bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of 3D Multicomponent Model for Cold Spray Process Using Nitrogen and Air
Authors: Rab Muhammad , Zahiri Saden , Masood Syed , Jahedi Mahnaz , Nagarajah Romesh
Published: October 2015

Cold spray is a unique coating technology that allows for solid state deposition of particles under atmospheric pressure. In this paper, a three dimensional, Computational Fluid Dynamics (CFD) multicomponent model is developed to estimate cold spray gas conditions involving both nitrogen and air. Calibration of the model followed by validation is accomplished by considering the thermal history of substrate exposed to cold spray supersonic jet. The developed holistic multicomponent model is effective in determining the state of gas and particles from injection point to the substrate surface with the advantage of optimizing very rapid cold spray deposition in nanoseconds. The validation of k-ε type CFD multicomponent model is done by using the temperature measured for a titanium substrate exposed to cold spray nitrogen at 800 °C and 3 MPa. Heat transfer and radiation are considered for the de Laval nozzle used in cold spray experiments. The calibrated multicomponent model has successfully estimated the state of propellant gas for the chosen high pressure and high temperature cold spray conditions. Moreover, the multicomponent model predictions are in good agreement with a previous holistic three dimensional cold spray model in which only nitrogen was used as the surrounding as well as the propellant gas.
Modified Legendre Wavelets Technique for Fractional Oscillation Equations
Authors: Mohyud-Din Syed , Iqbal Muhammad , Hassan Saleh
Published: October 2015

Physical Phenomena’s located around us are primarily nonlinear in nature and their solutions are of highest significance for scientists and engineers. In order to have a better representation of these physical models, fractional calculus is used. Fractional order oscillation equations are included among these nonlinear phenomena’s. To tackle with the nonlinearity arising, in these phenomena’s we recommend a new method. In the proposed method, Picard’s iteration is used to convert the nonlinear fractional order oscillation equation into a fractional order recurrence relation and then Legendre wavelets method is applied on the converted problem. In order to check the efficiency and accuracy of the suggested modification, we have considered three problems namely: fractional order force-free Duffing–van der Pol oscillator, forced Duffing–van der Pol oscillator and higher order fractional Duffing equations. The obtained results are compared with the results obtained via other techniques.
Exponential Synchronization of Two Complex Dynamical Networks of Random Disturbance with Both Mixed Coupled and Time-Varying Delay by Pinning Control
Authors: Wu Xuefei
Published: October 2015

In this paper, the exponentially synchronization in the mean square is investigated for two different stochastic complex networks with hybrid coupling and time-varying delay via pinning control. By utilizing the Lyapunov stability theory, stochastic analysis theory, as well as matrix analysis, the sufficient conditions are derived to guarantee the exponential synchronization for any initial values through a feedback scheme. The numerical simulation is provided to show the effectiveness of the theoretical results.
A Novel Design Method for Optimizing an Indirect Forced Circulation Solar Water Heating System Based on Life Cycle Cost Using a Genetic Algorithm
Authors: Ko Myeong
Published: October 2015

To maximize the energy performance and economic benefits of solar water heating (SWH) systems, the installation and operation-related design variables as well as those related to capacity must be optimized. This paper presents a novel design method for simultaneously optimizing the various design variables of an indirect forced-circulation SWH system that is based on the life cycle cost and uses a genetic algorithm. The effectiveness of the proposed method is assessed by evaluating the long-term performance corresponding to four cases, which are optimized using different annual solar fractions and sets of the design variables. When the installation and operation-related design variables were taken into consideration, it resulted in an efficient and economic design and an extra cost reduction of 3.2%–6.1% over when only the capacity-related design variables were considered. In addition, the results of parametric studies show that the slope and mass flow rate of the collector have a significant impact on the energy and economic performances of SWH systems. In contrast, the mass flow rate in the secondary circuit and the differences in the temperatures of the upper and lower dead bands of the differential controller have a smaller impact.
An Energy Management Service for the Smart Office
Authors: Rottondi Cristina , Duchon Markus , Koss Dagmar , Palamarciuc Andrei , Pití Alessandro , Verticale Giacomo , Schätz Bernhard
Published: October 2015

The evolution of the electricity grid towards the smart grid paradigm is fostering the integration of distributed renewable energy sources in smart buildings: a combination of local power generation, battery storage and controllable loads can greatly increase the energetic self-sufficiency of a smart building, enabling it to maximize the self-consumption of photovoltaic electricity and to participate in the energy market, thus taking advantage of time-variable tariffs to achieve economic savings. This paper proposes an energy management infrastructure specifically tailored for a smart office building, which relies on measured data and on forecasting algorithms to predict the future patterns of both local energy generation and power loads. The performance is compared to the optimal energy usage scheduling, which would be obtained assuming the exact knowledge of the future energy production and consumption trends, showing gaps below 10% with respect to the optimum.
A Non-Unity Torque Sharing Function for Torque Ripple Minimization of Switched Reluctance Generators in Wind Power Systems
Authors: Shin Hye-Ung , Park Kiwoo , Lee Kyo-Beum
Published: October 2015

