bluuebunny/crossref_metadata_2025 huggingface dataset:
ER-Mitochondria Communication in Cells of the Innate Immune System
Authors: Namgaladze Dmitry , Khodzhaeva Vera , Brüne Bernhard
Published: September 2019

In cells the interorganelle communication comprises vesicular and non-vesicular mechanisms. Non-vesicular material transfer predominantly takes place at regions of close organelle apposition termed membrane contact sites and is facilitated by a growing number of specialized proteins. Contacts of the endoplasmic reticulum (ER) and mitochondria are now recognized to be essential for diverse biological processes such as calcium homeostasis, phospholipid biosynthesis, apoptosis, and autophagy. In addition to these universal roles, ER-mitochondria communication serves also cell type-specific functions. In this review, we summarize the current knowledge on ER-mitochondria contacts in cells of the innate immune system, especially in macrophages. We discuss ER- mitochondria communication in the context of macrophage fatty acid metabolism linked to inflammatory and ER stress responses, its roles in apoptotic cell engulfment, activation of the inflammasome, and antiviral defense.
Characteristics of in Vivo Model Systems for Ovarian Cancer Studies
Authors: Tudrej Patrycja , Kujawa Katarzyna Aleksandra , Cortez Alexander Jorge , Lisowska Katarzyna Marta
Published: September 2019

An understanding of the molecular pathogenesis and heterogeneity of ovarian cancer holds promise for the development of early detection strategies and novel, efficient therapies. In this review, we discuss the advantages and limitations of animal models available for basic and preclinical studies. The fruit fly model is suitable mainly for basic research on cellular migration, invasiveness, adhesion, and the epithelial-to-mesenchymal transition. Higher-animal models allow to recapitulate the architecture and microenvironment of the tumor. We discuss a syngeneic mice model and the patient derived xenograft model (PDX), both useful for preclinical studies. Conditional knock-in and knock-out methodology allows to manipulate selected genes at a given time and in a certain tissue. Such models have built our knowledge about tumor-initiating genetic events and cell-of-origin of ovarian cancers; it has been shown that high-grade serous ovarian cancer may be initiated in both the ovarian surface and tubal epithelium. It is postulated that clawed frog models could be developed, enabling studies on tumor immunity and anticancer immune response. In laying hen, ovarian cancer develops spontaneously, which provides the opportunity to study the genetic, biochemical, and environmental risk factors, as well as tumor initiation, progression, and histological origin; this model can also be used for drug testing. The chick embryo chorioallantoic membrane is another attractive model and allows the study of drug response.
A Hierarchical Gamma Mixture Model-Based Method for Classification of High-Dimensional Data
Authors: Azhar Muhammad , Li Mark Junjie , Zhexue Huang Joshua
Published: September 2019

Data classification is an important research topic in the field of data mining. With the rapid development in social media sites and IoT devices, data have grown tremendously in volume and complexity, which has resulted in a lot of large and complex high-dimensional data. Classifying such high-dimensional complex data with a large number of classes has been a great challenge for current state-of-the-art methods. This paper presents a novel, hierarchical, gamma mixture model-based unsupervised method for classifying high-dimensional data with a large number of classes. In this method, we first partition the features of the dataset into feature strata by using k-means. Then, a set of subspace data sets is generated from the feature strata by using the stratified subspace sampling method. After that, the GMM Tree algorithm is used to identify the number of clusters and initial clusters in each subspace dataset and passing these initial cluster centers to k-means to generate base subspace clustering results. Then, the subspace clustering result is integrated into an object cluster association (OCA) matrix by using the link-based method. The ensemble clustering result is generated from the OCA matrix by the k-means algorithm with the number of clusters identified by the GMM Tree algorithm. After producing the ensemble clustering result, the dominant class label is assigned to each cluster after computing the purity. A classification is made on the object by computing the distance between the new object and the center of each cluster in the classifier, and the class label of the cluster is assigned to the new object which has the shortest distance. A series of experiments were conducted on twelve synthetic and eight real-world data sets, with different numbers of classes, features, and objects. The experimental results have shown that the new method outperforms other state-of-the-art techniques to classify data in most of the data sets.
Parameter Optimization Based BPNN of Atmosphere Continuous-Variable Quantum Key Distribution
Authors: Su Yu , Guo Ying , Huang Duan
Published: September 2019

The goal of continuous variable quantum key distribution (CVQKD) is to be diffusely used and adopted in diverse scenarios, so the adhibition of atmospheric channel will play a crucial part in constituting global secure quantum communications. Atmospheric channel transmittance is affected by many factors and does not vary linearly, leading to great changes in signal-to-noise ratio. It is crucial to choose the appropriate modulation variance under different turbulence intensities to acquire the optimal secret key rate. In this paper, the four-state protocol, back-propagation neural network (BPNN) algorithm was discussed in the proposed scheme. We employ BPNN to CVQKD, which could adjust the modulation variance to an optimum value for ensuring the system security and making the system performance optimal. The numerical results show that the proposed scheme is equipped to improve the secret key rate efficiently.
Lossless Contrast Enhancement of Color Images with Reversible Data Hiding
Authors: Wu Hao-Tian , Wu Yue , Guan Zhihao , Cheung Yiu-ming
Published: September 2019

