compared to the standalone SHSs sizes for tiers 4 and 5 of the MTF, respectively, thus quantifying the definite gains of an SHS-based microgrid over standalone SHSs. This study paves the way for visualizing SHS-based rural DC microgrids that can not only enable electricity access to the higher tiers of the MTF with lower battery storage needs but also make use of existing SHS infrastructure, thus enabling a technologically easy climb up the rural electrification ladder.
On Analytic Functions Involving the q-Ruscheweyeh Derivative
Authors: Noor Khalida Inayat
Published: March 2019

In this paper, we use concepts of q-calculus to introduce a certain type of q-difference operator, and using it define some subclasses of analytic functions. Inclusion relations, coefficient result, and some other interesting properties of these classes are studied.
Application of HEC-HMS Model for Flow Simulation in the Lake Tana Basin: The Case of Gilgel Abay Catchment, Upper Blue Nile Basin, Ethiopia
Authors: Tassew Bitew G. , Belete Mulugeta A. , Miegel K.
Published: March 2019

Understanding the complex relationships between rainfall and runoff processes is necessary for the proper estimation of the quantity of runoff generated in a watershed. The surface runoff was simulated using the Hydrologic Modelling System (HEC-HMS) for the Gilgel Abay Catchment (1609 km2), Upper Blue Nile Basin, Ethiopia. The catchment was delineated and its properties were extracted from a 30 m × 30 m Digital Elevation Model (DEM) of the Lake Tana Basin. The meteorological model was developed within HEC-HMS from rainfall data and the control specifications defined the period and time step of the simulation run. To account for the loss, runoff estimation, and flow routing, Soil Conservation Service Curve Number (SCS-CN), Soil Conservation Service Unit Hydrograph (SCS-UH) and Muskingum methods were used respectively. The rainfall-runoff simulation was conducted using six extreme daily time series events. Initial results showed that there is a clear difference between the observed and simulated peak flows and the total volume. Thereafter, a model calibration with an optimization method and sensitivity analysis was carried out. The result of the sensitivity analysis showed that the curve number is the sensitive parameter. In addition, the model validation results showed a reasonable difference in peak flow (Relative Error in peak, REP = 1.49%) and total volume (Relative Error in volume, REV = 2.38%). The comparison of the observed and simulated hydrographs and the model performance (NSE = 0.884) and their correlation (R2 = 0.925) showed that the model is appropriate for hydrological simulations in the Gilgel Abay Catchment.
Evacuation Priority Method in Tsunami Hazard Based on DMSP/OLS Population Mapping in the Pearl River Estuary, China
Authors: Mohamadi Bahaa , Chen Shuisen , Liu Jia
Published: March 2019

Evacuation plans are critical in case of natural disaster to save people’s lives. The priority of population evacuation on coastal areas could be useful to reduce the death toll in case of tsunami hazard. In this study, the population density remote sensing mapping approach was developed using population records in 2013 and Defense Meteorological Satellite Program’s Operational Linescan System (DMSP/OLS) night-time light (NTL) image of the same year for defining the coastal densest resident areas in Pearl River Estuary (PRE), China. Two pixel-based saturation correction methods were evaluated for application of population density mapping to enhance DMSP/OLS NTL image. The Vegetation Adjusted NTL Urban Index (VANUI) correction method (R2 (original/corrected): 0.504, Std. error: 0.0069) was found to be the better-fit correction method of NTL image saturation for the study area compared to Human Settlement Index (HSI) correction method (R2 (original/corrected): 0.219, Std. error: 0.1676). The study also gained a better dynamic range of HSI correction (0~25 vs. 0.1~5.07) compared to the previous one [27]. The town-level’s population NTL simulation model is built (R2 = 0.43, N = 47) for the first time in PRE with mean relative error (MSE) of 32% (N = 24, town level), On the other side, the tsunami hazard map was produced based on numerical modeling of potential tsunami wave height and velocity, combining with the river net system, elevation, slope, and vegetation cover factors. Both results were combined to produce an evacuation map in PRE. The simulation of tsunami exposure on density of population showed that the highest evacuation priority was found to be in most of Zhuhai city area and the coastal area of Shenzhen City under wave height of nine meters, while lowest evacuation priority was defined in Panyu and Nansha Districts of Guangzhou City, eastern and western parts of Zhongshan City, and northeast and northwest parts of Dongguan City. The method of tsunami risk simulation and the result of mapped tsunami exposure are of significance for direction to tsunami disaster-risk reduction or evacuation traffic arrangement in PRE or other coastal areas in the world.
Molecular Mechanisms Responsible for Diastolic Dysfunction in Diabetes Mellitus Patients
Authors: Nikolajević Starčević Jovana , Janić Miodrag , Šabovič Mišo
Published: March 2019

