bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasmon–exciton co‐driven surface catalytic reaction in electrochemical G‐SERS
Authors: Wang Peijie , Liu Wen , Lin Weihua , Sun Mengtao
Published: July 2017

We report the plasmon–exciton co‐driven surface catalytic reactions in the electrochemical G‐SERS in the liquid environments, where the graphene–Ag hybrid nanostructure forms the substrate for G‐SERS. Compared with the traditional plasmon‐driven chemical reaction in the electrochemical SERS in the liquid environments, we can see that great advantages of it on G‐SERS can be clearly demonstrated. G‐SERS can be potentially applied in the surface spectral analysis in electrochemical environments. Copyright © 2017 John Wiley & Sons, Ltd.
Rheological characterisation of gluten from triticale (x Triticosecale Wittmack)
Authors: Pruska‐Kędzior Anna , Makowska Agnieszka , Kędzior Zenon , Salmanowicz Bolesław P
Published: July 2017

BACKGROUND

Triticale gluten still remains very poorly characterised rheologically. In this study the mechanical spectra of gluten isolated from four triticale cultivars were registered and fitted with Cole–Cole functions yielding the visco‐elastic plateau parameters. Master spectra were calculated. A retardation test was performed and used to calculate the composite mechanical spectra and the width of visco‐elastic plateau l. Protein fractional composition of triticale flour and gluten was studied using capillary zone electrophoresis.

RESULTS

Differentiated HMW‐GS/SS compositions were identified in the triticale cultivars studied. The rheological parameters reached the following values: JN0 1.05·10−3 to 2.69·10−3 Pa−1, GN0 372 to 956 Pa, ω0 0.003 to 0.06 rad s−1, l 169 to 3121, Je0 1.57·10−3 to 5.03·10−3 Pa−1, Ge0 199 to 637 Pa and η0 1.06·107 to 3.93·107 Pa s.

CONCLUSIONS

Visco‐elastic properties of triticale gluten correspond to the lower end of medium visco‐elasticity shown by common wheat gluten. Master spectra and the composite mechanical spectra prove that four triticale glutens exhibit practically an identical type of visco‐elastic behaviour of a biopolymeric visco‐elastic liquid similar to wheat gluten. The visco‐elastic plateau parameters GN0, JN0, ω0 and l appeared significantly correlated with the contents of prolamins and secaloglutenins in triticale flours and glutens. © 2017 Society of Chemical Industry
Fruit quality of sweet pepper as affected by foliar Ca applications to mitigate the supply of saline water under a climate change scenario
Authors: Piñero María Carmen , Pérez‐Jiménez Margarita , López‐Marín Josefa , del Amor Francisco M
Published: July 2017

BACKGROUND

Sweet pepper fruit quality disorders have been related mainly to an unbalanced nutrient supply and non‐optimal growth conditions. Increases in the atmospheric CO2 concentration ([CO2]) have been associated with a reduction of transpiration, which can affect calcium (Ca) uptake as it is linked closely to water uptake. We investigated whether foliar application of Ca can counterbalance the effects of saline water and elevated [CO2].

RESULTS

High CO2 favoured generative growth instead of vegetative growth. Foliar Ca supply did not affect the marketable yield, but reduced the total yield when combined with salinity and 400 µmol mol−1 CO2. Salinity affected negatively the total yield but this was overcome when CO2 was applied. The B and K concentrations were reduced by foliar Ca application, while Ca and Mn were increased at 400 µmol mol−1 CO2. Salinity increased the Mn, Cl, and Na concentrations, regardless of the [CO2], and decreased K at 800 µmol mol−1 CO2. The total protein was affected negatively only by elevated [CO2], and the total free amino acid concentration was reduced by all treatments.

