bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming Oncogenic Mediated Tumor Immunity in Prostate Cancer
Authors: Bryant Geoffrey , Wang Lin , Mulholland David J.
Published: July 2017

Immunotherapy is being tested intensively in clinical trials for prostate cancer; it includes immune checkpoint inhibition, prostate specific antigen (PSA) vaccines and dendritic cell-based strategies. Despite increasing evidence for clinical responses, the consensus of multiple trials is that prostate cancers are poorly responsive to immunotherapy. Prostate cancer has a high degree of pathological and genetic heterogeneity compared to other cancer types, which may account for immunotherapeutic resistance. This hypothesis also implies that select types of prostate tumors may be differentially responsive to immune-based strategies and that the clinical stage, pathological grade and underlying genetic landscape may be important criteria in identifying tumors that respond to immune therapies. One strategy is to target oncogenic driver pathways in combination with immunotherapies with the goal of overcoming tumor immunity and broadening the number of patients achieving a clinical response. In this analysis, we address the hypothesis that driver oncogenic signaling pathways regulate cancer progression, tumor immunity and resistance to current immune therapeutics in prostate cancer. We propose that increased responsiveness may be achieved through the combined use of immunotherapies and inhibitors targeting tumor cell autonomous pathways that contribute towards anti-tumor immunity in patients with prostate cancer.
Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications
Authors: Kuang Haixue , Tang Zhenqiu , Zhang Chengyue , Wang Zhibin , Li Wenji , Yang Chunjuan , Wang Qiuhong , Yang Bingyou , Kong Ah-Ng
Published: July 2017

Nuclear factor erythroid-2 related factor 2 (Nrf2) is a vital transcription factor that regulates the anti-oxidative defense system. Previous reports suggested that the expression of the Nrf2 gene can be regulated by epigenetic modifications. The potential epigenetic effect of taxifolin (TAX), a potent cancer chemopreventive agent, in skin cancer chemoprotection is unknown. In this study, we investigated how Nrf2 is epigenetically regulated by TAX in JB6 P+ cells. TAX was found to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colony formation of JB6 P+ cells. TAX induced antioxidant response element (ARE)-luciferase activity in HepG2-C8 cells and up-regulated mRNA and protein levels of Nrf2 and its downstream genes heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), in JB6 P+ cells. Furthermore, bisulfite genomic sequencing revealed that TAX treatment reduces the methylation level of the first 15 CpGs sites in the Nrf2 promoter. Western blotting showed that TAX inhibits the expression levels of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) proteins. In summary, our results revealed that TAX can induce expression of Nrf2 and its downstream target genes in JB6 P+ cells by CpG demethylation. These finding suggest that TAX may exhibit a skin cancer preventive effect by activating Nrf2 via an epigenetic pathway.
BRS1 Function in Facilitating Lateral Root Emergence in Arabidopsis
Authors: Deng Qian , Wang Xue , Zhang Dongzhi , Wang Xiaoming , Feng Cuizhu , Xu Shengbao
Published: July 2017

The BRS1 (BRI1 Suppressor 1) gene encodes a serine carboxypeptidase that plays a critical role in the brassinosteroid signaling pathway. However, its specific biological function remains unclear. In this study, the developmental role of BRS1 was investigated in Arabidopsis thaliana. We found that overexpressing BRS1 resulted in significantly more lateral roots in different Arabidopsis ecotypes (WS2 and Col-0) and in brassinosteroid mutants (bri1-5 and det2-28). Further research showed that BRS1 facilitates the process whereby lateral root primordia break through the endodermis, cortex, and epidermis. Consistent with this, BRS1 was found to be highly expressed in the root endodermis and accumulated in the extracellular space around the dome of the lateral root primordia. Taken together, these results highlight the role of BRS1 in the process of lateral root emergence and provide new insight into the role of serine carboxypeptidases in plant root development.
Novel Molecular Insights about Lactobacillar Sortase-Dependent Piliation
Authors: Von Ossowski Ingemar
Published: July 2017

One of the more conspicuous structural features that punctuate the outer cell surface of certain bacterial Gram-positive genera and species is the sortase-dependent pilus. As these adhesive and variable-length protrusions jut outward from the cell, they provide a physically expedient and useful means for the initial contact between a bacterium and its ecological milieu. The sortase-dependent pilus displays an elongated macromolecular architecture consisting of two to three types of monomeric protein subunits (pilins), each with their own specific function and location, and that are joined together covalently by the transpeptidyl activity of a pilus-specific C-type sortase enzyme. Sortase-dependent pili were first detected among the Gram-positive pathogens and subsequently categorized as an essential virulence factor for host colonization and tissue invasion by these harmful bacteria. However, the sortase-dependent pilus was rebranded as also a niche-adaptation factor after it was revealed that “friendly” Gram-positive commensals exhibit the same kind of pilus structures, which includes two contrasting gut-adapted species from the Lactobacillus genus, allochthonous Lactobacillus rhamnosus and autochthonous Lactobacillus ruminis. This review will highlight and discuss what has been learned from the latest research carried out and published on these lactobacillar pilus types.
Secreted Protein Acidic and Rich in Cysteine (SPARC) Enhances Cell Proliferation, Migration, and Epithelial Mesenchymal Transition, and SPARC Expression is Associated with Tumor Grade in Head and Neck Cancer
Authors: Chang Chih-Hau , Yen Meng-Chi , Liao Ssu-Hui , Hsu Yu-Ling , Lai Chung-Sheng , Chang Kao-Ping , Hsu Ya-Ling
Published: July 2017

