bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell Imaging Counting as a Novel Ex Vivo Approach for Investigating Drug-Induced Hepatotoxicity in Zebrafish Larvae
Authors: Nguyen Xuan-Bac , Kislyuk Stanislav , Pham Duc-Hung , Kecskés Angela , Maes Jan , Cabooter Deirdre , Annaert Pieter , De Witte Peter , Ny Annelii
Published: February 2017

Drug-induced liver injury (DILI) is the most common reason for failures during the drug development process and for safety-related withdrawal of drugs from the pharmaceutical market. Therefore, having tools and techniques that can detect hepatotoxic properties in drug candidates at an early discovery stage is highly desirable. In this study, cell imaging counting was used to measure in a fast, straightforward, and unbiased way the effect of paracetamol and tetracycline, (compounds known to cause hepatotoxicity in humans) on the amount of DsRed-labeled hepatocytes recovered by protease digestion from Tg(fabp10a:DsRed) transgenic zebrafish. The outcome was in general comparable with the results obtained using two reference methods, i.e., visual analysis of liver morphology by fluorescence microscopy and size analysis of fluorescent 2D liver images. In addition, our study shows that administering compounds into the yolk is relevant in the framework of hepatotoxicity testing. Taken together, cell imaging counting provides a novel and rapid tool for screening hepatotoxicants in early stages of drug development. This method is also suitable for testing of other organ-related toxicities subject to the organs and tissues expressing fluorescent proteins in transgenic zebrafish lines.
Multinucleated Giant Cancer Cells Produced in Response to Ionizing Radiation Retain Viability and Replicate Their Genome
Authors: Mirzayans Razmik , Andrais Bonnie , Scott April , Wang Ying , Kumar Piyush , Murray David
Published: February 2017

Loss of wild-type p53 function is widely accepted to be permissive for the development of multinucleated giant cells. However, whether therapy-induced multinucleation is associated with cancer cell death or survival remains controversial. Herein, we demonstrate that exposure of p53-deficient or p21WAF1 (p21)-deficient solid tumor-derived cell lines to ionizing radiation (between 2 and 8 Gy) results in the development of multinucleated giant cells that remain adherent to the culture dish for long times post-irradiation. Somewhat surprisingly, single-cell observations revealed that virtually all multinucleated giant cells that remain adherent for the duration of the experiments (up to three weeks post-irradiation) retain viability and metabolize 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), and the majority (>60%) exhibit DNA synthesis. We further report that treatment of multinucleated giant cells with pharmacological activators of apoptosis (e.g., sodium salicylate) triggers their demise. Our observations reinforce the notion that radiation-induced multinucleation may reflect a survival mechanism for p53/p21-deficient cancer cells. With respect to evaluating radiosensitivity, our observations underscore the importance of single-cell experimental approaches (e.g., single-cell MTT) as the creation of viable multinucleated giant cells complicates the interpretation of the experimental data obtained by commonly-used multi-well plate colorimetric assays.
Localisation Microscopy of Breast Epithelial ErbB-2 Receptors and Gap Junctions: Trafficking after γ-Irradiation, Neuregulin-1β, and Trastuzumab Application
Authors: Pilarczyk Götz , Nesnidal Ines , Gunkel Manuel , Bach Margund , Bestvater Felix , Hausmann Michael
Published: February 2017

In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin- 1 β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ -irradiation or alternatively neuregulin- 1 β application mobilized ErbB receptors in a nucleograde fashion—a process attenuated by trastuzumab antibody application. This was accompanied by increased receptor density, indicating packing into transport units. Factors mobilizing ErbB receptors also mobilized plasma membrane resident gap junction channels. The time course of ErbB receptor activation and gap junction mobilization recapitulates the time course of non-homologous end-joining DNA repair. We explain our findings under terms of DNA injury-induced membrane receptor tyrosine kinase activation and retrograde trafficking. In addition, we interpret the phenomenon of retrograde co-trafficking of gap junction connexons stimulated by ErbB receptor activation.
Detecting Blood-Based Biomarkers in Metastatic Breast Cancer: A Systematic Review of Their Current Status and Clinical Utility
Authors: Berghuis A. , Koffijberg Hendrik , Prakash Jai , Terstappen Leon , IJzerman Maarten
Published: February 2017

Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC) of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%). Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence.
Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer
Authors: Liu Guangbo , Pei Fen , Yang Fengqing , Li Lingxiao , Amin Amit , Liu Songnian , Buchan J. , Cho William
Published: February 2017

Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics.
A Cancer Stem Cell Potent Cobalt(III)–Cyclam Complex Bearing Two Tolfenamic Acid Moieties
Authors: Cressey Paul , Eskandari Arvin , Suntharalingam Kogularamanan
Published: February 2017