CONCLUSION

The effect of Ca application differed according to the other treatments applied. This procedure should be optimised to overcome future climate impacts on fruit quality. © 2017 Society of Chemical Industry
Hansen solubility parameters for assay method optimization of simvastatin, ramipril, atenolol, hydrochlorothiazide and aspirin in human plasma using liquid chromatography with tandem mass spectrometry
Authors: Devalapalli Murali Mohan Reddy , Cheruvu Hanumanth Srikanth , Yertha Thejaswi , Veeravalli Vijaya Bhaskar , Sampathi Sunitha , Shivakumar Savithri
Published: July 2017

A simple, specific, sensitive, validated method was developed using liquid chromatography with tandem mass spectrometry with electrospray ionization of human plasma for the simultaneous estimation of drugs (simvastatin, ramipril, atenolol, hydrochlorothiazide, and aspirin) of PolycapTM capsule used in cardiovascular therapy. The interaction of these actives including internal standards between the stationary and mobile phase were investigated using Hansen solubility parameters. Chromatographic separation was performed on Phenomenex Synergi Polar‐RP (30 × 2 mm, 4 μm) column with a gradient mobile phase composition of acetonitrile and 5 mM ammonium formate for positive mode and 0.1% formic acid in both water and acetonitrile for negative mode. The flow rate and runtime were 1.0 mL/min and 3.5 min, respectively. Sample extraction was done by protein precipitation using acetonitrile, enabling a fast analysis. The calibration ranges from 0.1 to 100, 0.1 to 100, and 1 to 1000 ng/mL for simvastatin, ramipril, and atenolol using internal standard carbamazepine in positive mode, respectively, whereas it was 0.3–300 and 2–2000 ng/mL for hydrochlorothiazide and aspirin using internal standard 7‐hydroxy coumarin in negative mode, respectively. Hansen solubility parameters can be used as a high‐throughput optimizing tool for column and mobile phase selection in bioanalysis. This validated bioanalytical method has the potential for future fixed dose combination based preclinical and clinical studies that can save analysis time.
One‐Step Spontaneous Formation of Dual Wrinkling on Uniform‐Sized Microparticles Induced by Surface
Authors: Im Jinsol , Yoo Dongik , Kim Jihoon , Yoon Sukeun , Cho Kuk Young
Published: July 2017

This study demonstrates the wrinkle formation on biodegradable polymer‐blend microparticles prepared from an emulsion‐solvent evaporation method and investigates the formed patterns. A labyrinthine pattern is obtained for uniform‐sized microparticles, owing to the considerable size reduction during solvent evaporation. Changing the radius of the organic droplets dispersed in the aqueous solution switches the wrinkle pattern from labyrinth to bi‐phase. For the first time, the dual wrinkling structure is prepared; both labyrinthine texture and hexagonal dimple structures are spontaneously formed on the same microparticle surface. The former pattern is due to the surface instability from blends of hydrophobic polymer and amphiphilic block copolymer, while the latter is due to a mechanism similar that of the breath figure formed with organic phase change materials during solidification of microparticles. The general applicability of this approach is demonstrated on other pairs of polymer blends.
Combining Staudinger Reductive Amination and Amidification for the Control of Surface Hydrophobicity and Water Adhesion by Introducing Heterobifunctional Groups: Post‐ and Ante‐Approach
Authors: Kout Emna El , Trad Rawia Ben , Kateb Mejda El , Beji Mohammed , Laugier Jean‐Pierre , Godeau Guilhem , Guittard Frédéric , Darmanin Thierry
Published: July 2017

Here, the combination of both the Staudinger reductive amination and amidification to prepare highly hydrophobic surfaces is reported for the first time. This approach has been studied for surface ante and post‐deposition modification. In the ante‐deposition approach, the combination of both the reactions allows to develop a one‐pot new monomer bearing two different side chains (heterobifunctional surface). The developed monomer has been successfully polymerized and leads to hydrophobic surface (θ > 110°). Similar modifications performed as post‐treatment lead to highly hydrophobic feature (θ > 120°). The difference between the ante and post‐deposition modification is investigated for their roughness and morphologies. The results of this work allow explaining this difference on surface feature and show quality and drawback of both ante and post‐deposition strategies.
Internet diffusion and free riding in insurance markets: An empirical investigation
Authors: Goel Rajeev K.
Published: July 2017

This paper studies the effect of internet diffusion on free riding in insurance markets, with a focus on automobile insurance. Internet usage affects both the demand and supply sides of insurance markets, while also having a bearing on institutions. Our cross‐sectional analysis based on the United States supports the main hypothesis that greater internet diffusion reduced free riding by uninsured motorists. This response was fairly elastic and the reduction in the prevalence of uninsured motorists holds across different empirical specifications. Implications of these findings are discussed.
Dynamics of a ratio‐dependent stage‐structured predator‐prey model with delay
Authors: Song Yongli , Yin Tao , Shu Hongying
Published: July 2017