In diabetic patients, cardiomyopathy is an important cause of heart failure, but its pathophysiology has not been completely understood thus far. Myocardial hypertrophy and diastolic dysfunction have been considered the hallmarks of diabetic cardiomyopathy (DCM), while systolic function is affected in the latter stages of the disease. In this article we propose the potential pathophysiological mechanisms responsible for myocardial hypertrophy and increased myocardial stiffness leading to diastolic dysfunction in this specific entity. According to our model, increased myocardial stiffness results from both cellular and extracellular matrix stiffness as well as cell–matrix interactions. Increased intrinsic cardiomyocyte stiffness is probably the most important contributor to myocardial stiffness. It results from the impairment in cardiomyocyte cytoskeleton. Several other mechanisms, specifically affected by diabetes, seem to also be significantly involved in myocardial stiffening, i.e., impairment in the myocardial nitric oxide (NO) pathway, coronary microvascular dysfunction, increased inflammation and oxidative stress, and myocardial sodium glucose cotransporter-2 (SGLT-2)-mediated effects. Better understanding of the complex pathophysiology of DCM suggests the possible value of drugs targeting the listed mechanisms. Antidiabetic drugs, NO-stimulating agents, anti-inflammatory agents, and SGLT-2 inhibitors are emerging as potential treatment options for DCM.
Inhibitory Effect of CAPE and Kaempferol in Colon Cancer Cell Lines—Possible Implications in New Therapeutic Strategies
Authors: Budisan Liviuta , Gulei Diana , Jurj Ancuta , Braicu Cornelia , Zanoaga Oana , Cojocneanu Roxana , Pop Laura , Raduly Lajos , Barbat Alexandru , Moldovan Alin , Moldovan Cristian , Tigu Adrian Bogdan , Ionescu Calin , Atanasov Atanas G. , Irimie Alexandru , Berindan-Neagoe Ioana
Published: March 2019

Background: Phytochemicals are natural compounds synthesized as secondary metabolites in plants and represent an important source of molecules with therapeutic applications. Attention is accorded to their potential in anti-cancer therapies as single agents or adjuvant treatment. Herby, we evaluated the in vitro effects of a panel of natural compounds with focus on caffeic acid phenethyl ester (CAPE) and Kaempferol for the treatment of human colon cancer. Methods: We exposed two human colon cancer cell lines, RKO and HCT-116, followed by functional examination of cell viability, cell proliferation and invasion, cell cycle, apoptosis, and autophagy. Modifications in gene expression were investigated through microarray and detection of existing mutations and finding of new ones was done with the help of Next Generation Sequencing (NGS). Results: Both CAPE and Kaempferol inhibit cell proliferation, motility and invasion, and stimulate apoptosis and autophagy, concomitant with modifications in coding and noncoding genes’ expression. Moreover, there are pathogenic mutations that are no longer found upon treatment with CAPE and Kaempferol. Conclusions: Our findings indicate that CAPE and Kaempferol have the ability to negatively influence the development and advancement of colon cancer in vitro by specifically altering the cells at the molecular level; this activity can be exploited in possible adjuvant therapies once the optimal dose concentration with minimal side effects but with cancer inhibitory activity is set in vivo.
Miscanthus x giganteus Stem Versus Leaf-Derived Lignins Differing in Monolignol Ratio and Linkage
Authors: Bergs Michel , Völkering Georg , Kraska Thorsten , Pude Ralf , Do Xuan Tung , Kusch Peter , Monakhova Yulia , Konow Christopher , Schulze Margit
Published: March 2019

