bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the Safety Risk of Rural Roadsides Using a Bayesian Network Method
Authors: Tang Tianpei , Zhu Senlai , Guo Yuntao , Zhou Xizhao , Cao Yang
Published: April 2019

Evaluating the safety risk of rural roadsides is critical for achieving reasonable allocation of a limited budget and avoiding excessive installation of safety facilities. To assess the safety risk of rural roadsides when the crash data are unavailable or missing, this study proposed a Bayesian Network (BN) method that uses the experts’ judgments on the conditional probability of different safety risk factors to evaluate the safety risk of rural roadsides. Eight factors were considered, including seven factors identified in the literature and a new factor named access point density. To validate the effectiveness of the proposed method, a case study was conducted using 19.42 km long road networks in the rural area of Nantong, China. By comparing the results of the proposed method and run-off-road (ROR) crash data from 2015–2016 in the study area, the road segments with higher safety risk levels identified by the proposed method were found to be statistically significantly correlated with higher crash severity based on the crash data. In addition, by comparing the respective results evaluated by eight factors and seven factors (a new factor removed), we also found that access point density significantly contributed to the safety risk of rural roadsides. These results show that the proposed method can be considered as a low-cost solution to evaluating the safety risk of rural roadsides with relatively high accuracy, especially for areas with large rural road networks and incomplete ROR crash data due to budget limitation, human errors, negligence, or inconsistent crash recordings.
Cellular and Molecular Effects of High-Molecular-Weight Heparin on Matrix Metalloproteinase 9 Expression
Authors: Huber René , Attili/Abedalkhader Rozan , Küper Daniela , Hauke Lara , Lüns Bernadette , Brand Korbinian , Weissenborn Karin , Lichtinghagen Ralf
Published: April 2019

Blood sampling with different anticoagulants alters matrix metalloproteinase (MMP-) 9 expression, thus influencing its concentration and diagnostic validity. Here, we aimed to evaluate the effects of different anticoagulants on MMP-9 regulation. MMP-9 expression was assessed in response to ethylenediaminetetraacetic acid, citrate, and high-/low-molecular-weight heparin (HMWH, LMWH) in co-culture experiments using THP-1, Jurkat, and HT cells (representing monocytes, T, and B cells). Triple and double cell line co-culture experiments revealed that HMWH treatment of THP-1 and Jurkat led to a significant MMP-9 induction, whereas other anticoagulants and cell type combinations had no effect. Supernatant of HMWH-treated Jurkat cells also induced MMP-9 in THP-1 suggesting monocytes as MMP-9 producers. HMWH-induced cytokine/chemokine secretion was assessed in co-culture supernatant, and the influence of cytokines/chemokines on MMP-9 production was analyzed. These experiments revealed that Jurkat-derived IL-16 and soluble intercellular adhesion molecule (sICAM-) 1 are able to induce MMP-9 and IL-8 production by THP-1. As a consequence, the increased MMP-9 expression found in HMWH blood samples may be influenced by HMWH-dependent secretion of IL-16 and sICAM-1 by T cells resulting in an increased production of MMP-9 and IL-8 by monocytes. IL-8, in turn, may support MMP-9 and its own expression in a positive autocrine feedback loop.
The Roles of MicroRNA in Lung Cancer
Authors: Wu Kuan-Li , Tsai Ying-Ming , Lien Chi-Tun , Kuo Po-Lin , Hung Jen-Yu
Published: April 2019

Lung cancer is the most devastating malignancy in the world. Beyond genetic research, epigenomic studies—especially investigations of microRNAs—have grown rapidly in quantity and quality in the past decade. This has enriched our understanding about basic cancer biology and lit up the opportunities for potential therapeutic development. In this review, we summarize the involvement of microRNAs in lung cancer carcinogenesis and behavior, by illustrating the relationship to each cancer hallmark capability, and in addition, we briefly describe the clinical applications of microRNAs in lung cancer diagnosis and prognosis. Finally, we discuss the potential therapeutic use of microRNAs in lung cancer.
Current Advances in Molecular Mechanisms and Physiological Basis of Panicle Degeneration in Rice
Authors: Ali Asif , Xu Peizhou , Riaz Asad , Wu Xianjun
Published: April 2019

Panicle degeneration, also known as panicle abortion, is a serious defect and causes heavy losses to reproductive yield in cereals. Several mutants have been reported to display the phenotype of spikelet abortion in rice. Recent findings have resulted in significant breakthroughs, but comprehensive understanding about the molecular pathways and physiological basis of panicle degeneration still remain a dilemma. In this review, we have summarized all the responsible genes and mechanisms underlying the panicle development with a special focus on degeneration. Here, we hypothesized a model by using knowledge and coherent logic in order to understand the molecular regulation of panicle degeneration. In addition to this, we included all the previous discoveries, schools of thoughts, ancient working theories, and crosstalk of phytohormones and provided new insights for future studies.
3D Printing Custom Bioactive and Absorbable Surgical Screws, Pins, and Bone Plates for Localized Drug Delivery
Authors: Tappa Karthik , Jammalamadaka Udayabhanu , Weisman Jeffery A. , Ballard David H. , Wolford Dallas D. , Pascual-Garrido Cecilia , Wolford Larry M. , Woodard Pamela K. , Mills David K.
Published: April 2019