Cancer stem cells (CSCs) are thought to be responsible for cancer relapse. CSCs are a subtype of cancer cells with the ability to differentiate, self-renew, and form secondary or tertiary tumors. Current cancer treatments—including chemotherapy, radiation, and surgery—effectively remove bulk cancer cells but are unable to eliminate CSCs. Here, we present the synthesis, characterization, and anti-CSC properties of a cobalt(III)–cyclam complex bearing two tolfenamic acid moieties, 3. Notably, 3 displays sub-micromolar potency towards breast CSCs and bulk breast cancer cells. Detailed mechanistic studies show that 3 is taken up readily by breast CSCs, enters the nucleus, causes DNA damage, and induces caspase-dependent apoptosis. Furthermore, 3 inhibits cyclooxygenase-2 (COX-2) expression in CSCs. The mechanism of action of 3 is similar to that of a naproxen-appended cobalt(III)–cyclam complex, 1 recently reported by our group. The advantage of 3 over 1 is that it has the potential to remove whole tumor populations (bulk cancer cells and CSCs) with a single dose.
Cold Ambient Temperature Promotes Nosema spp. Intensity in Honey Bees (Apis mellifera)
Authors: Retschnig Gina , Williams Geoffrey , Schneeberger Annette , Neumann Peter
Published: February 2017

Interactions between parasites and environmental factors have been implicated in the loss of managed Western honey bee (=HB, Apis mellifera) colonies. Although laboratory data suggest that cold temperature may limit the spread of Nosema ceranae, an invasive species and now ubiquitous endoparasite of Western HBs, the impact of weather conditions on the distribution of this microsporidian in the field is poorly understood. Here, we conducted a survey for Nosema spp. using 18 Swiss apiaries (four colonies per apiary) over a period of up to 18 months. Samples consisting of 60 workers were collected monthly from each colony to estimate Nosema spp. intensity, i.e., the number of spores in positive samples using microscopy. Ambient apiary temperature was measured daily to estimate the proportion of days enabling HB flight (>10 °C at midday). The results show that Nosema spp. intensities were negatively correlated with the proportion of days enabling HB flight, thereby suggesting a significant and unexpected positive impact of cold ambient temperature on intensities, probably via regulation of defecation opportunities for infected hosts.
Sonic Hedgehog—‘Jack-of-All-Trades’ in Neural Circuit Formation
Authors: Zuñiga Nikole , Stoeckli Esther
Published: February 2017

As reflected by the term morphogen, molecules such as Shh and Wnts were identified based on their role in early development when they instruct precursor cells to adopt a specific cell fate. Only much later were they implicated in neural circuit formation. Both in vitro and in vivo studies indicated that morphogens direct axons during their navigation through the developing nervous system. Today, the best understood role of Shh and Wnt in axon guidance is their effect on commissural axons in the spinal cord. Shh was shown to affect commissural axons both directly and indirectly via its effect on Wnt signaling. In fact, throughout neural circuit formation there is cross-talk and collaboration of Shh and Wnt signaling. Thus, although the focus of this review is on the role of Shh in neural circuit formation, a separation from Wnt signaling is not possible.
The “Journal of Functional Morphology and Kinesiology” Journal Club Series: Highlights on Recent Papers in Movement Analysis
Authors: Wang Lingyan , Silva Luís , Di Rosa Michelino , Marques Carlos , Barreiros João , Cabri Jan
Published: February 2017

We are pleased to introduce the fourth Journal Club. This edition is focused on several relevant studies published in the last years in the field of movement analysis, chosen by our Editorial Board members. We hope to stimulate your curiosity in this field and to share with you the passion for the sport seen also from the scientific point of view.
3D Imaging with a Sonar Sensor and an Automated 3-Axes Frame for Selective Spraying in Controlled Conditions
Authors: Reiser David , Martín-López Javier , Memic Emir , Vázquez-Arellano Manuel , Brandner Steffen , Griepentrog Hans
Published: February 2017

Autonomous selective spraying could be a way for agriculture to reduce production costs, save resources, protect the environment and help to fulfill specific pesticide regulations. The objective of this paper was to investigate the use of a low-cost sonar sensor for autonomous selective spraying of single plants. For this, a belt driven autonomous robot was used with an attached 3-axes frame with three degrees of freedom. In the tool center point (TCP) of the 3-axes frame, a sonar sensor and a spray valve were attached to create a point cloud representation of the surface, detect plants in the area and perform selective spraying. The autonomous robot was tested on replicates of artificial crop plants. The location of each plant was identified out of the acquired point cloud with the help of Euclidian clustering. The gained plant positions were spatially transformed from the coordinates of the sonar sensor to the valve location to determine the exact irrigation points. The results showed that the robot was able to automatically detect the position of each plant with an accuracy of 2.7 cm and could spray on these selected points. This selective spraying reduced the used liquid by 72%, when comparing it to a conventional spraying method in the same conditions.
Estate Crops More Attractive than Community Forests in West Kalimantan, Indonesia
Authors: Langston James , Riggs Rebecca , Sururi Yazid , Sunderland Terry , Munawir Muhammad
Published: February 2017