As a renewable, Miscanthus offers numerous advantages such as high photosynthesis activity (as a C4 plant) and an exceptional CO2 fixation rate. These properties make Miscanthus very attractive for industrial exploitation, such as lignin generation. In this paper, we present a systematic study analyzing the correlation of the lignin structure with the Miscanthus genotype and plant portion (stem versus leaf). Specifically, the ratio of the three monolignols and corresponding building blocks as well as the linkages formed between the units have been studied. The lignin amount has been determined for M. x giganteus (Gig17, Gig34, Gig35), M. nagara (NagG10), M. sinensis (Sin2), and M. robustus (Rob4) harvested at different time points (September, December, and April). The influence of the Miscanthus genotype and plant component (leaf vs. stem) has been studied to develop corresponding structure-property relationships (i.e., correlations in molecular weight, polydispersity, and decomposition temperature). Lignin isolation was performed using non-catalyzed organosolv pulping and the structure analysis includes compositional analysis, Fourier transform infradred (FTIR), ultraviolet/visible (UV-Vis), hetero-nuclear single quantum correlation nuclear magnetic resonsnce (HSQC-NMR), thermogravimetric analysis (TGA), and pyrolysis gaschromatography/mass spectrometry (GC/MS). Structural differences were found for stem and leaf-derived lignins. Compared to beech wood lignins, Miscanthus lignins possess lower molecular weight and narrow polydispersities (<1.5 Miscanthus vs. >2.5 beech) corresponding to improved homogeneity. In addition to conventional univariate analysis of FTIR spectra, multivariate chemometrics revealed distinct differences for aromatic in-plane deformations of stem versus leaf-derived lignins. These results emphasize the potential of Miscanthus as a low-input resource and a Miscanthus-derived lignin as promising agricultural feedstock.
Antiproliferative and Cytotoxic Activity of Xanthohumol and Its Non-Estrogenic Derivatives in Colon and Hepatocellular Carcinoma Cell Lines
Authors: Logan Isabelle E. , Miranda Cristobal L. , Lowry Malcolm B. , Maier Claudia S. , Stevens Jan F. , Gombart Adrian F.
Published: March 2019

Xanthohumol (XN), a prenylated flavonoid found in hops, inhibits growth in a variety of cancer cell lines; however, its use raises concerns as gut microbiota and the host’s hepatic cytochrome P450 enzymes metabolize it into the most potent phytoestrogen known, 8-prenylnaringenin (8-PN). The XN derivatives dihydroxanthohumol (DXN) and tetrahydroxanthohumol (TXN) are not metabolized into 8-PN and they show higher tissue concentrations in vivo compared with XN when orally administered to mice at the same dose. Here we show that DXN and TXN possess improved anti-proliferative activity compared with XN in two colon (HCT116, HT29) and two hepatocellular (HepG2, Huh7) carcinoma cell lines, as indicated by their respective IC50 values. Furthermore, XN, DXN, and TXN induce extensive apoptosis in all these carcinoma cell lines. Finally, TXN induces G0/G1 cell cycle arrest in the colon carcinoma cell line HT29. Our findings suggest that DXN and TXN could show promise as therapeutic agents against colorectal and liver cancer in preclinical studies without the drawback of metabolism into a phytoestrogen.
Physiological Diversity of Spitsbergen Soil Microbial Communities Suggests Their Potential as Plant Growth-Promoting Bacteria
Authors: Hanaka Agnieszka , Ozimek Ewa , Majewska Małgorzata , Rysiak Anna , Jaroszuk-Ściseł Jolanta
Published: March 2019

The objective of the study was to assess the physiological diversity and metabolic activity of the soil bacterial communities inhabiting Spitsbergen soils in search of bacterial abilities facilitating plant growth promotion. In the soil, the total number of culturable microorganisms, the number of their individual physiological groups (including Siderophore Synthesizing; SSB and Phosphate Solubilizing Bacteria; PSB), the dehydrogenase (DH) activity, and the ability to utilize sources of C, N, P (EcoPlate) were analysed. In bacterial isolates, siderophores production, ACC (1-aminocyclopropane-1-carboxylate) deaminase (ACCD) activity, IAA (indole-3-acetic acid) synthesis were examined. The isolates were applied to the seeds of Phaseolus coccineus regarding their germination and root length. The results showed differences between copio- and oligotrophic bacteria. A usually high number of SSB was accompanied by the raised number of PSB. A bigger number of SSB was connected with low values of Fe in the soil. High DH activity was assisted by greater number of copio- and oligotrophic bacteria, raised average well color development value, and N and C contents in the soil. Germination index was more alike relative seed germination than relative root growth. IAA concentration and ACCD activity were conversely related. Synthesis of siderophores was matched with ACCD activity and its high level was combined with elevated germination index. In spite of different localization of soil samples, some isolates proved similar traits of activity. Distinct affiliation of isolates and their various localizations were displayed. Among all isolates tested, some possessed one main trait of activity, but most of them had two or more significant features for potential plant growth stimulation. These isolates could be an important source of useful bacteria.
Novel 8-Substituted Coumarins That Selectively Inhibit Human Carbonic Anhydrase IX and XII
Authors: Buran Kerem , Bua Silvia , Poli Giulio , Önen Bayram F. , Tuccinardi Tiziano , Supuran Claudiu
Published: March 2019