Additive manufacturing has great potential for personalized medicine in osseous fixation surgery, including maxillofacial and orthopedic applications. The purpose of this study was to demonstrate 3D printing methods for the fabrication of patient-specific fixation implants that allow for localized drug delivery. 3D printing was used to fabricate gentamicin (GS) and methotrexate (MTX)-loaded fixation devices, including screws, pins, and bone plates. Scaffolds with different infill ratios of polylactic acid (PLA), both without drugs and impregnated with GS and MTX, were printed into cylindrical and rectangular-shaped constructs for compressive and flexural strength mechanical testing, respectively. Bland PLA constructs showed significantly higher flexural strength when printed in a Y axis at 100% infill compared to other axes and infill ratios; however, there was no significant difference in flexural strength between other axes and infill ratios. GS and MTX-impregnated constructs had significantly lower flexural and compressive strength as compared to the bland PLA constructs. GS-impregnated implants demonstrated bacterial inhibition in plate cultures. Similarly, MTX-impregnated implants demonstrated a cytotoxic effect in osteosarcoma assays. This proof of concept work shows the potential of developing 3D printed screws and plating materials with the requisite mechanical properties and orientations. Drug-impregnated implants were technically successful and had an anti-bacterial and chemotherapeutic effect, but drug addition significantly decreased the flexural and compressive strengths of the custom implants.
Prediction of Wear on Tibial Inserts Made of UHMWPE, PEEK, and CFR-PEEK in Total Knee Arthroplasty Using Finite-Element Analysis
Authors: Koh Yong-Gon , Lee Jin-Ah , Kang Kyoung-Tak
Published: April 2019

The wear of tibial inserts in total knee arthroplasty (TKA) remains a major limitation of longevity. However, wear tests are expensive and time-consuming. Computational wear prediction using a finite-element (FE) model followed by validation through comparison with experimental data is effective for assessing new prosthetic designs or materials prior to functional testing and surgical implementation. In this study, the kinematics, volumetric wear, and wear depth of tibial inserts made of different materials (ultrahigh-molecular weight polyethylene (UHMWPE), polyetheretherketone (PEEK), and carbon fiber-reinforced PEEK (CFR–PEEK)) in TKA were evaluated by employing FE models and analysis. The differences among the materials were evaluated using adaptive wear modeling to predict the wear depth, volumetric wear, and kinematics under a gait loading condition. The volumetric wear and wear depth of the CFR–PEEK decreased by 87.4% and 61.3%, respectively, compared with those of the UHMWPE, whereas the PEEK exhibited increased volumetric wear and wear depth. These results suggest that CFR–PEEK is a good alternative to UHMWPE as a promising and suitable material for tibial inserts used in TKA. However, orthopedic research should be performed to evaluate the threshold conditions and appropriate applications for the newly developed and introduced biomaterial.
Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway
Authors: Jeong Su-Jin , Choi Jeong-Wook , Lee Min-Kyeong , Choi Youn-Hee , Nam Taek-Jeong
Published: April 2019

Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.
5-Arylidene(chromenyl-methylene)-thiazolidinediones: Potential New Agents against Mutant Oncoproteins K-Ras, N-Ras and B-Raf in Colorectal Cancer and Melanoma
Authors: Nastasă Cristina , Tamaian Radu , Oniga Ovidiu , Tiperciuc Brîndușa
Published: April 2019

Background and objectives: Cancer represents the miscommunication between and within the body cells. The mutations of the oncogenes encoding the MAPK pathways play an important role in the development of tumoral diseases. The mutations of KRAS and BRAF oncogenes are involved in colorectal cancer and melanoma, while the NRAS mutations are associated with melanoma. Thiazolidine-2,4-dione is a versatile scaffold in medicinal chemistry and a useful tool in the development of new antitumoral compounds. The aim of our study was to predict the pharmacokinetic/pharmacodynamic properties, the drug-likeness and lead-likeness of two series of synthetic 5-arylidene(chromenyl-methylene)-thiazolidinediones, the molecular docking on the oncoproteins K-Ras, N-Ras and B-Raf, and to investigate the cytotoxicity of the compounds, in order to select the best structural profile for potential anticancer agents. Materials and Methods: In our paper we studied the cytotoxicity of two series of thiazolidine-2,4-dione derivatives, their ADME-Tox properties and the molecular docking on a mutant protein of K-Ras, two isoforms of N-Ras and an isoform of B-Raf with 16 mutations. Results: The heterocyclic compounds strongly interact with K-Ras and N-Ras right after their posttranslational processing and/or compete with GDP for the nucleotide-binding site of the two GTPases. They are less active against the GDP-bound states of the two targets. All derivatives have a similar binding pattern in the active site of B-Raf. Conclusions: The data obtained encourage the further investigation of the 5-arylidene(chromenyl-methylene)-thiazolidinediones as potential new agents against the oncoproteins K-Ras, N-Ras and B-Raf.
Intravenous Paracetamol in Adjunct to Intravenous Ketoprofen for Postoperative Pain in Children Undergoing General Surgery: A Double-Blinded Randomized Study
Authors: Rugytė Danguolė , Gudaitytė Jūratė
Published: April 2019