Smallholder farmers and indigenous communities must cope with the opportunities and threats presented by rapidly spreading estate crops in the frontier of the agricultural market economy. Smallholder communities are subject to considerable speculation by outsiders, yet large-scale agriculture presents tradeoffs that they must navigate. We initiated a study in Sintang, West Kalimantan in 2012 and have returned annually for the last four years, building the baselines for a longer-term landscape approach to reconciling conservation and development tradeoffs in situ. Here, the stakeholders are heterogeneous, yet the land cover of the landscape is on a trajectory towards homogenous mono-cropping systems, primarily either palm oil or rubber. In one village on the frontier of the agricultural market economy, natural forests remain managed by the indigenous and local community but economics further intrude on forest use decisions. Conservation values are declining and the future of the forest is uncertain. As such, the community is ultimately attracted to more economically attractive uses of the land for local development oil palm or rubber mono-crop farms. We identify poverty as a threat to community-managed conservation success in the face of economic pressures to convert forest to intensive agriculture. We provide evidence that lucrative alternatives will challenge community-managed forests when prosperity seems achievable. To alleviate this trend, we identify formalized traditional management and landscape governance solutions to nurture a more sustainable landscape transition.
Online Shaming and the Right to Privacy
Authors: Laidlaw Emily
Published: February 2017

This paper advances privacy theory through examination of online shaming, focusing in particular on persecution by internet mobs. While shaming is nothing new, the technology used for modern shaming is new and evolving, making it a revealing lens through which to analyze points of analytical friction within and between traditional conceptions of privacy. To that end, this paper first explores the narrative and structure of online shaming, identifying broad categories of shaming of vigilantism, bullying, bigotry and gossiping, which are then used throughout the paper to evaluate different angles to the privacy problems raised. Second, this paper examines shaming through three dominant debates concerning privacy—privacy’s link with dignity, the right to privacy in public places and the social dimension of privacy. Certain themes emerged from this analysis. A common feature of online shaming is public humiliation. A challenge is to differentiate between a humbling (rightly knocking someone down a peg for a social transgression) and a humiliation that is an affront to dignity (wrongly knocking someone down a peg). In addition, the privacy concern of shamed individuals is not necessarily about intrusion on seclusion or revelation of embarrassing information, but rather about the disruption in their ability to continue to participate in online spaces free from attack. The privacy interest therefore becomes more about enabling participation in social spaces, enabling connections and relationships to form, and about enabling identity-making. Public humiliation through shaming can disrupt all of these inviting closer scrutiny concerning how law can be used as an enabling rather than secluding tool.
2-(tert-Butyl)-4-phenyloxetane
Authors: Perna Filippo , Vitale Paola , Summa Simona , Capriati Vito
Published: February 2017

The two geometric isomers of 2-(tert-butyl)-4-phenyloxetane have, for the first time, been prepared starting from the commercially available 4,4-dimethyl-1-phenylpentane-1,3-dione. The latter was reduced with NaBH4 to give a mixture of diastereomeric syn and anti diols which were then stereospecifically cyclized into the corresponding oxetanes with an overall yield for the two steps of 69.6%. The newly synthesized stereoisomeric four-membered oxygenated heterocycles were separated by column chromatography on silica gel and fully spectroscopically characterized.
Silicon Nitride Background in Nanophotonic Waveguide Enhanced Raman Spectroscopy
Authors: Dhakal Ashim , Wuytens Pieter , Raza Ali , Le Thomas Nicolas , Baets Roel
Published: February 2017

Recent studies have shown that evanescent Raman spectroscopy using a silicon nitride (SiN) nanophotonic waveguide platform has higher signal enhancement when compared to free-space systems. However, signal-to-noise ratio from the waveguide at a low analyte concentration is constrained by the shot-noise from the background light originating from the waveguide itself. Hence, understanding the origin and properties of this waveguide background luminescence (WGBL) is essential to developing mitigation strategies. Here, we identify the dominating component of the WGBL spectrum composed of a broad Raman scattering due to momentum selection-rule breaking in amorphous materials, and several peaks specific to molecules embedded in the core. We determine the maximum of the Raman scattering efficiency of the WGBL at room temperature for 785 nm excitation to be 4.5 ± 1 × 10−9 cm−1·sr−1, at a Stokes shift of 200 cm−1. This efficiency decreases monotonically for higher Stokes shifts. Additionally, we also demonstrate the use of slotted waveguides and quasi-transverse magnetic polarization as some mitigation strategies.
Shear Bond Strength of Al2O3 Sandblasted Y-TZP Ceramic to the Orthodontic Metal Bracket
Authors: Byeon Seon , Lee Min , Bae Tae
Published: February 2017

As the proportion of adult orthodontic treatment increases, mainly for aesthetic reasons, orthodontic brackets are directly attached to yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) restorations. This, study analyzed the shear bond strength (SBS) between various surface treated Y-TZP and orthodontic metal brackets. The Y-TZP specimens were conditioned by 110 μm Al2O3 sandblasting, or sandblasting followed by coating with one of the primers (silane, MDP, or an MDP-containing silane primer). After surface treatment, the orthodontic metal bracket was bonded to the specimen using a resin cement, and then 24 h storage in water and thermal cycling (5000 cycles, 5–55 °C), SBS was measured. Surface roughness was analyzed for surface morphology, and X-ray photoelectron spectroscopy (XPS) was employed for characterization of the chemical bond between the Y-TZP and the MDP-based primers (MDP, MDP containing silane primer). It was found that after surface treatment, the surface roughness of all groups increased. The groups treated with 110 μm Al2O3 sandblasting and MDP, or MDP-containing silane primer showed the highest SBS values, at 11.92 ± 1.51 MPa and 13.36 ± 2.31 MPa, respectively. The SBS values significantly decreased in all the groups after thermal cycling. Results from XPS analysis demonstrated the presence of chemical bonds between Y-TZP and MDP. Thus, the application of MDP-based primers after Al2O3 sandblasting enhances the resin bond strength between Y-TZP and the orthodontic metal bracket. However, bonding durability of all the surface-treated groups decreased after thermal cycling.
Magnetocaloric Properties of (MnFeRu)2(PSi) as Magnetic Refrigerants near Room Temperature
Authors: Ohnishi Takayuki , Soejima Kei , Yamashita Keiichiro , Wada Hirofumi
Published: February 2017