Recently, lossless contrast enhancement (CE) has been proposed so that a contrast-changed image can be converted to its original version by maintaining information entropy in it. As most of the lossless CE methods are proposed for grayscale images, artifacts are probably introduced after directly applying them to color images. For instance, color distortions may be caused after CE is separately conducted in each channel of the RGB (red, green, and blue) model. To cope with this issue, a new scheme is proposed based on the HSV (hue, saturation, and value) color model. Specifically, both hue and saturation components are kept unchanged while only the value component is modified. More precisely, the ratios between the RGB components are maintained while a reversible data hiding method is applied to the value component to achieve CE effects. The experimental results clearly show CE effects obtained with the proposed scheme, while the original color images can be perfectly recovered. Several metrics including image entropy were adopted to measure the changes made in CE procedure, while the performances were compared with those of one existing scheme. The evaluation results demonstrate that better image quality and increased information entropy can be simultaneously achieved with our proposed scheme.
Robust Current Predictive Control-Based Equivalent Input Disturbance Approach for PMSM Drive
Authors: Liu Xudong , Zhang Qi
Published: September 2019

The implementation and experimental validation of current control strategy based on predictive control and equivalent input disturbance approach is discussed for permanent magnet synchronous motor (PMSM) control system in the paper. First, to realize the current decoupling control, the deadbeat predictive current control technique is adopted in the current loop of PMSM. Indeed, it is well known that the traditional deadbeat current control cannot completely reject the disturbance and realize the zero error current tracking control. Then, according to the model uncertainties and the parameter variations in the motor, an equivalent input disturbance approach is introduced to estimate the lump disturbance in the system, which will be used in the feed-forward compensation. Thus, a compound current controller is designed, and the proposed algorithm reduces the tracking error caused by the disturbance; the robustness of the drive system is improved effectively. Finally, simulation and experiment are accomplished on the control prototype, and the results show the effectiveness of the proposed current control algorithm.
Optimal Scheduling of a Multi-Energy Power System with Multiple Flexible Resources and Large-Scale Wind Power
Authors: Che Quanhui , Lou Suhua , Wu Yaowu , Zhang Xiangcheng , Wang Xuebin
Published: September 2019

With the grid-connected operation of large-scale wind farms, the contradiction between supply and demand of power systems is becoming more and more prominent. The introduction of multiple types of flexible resources provides a new technical means for improving the supply–demand matching relationship of system flexibility and promoting wind power consumption. In this paper, multi-type flexible resources made up of deep peak regulation of thermal units, demand response, and energy storage were utilized to alleviate the peak regulation pressure caused by large-scale wind power integration. Based on current thermal plant deep peak regulation technology, a three-phase peak regulation cost model of thermal power generation considering the low load fatigue life loss and oil injection cost of the unit was proposed. Additionally, from the perspective of supply–demand balance of power system flexibility, the flexibility margin index of a power system containing source-load-storage flexible resources was put forward to assess the contribution from each flexibility provider to system flexibility. Moreover, an optimal dispatching model of a multi-energy power system with large-scale wind power and multi-flexible resources was constructed, aimed at the lowest total dispatching cost of the whole scheduling period. Finally, the model proposed in this paper was validated by a modified RTS96 system, and the effects of different flexibility resources and wind power capacity on the optimal scheduling results were discussed.
Advection-Based Coordinated Control for Wave-Energy Converter Array
Authors: Li Hong , Zhang Bo , Qiu Li , Chen Shiyu , Yuan Jianping , Luo Jianjun
Published: September 2019

This paper presents a coordinated control based on the advection consensus control algorithm to implement power dispatch for each wave-energy converter (WEC) in a WEC array. Under unbalanced conditions, the proposed algorithm is applied in order to control each WEC to output power coordinately, to enable the total output power of the WEC array to satisfy the time-varying load requirements. The purpose of the additional energy storage unit on each WEC is to smooth the power output of each WEC and to obtain more margin. Case studies include the demonstration of some simulations and experiments, and the results show that the WEC array under the proposed control method can accurately respond to the demand for power supply under unbalanced initial conditions.
Barriers, Driving Forces and Non-Energy Benefits for Battery Storage in Photovoltaic (PV) Systems in Modern Agriculture
Authors: Lane Anna-Lena , Boork Magdalena , Thollander Patrik
Published: September 2019

Battery storage has been highlighted as one way to increase the share of renewables in energy systems. The use of local battery storage is also beneficial when reducing power variations in the grid, thereby contributing to more robust and cost-effective energy systems. The purpose of this paper is to investigate barriers, drivers and non-energy benefits (NEB) for investments in battery storage in photovoltaic systems (PV) in the context of farmers with PV systems in Sweden. The study is based on a questionnaire about barriers, driving forces and NEB for investment in battery storage connected to PV. The questionnaire was sent to farmers in Sweden who already have photovoltaics installed and about 100 persons answered, a response rate of 59%. The major barriers found are related to the technical and economic risks of investing in battery storage. One of the main conclusions is that the highest-ranked driver, i.e., to use a larger part of the produced electricity oneself, turns out to be the highest priority for the grid-owner seeking to reduce the need for extensive investments in the grid. The primary NEBs found were the possibility of becoming independent from grid electricity.
Day Ahead Hourly Global Horizontal Irradiance Forecasting—Application to South African Data
Authors: Mpfumali Phathutshedzo , Sigauke Caston , Bere Alphonce , Mulaudzi Sophie
Published: September 2019