Background and objectives: The combination of non-steroidal anti-inflammatory drugs and paracetamol is widely used for pediatric postoperative pain management, although the evidence of superiority of a combination over either drug alone is insufficient. We aimed to find out if intravenous (i.v.) paracetamol in a dose of 60 mg kg−1 24 h−1, given in addition to i.v. ketoprofen (4.5 mg kg−1 24 h−1), improves analgesia, physical recovery, and satisfaction with postoperative well-being in children and adolescents following moderate and major general surgery. Materials and Methods: Fifty-four patients were randomized to receive either i.v. paracetamol or normal saline as a placebo in adjunct to i.v. ketoprofen. For rescue analgesia in patients after moderate surgery, i.v. tramadol (2 mg kg−1 up two doses in 24 h), and for children after major surgery, i.v. morphine-patient-controlled analgesia (PCA) were available. The main outcome measure was the amount of opioid consumed during the first 24 h after surgery. Pain level at 1 and over 24 h, time until the resumption of normal oral fluid intake, spontaneous urination after surgery, and satisfaction with postoperative well-being were also assessed. Results: Fifty-one patients (26 in the placebo group and 25 in the paracetamol group) were studied. There was no difference in required rescue tramadol doses (n = 11 in each group) or 24-h morphine consumption (mean difference (95% CI): 0.06 (–0.17; 0.29) or pain scores between placebo and paracetamol groups. In patients given morphine-PCA, time to normal fluid intake was faster in the paracetamol than the placebo subgroup: median difference (95% CI): 7.5 (1.3; 13.7) h, p = 0.02. Parental satisfaction score was higher in the paracetamol than the placebo group (mean difference: –1.3 (–2.5; –0.06), p = 0.04). Conclusions: There were no obvious benefits to opioid requirement or analgesia of adding regular intravenous paracetamol to intravenous ketoprofen in used doses. However, intravenous paracetamol may contribute to faster recovery of normal functions and higher satisfaction with postoperative well-being.
Effects of Silica-Particle Coating on a Silica Support for the Fabrication of High-Performance Silicalite-1 Membranes by Gel-Free Steam-Assisted Conversion
Authors: Ueno Kyohei , Negishi Hideyuki , Okuno Takuya , Tawarayama Hiromasa , Ishikawa Shinji , Miyamoto Manabu , Uemiya Shigeyuki , Oumi Yasunori
Published: April 2019

Silicalite-1 membranes with high pervaporation performance were prepared successfully on a silica-particle-coated tubular silica support using a gel-free steam-assisted conversion (SAC) method. The effects of the silica-particle layer formed on the top surface of the silica support and the physical properties of the silica particles themselves on the membrane-formation process were investigated. The silica particles coated served as the additional silica source for growing the silicalite-1 seed crystal layer into the silicalite-1 membrane. As a result, it was possible to form a dense and continuous membrane even under gel-free conditions. Furthermore, it was found that the properties of the silica particles, such as their primary particle diameter, had a determining effect on their solubility during the steam treatment, that is, on the supply rate of the silica source. The silicalite-1 membrane obtained using the spherical-silica-particle-coated support had an approximately 9-μm-thick separation layer and showed very high pervaporation performance, exhibiting a separation factor of 105 and a flux of 3.72 kg m−2 h−1 for a 10 wt % ethanol/water mixture at 323 K. Thus, the gel-free SAC method can be used with a silica support coated with silica particles to readily prepare high-performance membranes without producing any chemical waste.
Plasma Printing of an AISI316 Micro-Meshing Punch Array for Micro-Embossing onto Copper Plates
Authors: Shiratori Tomomi , Aizawa Tatsuhiko , Saito Yasuo , Wasa Kenji
Published: April 2019

Packaging using thermoplastic molding for hollowed GaN chips were requested for a leak-proof micro-joining between plastic molds and copper-based substrates. The design and engineering of micro-textures is a key technology for putting leak-proof packaging into practice. In the present paper, a micro-meshing punch array was prepared using plasma-nitriding-assisted printing. Two-dimensional original patterns were screen-printed onto an AISI316 die substrate and plasma nitrided at 673 K for 14.4 ks (or 4 h). The unprinted surfaces were selectively nitrogen super-saturated to have more nitrogen content than 5 mass% and a higher hardness than 1200 HV. The printed surfaces were selectively sand blasted to fabricate the micro-meshing punch array for micro-embossing. A computer numerically controlled stamping system was utilized to describe the micro-embossing behavior onto copper substrates and to investigate how the micro-textures on the array was transcribed onto the copper. Reduction of takt time as well as flexibility in the micro-grooving were discussed with reference to the picosecond laser machining and mechanical milling processes.
U-Pb Ages, O Isotope Compositions, Raman Spectrum, and Geochemistry of Cassiterites from the Xi’ao Copper-Tin Polymetallic Deposit in Gejiu District, Yunnan Province
Authors: Zhao Yuehua , Chen Shouyu , Huang Yuqiang , Zhao Jiangnan , Tong Xiang , Chen Xingshou
Published: April 2019