This paper deals with a new torque ripple minimization method for a Switched Reluctance Generator (SRG). Although, the SRG has many advantages including simple and robust construction, and high power density as a generator, it has not been widely employed in the industry. One of the major drawbacks of the SRG is its high torque ripple that results in high noise operation of the generator. In this paper, a non-unity Torque Sharing Function (TSF) is proposed to minimize the torque ripple over a wide speed range of operation. Simulations as well as experimental results are presented to verify the effectiveness of the proposed torque ripple minimization technique.
Reliability of Heterochromatic Flicker Photometry in Measuring Macular Pigment Optical Density among Preadolescent Children
Authors: McCorkle Sasha , Raine Lauren , Hammond Billy , Renzi-Hammond Lisa , Hillman Charles , Khan Naiman
Published: October 2015

Macular pigment optical density (MPOD)—assessed using customized heterochromatic flicker photometry (cHFP)—is related to better cognition and brain lutein among adults. However, the reliability of MPOD assessed by cHFP has not been investigated in children. We assessed inter-session reliability of MPOD using modified cHFP. 7–10-year-olds (n = 66) underwent cHFP over 2 visits using 11 examiners. Reliability was also assessed in a subsample (n = 46) with only 2 examiners. Among all participants, there was no significant difference between the two sessions (p = 0.59—session 1: 0.61 ± 0.28; session 2: 0.62 ± 0.27). There was no significant difference in the MPOD of boys vs. girls (p = 0.56). There was a significant correlation between sessions (Y = 0.52x + 0.31; R2 = 0.29, p ≤ 0.005), with a reliability of 0.70 (Cronbach’s α). Among the subsample with 2 examiners, there was a significant correlation between sessions (Y = 0.54x + 0.31; R2 = 0.32, p < 0.005), with a reliability of 0.72 (Cronbach’s α). In conclusion, there is moderate reliability for modified cHFP to measure MPOD in preadolescents. These findings provide support for future studies aiming to conduct noninvasive assessments of retinal xanthophylls and study their association with cognition during childhood.
A Strange Cartography: Leylines, Landscape and “Deep Mapping” in the Works of Alfred Watkins
Authors: Thurgill James
Published: October 2015

In 1921 the photographer, antiquarian and amateur archaeologist Alfred Watkins, delivered his newly formed thesis on the origins of ancient alignments in the west of England to the Woolhope Naturalists’ Field Club of Hereford. Watkins posited a correlation between ancient forts, moats, mounds, churches, trees and place names, which he had shown to produce straight lines running across the landscape. In 1922 Watkins published his first book on the subject, Early British Trackways, mixing amateur archaeology, social history and supposition to introduce what Watkins named “leylines” and setting out the guidelines for other would-be ley hunters. This paper explores Watkins’ ley hunting as a practice of “deep mapping”, examining its use as an applied spatial engagement with the hidden trajectories of the landscape. In addition to providing a concise cultural history of the leyline, with particular reference to the works of Alfred Watkins, this paper develops a critical engagement with ley-walking through an auto-ethnographic response to a leyline that has been mapped and walked in Norfolk, England.
A Combined Raindrop Aggregate Destruction Test-Settling Tube (RADT-ST) Approach to Identify the Settling Velocity of Sediment
Authors: Xiao Liangang , Hu Yaxian , Greenwood Philip , Kuhn Nikolaus
Published: October 2015

The use of sediment settling velocity based on mineral grain size distribution in erosion models ignores the effects of aggregation on settling velocity. The alternative approach, wet-sieved aggregate size distribution, on the other hand, cannot represent all destructive processes that eroded soils may experience under impacting raindrops. Therefore, without considering raindrop impact, both methods may lead to biased predictions of the redistribution of sediment and associated substances across landscapes. Rainfall simulation is an effective way to simulate natural raindrop impact under controlled laboratory conditions. However, very few methods have been developed to integrate rainfall simulation with the settling velocity of eroded sediment. This study aims to develop a new proxy, based on rainfall simulation, in order to identify the actual settling velocity distribution of aggregated sediment. A combined Raindrop Aggregate Destruction Test-Settling Tube (RADT-ST) approach was developed to (1) simulate aggregate destruction under a series of simulated rainfalls; and (2) measure the actual settling velocity distribution of destroyed aggregates. Mean Weight Settling Velocity (MWSV) of aggregates was used to investigate settling behaviors of different soils as rainfall kinetic energy increased. The results show the settling velocity of silt-rich raindrop impacted aggregates is likely to be underestimated by at least six times if based on mineral grain size distribution. The RADT-ST designed in this study effectively captures the effects of aggregation on settling behavior. The settling velocity distribution should be regarded as an evolving, rather than steady state parameter during erosion events. The combined RADT-ST approach is able to generate the quasi-natural sediment under controlled simulated rainfall conditions and is adequately sensitive to measure actual settling velocities of differently aggregated soils. This combined approach provides an effective tool to improve the parameterization of settling velocity input for erosion models.
Research Priorities for NCD Prevention and Climate Change: An International Delphi Survey
Authors: Colagiuri Ruth , Boylan Sinead , Morrice Emily
Published: October 2015