A novel series of 8-substituted coumarin-based compounds, characterized by the presence of alkylpiperazine and arylpiperazine chains, were synthesized and tested for their inhibitory activity against four human carbonic anhydrase (hCA) isoforms. All compounds displayed nanomolar potency against the cancer-related hCA IX and hCA XII; moreover, they were shown to be devoid of any inhibitory activity toward the cytosolic hCA I and hCA II up to 10 µM concentration in the assay system. Therefore, the synthesized coumarin ligands demonstrated to be potent and selective hCA IX/XII inhibitors, and were shown to be as potent as the reference inhibitor acetazolamide against hCA XII, with single-digit nanomolar Ki values. Molecular modeling studies provided a rationale for explaining the selectivity profile of these non-classic hCA inhibitors and their interactions with the enzymes, according to their specific mechanism of action, thus paving the way for future structure-based lead optimization studies.
NPR1 and Redox Rhythm: Connections, between Circadian Clock and Plant Immunity
Authors: Zhang Jingjing , Ren Ziyu , Zhou Yuqing , Ma Zheng , Ma Yanqin , Hou Dairu , Xu Ziqin , Huang Xuan
Published: March 2019

The circadian clock in plants synchronizes biological processes that display cyclic 24-h oscillation based on metabolic and physiological reactions. This clock is a precise timekeeping system, that helps anticipate diurnal changes; e.g., expression levels of clock-related genes move in synchrony with changes in pathogen infection and help prepare appropriate defense responses in advance. Salicylic acid (SA) is a plant hormone and immune signal involved in systemic acquired resistance (SAR)-mediated defense responses. SA signaling induces cellular redox changes, and degradation and rhythmic nuclear translocation of the non-expresser of PR genes 1 (NPR1) protein. Recent studies demonstrate the ability of the circadian clock to predict various potential attackers, and of redox signaling to determine appropriate defense against pathogen infection. Interaction of the circadian clock with redox rhythm promotes the balance between immunity and growth. We review here a variety of recent evidence for the intricate relationship between circadian clock and plant immune response, with a focus on the roles of redox rhythm and NPR1 in the circadian clock and plant immunity.
Role of Norepinephrine in IL-1β-Induced Chondrocyte Dedifferentiation under Physioxia
Authors: Speichert Saskia , Molotkov Natalie , El Bagdadi Karima , Meurer Andrea , Zaucke Frank , Jenei-Lanzl Zsuzsa
Published: March 2019

As part of the pathogenesis of osteoarthritis (OA), chondrocytes lose their phenotype and become hypertrophic, or dedifferentiate, mainly driven by interleukin-1β (IL-1β). The contribution of other factors to the dedifferentiation process is not completely understood. Recent studies suggested a dose-dependent role for the sympathetic neurotransmitter norepinephrine (NE) in OA chondrocyte metabolism. Therefore, the aim of this study was to analyze the contribution of NE (10−8 M, 10−6 M) to human articular OA chondrocyte dedifferentiation in the absence or presence of IL-1β (0.5 ng/mL). Here, we demonstrate that OA chondrocytes express α2A-, α2C- and β2-adrenoceptors (AR) and show the characteristic shift towards a fibroblast-like shape at day 7 in physioxic monolayer culture. NE alone did not affect morphology but, in combination with IL-1β, markedly accelerated this shift. Moderate glycosaminoglycan (GAG) staining was observed in untreated and NE-treated cells, while IL-1β strongly decreased GAG deposition. IL-1β alone or in combination with NE decreased SOX9, type II collagen, COMP, and aggrecan, and induced MMP13 and ADAMTS4 gene expression, indicating an accelerated dedifferentiation. NE alone did not influence gene expression and did not modulate IL-1β-mediated effects. In conclusion, these results indicate that low-grade inflammation exerts a dominant effect on chondrocyte dedifferentiation and should be targeted early in OA therapy.
Ginsenoside Rk1 Induces Apoptosis in Neuroblastoma Cells Through Loss of Mitochondrial Membrane Potential and Activation of Caspases
Authors: Oh Jung-Mi , Lee Jeongwoo , Im Wan-Taek , Chun Sungkun
Published: March 2019