The Xi’ao Cu-Sn polymetallic deposit is located in the inner alteration zone of the Laoka granite. The ore bodies extend to 400 m in the granite rock and primarily occur with fluorite and potassic alterations. Two cassiterite samples of altered rock-type ore and one tourmaline vein-type ore in the Xi’ao Cu-Sn polymetallic deposit yielded U-Pb ages of 83.3 ± 2.1 Ma, 84.9 ± 1.7 Ma, and 84.0 ± 5.6 Ma, respectively. The Raman spectrum peak values of A1g were shifted to a lower frequency, possibly due to the substitution of Sn with Nb, Ta, Fe, and Mn. Measured δ18O values of cassiterite samples and calculated δ18OH2O values for the ore-forming fluid indicate that the latter was mostly derived from magma. The high Fe and Mn abundances for cassiterite are consistent with those of hydrothermal origin. The Nb, Ta, and Ti contents indicate that cassiterites in the Xi’ao deposit likely formed in a metallogenic environment that was largely affected by granitic magmatism. Therefore, we conclude that the Xi’ao deposit is a magmatic hydrothermal deposit.
Injectable Alginate-Peptide Composite Hydrogel as a Scaffold for Bone Tissue Regeneration
Authors: Ghosh Moumita , Halperin-Sternfeld Michal , Grinberg Itzhak , Adler-Abramovich Lihi
Published: April 2019

The high demand for tissue engineering scaffolds capable of inducing bone regeneration using minimally invasive techniques prompts the need for the development of new biomaterials. Herein, we investigate the ability of Alginate incorporated with the fluorenylmethoxycarbonyl-diphenylalanine (FmocFF) peptide composite hydrogel to serve as a potential biomaterial for bone regeneration. We demonstrate that the incorporation of the self-assembling peptide, FmocFF, in sodium alginate leads to the production of a rigid, yet injectable, hydrogel without the addition of cross-linking agents. Scanning electron microscopy reveals a nanofibrous structure which mimics the natural bone extracellular matrix. The formed composite hydrogel exhibits thixotropic behavior and a high storage modulus of approximately 10 kPA, as observed in rheological measurements. The in vitro biocompatibility tests carried out with MC3T3-E1 preosteoblast cells demonstrate good cell viability and adhesion to the hydrogel fibers. This composite scaffold can induce osteogenic differentiation and facilitate calcium mineralization, as shown by Alizarin red staining, alkaline phosphatase activity and RT-PCR analysis. The high biocompatibility, excellent mechanical properties and similarity to the native extracellular matrix suggest the utilization of this hydrogel as a temporary three-dimensional cellular microenvironment promoting bone regeneration.
Synergistic Effect of Dual Particle-Size AuNPs on TiO2 for Efficient Photocatalytic Hydrogen Evolution
Authors: Zhao Qian , Zhang Qiaoli , Du Cui , Sun Shasha , Steinkruger Jay D. , Zhou Chen , Yang Shengyang
Published: April 2019

Design of efficient catalysts for photocatalytic water-splitting hydrogen evolution is of fundamental importance for the production of sustainable clean energy. In this study, a dual particle-size AuNPs/TiO2 composite containing both small (16.9 ± 5.5 nm) and large (45.0 ± 9.8 nm) AuNPs was synthesized by annealing two different sized AuNPs onto TiO2 nanosheets. Dual particle-size AuNPs/TiO2 composites of 2.1 wt% catalyze photocatalytic H2 evolution 281 times faster than pure TiO2. Control experiments indicate the observed rate increase for the 2.1 wt% dual particle-size AuNPs/TiO2 composites is larger than 2.1 wt% small AuNPs/TiO2 composites, or 2.1 wt% large AuNPs/TiO2 composites in isolation. The observed photocatalytic enhancement can be attributed to the synergistic effect of dual particle-size AuNPs on TiO2. Specifically, small-sized AuNPs can act as an electron sink to generate more electron-hole pairs, while the surface plasmon resonance (SPR) effect of large-sized AuNPs concurrently injects hot electrons into the TiO2 conduction band to enhance charge transfer. In addition, a gold-dicyanodiamine composite (GDC)-directed synthesis of 2.1 wt% dual particle-size AuNPs/TiO2 composites was also completed. Notably, a photocatalytic efficiency enhancement was observed that was comparable to the previously prepared 2.1 wt% dual particle-size AuNPs/TiO2 composites. Taken together, the synergistic effects of dual particle-size AuNPs on TiO2 can be potentially used as a foundation to develop semiconductor photocatalyst heterojunction with enhanced photocatalytic activity.
Structural and Thermal Characterisation of Nanofilms by Time-Resolved X-ray Scattering
Authors: Plech Anton , Krause Bärbel , Baumbach Tilo , Zakharova Margarita , Eon Soizic , Girmen Caroline , Buth Gernot , Bracht Hartmut
Published: April 2019

High time resolution in scattering analysis of thin films allows for determination of thermal conductivity by transient pump-probe detection of dissipation of laser-induced heating, TDXTS. We describe an approach that analyses the picosecond-resolved lattice parameter reaction of a gold transducer layer on pulsed laser heating to determine the thermal conductivity of layered structures below the transducer. A detailed modeling of the cooling kinetics by a Laplace-domain approach allows for discerning effects of conductivity and thermal interface resistance as well as basic depth information. The thermal expansion of the clamped gold film can be calibrated to absolute temperature change and effects of plastic deformation are discriminated. The method is demonstrated on two extreme examples of phononic barriers, isotopically modulated silicon multilayers with very small acoustic impedance mismatch and silicon-molybdenum multilayers, which show a high resistivity.
Novel Synthesis of Choline-Based Amino Acid Ionic Liquids and Their Applications for Separating Asphalt from Carbonate Rocks
Authors: Zhang Zisheng , Kang Ning , Zhou Jingjing , Li Xingang , He Lin , Sui Hong
Published: April 2019