Secreted protein acidic and rich in cysteine (SPARC) is a secreted protein which is involved in various biological processes. SPARC expression is associated with tumor metastasis and poor prognosis in several types of cancer. However, the SPARC-induced signaling pathway was not fully understood in head and neck cancer. In this study, our results showed that SPARC treatment promoted cell proliferation and migration in head and neck cancer cell lines FaDu and Detroit 562. In addition, SPARC induced expression of epithelial mesenchymal transition (EMT) regulators, including Slug, Snail, and Twist in Detroit 562. The results of phospho-kinase array analysis showed that SPARC treatment increased phosphorylation of some molecules including protein kinase B (PKB/AKT), ribosomal S6 kinase (RSK), and extracellular signal–regulated kinases (ERK). The expression of SPARC-induced EMT regulator Slug was suppressed by AKT inhibitor, but not ERK and RSK inhibitors. The SPARC expression in grade IV tumor samples is higher when compared to that in grade I–III tumor samples. Our results suggest that SPARC treatment enhances the EMT signaling pathway via activation of AKT, and exogenous SPARC and tumor expressing SPARC might be associated with tumor progression in head and neck cancers.
Tick Haller’s Organ, a New Paradigm for Arthropod Olfaction: How Ticks Differ from Insects
Authors: Carr Ann , D. Mitchell III Robert , Dhammi Anirudh , Bissinger Brooke W. , Sonenshine Daniel E. , Roe R. Michael
Published: July 2017

Ticks are the vector of many human and animal diseases; and host detection is critical to this process. Ticks have a unique sensory structure located exclusively on the 1st pairs of legs; the fore-tarsal Haller’s organ, not found in any other animals, presumed to function like the insect antennae in chemosensation but morphologically very different. The mechanism of tick chemoreception is unknown. Utilizing next-generation sequencing and comparative transcriptomics between the 1st and 4th legs (the latter without the Haller’s organ), we characterized 1st leg specific and putative Haller’s organ specific transcripts from adult American dog ticks, Dermacentor variabilis. The analysis suggested that the Haller’s organ is involved in olfaction, not gustation. No known odorant binding proteins like those found in insects, chemosensory lipocalins or typical insect olfactory mechanisms were identified; with the transcriptomic data only supporting a possible olfactory G-protein coupled receptor (GPCR) signal cascade unique to the Haller’s organ. Each component of the olfactory GPCR signal cascade was identified and characterized. The expression of GPCR, Gαo and β-arrestin transcripts identified exclusively in the 1st leg transcriptome, and putatively Haller’s organ specific, were examined in unfed and blood-fed adult female and male D. variabilis. Blood feeding to repletion in adult females down-regulated the expression of all three chemosensory transcripts in females but not in males; consistent with differences in post-feeding tick behavior between sexes and an expected reduced chemosensory function in females as they leave the host. Data are presented for the first time of the potential hormonal regulation of tick chemosensation; behavioral assays confirmed the role of the Haller’s organ in N,N-diethyl-meta-toluamide (DEET) repellency but showed no role for the Haller’s organ in host attachment. Further research is needed to understand the potential role of the GPCR cascade in olfaction.
Do Refuge Plants Favour Natural Pest Control in Maize Crops?
Authors: Quispe Reinaldo , Mazón Marina , Rodríguez-Berrío Alexander
Published: July 2017

The use of non-crop plants to provide the resources that herbivorous crop pests’ natural enemies need is being increasingly incorporated into integrated pest management programs. We evaluated insect functional groups found on three refuges consisting of five different plant species each, planted next to a maize crop in Lima, Peru, to investigate which refuge favoured natural control of herbivores considered as pests of maize in Peru, and which refuge plant traits were more attractive to those desirable enemies. Insects occurring in all the plants, including the maize crop itself, were sampled weekly during the crop growing cycle, from February to June 2011. All individuals collected were identified and classified into three functional groups: herbivores, parasitoids, and predators. Refuges were compared based on their effectiveness in enhancing the populations of predator and parasitoid insects of the crop enemies. Refuges A and B were the most effective, showing the highest richness and abundance of both predators and parasitoids, including several insect species that are reported to attack the main insect pests of maize (Spodoptera frugiperda and Rhopalosiphum maidis), as well as other species that serve as alternative hosts of these natural enemies.
A Multiparametric Approach Based on NT-proBNP, ST2, and Galectin3 for Stratifying One Year Prognosis of Chronic Heart Failure Outpatients
Authors: Grande Dario , Leone Marta , Rizzo Caterina , Terlizzese Paola , Parisi Giuseppe , Gioia Margherita , Leopizzi Tiziana , Segreto Antonio , Guida Piero , Romito Roberta , Ciccone Marco , Serio Francesca , Iacoviello Massimo
Published: July 2017