Neuroblastoma (NB) is the most common childhood cancer, with a very poor prognosis. More than 60% of children with NB die within five years; therefore, a more effective therapy for NB is required. Although ginsenoside has been shown to significantly inhibit the growth of various cancers, the effect of ginsenoside Rk1 on neuroblastoma has not been known yet. Hence, we examined the anticancer effects of highly pure Rk1 on neuroblastoma cell lines. The apoptotic effects of Rk1 on neuroblastoma cells were examined using cell viability assay, flow cytometry and cell staining assay, and the change in gene expression levels were analysed using RT-PCR, western blots, and immunohistochemistry. The metastatic effect of Rk1 was monitored by wound healing assay, invasion and migration with Matrigels. Rk1 inhibited neuroblastoma cell viability dose-dependently. Rk1-induced apoptosis was investigated through nuclear condensation and mitochondrial membrane potential loss, and it showed that Rk1 can induce cell cycle arrest at the G0/G1 phase but also inhibit the metastatic ability of neuroblastoma cells. Moreover, Rk1 (30 mg/kg) injections markedly inhibited xenograft tumor growth. These findings demonstrate that Rk1 might be valuable in the development of anti-cancer agents for neuroblastoma treatment.
Coagulase-Negative Staphylococci Pathogenomics
Authors: Argemi Xavier , Hansmann Yves , Prola Kevin , Prévost Gilles
Published: March 2019

Coagulase-negative Staphylococci (CoNS) are skin commensal bacteria. Besides their role in maintaining homeostasis, CoNS have emerged as major pathogens in nosocomial settings. Several studies have investigated the molecular basis for this emergence and identified multiple putative virulence factors with regards to Staphylococcus aureus pathogenicity. In the last decade, numerous CoNS whole-genome sequences have been released, leading to the identification of numerous putative virulence factors. Koch’s postulates and the molecular rendition of these postulates, established by Stanley Falkow in 1988, do not explain the microbial pathogenicity of CoNS. However, whole-genome sequence data has shed new light on CoNS pathogenicity. In this review, we analyzed the contribution of genomics in defining CoNS virulence, focusing on the most frequent and pathogenic CoNS species: S. epidermidis, S. haemolyticus, S. saprophyticus, S. capitis, and S. lugdunensis.
Peanut Sprout Extracts Attenuate Triglyceride Accumulation by Promoting Mitochondrial Fatty Acid Oxidation in Adipocytes
Authors: Seo Seok Hee , Jo Sang-Mi , Kim Jiyoung , Lee Myoungsook , Lee Yunkyoung , Kang Inhae
Published: March 2019

Peanut sprouts (PS), which are germinated peanut seeds, have recently been reported to have anti-oxidant, anti-inflammatory, and anti-obesity effects. However, the underlying mechanisms by which PS modulates lipid metabolism are largely unknown. To address this question, serial doses of PS extract (PSE) were added to 3T3-L1 cells during adipocyte differentiation. PSE (25 µg/mL) significantly attenuated adipogenesis by inhibiting lipid accumulation in addition to reducing the level of adipogenic protein and gene expression with the activation of AMP-activated protein kinase (AMPK). Other adipocyte cell models such as mouse embryonic fibroblasts C3H10T1/2 and primary adipocytes also confirmed the anti-adipogenic properties of PSE. Next, we investigated whether PSE attenuated lipid accumulation in mature adipocytes. We found that PSE significantly suppressed lipogenic gene expression, while fatty acid (FA) oxidation genes were upregulated. Augmentation of FA oxidation by PSE in mature 3T3-L1 adipocytes was confirmed via a radiolabeled-FA oxidation rate experiment by measuring the conversion of [3H]-oleic acid (OA) to [3H]-H2O. Furthermore, PSE enhanced the mitochondrial oxygen consumption rate (OCR), especially maximal respiration, and beige adipocyte formation in adipocytes. In summary, PSE was effective in reducing lipid accumulation in 3T3-L1 adipocytes through mitochondrial fatty acid oxidation involved in AMPK and mitochondrial activation.
Genome-Wide Identification and Expression Profiling of Wnt Family Genes in the Silkworm, Bombyx mori
Authors: Ding Xin , Liu Junxia , Zheng Lu , Song Jiangbo , Li Niannian , Hu Hai , Tong Xiaoling , Dai Fangyin
Published: March 2019

Wnt is a family of conserved glycoproteins that participate in a variety of important biological processes including embryo development, cell proliferation and differentiation, and tissue regeneration. The Wnt family is a metazoan novelty found in all animal phyla. Studies have revealed that the number of Wnt genes varies among species, presumably due to reproduction and loss of genes during evolution. However, a comprehensive inventory of Wnt genes in Lepidoptera is lacking. In this study, we identified the repertoire of Wnt genes in the silkworm and seven other species of Lepidoptera and obtained eight Wnt genes (Wnt1, Wnt5–Wnt7, Wnt9–Wnt11, and WntA) in each species. Four of these Wnt genes are clustered in two orientations (5′-Wnt9-Wnt1-Wnt6-Wnt10-3′ and 5′-Wnt10-Wnt6-Wnt1-Wnt9-3′) in both moths and butterflies. Transcript analysis of Wnt in silkworm embryonic stages showed that each BmWnt gene had a unique expression pattern during embryological development. Analysis of a larval stage revealed differential expression of Wnt family members in diverse tissues. Our study provides an overview of the Wnt family in Lepidoptera and will inspire further functional study of the Wnt genes in the silkworm.
Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks
Authors: Hardeland Rüdiger
Published: March 2019

Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes in the immune system, a deteriorating circadian system, and reductions in sirtuin-1 (SIRT1) activity. In non-tumor cells, several effects of melatonin are abolished by inhibiting SIRT1, indicating mediation by SIRT1. Melatonin is, in addition to its circadian and antioxidant roles, an immune stimulatory agent. However, it can act as either a pro- or anti-inflammatory regulator in a context-dependent way. Melatonin can stimulate the release of proinflammatory cytokines and other mediators, but also, under different conditions, it can suppress inflammation-promoting processes such as NO release, activation of cyclooxygenase-2, inflammasome NLRP3, gasdermin D, toll-like receptor-4 and mTOR signaling, and cytokine release by SASP (senescence-associated secretory phenotype), and amyloid-β toxicity. It also activates processes in an anti-inflammatory network, in which SIRT1 activation, upregulation of Nrf2 and downregulation of NF-κB, and release of the anti-inflammatory cytokines IL-4 and IL-10 are involved. A perhaps crucial action may be the promotion of macrophage or microglia polarization in favor of the anti-inflammatory phenotype M2. In addition, many factors of the pro- and anti-inflammatory networks are subject to regulation by microRNAs that either target mRNAs of the respective factors or upregulate them by targeting mRNAs of their inhibitor proteins.
Emerging Role of Eukaryote Ribosomes in Translational Control
Authors: Dalla Venezia Nicole , Vincent Anne , Marcel Virginie , Catez Frédéric , Diaz Jean-Jacques
Published: March 2019

Translation is one of the final steps that regulate gene expression. The ribosome is the effector of translation through to its role in mRNA decoding and protein synthesis. Many mechanisms have been extensively described accounting for translational regulation. However it emerged only recently that ribosomes themselves could contribute to this regulation. Indeed, though it is well-known that the translational efficiency of the cell is linked to ribosome abundance, studies recently demonstrated that the composition of the ribosome could alter translation of specific mRNAs. Evidences suggest that according to the status, environment, development, or pathological conditions, cells produce different populations of ribosomes which differ in their ribosomal protein and/or RNA composition. Those observations gave rise to the concept of “specialized ribosomes”, which proposes that a unique ribosome composition determines the translational activity of this ribosome. The current review will present how technological advances have participated in the emergence of this concept, and to which extent the literature sustains this concept today.
Cytarabine-Resistant FLT3-ITD Leukemia Cells are Associated with TP53 Mutation and Multiple Pathway Alterations—Possible Therapeutic Efficacy of Cabozantinib
Authors: Ko Ya-Chen , Hu Chung-Yi , Liu Zheng-Hau , Tien Hwei-Fang , Ou Da-Liang , Chien Hsiung-Fei , Lin Liang-In
Published: March 2019

Internal tandem duplication of FLT3 juxtamembrane domain (FLT3-ITD)-positive acute myeloid leukemia (AML) leads to poor clinical outcomes after chemotherapy. We aimed to establish a cytarabine-resistant line from FLT3-ITD-positive MV4-11 (MV4-11-P) cells and examine the development of resistance. The FLT3-ITD mutation was retained in MV4-11-R; however, the protein was underglycosylated and less phosphorylated in these cells. Moreover, the phosphorylation of ERK1/2, Akt, MEK1/2 and p53 increased in MV4-11-R. The levels of Mcl-1 and p53 proteins were also elevated in MV4-11-R. A p53 D281G mutant emerged in MV4-11-R, in addition to the pre-existing R248W mutation. MV4-11-P and MV4-11-R showed similar sensitivity to cabozantinib, sorafenib, and MK2206, whereas MV4-11-R showed resistance to CI-1040 and idarubicin. MV4-11-R resistance may be associated with inhibition of Akt phosphorylation, but not ERK phosphorylation, after exposure to these drugs. The multi-kinase inhibitor cabozantinib inhibited FLT3-ITD signaling in MV4-11-R cells and MV4-11-R-derived tumors in mice. Cabozantinib effectively inhibited tumor growth and prolonged survival time in mice bearing MV4-11-R-derived tumors. Together, our findings suggest that Mcl-1 and Akt phosphorylation are potential therapeutic targets for p53 mutants and that cabozantinib is an effective treatment in cytarabine-resistant FLT3-ITD-positive AML.
Water Network Dynamics Next to the Oxygen-Evolving Complex of Photosystem II
Authors: Reiss Krystle , Morzan Uriel N. , Grigas Alex T. , Batista Victor S.
Published: March 2019