In this study, a series of choline-based amino acid ionic liquids have been synthesized in an economic method and are used to assist solvents with extracting asphalt from carbonate rocks. All of the ionic liquids perform well in extracting asphalt, especially choline histidine, by which the single-step recovery of asphalt is up to 91%. Furthermore, oil product with higher quality (fewer solids entrained) is also obtained. Molecular dynamics simulation and thermodynamic equilibrium method are applied to investigate the role of amino acid ionic liquids via interaction energy calculation and surface free energy calculations. The simulation results suggest that the ionic liquid phase is beneficial for the transfer of oil fraction from the carbonate surface to the organic solvent phase. Moreover, the results of simulated calculation show that the introduction of a functional group with conjugated structures into ionic liquid, such as an imidazole ring and a benzene ring, is beneficial for enhancing oil recovery, which are in accordance with the results of experimental tests.
Comparison of Pro-Regenerative Effects of Carbohydrates and Protein Administrated by Shake and Non-Macro-Nutrient Matched Food Items on the Skeletal Muscle after Acute Endurance Exercise
Authors: Isenmann Eduard , Blume Franziska , Bizjak Daniel A. , Hundsdörfer Vera , Pagano Sarah , Schibrowski Sebastian , Simon Werner , Schmandra Lukas , Diel Patrick
Published: April 2019

Physical performance and regeneration after exercise is enhanced by the ingestion of proteins and carbohydrates. These nutrients are generally consumed by athletes via whey protein and glucose-based shakes. In this study, effects of protein and carbohydrate on skeletal muscle regeneration, given either by shake or by a meal, were compared. 35 subjects performed a 10 km run. After exercise, they ingested nothing (control), a protein/glucose shake (shake) or a combination of white bread and sour milk cheese (food) in a randomized cross over design. Serum glucose (n = 35), serum insulin (n = 35), serum creatine kinase (n = 15) and myoglobin (n = 15), hematologic parameters, cortisol (n = 35), inflammation markers (n = 27) and leg strength (n = 15) as a functional marker were measured. Insulin secretion was significantly stimulated by shake and food. In contrast, only shake resulted in an increase of blood glucose. Food resulted in a decrease of pro, and stimulation of anti-inflammatory serum markers. The exercise induced skeletal muscle damage, indicated by serum creatine kinase and myoglobin, and exercise induced loss of leg strength was decreased by shake and food. Our data indicate that uptake of protein and carbohydrate by shake or food reduces exercise induced skeletal muscle damage and has pro-regenerative effects.
Dietary Patterns, Skeletal Muscle Health, and Sarcopenia in Older Adults
Authors: Granic Antoneta , Sayer Avan A. , Robinson Sian M.
Published: April 2019

In recent decades, the significance of diet and dietary patterns (DPs) for skeletal muscle health has been gaining attention in ageing and nutritional research. Sarcopenia, a muscle disease characterised by low muscle strength, mass, and function is associated with an increased risk of functional decline, frailty, hospitalization, and death. The prevalence of sarcopenia increases with age and leads to high personal, social, and economic costs. Finding adequate nutritional measures to maintain muscle health, preserve function, and independence for the growing population of older adults would have important scientific and societal implications. Two main approaches have been employed to study the role of diet/DPs as a modifiable lifestyle factor in sarcopenia. An a priori or hypothesis-driven approach examines the adherence to pre-defined dietary indices such as the Mediterranean diet (MED) and Healthy Eating Index (HEI)—measures of diet quality—in relation to muscle health outcomes. A posteriori or data-driven approaches have used statistical tools—dimension reduction methods or clustering—to study DP-muscle health relationships. Both approaches recognise the importance of the whole diet and potential cumulative, synergistic, and antagonistic effects of foods and nutrients on ageing muscle. In this review, we have aimed to (i) summarise nutritional epidemiology evidence from four recent systematic reviews with updates from new primary studies about the role of DPs in muscle health, sarcopenia, and its components; (ii) hypothesise about the potential mechanisms of ‘myoprotective’ diets, with the MED as an example, and (iii) discuss the challenges facing nutritional epidemiology to produce the higher level evidence needed to understand the relationships between whole diets and healthy muscle ageing.
Cocoa Flavanols: Natural Agents with Attenuating Effects on Metabolic Syndrome Risk Factors
Authors: Jaramillo Flores Maria Eugenia
Published: April 2019

The interest in cacao flavanols is still growing, as bioactive compounds with potential benefits in the prevention of chronic diseases associated with inflammation, oxidative stress and metabolic disorders. Several analytical methodologies support that the flavanols in cacao-derived products can be absorbed, have bioactive properties, and thus can be responsible for their beneficial effects on human health. However, it must be considered that their biological actions and underlying molecular mechanisms will depend on the concentrations achieved in their target tissues. Based on the antioxidant properties of cacao flavanols, this review focuses on recent advances in research regarding their potential to improve metabolic syndrome risk factors. Additionally, it has included other secondary plant metabolites that have been investigated for their protective effects against metabolic syndrome. Studies using laboratory animals or human subjects represent strong available evidence for biological effects of cacao flavanols. Nevertheless, in vitro studies are also included to provide an overview of these phytochemical mechanisms of action. Further studies are needed to determine if the main cacao flavanols or their metabolites are responsible for the observed health benefits and which are their precise molecular mechanisms.
Uroguanylin Improves Leptin Responsiveness in Diet-Induced Obese Mice
Authors: Folgueira Cintia , Beiroa Daniel , González-Rellán María Jesús , Porteiro Begoña , Milbank Edward , Castelao Cecilia , García-Palacios María , Casanueva Felipe F , López Miguel , Diéguez Carlos , Seoane Luisa M. , Nogueiras Rubén
Published: April 2019