In this paper, we investigate the dynamics of a time‐delay ratio‐dependent predator‐prey model with stage structure for the predator. This predator‐prey system conforms to the realistically biological environment. The existence and stability of the positive equilibrium are thoroughly analyzed, and the sufficient and necessary conditions for the stability and instability of the positive equilibrium are obtained for the case without delay. Then, the influence of delay on the dynamics of the system is investigated using the geometric criterion developed by Beretta and Kuang. We show that the positive steady state can be destabilized through a Hopf bifurcation and there exist stability switches under some conditions. The formulas determining the direction and the stability of Hopf bifurcations are explicitly derived by using the center manifold reduction and normal form theory. Finally, some numerical simulations are performed to illustrate and expand our theoretical results.
Blowup in solutions of a quasilinear wave equation with variable‐exponent nonlinearities
Authors: Messaoudi Salim A. , Talahmeh Ala A.
Published: July 2017

We consider, in this paper, the following nonlinear equation with variable exponents:

where a,b>0 are constants and the exponents of nonlinearity m,p, and r are given functions. We prove a finite‐time blow‐up result for the solutions with negative initial energy and for certain solutions with positive energy.
Pseudo–almost‐periodic solutions for delayed differential equations with integrable dichotomies and bi–almost‐periodic Green functions
Authors: Pinto Manuel , Vidal Claudio
Published: July 2017

Using the existence of integrable bi–almost‐periodic Green functions of linear homogeneous differential equations and the contraction fixed point, we are able to prove the existence of almost and pseudo–almost‐periodic mild solutions under quite general hypotheses for the differential equation with constant delay

in a Banach space X, where τ>0 is a fixed constant. The results extend the corresponding ones in the case of exponential dichotomy. Some examples illustrate the importance of the concepts.
l‐Ornithine and l‐lysine stimulate gastrointestinal motility via transient receptor potential vanilloid 1
Authors: Nakato Junya , Ho Yee Yin , Omae Ryo , Mizushige Takafumi , Uchida Kunitoshi , Tominaga Makoto , Kim Minji , Goto Tsuyoshi , Takahashi Nobuyuki , Kawada Teruo , Akiduki Saori , Kanamoto Ryuhei , Ohinata Kousaku
Published: July 2017

Scope

The gastrointestinal (GI) tract senses and responds to intraluminal nutrients and these interactions often affect GI functions. We found that, among basic amino acids, l‐ornithine (Orn) and l‐lysine (Lys) stimulated but l‐arginine (Arg) suppressed GI motility after oral administration (24 mmol/kg) in mice (Orn and Lys, 14.3 and 26.4% promotion; Arg, 7.7% suppression). We investigated the mechanism of the action of Orn and Lys on GI motility.

Methods and results

Orn‐induced promotion of small intestinal transit was significantly inhibited (p<0.05) by oral administration of capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist. Moreover, the stimulatory effect of Orn and Lys was abolished in TRPV1‐knockout mice. In TRPV1‐transfected HEK293 cells, Orn and Lys (10 mM) evoked Ca2+ influx, which was blocked by ruthenium red, a TRP channel antagonist. These results suggest that Orn and Lys promote GI motility via activation of TRPV1. The GI motility stimulation by Orn and Lys was also blocked by atropine, a muscarinic acetylcholine receptor (mAChR) antagonist, or NG‐nitro‐l‐arginine methyl ester, a nitric oxide (NO) synthase inhibitor.

Conclusion

Orally administered Orn and Lys stimulate GI motility via TRPV1, mAChR and NO synthase in mice.
Test–retest reliability of wide‐pulse high‐frequency neuromuscular electrical stimulation evoked force
Authors: Neyroud Daria , Grosprêtre Sidney , Gondin Julien , Kayser Bengt , Place Nicolas
Published: July 2017