Climate change and non-communicable diseases (NCDs) are arguably the greatest global challenges of the 21st Century. However, the confluence between them remains under-examined and there is little evidence of a comprehensive, systematic approach to identifying research priorities to mitigate their joint impact. Consequently, we: (i) convened a workshop of academics (n = 25) from the Worldwide Universities Network to identify priority areas at the interface between NCDs and climate change; (ii) conducted a Delphi survey of international opinion leaders in public health and relevant other disciplines; and (iii) convened an expert panel to review and advise on final priorities. Three research areas (water security; transport; conceptualising NCD harms to support policy formation) were listed among the top 10 priorities by >90% of Delphi respondents, and ranked among the top 12 priorities by >60% of respondents who ranked the order of priority. A fourth area (reducing the carbon footprint of cities) was ranked highest by the same >60% of respondents. Our results are consistent with existing frameworks on health and climate change, and extends them by focusing specifically on NCDs. Researching these priorities could progress understanding of climate change and NCDs, and inform global and national policy decisions for mitigating associated harms.
The Effects of Targeted Deliveries of Lovastatin and Tocotrienol on Ossification-Related Gene Expressions in Fracture Healing in an Osteoporosis Rat Model
Authors: Ibrahim Nurul , Mohamed Norazlina , Soelaiman Ima , Shuid Ahmad
Published: October 2015

Osteoporotic drugs are used to prevent fragility fractures, but their role in fracture healing still remains unknown. Thus, alternative agents with suitable mode of delivery are needed to promote fracture healing. This study was performed to investigate the effects of direct deliveries of lovastatin and tocotrienol to fracture sites on ossification-related gene expression in fracture healing in a postmenopausal osteoporosis model. Forty-eight Sprague Dawley female rats were divided into six groups. Group I comprised the sham-operated rats, while Groups II–VI were ovariectomized rats. After 8 weeks, the right tibiae of all rats were fractured and stabilized. Group I and Group II were given two single injections of lovastatin and tocotrienol carriers. Group III was given an estrogen preparation at 64.5 µg/kg daily via oral gavages. Group IV was injected with lovastatin particles (750 µg/kg), while Group V was injected with tocotrienol particles (60 mg/kg). Group VI received two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks, the gene expressions were measured. Group VI showed significantly higher gene expressions of osteocalcin, BMP-2, VEGF-α, and RUNX-2 compared to Group II. In conclusion, combined treatment of lovastatin and tocotrienol upregulated the expression of genes related to fracture healing.
Occupational Exposure to Urban Air Pollution and Allergic Diseases
Authors: Vimercati Luigi , Gatti Maria , Baldassarre Antonio , Nettis Eustachio , Favia Nicola , Palma Marco , Martina Gabriella , Di Leo Elisabetta , Musti Marina
Published: October 2015

Exposure to air pollution is associated with increased morbidity from cardiovascular diseases, lung cancer, respiratory and allergic diseases. The aim of this study was to investigate allergic diseases in 111 traffic wardens compared to a control group of 101 administrative employees. All participating subjects underwent a physical examination, in which a complete medical history was taken and a dedicated allergological questionnaire administered. Spirometry, Specific IgE dosage (RAST) and skin prick tests (SPT) were done. Diagnostic investigations such as the nasal cytology, a specific nasal provocation test and rhinomanometry were also performed. Statistical analyses were performed using STATA version 11. The percentage of subjects with a diagnosis of allergy was higher in the exposed workers than in the controls. As regards the clinical tests, the positivity was higher for the group of exposed subjects. Among the exposed workers, those who worked on foot or motorcycle had a higher positivity in clinical trials compared to the traffic wardens who used the car. Our study showed a higher percentage of allergic subjects in the group of workers exposed to outdoor pollutants than in the controls. These results suggest that allergological tests should be included in the health surveillance protocols for workers exposed to outdoor pollutants.
Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF
Authors: Tang Tianle , Yang Yang , Chen Yawen , Tang Wenhao , Wang Fuqiang , Diao Xiaoping
Published: October 2015

Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae.
Local Edge Matching for Seamless Adjacent Spatial Datasets with Sequence Alignment
Authors: Huh Yong
Published: October 2015

This study proposes a local edge matching method with a sequence alignment technique for adjacent spatial datasets. By assuming that the common boundary edges of the datasets are point strings, the proposed method obtains the sequence for point edit operations to align the edges by using the string matching algorithm with the following operations: (1) snapping two points from each string to their average position, (2) removing a point from one string and (3) removing a point from the other string. The costs for these operations are derived from the deformation of the involved line segments in terms of the angle and length changes. The corresponding point pairs are then considered point pairs for which the snapping operation is chosen in a sequence. Based on these pairs, a border area of adjacent spatial datasets can be partitioned into sub-border areas where distinctive matching and alignment processes can be performed.
No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer’s Disease: A Randomised Controlled Trial
Authors: Phillips Michelle , Childs Caroline , Calder Philip , Rogers Peter
Published: October 2015

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer’s disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer’s disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.
Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders
Authors: Scholz Sonja , Bras Jose
Published: October 2015

Atypical parkinsonism syndromes, such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, are neurodegenerative diseases with complex clinical and pathological features. Heterogeneity in clinical presentations, possible secondary determinants as well as mimic syndromes pose a major challenge to accurately diagnose patients suffering from these devastating conditions. Over the last two decades, significant advancements in genomic technologies have provided us with increasing insights into the molecular pathogenesis of atypical parkinsonism and their intriguing relationships to related neurodegenerative diseases, fueling new hopes to incorporate molecular knowledge into our diagnostic, prognostic and therapeutic approaches towards managing these conditions. In this review article, we summarize the current understanding of genetic mechanisms implicated in atypical parkinsonism syndromes. We further highlight mimic syndromes relevant to differential considerations and possible future directions.
Staphylococcus aureus and MRSA Growth and Biofilm Formation after Treatment with Antibiotics and SeNPs
Authors: Cihalova Kristyna , Chudobova Dagmar , Michalek Petr , Moulick Amitava , Guran Roman , Kopel Pavel , Adam Vojtech , Kizek Rene
Published: October 2015

Methicillin-resistant Staphylococcus aureus (MRSA) is a dangerous pathogen resistant to β-lactam antibiotics. Due to its resistance, it is difficult to manage the infections caused by this strain. We examined this issue in terms of observation of the growth properties and ability to form biofilms in sensitive S. aureus and MRSA after the application of antibiotics (ATBs)—ampicillin, oxacillin and penicillin—and complexes of selenium nanoparticles (SeNPs) with these ATBs. The results suggest the strong inhibition effect of SeNPs in complexes with conventional ATBs. Using the impedance method, a higher disruption of biofilms was observed after the application of ATB complexes with SeNPs compared to the group exposed to ATBs without SeNPs. The biofilm formation was intensely inhibited (up to 99% ± 7% for S. aureus and up to 94% ± 4% for MRSA) after application of SeNPs in comparison with bacteria without antibacterial compounds whereas ATBs without SeNPs inhibited S. aureus up to 79% ± 5% and MRSA up to 16% ± 2% only. The obtained results provide a basis for the use of SeNPs as a tool for the treatment of bacterial infections, which can be complicated because of increasing resistance of bacteria to conventional ATB drugs.
Surface-Deacetylated Chitin Nano-Fiber/Hyaluronic Acid Composites as Potential Antioxidative Compounds for Use in Extended-Release Matrix Tablets
Authors: Anraku Makoto , Tabuchi Ryo , Ifuku Shinsuke , Ishiguro Takako , Iohara Daisuke , Hirayama Fumitoshi
Published: October 2015

In this study, we examined a possible use of a surface-deacetylated chitin nano-fiber (SDCH-NF) and hyaluronic acid (HA) interpolymer complex (IPC) tablet as a potential antioxidative compound in extended-release matrix tablets. The antioxidant properties of untreated chitin (UCH), SDCH-NF, and HA were examined using N-centered radicals derived from 1,1′-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). SDCH-NF and HA had acceptable scavenging abilities and were relatively efficient radical scavengers, but UCH was much less effective. The results suggest that SDCH-NF and HA could serve as scavengers of compounds related to the development of oxidative stress. An SDCH-NF/HA IPC tablet was prepared and evaluated as an extended-release tablet matrix using famotidine (FMT) as a model drug. The release of FMT from the IPC tablet (DCF-NF:HA = 1:1) was slower than that from a SDCH-NF only tablet. Turbidity measurements and X-ray diffraction (XRD) data also indicated that the optimum complexation ratio for IPC between SDCH-NF/HA is 1/1, resulting in a good relationship between turbidity or XRD of the complex and the release ratio of FMT. These results suggest that an SDCH-NF/HA tablet has the potential for use in an extended-release IPC tablet with a high antioxidant activity.
Biological Screening of Newly Synthesized BIAN N-Heterocyclic Gold Carbene Complexes in Zebrafish Embryos
Authors: Farooq Muhammad , Taha Nael , Butorac Rachel , Evans Daniel , Elzatahry Ahmed , Elsayed Elsayed , Wadaan Mohammad , Al-Deyab Salem , Cowley Alan
Published: October 2015