We have scaled up the production process of magnetic refrigerants near room temperature. The Mn2−yFey−xRuxP1−zSiz compounds with 0.03 ≤ x ≤ 0.16, y ≈ 0.75, and z ≈ 0.55 were synthesized and their magnetocaloric properties were examined. By changing the compositions and the annealing temperature, the Curie temperature was tuned between 275 and 315 K with 2~3 K steps. All the compounds underwent a first-order magnetic transition accompanied by thermal hysteresis of less than 2 K. The compounds showed excellent magnetocaloric properties: the magnetic entropy change was more than 10 J/K·kg and the refrigerant capacity was about 115 J/kg in a field change of 1.5 T. The detailed instructions to synthesize high-performance (MnFe)2PSi materials are given.
New Ethylenedithio-TTF Containing a 2,2,5,5-Tetramethylpyrrolin-1-yloxyl Radical through a Vinylene Spacer and Its FeCl4− Salt—Synthesis, Physical Properties and Crystal Structure Analyses
Authors: Horikiri Kazuki , Fujiwara Hideki
Published: February 2017

To develop novel magnetic conductors exhibiting conducting/magnetic bifunctionalities and peculiar responses to applied magnetic fields, we synthesized new EDT-TTF (ethylenedithiotetrathiafulvalene) donor containing a 2,2,5,5-tetramethylpyrrolin-1-yloxyl radical through a π-conjugated vinylene spacer 1 and examined its electronic and crystal structures, and physical properties. We also prepared its cation radical salts by an electrochemical oxidation method and successfully cleared the crystal structures and magnetic properties of the cation radical salts, 1·FeCl4 and 1·GaCl4. These salts have strongly dimerized one-dimensional arrays of the fully oxidized donor molecules, giving rise to the formation of spin-singlet state of the π cation radical spins in the dimer. On the other hand, the FeCl4- anion locates on the side of the dimers with very short S-Cl contacts and mediates very strong π-d interaction between the donor and anion moieties, resulting in the antiferromagnetic behavior of the Weiss temperature of θ = -3.9 K through its d-π-d interaction.
Recent Trends in Marine Phycotoxins from Australian Coastal Waters
Authors: Ajani Penelope , Harwood D. , Murray Shauna
Published: February 2017

Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the marine food web, are of growing concern for Australia. These harmful algae pose a threat to ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest growing food sectors in the world. With better monitoring, advanced analytical skills and an increase in microalgal expertise, many phycotoxins have been identified in Australian coastal waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern, warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012 resulted in an estimated total economic loss of~AUD$23M, indicating that there is an imperative to improve toxin and organism detection methods, clarify the toxin profiles of species of phytoplankton and carry out both intra‐ and inter‐species toxicity comparisons. Future work also includes the application of rapid, real‐time molecular assays for the detection of harmful species and toxin genes. This information, in conjunction with a better understanding of the life histories and ecology of harmful bloom species, may lead to more appropriate management of environmental, health and economic resources.
Aromatic Medicinal Plants of the Lamiaceae Family from Uzbekistan: Ethnopharmacology, Essential Oils Composition, and Biological Activities
Authors: Mamadalieva Nilufar , Akramov Davlat , Ovidi Elisa , Tiezzi Antonio , Nahar Lutfun , Azimova Shahnoz , Sarker Satyajit
Published: February 2017

Plants of the Lamiaceae family are important ornamental, medicinal, and aromatic plants, many of which produce essential oils that are used in traditional and modern medicine, and in the food, cosmetics, and pharmaceutical industry. Various species of the genera Hyssopus, Leonurus, Mentha, Nepeta, Origanum, Perovskia, Phlomis, Salvia, Scutellaria, and Ziziphora are widespread throughout the world, are the most popular plants in Uzbek traditional remedies, and are often used for the treatment of wounds, gastritis, infections, dermatitis, bronchitis, and inflammation. Extensive studies of the chemical components of these plants have led to the identification of many compounds, as well as essentials oils, with medicinal and other commercial values. The purpose of this review is to provide a critical overview of the literature surrounding the traditional uses, ethnopharmacology, biological activities, and essential oils composition of aromatic plants of the family Lamiaceae, from the Uzbek flora.
Laser Fabrication of Miniature Internal Thread in Glass Substrate
Authors: Degawa Hiroyuki , Urano Noriaki , Matsuo Shigeki
Published: February 2017