Introduction: We compare forces evoked by wide‐pulse high‐frequency (WPHF) neuromuscular electrical stimulation (NMES) delivered to a nerve trunk versus muscle belly and assess their test–retest intraindividual and interindividual reliability. Methods: Forces evoked during 2 sessions with WPHF NMES delivered over the tibial nerve trunk and 2 sessions over the triceps surae muscle belly were compared. Ten individuals participated in 4 sessions involving ten 20‐s WPHF NMES contractions interspaced by 40‐s recovery. Mean evoked force and force time integral of each contraction were quantified. Results: For both nerve trunk and muscle belly stimulation, intraindividual test–retest reliability was good (intraclass correlation coefficient > 0.9), and interindividual variability was large (coefficient of variation between 140% and 180%). Nerve trunk and muscle belly stimulation resulted in similar evoked forces. Discussion: WPHF NMES locations might be chosen by individual preference because intraindividual reliability was relatively good for both locations. Muscle Nerve 57: E70–E77, 2018.
Reward Capacity Predicts Leptin Dynamics During Laboratory‐Controlled Eating in Women as a Function of Body Mass Index
Authors: Holsen Laura M. , Jackson Benita
Published: July 2017

Objective

The role of leptin in mesolimbic signaling of non–food‐related rewards has been well established at the preclinical level, yet studies in humans are lacking. The present investigation explored the association between hedonic capacity and leptin dynamics and whether this association differed by BMI class.

Methods

In this cross‐sectional study of 75 women (42 with BMIs in the lean range and 33 with BMIs in the obesity range), serum leptin before and after meal consumption was measured. Reward capacity was assessed using the Snaith‐Hamilton Pleasure Scale (SHAPS). Multiple regression tested whether reward capacity was associated with the leptin area under the curve (AUC), with an interaction term to test differences between the lean and obesity groups.

Results

The interaction of SHAPS by BMI group was robust (β = −0.40, P = 0.005); among women with obesity, a greater SHAPS score was associated with a lower leptin AUC (β = −0.35, P = 0.002, adjusted R2 = 0.66). Among those in the lean group, the association was not statistically significant (β = −0.16, P = 0.252, adjusted R2 = 0.22). Findings were above and beyond BMI and age.

Conclusions

In this sample, a robust negative association between reward capacity and circulating leptin was stronger in women with obesity compared with lean counterparts. These findings suggest that despite likely leptin resistance, inhibitory leptin functioning related to nonfood rewards may be spared in women with obesity.
Thermal stability and fire reaction of poly(butylene succinate) nanocomposites using natural clays and FR additives
Authors: Dumazert Loic , Rasselet Damien , Pang Bo , Gallard Benjamin , Kennouche Salima , Lopez‐Cuesta José‐Marie
Published: July 2017

Thermal stability and fire retardancy of poly(1,4‐butanediol succinate) (PBS) nanocomposites with sepiolite and 2 halloysites was investigated using thermogravimetric analysis. Despite detrimental influence on thermal stability, confirmed by the use of isoconversional methods, nanoclays improve PBS fire behavior, studied using pyrolysis combustion flow calorimetry and cone calorimeter. Combinations of nanoclays with ammonium polyphosphate (APP) and aluminum diethyl phosphinate at 20 wt% global loading were tested using cone calorimeter at 50 kW/m2. It was noticed that the formation of protective structures of metallic phosphates with APP improves fire performance. The influence of ternary compositions combining sepiolite, APP, and lignin on fire performance was investigated. The composition having equimassic loading of each component leads to strong reductions in peak of heat release rate and Maximum of Average Heat Release Evolved (MAHRE) through the formation of a cohesive protective residue, containing new types of metallic phosphates and reinforced by sepiolite particles. This composition also allows smoke release rate to be minimized.
Poly(lactic acid)/(styrene‐ethylene‐butylene‐styrene)‐g‐maleic anhydride copolymer/sepiolite nanocomposites: Investigation of thermo‐mechanical and morphological properties
Authors: Nehra Ranjana , Maiti S.N. , Jacob Josemon
Published: July 2017