N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10–12 h. One hundred percent mortality was observed at concentrations ≥50 µM. At sub-lethal concentrations (10–30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%–40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules.
Minimizing off-Target Mutagenesis Risks Caused by Programmable Nucleases
Authors: Ishida Kentaro , Gee Peter , Hotta Akitsu
Published: October 2015

Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. However, because the accuracy of DNA recognition by these nucleases is not always perfect, off-target mutagenesis may result in undesirable adverse events in treated patients such as cellular toxicity or tumorigenesis. Therefore, designing nucleases and analyzing their activity must be carefully evaluated to minimize off-target mutagenesis. Furthermore, rigorous genomic testing will be important to ensure the integrity of nuclease modified cells. In this review, we provide an overview of available nuclease designing platforms, nuclease engineering approaches to minimize off-target activity, and methods to evaluate both on- and off-target cleavage of CRISPR-Cas9.
Elevated STAT3 Signaling-Mediated Upregulation of MMP-2/9 Confers Enhanced Invasion Ability in Multidrug-Resistant Breast Cancer Cells
Authors: Zhang Fei , Wang Zhiyong , Fan Yanling , Xu Qiao , Ji Wei , Tian Ran , Niu Ruifang
Published: October 2015

The development of multidrug resistance greatly impedes effective cancer therapy. Recent advances in cancer research have demonstrated that acquisition of multidrug resistance by cancer cells is usually accompanied by enhanced cell invasiveness. Several lines of evidence indicated that cross activation of other signaling pathways during development of drug resistance may increase invasive potential of multidrug-resistant (MDR) cancer cells. However, the accurate mechanism of this process is largely undefined. In this study, to better understand the associated molecular pathways responsible for cancer progression induced by drug resistance, a MDR human breast cancer cell line SK-BR-3/EPR with P-glycoprotein overexpression was established using stepwise long-term exposure to increasing concentration of epirubicin. The SK-BR-3/EPR cell line exhibited decreased cell proliferative activity, but enhanced cell invasive capacity. We showed that the expression of metastasis-related matrix metalloproteinase (MMP)-2/9 was elevated in SK-BR-3/EPR cells. Moreover, SK-BR-3/EPR cells showed elevated activation of STAT3. Activation of STAT3 signaling is responsible for enhanced invasiveness of SK-BR-3/EPR cells through upregulation of MMP-2/9. STAT3 is a well-known oncogene and is frequently implicated in tumorigenesis and chemotherapeutic resistance. Our findings augment insight into the mechanism underlying the functional association between MDR and cancer invasiveness.
Extending Deacon’s Notion of Teleodynamics to Culture, Language, Organization, Science, Economics and Technology (CLOSET)
Authors: Logan Robert
Published: October 2015

Terrence Deacon’s (2012) notion developed in his book Incomplete Nature (IN) that living organisms are teleodynamic systems that are self-maintaining, self-correcting and self-reproducing is extended to human social systems. The hypothesis is developed that culture, language, organization, science, economics and technology (CLOSET) can be construed as living organisms that evolve, maintain and reproduce themselves and are self-correcting, and hence are teleodynamic systems. The elements of CLOSET are to a certain degree autonomous, even though they are obligate symbionts dependent on their human hosts for the energy that sustains them.
Characterization and Curing Kinetics of Epoxy/Silica Nano-Hybrids
Authors: Yang Cheng-Fu , Wang Li-Fen , Wu Song-Mao , Su Chean-Cheng
Published: October 2015