Miniature internal threads (tapped holes) of S0.5 were fabricated in a glass substrate. Water-assisted laser drilling was applied for fabrication of the threads of S0.5 standard using a subnanosecond laser as a light source. The landscape of the inner surface of the threads was measured by a laser microscope, and showed reasonable agreement with the desired standard. As a proof of concept, a commercial external screw was fitted to the fabricated internal thread.
Special Issue on Ruthenium Complexes
Authors: Dragutan Ileana , Dragutan Valerian , Demonceau Albert
Published: February 2017

The organic chemistry of ruthenium has been one of the most vigorously growing research areas over the past decades. Considerable effort has been extended towards the design and application of a broad series of ruthenium complexes, which culminated with the development by Ryoji Noyori (2001 Nobel Prize for Chemistry) of chiral ruthenium catalysts for stereoselective hydrogenation reactions [1], and the discovery by Robert H. Grubbs (2005 Nobel Prize for Chemistry) of well-defined ruthenium– benzylidene catalysts for olefin metathesis [2] [...]
New Furan Derivatives from a Mangrove-Derived Endophytic Fungus Coriolopsis sp. J5
Authors: Chen Liang-Liang , Wang Pei , Chen Hui-Qin , Guo Zhi-Kai , Wang Hao , Dai Hao-Fu , Mei Wen-Li
Published: February 2017

Six new furan derivatives, named 5-(3-methoxy-3-oxopropyl)-furan-2-carboxylic acid (1), 1-(5-(2-hydroxypropanoyl)-furan-2-yl)-pentan-3-one (2), 2-hydroxy-1-(5-(1-hydroxypentyl)-furan-2-yl)-propan-1-one (3), 1-(5-(1,2-dihydroxypropyl)-furan-2-yl)-pentan-1-one (4), 5-(1-hydroxypent-4-en-1-yl)-furan-2-carboxylic acid (5) and 5-(3-hydroxypentyl)-furan-2-carboxylic acid (6), together with two new natural products, named 5-(1-hydroxypentyl)-furan-2-carboxylic acid (7) and (E)-5-(2-carboxyvinyl)-furan-2-carboxylic acid (8), were isolated from the solid rice fermentation of endophytic fungus Coriolopsis sp. J5, which was derived from mangrove plant Ceriops tagal. Their structures were unambiguously elucidated based on 1D and 2D NMR spectroscopy, and by HRESIMS measurements, as well as by comparison with the literature.
Magnetic Nanovectors for the Development of DNA Blood-Stage Malaria Vaccines
Authors: Al-Deen Fatin , Xiang Sue , Ma Charles , Wilson Kirsty , Coppel Ross , Selomulya Cordelia , Plebanski Magdalena
Published: February 2017

DNA vaccines offer cost, flexibility, and stability advantages, but administered alone have limited immunogenicity. Previously, we identified optimal configurations of magnetic vectors comprising superparamagnetic iron oxide nanoparticles (SPIONs), polyethylenimine (PEI), and hyaluronic acid (HA) to deliver malaria DNA encoding Plasmodium yoelii (Py) merozoite surface protein MSP119 (SPIONs/PEI/DNA + HA gene complex) to dendritic cells and transfect them with high efficiency in vitro. Herein, we evaluate their immunogenicity in vivo by administering these potential vaccine complexes into BALB/c mice. The complexes induced antibodies against PyMSP119, with higher responses induced intraperitoneally than intramuscularly, and antibody levels further enhanced by applying an external magnetic field. The predominant IgG subclasses induced were IgG2a followed by IgG1 and IgG2b. The complexes further elicited high levels of interferon gamma (IFN-γ), and moderate levels of interleukin (IL)-4 and IL-17 antigen-specific splenocytes, indicating induction of T helper 1 (Th1), Th2, and Th17 cell mediated immunity. The ability of such DNA/nanoparticle complexes to induce cytophilic antibodies together with broad spectrum cellular immunity may benefit malaria vaccines.
Effects of an Encapsulated Fruit and Vegetable Juice Concentrate on Obesity-Induced Systemic Inflammation: A Randomised Controlled Trial
Authors: Williams Evan , Baines Katherine , Berthon Bronwyn , Wood Lisa
Published: February 2017