In this study, sepiolite nanoclay is used as reinforcing agent for poly(lactic acid) (PLA)/(styrene‐ethylene‐butylene‐styrene)‐g‐maleic anhydride copolymer (SEBS‐g‐MA) 90/10 (w/w) blend. Effects of sepiolite on thermal behavior, morphology, and thermomechanical properties of PLA/SEBS‐g‐MA blend were investigated. Differential scanning calorimetry results showed 7% improvement in crystallinity at 0.5 wt% of sepiolite. The nanocomposite exhibited approximately 36% increase in the tensile modulus and 17% increase in toughness as compared with the blend matrix at 0.5 and 2.5 wt% of sepiolite respectively. Field emission scanning electron microscopy and transmission electron microscopy images exhibited sepiolite‐induced morphological changes and dispersion of sepiolite in both PLA and SEBS‐g‐MA phases. Dynamic mechanical analysis and wide angle X‐ray diffraction present evidences in support of the reinforcing nature of sepiolite and phase interaction between the filler and the matrix. This study confirms that sepiolite can improve tensile modulus and toughness of PLA/SEBS‐g‐MA blend.
Antibacterial photocatalytic self‐cleaning poly(vinylidene fluoride) membrane for dye wastewater treatment
Authors: Peng Yixin , Yu Zongxue , Pan Yang , Zeng Guangyong
Published: July 2017

Membrane technology has been successfully applied for the removal of dyes from wastewater in the textile industry. A novel poly(vinylidene fluoride) (PVDF) membrane was prepared via blending with different dosages of Ag‐TiO2‐APTES composite for dyeing waste water treatment in our study. And the effect of Ag‐TiO2‐APTES blended into the PVDF membrane was discussed, including the rejection rate of methylene blue (MB) dye, membrane morphology, surface hydrophilicity, antibacterial activity, and a certain photocatalytic self‐cleaning performance. X‐ray diffraction and Fourier transform infrared characterization confirmed that Ag‐TiO2 was functionalized by amount of hydroxyl group (−OH) and amino group (NH−), which provided by APTES. Contact angle measurement certified that the hydrophilicity of the membrane surface increased, with the contact angle decrease to 61.4° compared with 81.8° of original PVDF membrane. MB rejection rate was also increased to 90.1% after addition of Ag‐TiO2‐APTES, and the rejection of original membrane was only 74.3%. The morphologies of membranes were observed by scanning electron microscope, which indicated that Ag‐TiO2‐APTES had a good dispersion in membrane matrix and also improved the microstructure of membranes. Besides, UV irradiation experiments were performed on the composite films contaminated by MB, and the result showed that Ag‐TiO2‐APTES nanoparticle provided PVDF membrane with a certain photodegradation capacity under UV irradiation. Moreover, antibacterial activity of the composite membrane was also demonstrated through antibacterial experiment, Escherichia coli as the representative bacteria. Perhaps, this research may provide a new way for PVDF blending modification.
The peritoneum: healing, immunity, and diseases
Authors: Capobianco Annalisa , Cottone Lucia , Monno Antonella , Manfredi Angelo A , Rovere‐Querini Patrizia
Published: July 2017

The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non‐neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self‐antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Electromagnetic interference shielding effectiveness of composites based on polyurethane derived from castor oil and nanostructured carbon fillers
Authors: Merlini Claudia , Pegoretti Alessandro , Vargas Patricia Cristine , da Cunha Tairan F. , Ramôa Sílvia D.A.S. , Soares Bluma G. , Barra Guilherme M. O.
Published: July 2017

Graphene nanoplatelets (xGnP), expanded graphite (EG), multiwall carbon nanotubes (MWCNTs), and carbon black (CB) were dispersed in various amounts in a thermosetting polyurethane (PU) matrix derived from castor oil and composite plaques were obtained by compression molding. The electrical percolation threshold was found to be 0.1 vol% for MWCNT, 0.5 vol% for xGnP, 2.8 vol% for CB, and 2.7 vol% for EG‐filled systems. The relation between electrical conductivity, morphology, and electromagnetic interference shielding effectiveness (EMI SE) of the resulting composites was studied to understand how the EMI SE is influenced by morphology and electrical conductivity of each filler. The composites display significantly distinct EMI SE values, depending on the type of carbon filler and its volume fraction. Composite based in PU/EG and PU/xGnP exhibited the highest EMI SE values (70 and 47 −dB, respectively); however, PU/MWCNT composites showed higher EMI SE (24 −dB) value at the same filler content (3 vol%) than the other composite system. POLYM. COMPOS., 40:E78–E87, 2019. © 2017 Society of Plastics Engineers
Polyethylene‐g‐starch nanoparticle biocomposites: Physicochemical properties and biodegradation studies
Authors: Sheeja  , Manaf O. , Juraij K. , Sneha Sundaran P. , Ashitha K. , Aleena L.S. , Sujith A.
Published: July 2017