Due to its variability, solar power generation poses challenges to grid energy management. In order to ensure an economic operation of a national grid, including its stability, it is important to have accurate forecasts of solar power. The current paper discusses probabilistic forecasting of twenty-four hours ahead of global horizontal irradiance (GHI) using data from the Tellerie radiometric station in South Africa for the period August 2009 to April 2010. Variables are selected using a least absolute shrinkage and selection operator (Lasso) via hierarchical interactions and the parameters of the developed models are estimated using the Barrodale and Roberts’s algorithm. Two forecast combination methods are used in this study. The first is a convex forecast combination algorithm where the average loss suffered by the models is based on the pinball loss function. A second forecast combination method, which is quantile regression averaging (QRA), is also used. The best set of forecasts is selected based on the prediction interval coverage probability (PICP), prediction interval normalised average width (PINAW) and prediction interval normalised average deviation (PINAD). The results demonstrate that QRA gives more robust prediction intervals than the other models. A comparative analysis is done with two machine learning methods—stochastic gradient boosting and support vector regression—which are used as benchmark models. Empirical results show that the QRA model yields the most accurate forecasts compared to the machine learning methods based on the probabilistic error measures. Results on combining prediction interval limits show that the PMis the best prediction limits combination method as it gives a hit rate of 0.955 which is very close to the target of 0.95. This modelling approach is expected to help in optimising the integration of solar power in the national grid.
Drought Enhances the Role of Competition in Mediating the Relationship between Tree Growth and Climate in Semi-Arid Areas of Northwest China
Authors: Lu Kanglong , Chen Ning , Zhang Cankun , Dong Xiaoxue , Zhao Changming
Published: September 2019

Climate variability can exert a powerful impact on biotic competition, but past studies have focused largely on short-lived species, with a lack of attention to long-lived species such as trees. Therefore, there is a need to evaluate how competition regulates the climate-growth relationship in mature trees. We sampled the dominant tree species, Picea wilsonii Mast., on Xinglong Mountain, China, and studied the above issues by analyzing the relationship between tree radial growth, precipitation, and competition. In relatively wet years (precipitation > average), there was no significant difference in climate sensitivity between different competition classes. However, trees suffering from highly competitive stress were more sensitive to climate variability in all years, and particularly in the subset of years that was relatively drought (precipitation < average). These results suggest that competition enhances its ability to regulate tree growth response to climate variability in adverse weather conditions. Competition for resources between trees was asymmetrical, and an increase in height could give trees a disproportionate benefit. Thus, at trunk-level, both basal area incremental growth and intrinsic water-use efficiency of trees subjected to low competitive stress were significantly higher than trees that are subjected to highly competitive stress. Although the intrinsic water-use efficiency of trees under highly competitive stress increased more rapidly as the drought level increases, this did not change the fact that the radial growth of them declined more. Our research is valuable for the development of individual-tree growth models and advances our understanding for forest management under global climate change.
The Pituitary Transcriptional Response Related to Feed Conversion in Pigs
Authors: Piórkowska Katarzyna , Żukowski Kacper , Tyra Mirosław , Szyndler-Nędza Magdalena , Szulc Karolina , Skrzypczak Ewa , Ropka-Molik Katarzyna
Published: September 2019

Over the decades, pig breeding objectives have focused on improving the meat content in the carcass without taking into consideration the more effective fattening indicators that affect feed conversion. At present, pig growth traits associated particularly with animal feeding have become crucial due to their economic significance. This is especially evident in countries where pigs are maintained on large farms. The present study indicates that pituitary differentially expressed genes (DEGs) are activated in response to variable feed conversion (FC) in pigs. The experiment included two native Polish breeds: Puławska and Złotnicka White (ZW). The whole pituitary transcriptome was sequenced using next-generation sequencing (NGS) technology. The RNA-seq method identified over 500 and 300 DEGs in the pituitaries of the ZW and the Puławska pig populations, respectively, that were associated with hormonal regulation, notch signaling, and Wnt pathways. Lower FC in the ZW pigs favoured increased fat content in the body and significantly higher prolactin expression. The obtained results indicate that low FC values in pigs are related to slower growth or increased fat content, which suggests various pituitary responses. Therefore, the identified candidate genes were not directly associated with feed conversion values but with other factors. However, the present study delivers new insights into pituitary regulation in pigs.
The Universal 3D QSAR Model for Dopamine D2 Receptor Antagonists
Authors: Zięba Agata , Żuk Justyna , Bartuzi Damian , Matosiuk Dariusz , Poso Antti , Kaczor Agnieszka A.
Published: September 2019