Phytochemicals from fruit and vegetables reduce systemic inflammation. This study examined the effects of an encapsulated fruit and vegetable (F&V) juice concentrate on systemic inflammation and other risk factors for chronic disease in overweight and obese adults. A double-blinded, parallel, randomized placebo-controlled trial was conducted in 56 adults aged ≥40 years with a body mass index (BMI) ≥28 kg/m2. Before and after eight weeks daily treatment with six capsules of F&V juice concentrate or placebo, peripheral blood gene expression (microarray, quantitative polymerase chain reaction (qPCR)), plasma tumour necrosis factor (TNF)α (enzyme-linked immunosorbent assay (ELISA)), body composition (Dual-energy X-ray absorptiometry (DEXA)) and lipid profiles were assessed. Following consumption of juice concentrate, total cholesterol, low-density lipoprotein (LDL) cholesterol and plasma TNFα decreased and total lean mass increased, while there was no change in the placebo group. In subjects with high systemic inflammation at baseline (serum C-reactive protein (CRP) ≥3.0 mg/mL) who were supplemented with the F&V juice concentrate (n = 16), these effects were greater, with decreased total cholesterol, LDL cholesterol and plasma TNFα and increased total lean mass; plasma CRP was unchanged by the F&V juice concentrate following both analyses. The expression of several genes involved in lipogenesis, the nuclear factor-κB (NF-κB) and 5′ adenosine monophosphate-activated protein kinase (AMPK) signalling pathways was altered, including phosphomevalonate kinase (PMVK), zinc finger AN1-type containing 5 (ZFAND5) and calcium binding protein 39 (CAB39), respectively. Therefore, F&V juice concentrate improves the metabolic profile, by reducing systemic inflammation and blood lipid profiles and, thus, may be useful in reducing the risk of obesity-induced chronic disease.
Impact of Flavonols on Cardiometabolic Biomarkers: A Meta‐Analysis of Randomized Controlled Human Trials to Explore the Role of Inter‐Individual Variability
Authors: Menezes Regina , Rodriguez‐Mateos Ana , Kaltsatou Antonia , González‐Sarrías Antonio , Greyling Arno , Giannaki Christoforos , Andres‐Lacueva Cristina , Milenkovic Dragan , Gibney Eileen , Dumont Julie , Schär Manuel , Garcia‐Aloy Mar , Palma‐Duran Susana , Ruskovska Tatjana , Maksimova Viktorija , Combet Emilie , Pinto Paula
Published: February 2017

Several epidemiological studies have linked flavonols with decreased risk of cardiovascular disease (CVD). However, some heterogeneity in the individual physiological responses to the consumption of these compounds has been identified. This meta‐analysis aimed to study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood pressure and plasma glucose, as well as factors affecting their inter‐individual variability. Data from 18 human randomized controlled trials were pooled and the effect was estimated using fixed or random effects meta‐analysis model and reported as difference in means (DM). Variability in the response of blood lipids to supplementation with flavonols was assessed by stratifying various population subgroups: age, sex, country, and health status. Results showed significant reductions in total cholesterol (DM = −0.10 mmol/L; 95% CI: −0.20, −0.01), LDL cholesterol (DM = −0.14 mmol/L; Nutrients 2017, 9, 117 2 of 21 95% CI: −0.21, 0.07), and triacylglycerol (DM = −0.10 mmol/L; 95% CI: −0.18, 0.03), and a significant increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also observed in fasting plasma glucose (DM = −0.18 mmol/L; 95%CI: −0.29, −0.08), and in blood pressure (SBP: DM = −4.84 mmHg; 95% CI: −5.64, −4.04; DBP: DM = −3.32 mmHg; 95% CI: -4.09, -2.55). Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk, however, country of origin and health status may influence the effect of flavonol intake on blood lipid levels
Macronutrient Intakes in 553 Dutch Elite and Sub-Elite Endurance, Team, and Strength Athletes: Does Intake Differ between Sport Disciplines?
Authors: Wardenaar Floris , Brinkmans Naomi , Ceelen Ingrid , Van Rooij Bo , Mensink Marco , Witkamp Renger , De Vries Jeanne
Published: February 2017

Web-based 24-h dietary recalls and questionnaires were obtained from 553 Dutch well-trained athletes. The total energy and macronutrient intake was compared between discipline-categories (endurance, team, and strength) within gender, and dietary inadequacy, i.e., too low or high intakes, according to selected recommendations and guidelines, was evaluated by applying a probability approach. On average, 2.83 days per person were reported with a mean energy intake of 2566–2985 kcal and 1997–2457 kcal per day, for men and women, respectively. Between disciplines, small differences in the mean intake of energy and macronutrients were seen for both men and women. Overall, 80% of the athletes met the suggested lower-limit sport nutrition recommendation of 1.2 g·kg−1 of protein per day. The carbohydrate intake of 50%–80% of athletes was between 3 and 5 g·kg−1 bodyweight, irrespective of the category of their discipline. This can be considered as low to moderate, in view of their daily total exercise load (athletes reported on average ~100 minutes per day). In conclusion, only small differences in the mean energy and macronutrient intake between elite endurance, strength, and team sport athletes, were found. The majority of the athletes were able to meet the generally accepted protein recommendation for athletes, of 1.2 g·kg−1. However, for most athletes, the carbohydrate intake was lower than generally recommended in the existing consensus guidelines on sport nutrition. This suggests that athletes could either optimize their carbohydrate intake, or that average carbohydrate requirements merit a re-evaluation.
Nutrients in Energy and One-Carbon Metabolism: Learning from Metformin Users
Authors: Luciano-Mateo Fedra , Hernández-Aguilera Anna , Cabre Noemi , Camps Jordi , Fernández-Arroyo Salvador , Lopez-Miranda Jose , Menendez Javier , Joven Jorge
Published: February 2017