Low density polyethylene‐g‐maleic anhydride‐g‐starch nanoparticle (LMNS) biocomposites have been synthesized in water medium. LMNS biocomposites were fabricated with different starch nanoparticle (NS) loadings (2, 4, 6, 8, and 10 wt%) by compression molding technique. Fourier transform infrared spectroscopy revealed ester linkage between maleic anhydride grafted low density polyethylene (LM) and NS, thereby confirming the improved compatibility of the biocomposites. Thermal analysis confirmed the chemical linkage of NS on LM chains. The wettability and surface roughness characteristics of biocomposites were evaluated by water sorption, static contact angle, and atomic force microscopy. Water sorption was improved due to the increase of NS content in samples, whereas the water contact angle and surface roughness were diminished. The load at maximum, tensile strength and percentage of elongation at break for the biocomposites were enhanced with the increase in NS content. The morphology analysis of samples revealed homogenous distribution and good interfacial adhesion. The biodegradation enhancement of samples has been revealed by fungal and soil burial tests. POLYM. COMPOS., 39:E426–E440, 2018. © 2017 Society of Plastics Engineers
Melt‐spinning of carboxylated MWNTs‐reinforced polyamide 6 fibers with solid mixing nanocomposites
Authors: Tian Chen , Yu‐Zhou Wang , Hai‐Hui Liu , Xing‐Xiang Zhang
Published: July 2017

Nanocomposite fibers of carboxylated multiwalled carbon nanotubes (MWNTs‐COOH)‐reinforced polyamide 6 (PA6), which have good mechanical properties, were fabricated by a ball‐milling and melt spinning process. The ball‐milling method was used to prepare PA6/MWNTs‐COOH nanocomposite powders to address the key issue of dispersing MWNTs‐COOH into the PA6 matrix uniformly. The effects of both the milling time and MWNTs‐COOH loading on the mechanical properties of PA6/MWNTs‐COOH nanocomposite fibers were investigated. Transmission electron microscopy, Raman spectroscopy, and X‐ray diffraction were used to study the morphology and microstructure of MWNTs‐COOH in compound powders after ball‐milling. Scanning electron microscopy micrographs indicated that secondary agglomeration of MWNTs‐COOH occurred after ball‐milling for 5 h, and the best dispersing time was 3 h. The mechanical properties of the nanocomposite fibers fabricated by ball‐milling were much higher than those of the control and composites fabricated by conventional melt mixing. The results of the differential scanning calorimetry revealed the close relationship between the dispersibility and crystallinity. This method, which does not require the use of solvent, has great potential for industrial application. POLYM. COMPOS., 39:4298–4309, 2018. © 2017 Society of Plastics Engineers
Analysis of safety‐related regulatory actions by Japan's pharmaceutical regulatory agency
Authors: Ishiguro Chieko , Misu Takashi , Iwasa Eiko , Izawa Tadashi
Published: July 2017

Purpose

To evaluate the safety‐related regulatory actions implemented by Japan's Pharmaceuticals and Medical Devices Agency (PMDA) in 2012.

Methods

We analyzed serious safety issues appended to drug package inserts (PIs) in Japan in 2012. The issues were characterized according to drug class, adverse event, years since drug approval, initiator of regulatory actions, revised section of PI, and evidence source. We also quantified the durations from signal detection to tentative decision and from tentative decision to regulatory action.

Results

We identified 144 serious safety issues during the study period, and the majority of evidence originated from spontaneous reports (83.5%). The PMDA initiated regulatory actions for half of all safety issues, and the median duration from drug approval to regulatory action was 8 years (interquartile range [IQR], 3–26.5 years). The median duration was 49 days (IQR, 0–362 days) from signal detection to tentative decision and 84 days (IQR, 63–136 days) from tentative decision to regulatory action. Several safety issues involving older drugs and multiple products had protracted decision‐making durations.

Conclusions

Most safety issues led to prompt regulatory actions predominantly based on spontaneous reports. Some safety issues that were not easily detected by the spontaneous reporting system were identified years after approval. In addition, several safety issues required assessments of multiple drug products, which prolonged the decision‐making process.
Risk of liver decompensation with cumulative use of mitochondrial toxic nucleoside analogues in HIV/hepatitis C virus coinfection
Authors: Lo Re Vincent , Zeldow Bret , Kallan Michael J. , Tate Janet P. , Carbonari Dean M. , Hennessy Sean , Kostman Jay R. , Lim Joseph K. , Goetz Matthew Bidwell , Gross Robert , Justice Amy C. , Roy Jason A.
Published: July 2017

Purpose

Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV‐associated liver fibrosis and increase the risk of hepatic decompensation and death.