In order to search for novel antipsychotics acting through the D2 receptor, it is necessary to know the structure–activity relationships for dopamine D2 receptor antagonists. In this context, we constructed the universal three-dimensional quantitative structure–activity relationship (3D- QSAR) model for competitive dopamine D2 receptor antagonists. We took 176 compounds from chemically different groups characterized by the half maximal inhibitory concentration (IC50)from the CHEMBL database and docked them to the X-ray structure of the human D2 receptor in the inactive state. Selected docking poses were applied for Comparative Molecular Field Analysis (CoMFA) alignment. The obtained CoMFA model is characterized by a cross-validated coefficient Q2 of 0.76 with an optimal component of 5, R2 of 0.92, and an F value of 338.9. The steric and electrostatic field contributions are 67.4% and 32.6%, respectively. The statistics obtained prove that the CoMFA model is significant. Next, the IC50 of the 16 compounds from the test set was predicted with R2 of 0.95. Finally, a progressive scrambling test was carried out for additional validation. The CoMFA fields were mapped onto the dopamine D2 receptor binding site, which enabled a discussion of the structure–activity relationship based on ligand–receptor interactions. In particular, it was found that one of the desired steric interactions covers the area of a putative common allosteric pocket suggested for some other G protein-coupled receptors (GPCRs), which would suggest that some of the known dopamine receptor antagonists are bitopic in their essence. The CoMFA model can be applied to predict the potential activity of novel dopamine D2 receptor antagonists.
Design, Synthesis, and Anti-Bacterial Evaluation of Triazolyl-Pterostilbene Derivatives
Authors: Tang Kai-Wei , Yang Shih-Chun , Tseng Chih-Hua
Published: September 2019

Staphylococcus aureus resistance to current antibiotics has become the greatest global challenge facing public health. The development of new antimicrobial agents is urgent and important and is needed to provide additional therapeutic options. In our previous study, we found out that pterostilbene exhibited potent antibacterial activity, especially against methicillin-resistant Staphylococcus aureus (MRSA). According to previous studies, 1,2,3-triazole, with the characteristic of increasing the interaction with the target readily and enhancing water solubility, were widely used in the approved anti-bacterial drugs. Therefore, these results attract our interest to use the structure of pterostilbene as a scaffold for the hybrid 1,2,3-triazole moiety to develop a novel anti-MRSA infection agent. In this study, we demonstrated the design and synthesis of a series of triazolylpterostilbene derivatives. Among these compounds, compound 4d exhibited the most potent anti-MRSA activity with a minimum inhibitory concentration (MIC) value of 1.2–2.4 μg/mL and a minimum bactericidal concentration (MBC) value of 19.5–39 μg/mL. The structure–activity relationship and antibacterial mechanism were investigated in this study. Molecular docking studies were carried out to verify and rationalize the biological results. In this study, the results confirmed that our design could successfully increase the inhibitory activity and specificity against MRSA. Compound 4d could be used as a candidate for anti-bacterial agents and in depth vivo studies should be further investigated.
Genome-Wide Analysis Reveals the Role of Mediator Complex in the Soybean—Phytophthora sojae Interaction
Authors: Xue Dong , Guo Na , Zhang Xiao-Li , Zhao Jin-Ming , Bu Yuan-Peng , Jiang Dian-Liang , Wang Xiao-Ting , Wang Hai-Tang , Guan Rong-Zhan , Xing Han
Published: September 2019

The mediator complex is an essential link between transcription factors and RNA polymerase II, and mainly functions in the transduction of diverse signals to genes involved in different pathways. Limited information is available on the role of soybean mediator subunits in growth and development, and their participation in defense response regulation. Here, we performed genome-wide identification of the 95 soybean mediator subunits, which were unevenly localized on the 20 chromosomes and only segmental duplication events were detected. We focused on GmMED16-1, which is highly expressed in the roots, for further functional analysis. Transcription of GmMED16-1 was induced in response to Phytophthora sojae infection. Agrobacterium rhizogenes mediated soybean hairy root transformation was performed for the silencing of the GmMED16-1 gene. Silencing of GmMED16-1 led to an enhanced susceptibility phenotype and increased accumulation of P. sojae biomass in hairy roots of transformants. The transcript levels of NPR1, PR1a, and PR5 in the salicylic acid defense pathway in roots of GmMED16-1-silenced transformants were lower than those of empty-vector transformants. The results provide evidence that GmMED16-1 may participate in the soybean–P. sojae interaction via a salicylic acid-dependent process.
Co-Operation between Aneuploidy and Metabolic Changes in Driving Tumorigenesis
Authors: Newman David L. , Gregory Stephen L.
Published: September 2019

Alterations from the normal set of chromosomes are extremely common as cells progress toward tumourigenesis. Similarly, we expect to see disruption of normal cellular metabolism, particularly in the use of glucose. In this review, we discuss the connections between these two processes: how chromosomal aberrations lead to metabolic disruption, and vice versa. Both processes typically result in the production of elevated levels of reactive oxygen species, so we particularly focus on their role in mediating oncogenic changes.
Glycan Binding Profiling of Jacalin-Related Lectins from the Pteria Penguin Pearl Shell
Authors: Ogawa Tomohisa , Sato Rie , Naganuma Takako , Liu Kayeu , Lakudzala Agness Ethel , Muramoto Koji , Osada Makoto , Yoshimi Kyosuke , Hiemori Keiko , Hirabayashi Jun , Tateno Hiroaki
Published: September 2019