The gastrointestinal-brain axis is a key mediator of the body weight and energy homeostasis regulation. Uroguanylin (UGN) has been recently proposed to be a part of this gut-brain axis regulating food intake, body weight and energy expenditure. Expression of UGN is regulated by the nutritional status and dependent on leptin levels. However, the exact molecular mechanisms underlying this UGN-leptin metabolic regulation at a hypothalamic level still remains unclear. Using leptin resistant diet-induced obese (DIO) mice, we aimed to determine whether UGN could improve hypothalamic leptin sensitivity. The present work demonstrates that the central co-administration of UGN and leptin potentiates leptin’s ability to decrease the food intake and body weight in DIO mice, and that UGN activates the hypothalamic signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositide 3-kinases (PI3K) pathways. At a functional level, the blockade of PI3K, but not STAT3, blunted UGN-mediated leptin responsiveness in DIO mice. Overall, these findings indicate that UGN improves leptin sensitivity in DIO mice.
Effects of Creatine Supplementation on Athletic Performance in Soccer Players: A Systematic Review and Meta-Analysis
Authors: Mielgo-Ayuso Juan , Calleja-Gonzalez Julio , Marqués-Jiménez Diego , Caballero-García Alberto , Córdova Alfredo , Fernández-Lázaro Diego
Published: April 2019

Studies have shown that creatine supplementation increases intramuscular creatine concentrations, favoring the energy system of phosphagens, which may help explain the observed improvements in high-intensity exercise performance. However, research on physical performance in soccer has shown controversial results, in part because the energy system used is not taken into account. The main aim of this investigation was to perform a systematic review and meta-analysis to determine the efficacy of creatine supplementation for increasing performance in skills related to soccer depending upon the type of metabolism used (aerobic, phosphagen, and anaerobic metabolism). A structured search was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines in the Medline/PubMed and Web of Science, Cochrane Library, and Scopus databases until January 2019. The search included studies with a double-blind and randomized experimental design in which creatine supplementation was compared to an identical placebo situation (dose, duration, timing, and drug appearance). There were no filters applied to the soccer players’ level, gender, or age. A final meta-analysis was performed using the random effects model and pooled standardized mean differences (SMD) (Hedges’s g). Nine studies published were included in the meta-analysis. This revealed that creatine supplementation did not present beneficial effects on aerobic performance tests (SMD, −0.05; 95% confidence interval (CI), −0.37 to 0.28; p = 0.78) and phosphagen metabolism performance tests (strength, single jump, single sprint, and agility tests: SMD, 0.21; 95% CI, −0.03 to 0.45; p = 0.08). However, creatine supplementation showed beneficial effects on anaerobic performance tests (SMD, 1.23; 95% CI, 0.55–1.91; p <0.001). Concretely, creatine demonstrated a large and significant effect on Wingate test performance (SMD, 2.26; 95% CI, 1.40–3.11; p <0.001). In conclusion, creatine supplementation with a loading dose of 20–30 g/day, divided 3–4 times per day, ingested for 6 to 7 days, and followed by 5 g/day for 9 weeks or with a low dose of 3 mg/kg/day for 14 days presents positive effects on improving physical performance tests related to anaerobic metabolism, especially anaerobic power, in soccer players.
Fridamycin A, a Microbial Natural Product, Stimulates Glucose Uptake without Inducing Adipogenesis
Authors: Yoon Sun-Young , Lee Seoung Rak , Hwang Ji Young , Benndorf René , Beemelmanns Christine , Chung Sang J. , Kim Ki Hyun
Published: April 2019

Type 2 diabetes is a complex, heterogeneous, and polygenic disease. Currently, available drugs for treating type 2 diabetes predominantly include sulfonylureas, α-glucosidase inhibitors, and biguanides. However, long-term treatment with these therapeutic drugs is often accompanied by undesirable side effects, which have driven interest in the development of more effective and safer antidiabetic agents. To address the urgent need for new chemical solutions, we focused on the analysis of structurally novel and/or biologically new metabolites produced by insect-associated microbes as they have recently been recognized as a rich source of natural products. Comparative LC/MS-based analysis of Actinomadura sp. RB99, isolated from a fungus-growing termite, led to the identification of the type II polyketide synthase-derived fridamycin A. The structure of fridamycin A was confirmed by 1H NMR data and LC/MS analysis. The natural microbial product, fridamycin A, was examined for its antidiabetic properties in 3T3-L1 adipocytes, which demonstrated that fridamycin A induced glucose uptake in 3T3-L1 cells by activating the AMP-activated protein kinase (AMPK) signaling pathway but did not affect adipocyte differentiation, suggesting that the glucose uptake took place through activation of the AMPK signaling pathway without inducing adipogenesis. Our results suggest that fridamycin A has potential to induce fewer side effects such as weight gain compared to rosiglitazone, a commonly used antidiabetic drug, and that fridamycin A could be a novel potential therapeutic candidate for the management of type 2 diabetes.
Kinetic Approach to Pair Production in Strong Fields—Two Lessons for Applications to Heavy-Ion Collisions
Authors: Blaschke David B. , Juchnowski Lukasz , Otto Andreas
Published: April 2019