The influence of the environment on the functionality of the oxygen-evolving complex (OEC) of photosystem II has long been a subject of great interest. In particular, various water channels, which could serve as pathways for substrate water diffusion, or proton translocation, are thought to be critical to catalytic performance of the OEC. Here, we address the dynamical nature of hydrogen bonding along the water channels by performing molecular dynamics (MD) simulations of the OEC and its surrounding protein environment in the S1 and S2 states. Through the eigenvector centrality (EC) analysis, we are able to determine the characteristics of the water network and assign potential functions to the major channels, namely that the narrow and broad channels are likely candidates for proton/water transport, while the large channel may serve as a path for larger ions such as chloride and manganese thought to be essential during PSII assembly.
Combined Treatment with Doxorubicin and Rapamycin Is Effective against In Vitro and In Vivo Models of Human Glioblastoma
Authors: Iorio Anna Lisa , Da Ros Martina , Pisano Claudio , de Martino Maurizio , Genitori Lorenzo , Sardi Iacopo
Published: March 2019

Despite numerous clinical trials, glioblastoma (GBM) remains a tumor that is difficult to treat. The aim of this study was to investigate the potential of a new pharmacological approach, combining doxorubicin (Dox) and rapamycin (Rapa), in in vitro and in vivo GBM models. Cytotoxic and anti-proliferative effects of Rapa plus Dox treatments were analyzed in GBM cell lines. The in vivo effectiveness of these treatments was investigated in an orthotopic xenograft mice model of GBM. In vitro results demonstrated that prolonged exposure to Rapa sensitize GBM cells to Dox treatments. In vivo results demonstrated that Rapa (5 mg/kg) plus Dox (5 mg/kg) determined the major tumor growth inhibition (−97.29% vs. control) but results in greater toxicity. The combination Rapa plus Dox (2.5 mg/kg) showed a tumor inhibition like Rapa plus Dox (5 mg/kg) with a toxicity comparable to Rapa alone. Thus, this study demonstrated the efficacy of this pharmacological approach, providing the rationale for a clinical application of this combinational therapy in “poor-responder” GBM patients.
Maternal Venous Hemodynamic Dysfunction in Proteinuric Gestational Hypertension: Evidence and Implications
Authors: Gyselaers Wilfried
Published: March 2019

This review summarizes current knowledge from experimental and clinical studies on renal function and venous hemodynamics in normal pregnancy, in gestational hypertension (GH) and in two types of preeclampsia: placental or early-onset preeclampsia (EPE) and maternal or late-onset (LPE) preeclampsia, presenting at <34 weeks and ≥34 weeks respectively. In addition, data from maternal venous Doppler studies are summarized, showing evidence for (1) the maternal circulation functioning closer to the upper limits of capacitance than in non-pregnant conditions, with intrinsic risks for volume overload, (2) abnormal venous Doppler measurements obtainable in preeclampsia, more pronounced in EPE than LPE, however not observed in GH, and (3) abnormal venous hemodynamic function installing gradually from first to third trimester within unique pathways of general circulatory deterioration in GH, EPE and LPE. These associations have important clinical implications in terms of screening, diagnosis, prevention and management of gestational hypertensive diseases. They invite for further hypothesis-driven research on the role of retrograde venous congestion in the etiology of preeclampsia-related organ dysfunctions and their absence in GH, and also challenge the generally accepted view of abnormal placentation as the primary cause of preeclampsia. The striking similarity between abnormal maternal venous Doppler flow patterns and those observed at the ductus venosus and other abdominal veins of the intra-uterine growth restricted fetus, also invites to explore the role of venous congestion in the intra-uterine programming of some adult diseases.
How Effective Is Pulse Arrival Time for Evaluating Blood Pressure? Challenges and Recommendations from a Study Using the MIMIC Database
Authors: Liang Yongbo , Abbott Derek , Howard Newton , Lim Kenneth , Ward Rabab , Elgendi Mohamed
Published: March 2019