Galectin-3 and ST2 are emerging biomarkers involved in myocardial fibrosis. We evaluate the relevance of a multiparametric biomarker approach based on increased serum levels of NT-proBNP, galectin-3, and ST2 in stratifying the prognosis of chronic heart failure (CHF) outpatients. In 315 CHF outpatients in stable clinical condition clinical and echocardiographic evaluations were performed. Routine chemistry and serum levels of NT-proBNP, galectin-3, and ST2 were also assessed. During a 12 month follow-up, cardiovascular death, and/or heart failure (HF) occurred in 64 patients. The presence of NT-proBNP, galectin-3, and ST2 were higher than the recommended cutoffs and were all associated with events at univariate Cox regression analysis, as well as in a multivariate analysis including the three biomarkers. When a score based on the number of biomarkers above the recommended cut-offs was used (in a range of 0–3), it was associated with events both with respect to the univariate (HR 2.96, 95% CI 2.21–3.95, p < 0.001, C-index 0.78) and the multivariate (HR 1.52, 95% CI 1.06–2.17, p: 0.023, C-index 0.87) analyses, after correction for the variables of a reference model. Our results suggest that an easy prognostic approach based on the combination of three biomarkers, although with partially-overlapping pathophysiological mechanisms, is able to identify patients with the highest risk of heart failure progression.
Assessment of Geometric Distortion in Six Clinical Scanners Using a 3D-Printed Grid Phantom
Authors: Jafar Maysam , Jafar Yassir , Dean Christopher , Miquel Marc
Published: July 2017

A cost-effective regularly structured three-dimensional (3D) printed grid phantom was developed to enable the quantification of machine-related magnetic resonance (MR) distortion. This phantom contains reference features, “point-like” objects, or vertices, which resulted from the intersection of mesh edges in 3D space. 3D distortions maps were computed by comparing the locations of corresponding features in both MR and computer tomography (CT) data sets using normalized cross correlation. Results are reported for six MRI scanners at both 1.5 T and 3.0 T field strengths within our institution. Mean Euclidean distance error for all MR volumes in this study, was less than 2 mm. The maximum detected error for the six scanners ranged from 2.4 mm to 6.9 mm. The conclusions in this study agree well with previous studies that indicated that MRI is quite accurate near the centre of the field but is more spatially inaccurate toward the edges of the magnetic field.
Measuring Scientific Reasoning for Graduate Admissions in Psychology and Related Disciplines
Authors: Sternberg Robert J. , Sternberg Karin
Published: July 2017

In two studies, we examined the convergent and discriminant validation of a new assessment of scientific reasoning that could be used for graduate admissions in psychology, educational psychology, human development, and in the psychological sciences more generally. The full assessment ultimately consisted of tests of generating hypotheses, generating experiments, drawing conclusions, serving as a reviewer of a scientific article, and serving as an editor of a scientific journal. The tests had generally good convergent-discriminant validity. Certain socially defined ethnic/racial group differences were observed.
Mobilizing Instruction in a Second-Language Context: Learners’ Perceptions of Two Speech Technologies
Authors: Liakin Denis , Cardoso Walcir , Liakina Natallia
Published: July 2017

We report the results of two empirical studies that investigated the use of mobile text-to-speech synthesizers (TTS) and automatic speech recognition (ASR) as tools to promote the development of pronunciation skills in L2 French. Specifically, the study examined learners’ perceptions of the pedagogical use of these tools in learning a French segment (the vowel /y/, as in tu ‘you’) and a suprasegmental feature (across-word resyllabification/liaison, observed in petit enfant ‘small child’), in a mobile-assisted context. Our results indicate that, when used in a “learn anytime anywhere” mobile setting, the participants believe that they have: (1) increased and enhanced access to input; and (2) multiple opportunities for speech output and (3) for the development of prediction skills. Interestingly, these findings meet the requirements for successful L2 learning, one that recommends the inclusion of pedagogical activities that promote exposure to input (Nation & Newton 2009), multiple opportunities for output (Swain 1995), and the development of prediction skills (Dickerson 2015) to foster learner autonomy and, consequently, to maximize classroom time by extending the reach of the classroom. Our findings also indicate that participants recognize the pedagogical importance of TTS and ASR, and enjoy the mobile-enhanced learning environment afforded by these two technologies.
Friction and Wear of Self-Lubricating Materials for Hydropower Applications under Different Lubricating Conditions
Authors: Berglund Kim , Shi Yijun
Published: July 2017