The kinetic-equation approach to particle production in strong, time-dependent external fields is revisited and three limiting cases are discussed for different field patterns: the Sauter pulse, a harmonic pulse with a Gaussian envelope, and a Poisson-distributed stochastic field. It is shown that for transient subcritical electric fields E ( t ) a finite residual particle number density n ( ∞ ) would be absent if the field-dependence of the dynamical phase in the Schwinger source term would be neglected. In this case the distribution function of created particles follows the law f ( t ) ∼ E 2 ( t ) . Two lessons for particle production in heavy-ion collisions are derived from this exercise. First: the shorter the (Sauter-type) pulse, the higher the residual density of produced particles. Second: although the Schwinger process in a string-type field produces a non-thermal particle spectrum, a Poissonian distribution of the (fluctuating) strings produces a thermal spectrum with an apparent temperature that coincides with the Hawking–Unruh temperature for the mean value of the string tension.
Translational PBPK Modeling of the Protein Therapeutic and CD95L Inhibitor Asunercept to Develop Dose Recommendations for Its First Use in Pediatric Glioblastoma Patients
Authors: Hanke Nina , Kunz Claudia , Thiemann Meinolf , Fricke Harald , Lehr Thorsten
Published: April 2019

The protein therapeutic and CD95L inhibitor asunercept is currently under clinical investigation for the treatment of glioblastoma and myelodysplastic syndrome. The purpose of this study was to predict the asunercept pharmacokinetics in children and to give dose recommendations for its first use in pediatric glioblastoma patients. A physiologically-based pharmacokinetic (PBPK) model of asunercept in healthy and diseased adults was successfully developed using the available clinical Phase I and Phase II study data. This model was then extrapolated to different pediatric populations, to predict the asunercept exposure in children and to find equivalent starting doses. Simulation of the asunercept serum concentration-time curves in children between 1–18 years of age shows that a dosing regimen based on body weight results in a similar asunercept steady-state exposure in all patients (pediatric or adult) above 12 years of age. For children between 1–12 years, higher doses per kg body weight are recommended, with the highest dose for the very young patients. Translational PBPK modeling is strongly encouraged by regulatory agencies to help with the initial dose selection for pediatric trials. To our knowledge, this is the first report of pediatric PBPK to support the dose selection of a therapeutic protein before its administration to children.
Modelling the Effect of Process Parameters on the Wet Extrusion and Spheronisation of High-Loaded Nicotinamide Pellets Using a Quality by Design Approach
Authors: Theismann Eva-Maria , K. Keppler Julia , Owen Martin , Schwarz Karin , Schlindwein Walkiria
Published: April 2019

The aim of the present study was to develop an alternative process to spray granulation in order to prepare high loaded spherical nicotinamide (NAM) pellets by wet extrusion and spheronisation. Therefore, a quality by design approach was implemented to model the effect of the process parameters of the extrusion-spheronisation process on the roundness, roughness and useable yield of the obtained pellets. The obtained results were compared to spray granulated NAM particles regarding their characteristics and their release profile in vitro after the application of an ileocolon targeted shellac coating. The wet extrusion-spheronisation process was able to form highly loaded NAM pellets (80%) with a spherical shape and a high useable yield of about 90%. However, the water content range was rather narrow between 24.7% and 21.3%. The design of experiments (DoE), showed that the spheronisation conditions speed, time and load had a greater impact on the quality attributes of the pellets than the extrusion conditions screw design, screw speed and solid feed rate (hopper speed). The best results were obtained using a low load (15 g) combined with a high rotation speed (900 m/min) and a low time (3–3.5 min). In comparison to spray granulated NAM pellets, the extruded NAM pellets resulted in a higher roughness and a higher useable yield (63% vs. 92%). Finally, the coating and dissolution test showed that the extruded and spheronised pellets are also suitable for a protective coating with an ileocolonic release profile. Due to its lower specific surface area, the required shellac concentration could be reduced while maintaining the release profile.
Shape Memory Behavior of Natural Eucommia ulmoides Gum and Low-Density Polyethylene Blends with Two Response Temperatures
Authors: Xia Lin , Chen Shuai , Fu Wenxin , Qiu Guixue
Published: April 2019

A series of shape memory blends of natural Eucommia ulmoides gum (EUG) and low-density polyethylene (LDPE) with a bicontinuous cross-linked structure were prepared by a physical blending method, which could be used in the field of thermal response with two different temperatures. We report the shape memory properties of these blended materials with two response temperatures for the first time. The mechanical, curing, thermal and shape memory properties of the blends were studied in this manuscript. Schematic diagrams are proposed to illustrate the dual shape memory behaviors of the EUG/LDPE blends. Our study focused on observing the relationship between the shape memory behavior and the microscopic crystalline phase states in the blends. In the blends, both the cross-linked network and the LDPE crystalline regions could act as fixed domains, while the crystalline regions of LDPE or EUG could act as the reversible domain. The shape memory properties were mainly determined by the components of the fixed and reversible domains. We focused on the shape memory behavior of blends at 60 °C and 130 °C in this manuscript. The results showed that when the peroxide dicumyl peroxide (DCP) dosage was 1.0 phr, the blends exhibited acceptable shape behavior at 60 °C (R1f = 74.8%, R1r = 63.3%). At the same time, when DCP dosage was 0.4 phr, the shape memory behavior of the blends at 130 °C was good and much better than that at 60 °C (R2f = 91.1%, R2r = 89.4%).
Dispersion of Boron Nitride Nanotubes by Pluronic Triblock Copolymer in Aqueous Solution
Authors: Jeon Sang-Woo , Kang Shin-Hyun , Choi Jung Chul , Kim Tae-Hwan
Published: April 2019