We determined the primary structures of jacalin-related lectins termed PPL3s (PPL3A, 3B, and 3C, which are dimers consisting of sequence variants α + α, α + β, β + β, respectively) and PPL4, which is heterodimer consisting of α + β subunits, isolated from mantle secretory fluid of Pteria penguin (Mabe) pearl shell. Their carbohydrate-binding properties were analyzed, in addition to that of PPL2A, which was previously reported as a matrix protein. PPL3s and PPL4 shared only 35–50% homology to PPL2A, respectively; they exhibited significantly different carbohydrate-binding specificities based on the multiple glycan binding profiling data sets from frontal affinity chromatography analysis. The carbohydrate-binding specificity of PPL3s was similar to that of PPL2A, except only for Man3Fuc1Xyl1GlcNAc2 oligosaccharide, while PPL4 showed different carbohydrate-binding specificity compared with PPL2A and PPL3s. PPL2A and PPL3s mainly recognize agalactosylated- and galactosylated-type glycans. On the other hand, PPL4 binds to high-mannose-and hybrid-type N-linked glycans but not agalactosylated- and galactosylated-type glycans.
Regenerative Potential of the Product “CardioCell” Derived from the Wharton’s Jelly Mesenchymal Stem Cells for Treating Hindlimb Ischemia
Authors: Musiał-Wysocka Aleksandra , Kot Marta , Sułkowski Maciej , Majka Marcin
Published: September 2019

In recent years, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality in regenerative medicine. They hold great promise for treating civilization-wide diseases, including cardiovascular diseases, such as acute myocardial infarction and critical limb ischemia. MSCs isolated from Wharton’s jelly (WJ-MSCs) may be utilized in both cell-based therapy and vascular graft engineering to restore vascular function, thereby providing therapeutic benefits for patients. The efficacy of WJ-MSCs lies in their multipotent differentiation ability toward vascular smooth muscle cells, endothelial cells and other cell types, as well as their capacity to secrete various trophic factors, which are potent in promoting angiogenesis, inhibiting apoptosis and modulating immunoreaction. Ischemic limb disease is caused by insufficient nutrient and oxygen supplies resulting from damaged peripheral arteries. The lack of nutrients and oxygen causes severe tissue damage in the limb, thereby resulting in severe morbidities and mortality. The therapeutic effects of the conventional treatments are still not sufficient. Cell transplantations in small animal model (mice) are vital for deciphering the mechanisms of MSCs’ action in muscle regeneration. The stimulation of angiogenesis is a promising strategy for the treatment of ischemic limbs, restoring blood supply for the ischemic region. In the present study, we focus on the therapeutic properties of the human WJ-MSCs derived product, Cardio. We investigated the role of CardioCell in promoting angiogenesis and relieving hindlimb ischemia. Our results confirm the healing effect of CardioCell and strongly support the use of the WJ-MSCs in regenerative medicine.
NK Cells as Potential Targets for Immunotherapy in Endometriosis
Authors: Ścieżyńska Aneta , Komorowski Michał , Soszyńska Marta , Malejczyk Jacek
Published: September 2019

Endometriosis is a common gynecological disease defined by the presence of endometrial-like tissue outside the uterus, most frequently on the pelvic viscera and ovaries, which is associated with pelvic pains and infertility. It is an inflammatory disorder with some features of autoimmunity. It is accepted that ectopic endometriotic tissue originates from endometrial cells exfoliated during menstruation and disseminating into the peritoneum by retrograde menstrual blood flow. It is assumed that the survival of endometriotic cells in the peritoneal cavity may be partially due to their abrogated elimination by natural killer (NK) cells. The decrease of NK cell cytotoxic activity in endometriosis is associated with an increased expression of some inhibitory NK cell receptors. It may be also related to the expression of human leukocyte antigen G (HLA-G), a ligand for inhibitory leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) receptors. The downregulated cytotoxic activity of NK cells may be due to inhibitory cytokines present in the peritoneal milieu of patients with endometriosis. The role of NK cell receptors and their ligands in endometriosis is also confirmed by genetic association studies. Thus, endometriosis may be a subject of immunotherapy by blocking NK cell negative control checkpoints including inhibitory NK cell receptors. Immunotherapies with genetically modified NK cells also cannot be excluded.
Common Variants in 22 Genes Regulate Response to Metformin Intervention in Children with Obesity: A Pharmacogenetic Study of a Randomized Controlled Trial
Authors: Anguita-Ruiz Augusto , Pastor-Villaescusa Belén , Leis Rosaura , Bueno Gloria , Hoyos Raúl , Vázquez-Cobela Rocío , Latorre-Millán Miriam , Cañete M. Dolores , Caballero-Villarraso Javier , Gil Ángel , Cañete Ramón , Aguilera Concepción M.
Published: September 2019