Self-lubricating bearings in hydropower applications are often lubricated with water under boundary lubricating conditions. Polyhydric alcohols replacing water have shown the potential to reduce both friction and wear. The objective of this work is, therefore, to evaluate the effect of a polyhydric alcohol-based environmentally-acceptable lubricant (EAL) on the friction and wear of self-lubricating materials for conformal contacts under boundary lubricating conditions. The lubricating properties of four commercially-available self-lubricating bearing materials were investigated under three different lubricating conditions: dry, water and a new polyhydric alcohol-based EAL. Bearing materials include one metallic composite and three polymer composites. A reciprocating motion test rig was used to evaluate the wear and friction properties. Surface analysis was performed by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and optical profilometry. Results show that the wear rate for the polymer composites is increased when water is present compared to dry operating conditions. The new polyhydric alcohol-based EAL substantially improves both friction and anti-wear performance of all four self-lubricating bearing materials compared to both dry and water conditions. Surface analysis indicates that the material transfer to the counter-surface is limited when the polyhydric alcohol-based EAL is used.
Wear Performance of Calcium Carbonate-Containing Knee Spacers
Authors: Mueller Ulrike , Reinders Joern , Smith-Romanski Sydney , Kretzer Jan
Published: July 2017

Articulating spacers should be wear-resistant and load-bearing to avoid prolonged immobilization of the patient and to reduce morbidity. However, due to the articulation of both components, a release of cement wear particles is to be expected. The aim of this study was to investigate the wear performance of a new spacer cement that contains calcium carbonate as a radio-opaque substance, in comparison to an established barium sulphate-containing spacer material, and also to characterize the amount, morphology, and size distributions of the released cement particles in detail. Force-controlled simulation was carried out on an AMTI knee simulator. The test parameters were in accordance with the standard ISO 14243-1 with a 50% reduced axial force. Tests were run for 500,000 cycles at a frequency of 1 Hz. For wear analysis, photographic documentation of the wear scars, gravimetric wear measurements and wear particle analysis were performed. The barium sulphate spacer material showed a total articular wear of 375.53 ± 161.22 mg. For the calcium carbonate-containing cement, reduced articular wear of 136.32 ± 37.58 mg was determined. Isolated cement wear particles of the barium sulphate-containing cement had a diameter of 0.429 ± 0.224 μm and were significantly larger compared to the calcium carbonate-containing cement (0.380 ± 0.216 μm, p = 0.02). The calcium carbonate-containing cement showed better wear performance in terms of gravimetric wear and particle release. Thus, calcium carbonate seems to be a promising material as a radio-opaque substrate in cement spacers.
An Advanced Characterization Method for the Elastic Modulus of Nanoscale Thin-Films Using a High-Frequency Micromechanical Resonator
Authors: Kim Yun Young
Published: July 2017

Nanoscale materials have properties that frequently differ from those of their bulk form due to the scale effect, and therefore a measurement technique that can take account of such material characteristics with high accuracy and sensitivity is required. In the present study, advanced nanomechanical metrology was developed for evaluation of elastic properties of thin-film materials. A 52 nm thick chromium (Cr) film was deposited on a high-speed micromechanical resonator using an e-beam evaporator, and the structure was excited to resonate using an ultrasonic platform. The resonant frequencies for the first and second flexural vibration modes were measured using laser interferometry, and they were compared to analytical estimation from the classical beam theory. Results show that the experimental data are in excellent agreement with the theory, within 1% of the relative error, and a mass sensitivity up to 10.5 Hz/fg was achieved. Thus, the scale effect that reduced the Young’s modulus of Cr by 49.8% compared to its bulk property was correctly recognized by the proposed method.
Hydrothermal Sterilization Improves Initial Osteoblast Responses on Sandpaper-Polished Titanium
Authors: Shi Xingling , Xu Lingli , Wang Qingliang , Sunarso  , Xu Lin
Published: July 2017

Hydrocarbon contamination accumulated on titanium (Ti) implant surfaces during storage and sterilization is unavoidable and difficult to remove. It impairs the bioactivity of implants, restricts initial interactions between implants and the surrounding biological environment, and has become a common challenge for Ti implants. To overcome this problem, sterilization was considered as the final surface modification and a novel method, hydrothermal sterilization (HS), was proposed. Briefly, stored sandpaper-polished Ti specimens were sterilized in a glass container with pure water at 121 °C for 20 min and kept in the same water until utilization. As a control, another group of specimens was sterilized with conventional autoclaving (AC) at 121 °C for 20 min and stored in sterilization pouches after being dried at 60 °C. Compared with AC, HS deposited numerous nano-sized particles on the substrates, reduced the atomic percentage of the surface carbon, and transformed the Ti surface to a super hydrophilic status. HS also increased the attachment rate, spread, proliferation, and the mineralized nodule areas of rat bone marrow-derived osteoblasts. These results suggest that HS enhances the bioactivity of Ti implants for osteoblasts, and that this biofunctionalization was attributed to nanostructure construction, hydrophilic conversion, and the effective removal of hydrocarbons. Hydrothermal sterilization is proposed to be used as a universal sterilization method for all kinds of titanium implants without apatite coating.
Study of the Technical Feasibility of Increasing the Amount of Recycled Concrete Waste Used in Ready-Mix Concrete Production
Authors: Fraile-Garcia Esteban , Ferreiro-Cabello Javier , López-Ochoa Luis , López-González Luis
Published: July 2017