The sol-gel technique was used to prepare epoxy/silica nano-hybrids. The thermal characteristics, curing kinetics and structure of epoxy/silica nano-hybrids were studied using differential scanning calorimetry (DSC), 29Si nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM). To improve the compatibility between the organic and inorganic phases, a coupling agent was used to modify the diglycidyl ether of bisphenol A (DGEBA) epoxy. The sol-gel technique enables the silica to be successfully incorporated into the network of the hybrids, increasing the thermal stability and improving the mechanical properties of the prepared epoxy/silica nano-hybrids. An autocatalytic mechanism of the epoxy/SiO2 nanocomposites was observed. The low reaction rate of epoxy in the nanocomposites is caused by the steric hindrance in the network of hybrids that arises from the consuming of epoxide group in the network of hybrids by the silica. In the nanocomposites, the nano-scale silica particles had an average size of approximately 35 nm, and the particles were well dispersed in the epoxy matrix, according to the TEM images.
The Histone Deacetylase Inhibitor JAHA Down-Regulates pERK and Global DNA Methylation in MDA-MB231 Breast Cancer Cells
Authors: Librizzi Mariangela , Chiarelli Roberto , Bosco Liana , Sansook Supojjanee , Gascon Jose , Spencer John , Caradonna Fabio , Luparello Claudio
Published: October 2015

The histone deacetylase inhibitor N1-(ferrocenyl)-N8-hydroxyoctanediamide (JAHA) down-regulates extracellular-signal-regulated kinase (ERK) and its activated form in triple-negative MDA-MB231 breast cancer cells after 18 h and up to 30 h of treatment, and to a lesser extent AKT and phospho-AKT after 30 h and up to 48 h of treatment. Also, DNA methyltransferase 1 (DNMT1), 3b and, to a lesser extent, 3a, downstream ERK targets, were down-regulated already at 18 h with an increase up to 48 h of exposure. Methylation-sensitive restriction arbitrarily-primed (MeSAP) polymerase chain reaction (PCR) analysis confirmed the ability of JAHA to induce genome-wide DNA hypomethylation at 48 h of exposure. Collective data suggest that JAHA, by down-regulating phospho-ERK, impairs DNMT1 and 3b expression and ultimately DNA methylation extent, which may be related to its cytotoxic effect on this cancer cytotype.
Reduction Expansion Synthesis as Strategy to Control Nitrogen Doping Level and Surface Area in Graphene
Authors: Canty Russell , Gonzalez Edwin , MacDonald Caleb , Osswald Sebastian , Zea Hugo , Luhrs Claudia
Published: October 2015

Graphene sheets doped with nitrogen were produced by the reduction-expansion (RES) method utilizing graphite oxide (GO) and urea as precursor materials. The simultaneous graphene generation and nitrogen insertion reactions are based on the fact that urea decomposes upon heating to release reducing gases. The volatile byproducts perform two primary functions: (i) promoting the reduction of the GO and (ii) providing the nitrogen to be inserted in situ as the graphene structure is created. Samples with diverse urea/GO mass ratios were treated at 800 °C in inert atmosphere to generate graphene with diverse microstructural characteristics and levels of nitrogen doping. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to study the microstructural features of the products. The effects of doping on the samples structure and surface area were studied by X-ray diffraction (XRD), Raman Spectroscopy, and Brunauer Emmet Teller (BET). The GO and urea decomposition-reduction process as well as nitrogen-doped graphene stability were studied by thermogravimetric analysis (TGA) coupled with mass spectroscopy (MS) analysis of the evolved gases. Results show that the proposed method offers a high level of control over the amount of nitrogen inserted in the graphene and may be used alternatively to control its surface area. To demonstrate the practical relevance of these findings, as-produced samples were used as electrodes in supercapacitor and battery devices and compared with conventional, thermally exfoliated graphene.
A Surface Micromachined CMOS MEMS Humidity Sensor
Authors: Huang Jian-Qiu , Li Fei , Zhao Min , Wang Kai
Published: October 2015

This paper reports a CMOS MEMS (complementary metal oxide semiconductor micro electromechanical system) piezoresistive humidity sensor fabricated by a surface micromachining process. Both pre-CMOS and post-CMOS technologies were used to fabricate the piezoresistive humidity sensor. Compared with a bulk micromachined humidity sensor, the machining precision and the sizes of the surface micromachined humidity sensor were both improved. The package and test systems of the sensor were designed. According to the test results, the sensitivity of the sensor was 7 mV/%RH (relative humidity) and the linearity of the sensor was 1.9% at 20 °C. Both the sensitivity and linearity were not sensitive to the temperature but the curve of the output voltage shifted with the temperature. The hysteresis of the humidity sensor decreased from 3.2% RH to 1.9% RH as the temperature increased from 10 to 40 °C. The recovery time of the sensor was 85 s at room temperature (25 °C).
In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla
Authors: Pamplona Sônia , Sá Paulo , Lopes Dielly , Costa Edmar , Yamada Elizabeth , Silva Consuelo , Arruda Mara , Souza Jesus , Da Silva Milton
Published: October 2015

Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 μg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.
Phosphonylated Acyclic Guanosine Analogues with the 1,2,3-Triazole Linker
Authors: Głowacka Iwona , Andrei Graciela , Schols Dominique , Snoeck Robert , Piotrowska Dorota
Published: October 2015

A novel series of {4-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates and {4-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methyl]-1H-1,2,3-triazol-1-yl}alkylphosphonates as acyclic analogues of guanosine were synthesized and assessed for antiviral activity against a broad range of DNA and RNA viruses and for their cytostatic activity toward three cancerous cell lines (HeLa, L1210 and CEM). They were devoid of antiviral activity; however, several phosphonates were found slightly cytostatic against HeLa cells at an IC50 in the 80–210 µM range. Compounds (1R,2S)-17k and (1S,2S)-17k showed the highest inhibitory effects (IC50 = 15–30 µM) against the proliferation of murine leukemia (L1210) and human T-lymphocyte (CEM) cell lines.
Synthesis, Hydrolysis, and Protonation-Promoted Intramolecular Reductive Breakdown of Potential NRTIs: Stavudine α-P-Borano-γ-P-N-l-tryptophanyltriphosphates
Authors: Xu Zhihong , Shaw Barbara
Published: October 2015

Phosphorus-modified prodrugs of dideoxynucleoside triphosphates (ddNTPs) have shown promise as pronucleotide strategies for improving antiviral activity compared to their parent dideoxynucleosides. Borane modified NTPs offer a promising choice as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). However, the availability of α-P-borano-γ-P-substituted NTP analogs remains limited due to challenges with synthesis and purification. Here, we report the chemical synthesis and stability of a new potential class of NRTI prodrugs: stavudine (d4T) 5′-α-P-borano-γ-P-N-L-tryptophanyltriphosphates. One-pot synthesis of these compounds was achieved via a modified cyclic trimetaphosphate approach. Pure Rp and Sp diastereomers were obtained after HPLC separation. Based on LC-MS analysis, we report degradation pathways, half-lives (5–36 days) and mechanisms arising from structural differences to generate the corresponding borano tri- and di-phosphates, and H-phosphonate, via several parallel routes in buffer at physiologically relevant pH and temperature. Here, the major hydrolysis products, d4T α-P-boranotriphosphate Rp and Sp isomers, were isolated by HPLC and identified with spectral data. We first propose that one of the major degradation products, d4T H-phosphonate, was generated from the d4T pronucleotides via a protonation-promoted intramolecular reduction followed by a second step nucleophilic attack. This report could provide valuable information for pronucleotide-based drug design in terms of selective release of target nucleotides.
Synthesis and Crystallographic Insight into the Structural Aspects of Some Novel Adamantane-Based Ester Derivatives
Authors: Kumar C. , Kwong Huey , Mah Siau , Chia Tze , Loh Wan-Sin , Quah Ching , Lim Gin , Chandraju Siddegowda , Fun Hoong-Kun
Published: October 2015

Adamantyl-based compounds are commercially important in the treatments for neurological conditions and type-2 diabetes, aside from their anti-viral abilities. Their values in drug design are chronicled as multi-dimensional. In the present study, a series of 2-(adamantan-1-yl)-2-oxoethyl benzoates, 2(a–q), and 2-(adamantan-1-yl)-2-oxoethyl 2-pyridinecarboxylate, 2r, were synthesized by reacting 1-adamantyl bromomethyl ketone with various carboxylic acids using potassium carbonate in dimethylformamide medium at room temperature. Three-dimensional structures studied using X-ray diffraction suggest that the adamantyl moiety can serve as an efficient building block to synthesize 2-oxopropyl benzoate derivatives with synclinal conformation with a looser-packed crystal packing system. Compounds 2a, 2b, 2f, 2g, 2i, 2j, 2m, 2n, 2o, 2q and 2r exhibit strong antioxidant activities in the hydrogen peroxide radical scavenging test. Furthermore, three compounds, 2p, 2q and 2r, show good anti-inflammatory activities in the evaluation of albumin denaturation.
Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception
Authors: Mancuso Giuseppe , Borgonovo Gigliola , Scaglioni Leonardo , Bassoli Angela
Published: October 2015

Ruta graveolens (rue) is a spontaneous plant in the Mediterranean area with a strong aroma and a very intense bitter taste, used in gastronomy and in folk medicine. From the leaves, stems and fruits of rue, we isolated rutin, rutamarin, three furanocoumarins, two quinolinic alkaloids, a dicoumarin and two long chain ketones. Bitter taste and chemesthetic properties have been evaluated by in vitro assays with twenty receptors of the TAS2R family and four TRP ion channels involved in gustation and nociception. Among the alkaloids, skimmianine was active as a specific agonist of T2R14, whereas kokusaginin did not activate any of the tested receptors. The furanocoumarins activates TAS2R10, 14, and 49 with different degrees of selectivity, as well as the TRPA1 somatosensory ion channel. Rutamarin is an agonist of TRPM5 and TRPV1 and a strong antagonist of TRPM8 ion channels.
Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants
Authors: Tsuchiya Hironori
Published: October 2015