Boron nitride nanotubes (BNNTs) have been of interest for their excellent thermal, electrical, and mechanical properties, and they have a broad spectrum of potential applications, such as in piezoelectric materials, reinforcement of materials, and electrothermal insulation materials. For practical use of BNNTs, it is desirable to disperse them in aqueous solution, which improves convenience of handling. However, it is still difficult to make a homogenous and stable BNNT dispersion in aqueous solution, due to their strong van der Waals interactions and hydrophobic surface. To solve these problems, we used Pluronic P85 and F127, which have both hydrophilic groups and hydrophobic groups. Here, we report the wrapped structure of a Pluronic polymer-BNNT dispersion by using small-angle neutron scattering, UV–Vis spectroscopy, thermogravimetric analysis, and atomic force microscopy.
Influence of Temperature on Charge Accumulation in Low-Density Polyethylene Based on Depolarization Current and Space Charge Decay
Authors: Li Guochang , Wang Jiaxing , Han Wang , Wei Yanhui , Li Shengtao
Published: April 2019

Temperature is one of the key factors affecting space charge accumulation in high voltage direct current (HVDC) cable insulation material. The influence of temperature on charge accumulation in low density polyethylene (LDPE) has been investigated with a combined thermally stimulated depolarization current (TSDC) method and pulsed electro-acoustic (PEA) method. The experimental results indicate that there exists a transition temperature region of charge accumulation around 50 °C. The total accumulated charges all firstly increase and then decrease with the increasing polarization temperature under three typical polarization electric fields, and they have more accumulated charges in LDPE around 50 °C. The phenomenon has a close link with the dynamic processes of charge trapping and de-trapping, which were verified by TSDC results. At room temperature, the trapped charges are difficult to release from the traps, and these homocharges near the cathode can depress the further injection of the charges. More charges can be injected from the electrodes with the increase of temperature, while the charge migration is relatively lower before 50 °C, leading to more accumulated charges. When the temperature exceeds around 50 °C, the molecular movement is accelerated which can enhance the hopping probability of charges between the adjacent traps, resulting in few accumulated charges.
Boosting the Adhesivity of π-Conjugated Polymers by Embedding Platinum Acetylides towards High-Performance Thermoelectric Composites
Authors: Wan Tao , Yin Xiaojun , Pan Chengjun , Liu Danqing , Zhou Xiaoyan , Gao Chunmei , Wong Wai-Yeung , Wang Lei
Published: April 2019

Single-walled carbon nanotubes (SWCNTs) incorporated with π-conjugated polymers, have proven to be an effective approach in the production of advanced thermoelectric composites. However, the studied polymers are mainly limited to scanty conventional conductive polymers, and their performances still remain to be improved. Herein, a new planar moiety of platinum acetylide in the π-conjugated system is introduced to enhance the intermolecular interaction with the SWCNTs via π–π and d–π interactions, which is crucial in regulating the thermoelectric performances of SWCNT-based composites. As expected, SWCNT composites based on the platinum acetylides embedded polymers displayed a higher power factor (130.7 ± 3.8 μW·m−1·K−2) at ambient temperature than those without platinum acetylides (59.5 ± 0.7 μW·m−1·K−2) under the same conditions. Moreover, the strong interactions between the platinum acetylide-based polymers and the SWCNTs are confirmed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) measurements.
Religious Experience and Yoga
Authors: Chapple Christopher Key
Published: April 2019

Yoga practice provides access to religious experience, which has been defined by William James as “immediate luminousness, philosophical reasonableness, and moral helpfulness.” In this paper the processes of Yoga will be summarized as found in the Bhagavad Gῑtā and the Yoga Sūtra. This article concludes with instructions on how to perform a practice that integrates Yoga breathing and movement with reflections on the Sāṃkhya descriptions of physical and emotional realities (tattvas and bhāvas).
Religious Studies as Neoliberal “Triple Mediation”: Toward a Deconstruction of Its “Colonial Difference”
Authors: Raschke Carl
Published: April 2019

This article makes the case, citing the work of David Chidester, Achille Mbembe, Tomoko Masuzawa, and Walter Mignolo, that the academic study of religion (often known as “religious studies” in the Anglophone world, Religionswissenschften or sciences religieuses in Continental Europe) remains both historically, and to a large extent contemporaneously, a “colonial” discipline derived from what Michel Foucault termed the structures of “power/knowledge”, imposed on the cognitive and philosophical traditions of non-Western and indigenous peoples. It argues that the “archetype” of rationality taken for granted in much Western scholarship about “religion” amounts to what Chidester terms a “triple mediation” between the imperial domination and colonial classification and administration of subjugated peoples and their symbolical practices and cultural memory—one which, in fact, has been re-inscribed in present day “neoliberal” fantasies of one world “without religion”. Finally, the article proposes a new “deconstructive” reading of theories of religion using post-structuralist instead of Enlightenment methodologies.