Metformin is a first-line oral antidiabetic agent that has shown additional effects in treating obesity and metabolic syndrome. Inter-individual variability in metformin response could be partially explained by the genetic component. Here, we aimed to test whether common genetic variants can predict the response to metformin intervention in obese children. The study was a multicenter and double-blind randomized controlled trial that was stratified according to sex and pubertal status in 160 children with obesity. Children were randomly assigned to receive either metformin (1g/d) or placebo for six months after meeting the defined inclusion criteria. We conducted a post hoc genotyping study in 124 individuals (59 placebo, 65 treated) comprising finally 231 genetic variants in candidate genes. We provide evidence for 28 common variants as promising pharmacogenetics regulators of metformin response in terms of a wide range of anthropometric and biochemical outcomes, including body mass index (BMI) Z-score, and glucose, lipid, and inflammatory traits. Although no association remained statistically significant after multiple-test correction, our findings support previously reported variants in metformin transporters or targets as well as identify novel and promising loci, such as the ADYC3 and the BDNF genes, with plausible biological relation to the metformin’s action mechanism. Trial Registration: Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011 (URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023061-21/ES).
A Novel Ex Vivo System Using 3D Polymer Scaffold to Culture Circulating Tumor Cells from Breast Cancer Patients Exhibits Dynamic E-M Phenotypes
Authors: De Tamasa , Goyal Shina , Balachander Gowri , Chatterjee Kaushik , Kumar Prashant , Babu K. Govind , Rangarajan Annapoorni
Published: September 2019

The majority of the cancer-associated deaths is due to metastasis—the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a new prognostic and diagnostic marker, as well as a screening tool for patients with metastatic disease. However, very little is known about the biology of CTCs in cancer metastasis. An increased understanding of CTC biology, their heterogeneity, and interaction with other cells can help towards a better understanding of the metastatic process, as well as identify novel drug targets. Here we present a novel ex vivo 3D system for culturing CTCs from breast cancer patient blood samples using porous poly(ε-caprolactone) (PCL) scaffolds. As a proof of principle study, we show that ex vivo culture of 12/16 (75%) advanced stage breast cancer patient blood samples were enriched for CTCs identified as CK+ (cytokeratin positive) and CD45− (CD45 negative) cells. The deposition of extracellular matrix proteins on the PCL scaffolds permitted cellular attachment to these scaffolds. Detection of Ki-67 and bromodeoxyuridine (BrdU) positive cells revealed proliferating cell population in the 3D scaffolds. The CTCs cultured without prior enrichment exhibited dynamic differences in epithelial (E) and mesenchymal (M) composition. Thus, our 3D PCL scaffold system offers a physiologically relevant model to be used for studying CTC biology as well as for individualized testing of drug susceptibility. Further studies are warranted for longitudinal monitoring of epithelial–mesenchymal transition (EMT) in CTCs for clinical association.
Characterization and Mechanical Proprieties of New TiMo Alloys Used for Medical Applications
Authors: Sandu Andrei Victor , Baltatu Madalina Simona , Nabialek Marcin , Savin Adriana , Vizureanu Petrica
Published: September 2019

Ti-based alloys are accessible for use in the human body due to their good mechanical properties, corrosion resistance, and biocompatibilities. These main properties of alloys are important criteria for choosing biomedical implants for human bones or for other kinds of applications in general medicine. This paper presents a comparison of four new Ti-based alloys desired to satisfy various requirements for biomedical implants. The materials were prepared with recipes for two new system alloys, TiMoZrTa (TMZT) and TiMoSi (TMS), alloys with nontoxic elements. The presented research contains microstructure images, indentation tests, Vickers hardness, XRD, and corrosion resistance, showing better characteristics than most commercial products used as implants (Young’s modulus closer to the human bone).
Studying Grain Boundary Strengthening by Dislocation-Based Strain Gradient Crystal Plasticity Coupled with a Multi-Phase-Field Model
Authors: Amin Waseem , Ali Muhammad , Vajragupta Napat , Hartmaier Alexander
Published: September 2019

One ambitious objective of Integrated Computational Materials Engineering (ICME) is to shorten the materials development cycle by using computational materials simulation techniques at different length scales. In this regard, the most important aspects are the prediction of the microstructural evolution during material processing and the understanding of the contributions of microstructural features to the mechanical response of the materials. One possible solution to such a challenge is to apply the Phase Field (PF) method because it can predict the microstructural evolution under the influence of different internal or external stimuli, including deformation. To accomplish this, it is necessary to take into account plasticity or, specifically, non-homogeneous plastic deformation, which is particularly important for investigating the size effects in materials emerging at the micron length scale. In this work, we present quasi-2D simulations of plastic deformation in a face centred cubic system using a finite strain formulation. Our model consists of dislocation-based strain gradient crystal plasticity implemented into a PF code. We apply this model to study the influence of grain size on the mechanical behavior of polycrystals, which includes dislocation storage and annihilation. Furthermore, the initial state of the material before deformation is also considered. The results show that a dislocation-based strain gradient crystal plasticity model can capture the Hall-Petch effect in many aspects. The model reproduced the correct functional dependence of the flow stress of the polycrystal on grain size without assigning any special properties to the grain boundaries. However, the predicted Hall-Petch coefficients are significantly smaller than those found typically in experiments. In any case, we found a good qualitative agreement between our findings and experimental results.
Flexural Wave Propagation in Mass Chain-Filled Carbon Nanotubes
Authors: Liu Rumeng , Zhao Junhua , Wang Lifeng
Published: September 2019