Cardiovascular disease (CVD) is the number one cause of non-infectious morbidity and mortality in the world. The detection, measurement, and management of high blood pressure play an essential role in the prevention and control of CVDs. However, owing to the limitations and discomfort of traditional blood pressure (BP) detection techniques, many new cuff-less blood pressure approaches have been proposed and explored. Most of these involve arterial wave propagation theory, which is based on pulse arrival time (PAT), the time interval needed for a pulse wave to travel from the heart to some distal place on the body, such as the finger or earlobe. For this study, the Medical Information Mart for Intensive Care (MIMIC) database was used as a benchmark for PAT analysis. Many researchers who use the MIMIC database make the erroneous assumption that all the signals are synchronized. Therefore, we decided to investigate the calculation of PAT intervals in the MIMIC database and check its usefulness for evaluating BP. Our findings have important implications for the future use of the MIMIC database, especially for BP evaluation.
A CFD-Based Frequency Response Method Applied in the Determination of Dynamic Coefficients of Hydrodynamic Bearings. Part 1: Theory
Authors: Snyder Troy , Braun Minel
Published: March 2019

A general, CFD-based frequency response method for obtaining the dynamic coefficients of hydrodynamic bearings is presented. The method is grounded in experimental parameter identification methods and is verified for an extremely long, slider bearing geometry as well as short and long journal bearing geometries. The influence of temporal inertia on the dynamic response of the bearings is discussed and quantified through the inclusion of added mass coefficients within the mechanical models of the hydrodynamic bearing films. Methods to separate the dynamic stiffness into static stiffness and added mass contributions are presented and their results compared. Harmonic perturbations are applied to the bearings at varying frequencies to determine the frequency dependence of the dynamic coefficients and to facilitate the decomposition of the dynamic stiffness into its constituents. Added mass effects are shown to be significant for the extremely long slider bearing geometry and negligible for the short and long journal bearing geometries under operating conditions motivated by those typical of marine bearings.
The Use of the Evenness of Eigenvalues of Similarity Matrices to Test for Predictivity of Ecosystem Classifications
Authors: Feoli Enrico , Ganis Paola
Published: March 2019

The use of the evenness (E(λ)) of the eigenvalues of similarity matrices corresponding to different hierarchical levels of ecosystem classifications, is suggested to test correlation (or predictivity) between biological communities and environmental factors as one alternative of analysis of variance (parametric or non-parametric). The advantage over traditional methods is the fact that similarity matrices can be obtained from any kind of data (mixed and missing data) by indices such as those of Goodall and Gower. The significance of E(λ) is calculated by permutation techniques. One example of application of E(λ) is given by a data set describing plant community types (beech forests of the Italian peninsula).
3D Visualization through the Hologram for the Learning of Area and Volume Concepts
Authors: Orcos Lara , Jordán Cristina , Magreñán Alberto
Published: March 2019

This study aims to implement and evaluate a methodological proposal using the hologram as a teaching medium for the learning of concepts related to areas and volumes of geometrical bodies. The study has been carried out with a sample of 78 students in the third year of secondary education from a privately-owned but state-funded school in Madrid. Thirty-five students who have been taught traditionally formed the control group, and 43 formed the experimental group in which the methodology was implemented. To evaluate its goodness, we have used the Student’s t-test to assess the existence of significant differences between both groups. The results reported by the test show that there is a difference of 3.9 points between the scores of both groups which is significant at the level of 0.05. In addition, the user experience in the experimental group has also been evaluated to assess the students’ opinions of the hologram in the learning process. The overall results have assisted us in corroborating the efficacy of the hologram as a teaching medium.
Fractional Calculus of Extended Mittag-Leffler Function and Its Applications to Statistical Distribution
Authors: Araci Serkan , Rahman Gauhar , Ghaffar Abdul , Azeema  , Nisar Kottakkaran Sooppy
Published: March 2019

Several fractional calculus operators have been introduced and investigated. In this sequence, we aim to establish the Marichev-Saigo-Maeda (MSM) fractional calculus operators and Caputo-type MSM fractional differential operators of extended Mittag-Leffler function (EMLF). We also investigate the statistical distribution associated with the EMLF. Finally, we derive some of the particular cases of the main results.
Review of Aluminum-To-Steel Welding Technologies for Car-Body Applications
Authors: Gullino Alessio , Matteis Paolo , D’Aiuto Fabio
Published: March 2019

Hybrid car bodies fabricated by joining parts made with steel and aluminum alloys are becoming increasingly common. This provides an affordable mean to decrease the car weight by using lighter or more advanced materials only where they can achieve the maximum benefit. This development is driven mainly by recent regulations on carbon dioxide emissions, and hinges on the deployment of effective joining technologies. In most cases, such technologies were not previously used in the car sector, and must be adapted to its requirements. Several dissimilar welding technologies, based on either fusion welding or solid-state welding, are reviewed here, focusing on dissimilar joining among steels and wrought aluminum alloys. These technologies are either presently being introduced in the car industry, or are used in other sectors and could be applied in the car industry in the near future.