The construction industry generates a considerable amount of waste. Faced with this undesirable situation, the ready-mix concrete sector, in particular, has invested energy and resources into reusing its own waste in its production process as it works towards the goal of more sustainable construction. This study examines the feasibility of incorporating two types of concrete waste, which currently end up in landfill, into the production process of ready-mix concrete: the waste generated during the initial production stage (ready-mix concrete waste), and waste created when demolition waste is treated to obtain artificial aggregate. The first phase of the study’s methodology corroborates the suitability of the recycled aggregate through characterization tests. After this phase, the impact of incorporating different percentages of recycled coarse aggregate is evaluated by examining the performance of the produced concrete. The replacement rate varied between 15% and 50%. The results indicate that recycled aggregates are, indeed, suitable to be incorporated into ready-mix concrete production. The impact on the final product’s performance is different for the two cases examined herein. Incorporating aggregates from generic concrete blocks led to a 20% decrease in the produced concrete’s strength performance. On the other hand, using recycled aggregates made from the demolition waste led to a smaller decrease in the concrete’s performance: about 8%. The results indicate that with adequate management and prior treatment, the waste from these plants can be re-incorporated into their production processes. If concrete waste is re-used, concrete production, in general, becomes more sustainable for two reasons: less waste ends up as landfill and the consumption of natural aggregates is also reduced.
Color Shift Failure Prediction for Phosphor-Converted White LEDs by Modeling Features of Spectral Power Distribution with a Nonlinear Filter Approach
Authors: Fan Jiajie , Mohamed Moumouni Guero , Qian Cheng , Fan Xuejun , Zhang Guoqi , Pecht Michael
Published: July 2017

With the expanding application of light-emitting diodes (LEDs), the color quality of white LEDs has attracted much attention in several color-sensitive application fields, such as museum lighting, healthcare lighting and displays. Reliability concerns for white LEDs are changing from the luminous efficiency to color quality. However, most of the current available research on the reliability of LEDs is still focused on luminous flux depreciation rather than color shift failure. The spectral power distribution (SPD), defined as the radiant power distribution emitted by a light source at a range of visible wavelength, contains the most fundamental luminescence mechanisms of a light source. SPD is used as the quantitative inference of an LED’s optical characteristics, including color coordinates that are widely used to represent the color shift process. Thus, to model the color shift failure of white LEDs during aging, this paper first extracts the features of an SPD, representing the characteristics of blue LED chips and phosphors, by multi-peak curve-fitting and modeling them with statistical functions. Then, because the shift processes of extracted features in aged LEDs are always nonlinear, a nonlinear state-space model is then developed to predict the color shift failure time within a self-adaptive particle filter framework. The results show that: (1) the failure mechanisms of LEDs can be identified by analyzing the extracted features of SPD with statistical curve-fitting and (2) the developed method can dynamically and accurately predict the color coordinates, correlated color temperatures (CCTs), and color rendering indexes (CRIs) of phosphor-converted (pc)-white LEDs, and also can estimate the residual color life.
Strengthening Effect of Extruded Mg-8Sn-2Zn-2Al Alloy: Influence of Micro and Nano-Size Mg2Sn Precipitates
Authors: Cheng Weili , Bai Yang , Wang Lifei , Wang Hongxia , Bian Liping , Yu Hui
Published: July 2017

In this study, Mg-8Sn-2Zn-2Al (TZA822) alloys with varying Mg2Sn contents prior to extrusion were obtained by different pre-treatments (without and with T4), and the strengthening response related to micro and nano-size Mg2Sn precipitates in the extruded TZA822 alloys was reported. The results showed that the morphology of nano-size Mg2Sn precipitates exhibits a significant change in basal plane from rod-like to spherical, owing to the decrement in the fraction of micro-size particles before extrusion. Meanwhile, the spherical Mg2Sn precipitates provided a much stronger strengthening effect than did the rod-like ones, which was ascribed to uniform dispersion and refinement of spherical precipitates to effectively hinder basal dislocation slip. As a consequence, the extruded TZA822 alloy with T4 showed a higher tensile yield strength (TYS) of 245 MPa, ultimate tensile strength (UTS) of 320 MPa and elongation (EL) of 26.5%, as well as a lower degree of yield asymmetry than their counterpart without T4. Detailed reasons for the strengthening effect were given and analyzed.
Urinary Excretion of Tetrodotoxin Modeled in a Porcine Renal Proximal Tubule Epithelial Cell Line, LLC-PK1
Authors: Matsumoto Takuya , Ishizaki Yui , Mochizuki Keika , Aoyagi Mitsuru , Mitoma Yoshiharu , Ishizaki Shoichiro , Nagashima Yuji
Published: July 2017