In addition to interacting with functional proteins such as receptors, ion channels, and enzymes, a variety of drugs mechanistically act on membrane lipids to change the physicochemical properties of biomembranes as reported for anesthetic, adrenergic, cholinergic, non-steroidal anti-inflammatory, analgesic, antitumor, antiplatelet, antimicrobial, and antioxidant drugs. As well as these membrane-acting drugs, bioactive plant components, phytochemicals, with amphiphilic or hydrophobic structures, are presumed to interact with biological membranes and biomimetic membranes prepared with phospholipids and cholesterol, resulting in the modification of membrane fluidity, microviscosity, order, elasticity, and permeability with the potencies being consistent with their pharmacological effects. A novel mechanistic point of view of phytochemicals would lead to a better understanding of their bioactivities, an insight into their medicinal benefits, and a strategic implication for discovering drug leads from plants. This article reviews the membrane interactions of different classes of phytochemicals by highlighting their induced changes in membrane property. The phytochemicals to be reviewed include membrane-interactive flavonoids, terpenoids, stilbenoids, capsaicinoids, phloroglucinols, naphthodianthrones, organosulfur compounds, alkaloids, anthraquinonoids, ginsenosides, pentacyclic triterpene acids, and curcuminoids. The membrane interaction’s applicability to the discovery of phytochemical drug leads is also discussed while referring to previous screening and isolating studies.
Voltammetric Determination of Ferulic Acid Using Polypyrrole-Multiwalled Carbon Nanotubes Modified Electrode with Sample Application
Authors: Abdel-Hamid Refat , Newair Emad
Published: October 2015

A polypyrrole-multiwalled carbon nanotubes modified glassy carbon electrode-based sensor was devised for determination of ferulic acid (FA). The fabricated sensor was prepared electrochemically using cyclic voltammetry (CV) and characterized using CV and scanning electron microscope (SEM). The electrode shows an excellent electrochemical catalytic activity towards FA oxidation. Under optimal conditions, the anodic peak current correlates linearly to the FA concentration throughout the range of 3.32 × 10−6 to 2.59 × 10−5 M with a detection limit of 1.17 × 10−6 M (S/N = 3). The prepared sensor is highly selective towards ferulic acid without the interference of ascorbic acid. The sensor applicability was tested for total content determination of FA in a commercial popcorn sample and showed a robust functionality.
Prevalence and Predictors of Functional Vitamin K Insufficiency in Mothers and Newborns in Uganda
Authors: Santorino Data , Siedner Mark , Mwanga-Amumpaire Juliet , Shearer Martin , Harrington Dominic , Wariyar Unni
Published: October 2015

Vitamin K deficiency bleeding (VKDB) in infancy is a serious but preventable cause of mortality or permanent disability. Lack of epidemiologic data for VKDB in sub-Saharan Africa hinders development and implementation of effective prevention strategies. We used convenience sampling to consecutively enroll mothers delivering in a southwestern Uganda Hospital. We collected socio-demographic and dietary information, and paired samples of maternal venous and neonatal cord blood for the immunoassay of undercarboxylated prothrombin (PIVKA-II), a sensitive marker of functional vitamin K (VK) insufficiency. We used univariable and multivariable logistic regression models to identify predictors of VK insufficiency. We detected PIVKA-II of ≥0.2 AU (Arbitrary Units per mL)/mL (indicative of VK insufficiency) in 33.3% (47/141) of mothers and 66% (93/141) of newborns. Importantly, 22% of babies had PIVKA-II concentrations ≥5.0 AU/mL, likely to be associated with abnormal coagulation indices. We found no significant predictors of newborn VK insufficiency, including infant weight (AOR (adjusted odds ratio) 1.85, 95% CI (confidence interval) 0.15–22.49), gender (AOR 0.54, 95% CI 0.26–1.11), term birth (AOR 0.72, 95% CI 0.20–2.62), maternal VK-rich diet (AOR 1.13, 95% CI 0.55–2.35) or maternal VK insufficiency (AOR 0.99, 95% CI 0.47–2.10). VK insufficiency is common among mothers and newborn babies in southwestern Uganda, which in one fifth of babies nears overt deficiency. Lack of identifiable predictors of newborn VK insufficiency support strategies for universal VK prophylaxis to newborns to prevent VKDB.