The propagation characteristics of terahertz (THz) flexural waves in mass chain-filled single-walled carbon nanotubes (MCSCs) are studied using a continuum mechanics approach and molecular dynamics (MD) simulations, where each single-walled carbon nanotube (SWCNT) is modeled as a nonlocal Timoshenko beam based on the nonlocal strain gradient theory. The effect of the surrounding elastic medium and the van der Waals (vdW) interactions between the mass chain and the SWCNT on the wave propagation is quantitatively considered in governing equations, respectively. The analytical expressions of two flexural wave branches and the bandgap between the two branches are derived. When combining our MD simulations of the carbon-atom chain-filled SWCNT, the wave within the bandgap disperses rapidly, and the mass chain has a significant influence on the phase velocity of the flexural wave. The present theoretical solution has a high accuracy in a wide frequency range up to the THz region. In particular, the surrounding elastic medium of the MCSCs remarkably affects the phase velocity for low frequencies, but not for high frequencies. The present study indicates that the wave propagation of a SWCNT could be modulated by changing the filled mass chain and the surrounding elastic medium.
A Monolithic Gimbal Micro-Mirror Fabricated and Remotely Tuned with a Femtosecond Laser
Authors: Nazir Saood Ibni , Bellouard Yves
Published: September 2019

With the advent of ultrafast lasers, new manufacturing techniques have come into existence. In micromachining, the use of femtosecond lasers not only offers the possibility for three-dimensional monolithic fabrication inside a single optically transparent material, but also a means for remotely, and arbitrarily, deforming substrates with nanometer resolution. Exploiting this principle and combining it with flexure design, we demonstrate a monolithic micro-mirror entirely made with a femtosecond laser and whose orientation is tuned in a non-contact manner by exposing some part of the device to low energy femtosecond pulses. Given the non-contact nature of the process, the alignment can be very precisely controlled with a resolution that is many orders of magnitude better than conventional techniques based on mechanical positioners.
Integration of Horizontal and Vertical Microfluidic Modules for Core-Shell Droplet Generation and Chemical Application
Authors: Yoon Dong , Nozaki Yoshito , Tanaka Daiki , Sekiguchi Tetsushi , Shoji Shuichi
Published: September 2019

This paper presents a method for utilizing three-dimensional microfluidic channels fully to realize multiple functions in a single device. The final device structure was achieved by combining three independent modules that consisted of horizontal and vertical channels. The device allowed for the one-step generation of water-in-oil-in-water droplets without the need for partial treatment of the polydimethylsiloxane channel surface using separate modules for generating water-in-oil droplets on the horizontal plane and oil-in-water droplets on the vertical plane. The second vertically structured module provided an efficient flow for the generation of highly wettable liquid droplets, and tuning of the first horizontally structured module enabled different modes of inner-core encapsulation within the oil shell. The successful integration of the vertical and horizontal channels for core-shell droplet generation and the chemical synthesis of a metal complex within the droplets were evaluated. The proposed approach of integrating independent modules will expand and enhance the functions of microfluidic platforms.
Cord-Based Microfluidic Chips as A Platform for ELISA and Glucose Assays
Authors: Elomaa Jenny , Gallegos Laura , Gomez Frank A.
Published: September 2019

This paper describes the development and application of microfluidic cord-based analytical devices (µCADs) in two enzyme-linked immunosorbent assays (ELISAs) and glucose assay. In this study, biotinylated goat anti-mouse immunoglobulin (IgG) antibody, rabbit IgG antibody, and glucose are quantitatively detected. In the ELISA systems, the antibody is spotted on the cord at the detection site and a series of washes, followed by streptavidin-alkaline phosphatase (Strep-ALP) or alkaline phosphatase (ALP)-conjugated secondary antibody and colorimetric substrate, completing the experiment. The devices are subsequently scanned and analyzed yielding a correlation between inverse yellow or inverse blue intensity and antibody concentration. For the first ELISA, a linear range of detection was observed at lower concentrations (2.50 × 10−4–1.75 × 10−3 mg/mL) of Strep-ALP with saturation of the enzyme achieved at higher concentrations (>2.50 × 10−4). For the second ELISA, the L50 was demonstrated to be 167.6 fmol/zone. The glucose assay consisted of spotting increasing concentrations of glucose on the analysis sites and transporting, via capillary action, a solution containing glucose oxidase (GOx), horseradish peroxidase (HRP), and potassium iodide (KI) to the detection sites realizing a yellow-brown color indicating oxidation of iodide to iodine. The device was then dried, scanned, and analyzed to show the correlation between yellow inverse intensity and glucose. Glucose in artificial urine showed good correlation using the devices.
LC–MS/MS Method for Simultaneous Determination of Linarin and Its Metabolites in Rat Plasma and Liver Tissue Samples: Application to Pharmacokinetic and Liver Tissue Distribution Study After Oral Administration of Linarin
Authors: Li Yang , Guang Chenxi , Zhao Na , Feng Xinchi , Qiu Feng
Published: September 2019