Metabolic vulnerability is associated with age-related diseases and concomitant co-morbidities, which include obesity, diabetes, atherosclerosis and cancer. Most of the health problems we face today come from excessive intake of nutrients and drugs mimicking dietary effects and dietary restriction are the most successful manipulations targeting age-related pathways. Phenotypic heterogeneity and individual response to metabolic stressors are closely related food intake. Understanding the complexity of the relationship between dietary provision and metabolic consequences in the long term might provide clinical strategies to improve healthspan. New aspects of metformin activity provide a link to many of the overlapping factors, especially the way in which organismal bioenergetics remodel one-carbon metabolism. Metformin not only inhibits mitochondrial complex 1, modulating the metabolic response to nutrient intake, but also alters one-carbon metabolic pathways. Here, we discuss findings on the mechanism(s) of action of metformin with the potential for therapeutic interpretations.
A Biodegradable Microneedle Cuff for Comparison of Drug Effects through Perivascular Delivery to Balloon-Injured Arteries
Authors: Kim Dae-Hyun , Jang Eui , Lee Kang , Lee Ji , Park Seung , Seo Il , Lee Kang , Lee Seung , Ryu WonHyoung , Youn Young-Nam
Published: February 2017

Restenosis at a vascular anastomosis site is a major cause of graft failure and is difficult to prevent by conventional treatment. Perivascular drug delivery has advantages as drugs can be diffused to tunica media and subintima while minimizing the direct effect on endothelium. This in vivo study investigated the comparative effectiveness of paclitaxel, sirolimus, and sunitinib using a perivascular biodegradable microneedle cuff. A total of 31 New Zealand white rabbits were used. Rhodamine was used to visualize drug distribution (n = 3). Sirolimus- (n = 7), sunitinib- (n = 7), and paclitaxel-loaded (n = 7) microneedle cuffs were placed at balloon-injured abdominal aortae and compared to drug-free cuffs (n = 7). Basic histological structures were not affected by microneedle devices, and vascular wall thickness of the device-only group was similar to that of normal artery. Quantitative analysis revealed significantly decreased neointima formation in all drug-treated groups (p < 0.001). However, the tunica media layer of the paclitaxel-treated group was significantly thinner than that of other groups and also showed the highest apoptotic ratio (p < 0.001). Proliferating cell nuclear antigen (PCNA)-positive cells were significantly reduced in all drug-treated groups. Sirolimus or sunitinib appeared to be more appropriate for microneedle devices capable of slow drug release because vascular wall thickness was minimally affected.
De Novo Sequencing of Top-Down Tandem Mass Spectra: A Next Step towards Retrieving a Complete Protein Sequence
Authors: Vyatkina Kira
Published: February 2017

De novo sequencing of tandem (MS/MS) mass spectra represents the only way to determine the sequence of proteins from organisms with unknown genomes, or the ones not directly inscribed in a genome—such as antibodies, or novel splice variants. Top-down mass spectrometry provides new opportunities for analyzing such proteins; however, retrieving a complete protein sequence from top-down MS/MS spectra still remains a distant goal. In this paper, we review the state-of-the-art on this subject, and enhance our previously developed Twister algorithm for de novo sequencing of peptides from top-down MS/MS spectra to derive longer sequence fragments of a target protein.
The Impact of Pay-As-You-Throw Schemes on Municipal Solid Waste Management: The Exemplar Case of the County of Aschaffenburg, Germany
Authors: Morlok Juergen , Schoenberger Harald , Styles David , Galvez-Martos Jose-Luis , Zeschmar-Lahl Barbara
Published: February 2017

The “pay-as-you-throw” (PAYT) scheme is an economic instrument for waste management that applies the “polluter pays” principle by charging the inhabitants of municipalities according to the amount of residual, organic, and bulky waste they send for third-party waste management. When combined with well-developed infrastructure to collect the different waste fractions (residual waste, paper and cardboard, plastics, bio waste, green cuttings, and many recyclables) as well as with a good level of citizens’ awareness, its performance has frequently been linked to an increase in the collection rates of recyclables. However, the establishment and operation of PAYT systems can require significant resource inputs from municipalities. In this paper, PAYT is analysed through a case study from the German County of Aschaffenburg, covering nearly 20 years of implementation across 32 municipalities with 173,000 inhabitants. Key performance indicators include temporal trends in the county’s recyclables collection rate, waste treatment fees for residents, and municipal waste management costs, benchmarked against German municipalities not implementing PAYT. We conclude that PAYT could make an important contribution towards material reuse and recycling objectives for the new circular economy.
Volatile Organic Compounds Sensing Using Optical Fibre Long Period Grating with Mesoporous Nano-Scale Coating
Authors: Hromadka Jiri , Korposh Sergiy , Partridge Matthew , James Stephen , Davis Frank , Crump Derrick , Tatam Ralph
Published: February 2017

A long period grating (LPG) modified with a mesoporous film infused with a calixarene as a functional compound was employed for the detection of individual volatile organic compounds (VOCs) and their mixtures. The mesoporous film consisted of an inorganic part, SiO2 nanoparticles (NPs), along with an organic moiety of poly(allylamine hydrochloride) polycation PAH, which was finally infused with the functional compound, p-sulphanato calix[4]arene (CA[4]) or p-sulphanato calix[8]arene (CA[8]). The LPG sensor was designed to operate at the phase matching turning point to provide the highest sensitivity. The sensing mechanism is based on the measurement of the refractive index (RI) change induced by a complex of the VOCs with calixarene. The LPG, modified with a coating of 5 cycles of (SiO2 NPs/PAH) and infused with CA[4] or CA[8], was exposed to chloroform, benzene, toluene and acetone vapours. The British Standards test of the VOCs emissions from material (BS EN ISO 16000-9:2006) was used to test the LPG sensor performance.
Novel Hierarchical Fall Detection Algorithm Using a Multiphase Fall Model
Authors: Hsieh Chia-Yeh , Liu Kai-Chun , Huang Chih-Ning , Chu Woei-Chyn , Chan Chia-Tai
Published: February 2017