This study examined the urinary excretion of tetrodotoxin (TTX) modeled in a porcine renal proximal tubule epithelial cell line, LLC-PK1. Time course profiles of TTX excretion and reabsorption across the cell monolayers at 37 °C showed that the amount of TTX transported increased linearly for 60 min. However, at 4 °C, the amount of TTX transported was approximately 20% of the value at 37 °C. These results indicate that TTX transport is both a transcellular and carrier-mediated process. Using a transport inhibition assay in which cell monolayers were incubated with 50 µM TTX and 5 mM of a transport inhibitor at 37 °C for 30 min, urinary excretion was significantly reduced by probenecid, tetraethylammonium (TEA), l-carnitine, and cimetidine, slightly reduced by p-aminohippuric acid (PAH), and unaffected by 1-methyl-4-phenylpyridinium (MPP+), oxaliplatin, and cefalexin. Renal reabsorption was significantly reduced by PAH, but was unaffected by probenecid, TEA and l-carnitine. These findings indicate that TTX is primarily excreted by organic cation transporters (OCTs) and organic cation/carnitine transporters (OCTNs), partially transported by organic anion transporters (OATs) and multidrug resistance-associated proteins (MRPs), and negligibly transported by multidrug and toxic compound extrusion transporters (MATEs).
The Biological Activities of Sesterterpenoid-Type Ophiobolins
Authors: Tian Wei , Deng Zixin , Hong Kui
Published: July 2017

Ophiobolins (Ophs) are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A–W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR) cells and cancer stem cells (CSCs). Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure–activity relationship to lay the foundation for the future developments and applications of these promising molecules.
Signaling within Allosteric Machines: Signal Transmission Pathways Inside G Protein-Coupled Receptors
Authors: Bartuzi Damian , Kaczor Agnieszka , Matosiuk Dariusz
Published: July 2017

In recent years, our understanding of function of G protein-coupled receptors (GPCRs) has changed from a picture of simple signal relays, transmitting only a particular signal to a particular G protein heterotrimer, to versatile machines, capable of various responses to different stimuli and being modulated by various factors. Some recent reports provide not only the data on ligands/modulators and resultant signals induced by them, but also deeper insights into exact pathways of signal migration and mechanisms of signal transmission through receptor structure. Combination of these computational and experimental data sheds more light on underlying mechanisms of signal transmission and signaling bias in GPCRs. In this review we focus on available clues on allosteric pathways responsible for complex signal processing within GPCRs structures, with particular emphasis on linking compatible in silico- and in vitro-derived data on the most probable allosteric connections.
A Protein Diet Score, Including Plant and Animal Protein, Investigating the Association with HbA1c and eGFR—The PREVIEW Project
Authors: Møller Grith , Sluik Diewertje , Ritz Christian , Mikkilä Vera , Raitakari Olli T. , Hutri-Kähönen Nina , Dragsted Lars O. , Larsen Thomas M. , Poppitt Sally D. , Silvestre Marta P. , Feskens Edith J.M. , Brand-Miller Jennie , Raben Anne
Published: July 2017

Higher-protein diets have been advocated for body-weight regulation for the past few decades. However, the potential health risks of these diets are still uncertain. We aimed to develop a protein score based on the quantity and source of protein, and to examine the association of the score with glycated haemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR). Analyses were based on three population studies included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World): NQplus, Lifelines, and the Young Finns Study. Cross-sectional data from food-frequency questionnaires (n = 76,777 subjects) were used to develop a protein score consisting of two components: 1) percentage of energy from total protein, and 2) plant to animal protein ratio. An inverse association between protein score and HbA1c (slope −0.02 ± 0.01 mmol/mol, p < 0.001) was seen in Lifelines. We found a positive association between the protein score and eGFR in Lifelines (slope 0.17 ± 0.02 mL/min/1.73 m2, p < 0.0001). Protein scoring might be a useful tool to assess both the effect of quantity and source of protein on health parameters. Further studies are needed to validate this newly developed protein score.
Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague–Dawley Rats
Authors: Al Zarzour Raghdaa , Ahmad Mariam , Asmawi Mohd. , Kaur Gurjeet , Saeed Mohammed , Al-Mansoub Majed , Saghir Sultan , Usman Nasiba , Al-Dulaimi Dhamraa , Yam Mun
Published: July 2017

Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague–Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC–HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis.
Dose-Dependent Prebiotic Effect of Lactulose in a Computer-Controlled In Vitro Model of the Human Large Intestine
Authors: Bothe Melanie , Maathuis Annet , Bellmann Susann , Van der Vossen Jos , Berressem Dirk , Koehler Annalena , Schwejda-Guettes Susann , Gaigg Barbara , Kuchinka-Koch Angelika , Stover John
Published: July 2017

Lactulose, a disaccharide of galactose and fructose, used as a laxative or ammonia-lowering drug and as a functional food ingredient, enhances growth of Bifidobacterium and Lactobacillus at clinically relevant dosages. The prebiotic effect of subclinical dosages of Lactulose, however, remains to be elucidated. This study analyses changes in the microbiota and their metabolites after a 5 days Lactulose treatment using the TIM-2 system, a computer-controlled model of the proximal large intestine representing a complex, high density, metabolically active, anaerobic microbiota of human origin. Subclinical dosages of 2–5 g Lactulose were used. While 2 g Lactulose already increased the short-chain fatty acid levels of the intestinal content, 5 g Lactulose were required daily for 5 days in this study to exert the full beneficial prebiotic effect consisting of higher bacterial counts of Bifidobacterium, Lactobacillus, and Anaerostipes, a rise in acetate, butyrate and lactate, as well as a decrease in branched-chain fatty acids, pH (suggested by an increase in NaOH usage), and ammonia.
Defining the Role of the Pharmacy Technician and Identifying Their Future Role in Medicines Optimisation
Authors: Boughen Melanie , Sutton Jane , Fenn Tess , Wright David
Published: July 2017

Background: Traditionally, pharmacy technicians have worked alongside pharmacists in community and hospital pharmacy. Changes within pharmacy provide opportunity for role expansion and with no apparent career pathway, there is a need to define the current pharmacy technician role and role in medicines optimisation. Aim: To capture the current roles of pharmacy technicians and identify how their future role will contribute to medicines optimisation. Methods: Following ethical approval and piloting, an online survey to ascertain pharmacy technicians’ views about their roles was undertaken. Recruitment took place in collaboration with the Association of Pharmacy Technicians UK. Data were exported to SPSS, data screened and descriptive statistics produced. Free text responses were analysed and tasks collated into categories reflecting the type of work involved in each task. Results: Responses received were 393 (28%, n = 1380). Results were organised into five groups: i.e., hospital, community, primary care, General Practitioner (GP) practice and other (which included HM Prison Service). Thirty tasks were reported as commonly undertaken in three or more settings and 206 (84.7%, n = 243) pharmacy technicians reported they would like to expand their role. Conclusions: Tasks core to hospital and community pharmacy should be considered for inclusion to initial education standards to reflect current practice. Post qualification, pharmacy technicians indicate a significant desire to expand clinically and managerially allowing pharmacists more time in patient-facing/clinical roles.
Development of Molecular Distillation Based Simulation and Optimization of Refined Palm Oil Process Based on Response Surface Methodology
Authors: Tehlah Noree , Kaewpradit Pornsiri , Mujtaba Iqbal
Published: July 2017

The deodorization of the refined palm oil process is simulated here using ASPEN HYSYS. In the absence of a library molecular distillation (MD) process in ASPEN HYSYS, first, a single flash vessel is considered to represent a falling film MD process which is simulated for a binary system taken from the literature and the model predictions are compared with the published work based on ASPEN PLUS and DISMOL. Second, the developed MD process is extended to simulate the deodorization process. Parameter estimation technique is used to estimate the Antoine’s parameters based on literature data to calculate the pure component vapor pressure. The model predictions are then validated against the patented results of refining edible oil rich in natural carotenes and vitamin E and simulation results were found to be in good agreement, within a ±2% error of the patented results. Third, Response Surface Methodology (RSM) is employed to develop non-linear second-order polynomial equations based model for the deodorization process and the effects of various operating parameters on the performance of the process are studied. Finally, an optimization framework is developed to maximize the concentration of beta-carotene, tocopherol and free fatty acid while optimizing the feed flow rate, temperature and pressure subject to process constrains. The optimum results of feed flow rate, temperature, and pressure were determined as 1291 kg/h, 147 °C and 0.0007 kPa respectively, and the concentration responses of beta- carotene, tocopherol and free fatty acid were found to be 0.000575, 0.000937 and 0.999840 respectively.
New Approach for Calculating the Effective Dielectric Constant of the Moist Soil for Microwaves
Authors: Park Chang-Hwan , Behrendt Andreas , LeDrew Ellsworth , Wulfmeyer Volker
Published: July 2017