Linarin, a flavone glycoside, is considered to be a promising natural product due to its diverse pharmacological activities. Recently, it has been brought into focus for its potential to treat liver failure. In this study, a rapid and sensitive liquid chromatography electrospray-ionization tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of linarin and its three metabolites (acacetin, apigenin, and p-hydroxy benzaldehyde) in plasma and liver tissue samples of normal rats and rats with d-galactosamine (d-GalN)-induced liver injury. After liquid–liquid extraction (LLE) with ethyl acetate, chromatographic separation of the four analytes was achieved using an ACQUITY UPLC BEH-C18 (1.7 μm, 2.1 × 50 mm) with a mobile phase of 0.01% formic acid in methanol and 0.01% formic acid at a flow rate of 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer via an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in the negative ionization mode. The method had a good linearity over the concentration range of 1.00–200 ng/mL for linarin and its metabolites. The validated method was successfully applied to the pharmacokinetic and liver tissue distribution study of linarin and its metabolites after a single oral administration of linarin (90 mg/kg) to rats.
Synthesis of 1,2,3-Triazolium Ionic Liquid-Supported Chiral Imidazolidinones and Their Application in Asymmetric Alkylation Reaction
Authors: Jeong Yunkyung , Park Yunjeong , Ryu Jae-Sang
Published: September 2019

New 1,2,3-triazolium ionic liquid-supported chiral imidazolidinones were developed. The feasibility of the ionic liquid-supported imidazolidinones as chiral auxiliaries was demonstrated in sequential propionylation-alkylation-cleavage reactions, which provided the chiral product with good to excellent chemical yields (up to 90%) and high selectivities (up to 94% ee). The progress of the reactions could be monitored by TLC and NMR, and the ionic liquid-supported chiral auxiliaries could be recovered by simple extraction.
Supercritical Carbon Dioxide (scCO2) Extraction of Phenolic Compounds from Lavender (Lavandula angustifolia) Flowers: A Box-Behnken Experimental Optimization
Authors: Tyśkiewicz Katarzyna , Konkol Marcin , Rój Edward
Published: September 2019

Due to their numerous health benefits associated with various diseases and anti-oxidation properties, the phenolic compounds collectively referred to as phytochemicals have attracted a lot of interest, however, a single extraction method for polyphenols has not been developed yet. Supercritical fluid extraction, a green extraction method, provides the final product without organic solvent residues. In this work the extraction of lavender was performed using supercritical carbon dioxide. A statistical experimental design based on the Box-Behnken (B-B) method was planned, and the extraction yields and total phenolic contents were measured for three different variables: pressure, temperature and extraction time. The ranges were 200–300 bar, 40–60 °C and 15–45 min. The extracts yields from scCO2 extraction were in the range of 4.3–9.2 wt.%. The highest yield (9.2 wt.%) was achieved at a temperature of 60 °C under the pressure of 250 bar after 45 min. It also corresponded to the highest total phenolic content (10.17 mg GAE/g extract). Based on the study, the statistically generated optimal extraction conditions to obtain the highest total phenolic compounds concentration from flowers of Lavandula angustifolia were a temperature of 54.5 °C, pressure of 297.9 bar, and the time of 45 min. Based on the scavenging activity percentage (AA%) of scCO2 extracts, it is concluded that the increase of extraction pressure had a positive influence on the increase of AA% values.
A Novel One-Dimensional Porphyrin-Based Covalent Organic Framework
Authors: Zhang Miao , Zheng Ruijin , Ma Ying , Chen Ruiping , Sun Xun , Sun Xuan
Published: September 2019

A novel one-dimensional covalent organic framework (COF-K) was firstly designed and synthesized through a Schiff-based reaction from a porphyrin building block and a nonlinear right-angle building block. The COF-K exhibited high BET surface area and narrow pore size of 1.25 nm and gave a CO2 adsorption capacity of 89 mg g−1 at 273K and 1bar.
Zinc Oxide Nanoparticles Cytotoxicity and Release from Newly Formed PMMA–ZnO Nanocomposites Designed for Denture Bases
Authors: Cierech Mariusz , Wojnarowicz Jacek , Kolenda Adam , Krawczyk-Balska Agata , Prochwicz Emilia , Woźniak Bartosz , Łojkowski Witold , Mierzwińska-Nastalska Elżbieta
Published: September 2019

The goal of the study was to investigate the level of zinc oxide nanoparticles (ZnO NPs) release from polymethyl methacrylate (PMMA)–ZnO nanocomposites (2.5%, 5%, and 7.5% w/w), as well as from the ZnO NPs layer produced on pure PMMA, and the impact of the achieved final ZnO NPs concentration on cytotoxicity, before the potential use as an alternative material for denture bases. The concentration of ZnO nanoparticles released to the aqueous solution of Zn2+ ions was assessed using optical emission spectrometry with inductively coupled plasma (ICP-OES). In the control group (pure PMMA), the released mean for ZnO was 0.074 mg/L and for individual nanocomposites at concentrations of 2.5%, 5%, and 7.5% was 2.281 mg/L, 2.143 mg/L, and 3.512 mg/L, respectively. The median for the ZnO NPs layer produced on PMMA was 4.878 mg/L. In addition, in vitro cytotoxicity of ZnO NPs against the human HeLa cell line was determined through the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. The cytotoxicity studies demonstrate that ZnO nanoparticles in the concentrations up to 20 mg/L have no adverse effect on HeLa cells. When compared with the released and cytotoxic concentrations of ZnO NPs, it can be expected that ZnO released from dental prostheses to the oral cavity environment will have no cytotoxic effect on host cells.