Falls are the primary cause of accidents for the elderly in the living environment. Reducing hazards in the living environment and performing exercises for training balance and muscles are the common strategies for fall prevention. However, falls cannot be avoided completely; fall detection provides an alarm that can decrease injuries or death caused by the lack of rescue. The automatic fall detection system has opportunities to provide real-time emergency alarms for improving the safety and quality of home healthcare services. Two common technical challenges are also tackled in order to provide a reliable fall detection algorithm, including variability and ambiguity. We propose a novel hierarchical fall detection algorithm involving threshold-based and knowledge-based approaches to detect a fall event. The threshold-based approach efficiently supports the detection and identification of fall events from continuous sensor data. A multiphase fall model is utilized, including free fall, impact, and rest phases for the knowledge-based approach, which identifies fall events and has the potential to deal with the aforementioned technical challenges of a fall detection system. Seven kinds of falls and seven types of daily activities arranged in an experiment are used to explore the performance of the proposed fall detection algorithm. The overall performances of the sensitivity, specificity, precision, and accuracy using a knowledge-based algorithm are 99.79%, 98.74%, 99.05% and 99.33%, respectively. The results show that the proposed novel hierarchical fall detection algorithm can cope with the variability and ambiguity of the technical challenges and fulfill the reliability, adaptability, and flexibility requirements of an automatic fall detection system with respect to the individual differences.
A Miniature Magnetic-Force-Based Three-Axis AC Magnetic Sensor with Piezoelectric/Vibrational Energy-Harvesting Functions
Authors: Hung Chiao-Fang , Yeh Po-Chen , Chung Tien-Kan
Published: February 2017

In this paper, we demonstrate a miniature magnetic-force-based, three-axis, AC magnetic sensor with piezoelectric/vibrational energy-harvesting functions. For magnetic sensing, the sensor employs a magnetic–mechanical–piezoelectric configuration (which uses magnetic force and torque, a compact, single, mechanical mechanism, and the piezoelectric effect) to convert x-axis and y-axis in-plane and z-axis magnetic fields into piezoelectric voltage outputs. Under the x-axis magnetic field (sine-wave, 100 Hz, 0.2–3.2 gauss) and the z-axis magnetic field (sine-wave, 142 Hz, 0.2–3.2 gauss), the voltage output with the sensitivity of the sensor are 1.13–26.15 mV with 8.79 mV/gauss and 1.31–8.92 mV with 2.63 mV/gauss, respectively. In addition, through this configuration, the sensor can harness ambient vibrational energy, i.e., possessing piezoelectric/vibrational energy-harvesting functions. Under x-axis vibration (sine-wave, 100 Hz, 3.5 g) and z-axis vibration (sine-wave, 142 Hz, 3.8 g), the root-mean-square voltage output with power output of the sensor is 439 mV with 0.333 μW and 138 mV with 0.051 μW, respectively. These results show that the sensor, using this configuration, successfully achieves three-axis magnetic field sensing and three-axis vibration energy-harvesting. Due to these features, the three-axis AC magnetic sensor could be an important design reference in order to develop future three-axis AC magnetic sensors, which possess energy-harvesting functions, for practical industrial applications, such as intelligent vehicle/traffic monitoring, processes monitoring, security systems, and so on.
Dynamic Voltage-Frequency and Workload Joint Scaling Power Management for Energy Harvesting Multi-Core WSN Node SoC
Authors: Li Xiangyu , Xie Nijie , Tian Xinyue
Published: February 2017

This paper proposes a scheduling and power management solution for energy harvesting heterogeneous multi-core WSN node SoC such that the system continues to operate perennially and uses the harvested energy efficiently. The solution consists of a heterogeneous multi-core system oriented task scheduling algorithm and a low-complexity dynamic workload scaling and configuration optimization algorithm suitable for light-weight platforms. Moreover, considering the power consumption of most WSN applications have the characteristic of data dependent behavior, we introduce branches handling mechanism into the solution as well. The experimental result shows that the proposed algorithm can operate in real-time on a lightweight embedded processor (MSP430), and that it can make a system do more valuable works and make more than 99.9% use of the power budget.
Towards Building a Computer Aided Education System for Special Students Using Wearable Sensor Technologies
Authors: Mehmood Raja , Lee Hyo
Published: February 2017

Human computer interaction is a growing field in terms of helping people in their daily life to improve their living. Especially, people with some disability may need an interface which is more appropriate and compatible with their needs. Our research is focused on similar kinds of problems, such as students with some mental disorder or mood disruption problems. To improve their learning process, an intelligent emotion recognition system is essential which has an ability to recognize the current emotional state of the brain. Nowadays, in special schools, instructors are commonly use some conventional methods for managing special students for educational purposes. In this paper, we proposed a novel computer aided method for instructors at special schools where they can teach special students with the support of our system using wearable technologies.