Microwave remote sensing techniques are used, among others, for temporally and spatially highly-resolved observations of land-surface properties, e.g., for the management of agricultural productivity and water resource, as well as to improve the performances of numerical weather prediction and climate simulations with soil moisture data. In this context, the effective dielectric constant of the soil is a key variable to quantify the land surface properties. We propose a new approach for the effective dielectric constant of the multiphase soil that is based on an arithmetic average of the dielectric constants of the land-surface components with damping. The results show, on average, better agreement with experimental data than previous approaches. Furthermore, the proposed new model overcomes the theoretical limitation of previous models in the incorporation of non-physical parameters to simulate measured data experimentally with satisfactory accuracy. For microwave remote sensing such as SMAP (Soil Moisture Active Passive), SMOS (Soil Moisture and Ocean Salinity) and AMSR-E (Advanced Microwave Scanning Radiometer for EOS), the physical-based model in our study showed a 23–35% RMSE (root-mean-square error) reduction compared to the most prevalent refractive mixing model in the prediction of the dielectric constant for the real and imaginary part, respectively. Furthermore, in radiowave bands used in portable soil sensors such as TDR (time-domain reflectometer) and GPR (ground-penetrating radar) the new dielectric mixing model reduced RMSE by up to 53% in the prediction of the dielectric constant. We found that the permittivity over the saturation point (porosity of dry soil) has a very different and varying pattern compared to that measured in the unsaturated condition. However, in our study, this pattern was mathematically derived from the same mixing rule applied for the unsaturated condition. It is expected that the new dielectric mixing model might help to improve the accuracy of flood monitoring by satellite.
Development of Three-Dimensional Dental Scanning Apparatus Using Structured Illumination
Authors: Ahn Jae , Park Anjin , Kim Ju , Lee Byeong , Eom Joo
Published: July 2017

We demonstrated a three-dimensional (3D) dental scanning apparatus based on structured illumination. A liquid lens was used for tuning focus and a piezomotor stage was used for the shift of structured light. A simple algorithm, which detects intensity modulation, was used to perform optical sectioning with structured illumination. We reconstructed a 3D point cloud, which represents the 3D coordinates of the digitized surface of a dental gypsum cast by piling up sectioned images. We performed 3D registration of an individual 3D point cloud, which includes alignment and merging the 3D point clouds to exhibit a 3D model of the dental cast.
Passive Downhole Pressure Sensor Based on Surface Acoustic Wave Technology
Authors: Quintero Sully , Figueiredo Sávio , Takahashi Victor , Llerena Roberth , Braga Arthur
Published: July 2017

A passive surface acoustic wave (SAW) pressure sensor was developed for real-time pressure monitoring in downhole application. The passive pressure sensor consists of a SAW resonator, which is attached to a circular metal diaphragm used as a pressure transducer. While the membrane deflects as a function of pressure applied, the frequency response changes due to the variation of the SAW propagation parameters. The sensitivity and linearity of the SAW pressure sensor were measured to be 8.3 kHz/bar and 0.999, respectively. The experimental results were validated with a hybrid analytical–numerical analysis. The good results combined with the robust design and packaging for harsh environment demonstrated it to be a promising sensor for industrial applications.
Development and Application of a Structural Health Monitoring System Based on Wireless Smart Aggregates
Authors: Yan Shi , Ma Haoyan , Li Peng , Song Gangbing , Wu Jianxin
Published: July 2017

Structural health monitoring (SHM) systems can improve the safety and reliability of structures, reduce maintenance costs, and extend service life. Research on concrete SHMs using piezoelectric-based smart aggregates have reached great achievements. However, the newly developed techniques have not been widely applied in practical engineering, largely due to the wiring problems associated with large-scale structural health monitoring. The cumbersome wiring requires much material and labor work, and more importantly, the associated maintenance work is also very heavy. Targeting a practical large scale concrete crack detection (CCD) application, a smart aggregates-based wireless sensor network system is proposed for the CCD application. The developed CCD system uses Zigbee 802.15.4 protocols, and is able to perform dynamic stress monitoring, structural impact capturing, and internal crack detection. The system has been experimentally validated, and the experimental results demonstrated the effectiveness of the proposed system. This work provides important support for practical CCD applications using wireless smart aggregates.
Vibration Measurement Method of a String in Transversal Motion by Using a PSD
Authors: Yang Che-Hua , Wu Tai-Chieh
Published: July 2017

A position sensitive detector (PSD) is frequently used for the measurement of a one-dimensional position along a line or a two-dimensional position on a plane, but is more often used for measuring static or quasi-static positions. Along with its quick response when measuring short time-spans in the micro-second realm, a PSD is also capable of detecting the dynamic positions of moving objects. In this paper, theoretical modeling and experiments are conducted to explore the frequency characteristics of a vibrating string while moving transversely across a one-dimensional PSD. The theoretical predictions are supported by the experiments. When the string vibrates at its natural frequency while moving transversely, the PSD will detect two frequencies near this natural frequency; one frequency is higher than the natural frequency and the other is lower. Deviations in these two frequencies, which differ from the string’s natural frequency, increase while the speed of motion increases.