Methods

We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI‐containing ART within the Veterans Aging Cohort Study (2002‐2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV‐/HCV‐coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs.

Results

Over 7033 person‐years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person‐years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person‐years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1‐11 mo: HR, 1.79 [95% confidence interval (CI), 0.74‐4.31]; 12‐35 mo: HR, 1.39 [95% CI, 0.68‐2.87]; 36‐71 mo: HR, 2.27 [95% CI, 0.92‐5.60]; >71 mo: HR, 4.66 [95% CI, 1.04‐20.83]; P = .045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1‐11 mo: HR, 2.24 [95% CI, 1.04‐4.81]; 12‐35 mo: HR, 2.05 [95% CI, 0.68‐6.20]; 36‐71 mo: HR, 3.04 [95% CI, 1.12‐8.26]; >71 mo: HR, 3.93 [95% CI, 0.75‐20.50]; P = .030).

Conclusions

These findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients.
Proteomic Analysis of Neuroblastoma‐Derived Exosomes: New Insights into a Metastatic Signature
Authors: Colletti Marta , Petretto Andrea , Galardi Angela , Di Paolo Virginia , Tomao Luigi , Lavarello Chiara , Inglese Elvira , Bruschi Maurizio , Lopez Ana Amor , Pascucci Luisa , Geoerger Birgit , Peinado Hector , Locatelli Franco , Di Giannatale Angela
Published: July 2017

Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Around 70% of patients with metastatic disease at diagnosis present bone‐marrow infiltration, which is considered a marker of poor outcome; however, the mechanism underlying this specific tropism has to be elucidated. Tumor‐derived exosomes may support metastatic progression in several tumors by interacting with the microenvironment, and may serve as tumor biomarkers. The main objective of this study is to identify an exosomal signature associated with NB metastatic bone‐marrow dissemination. Therefore, the proteomic cargo of exosomes isolated from NB cell lines derived from primary tumor and bone‐marrow metastasis is characterized. The comparison among exosomal proteins show 15 proteins exclusively present in primary tumor‐derived exosomes, mainly involved in neuronal development, and 6 proteins in metastasis‐derived exosomes related to cancer progression. Significant proteins obtain with statistical analysis performed between the two groups, reveal that primary tumor exosomes contain a higher level of proteins involved in extra‐cellular matrix (ECM) assembly and adhesion, as well as in neuronal development. Exosomes isolated from bone‐marrow metastasis exhibit proteins involved in ameboidal cell migration and mitochondrial activity. This work suggests that proteomic profiling of NB‐derived exosomes reflects the tumor stage and may be considered as potential tumor biomarker.
Assisted autogenic drainage in infants and young children hospitalized with uncomplicated pneumonia, a pilot study
Authors: Corten Lieselotte , Jelsma Jennifer , Human Anri , Rahim Sameer , Morrow Brenda M.
Published: July 2017

Background and purpose

Pneumonia is the most important respiratory problem in low‐to‐middle income countries. Airway clearance therapy continues to be used in children with pneumonia and secretion retention; however, there is lack of evidence to support or reject this treatment. This study aimed to investigate the feasibility of a randomized controlled trial (RCT) on the efficacy and safety of assisted autogenic drainage (AAD) compared to standard nursing care in children hospitalized with uncomplicated pneumonia.

Methods

A single‐blinded pilot RCT was conducted on 29 children (median age 3.5 months, IQR 1.5–9.4) hospitalized with uncomplicated pneumonia. The intervention group received standard nursing care with additional bi‐daily AAD, for 10 to 30 min. The control group only received standard nursing care, unless otherwise deemed necessary by the physician or physiotherapist. The primary outcome measure was duration of hospitalization. The secondary outcome measures included days of fever and supplemental oxygen support; respiratory rate (RR) and heart rate adjusted for age; RR and oxygen saturation pre‐, post‐, and 1‐hr post‐treatment; oxygen saturation; adverse events; and mortality.

Results

No difference was found for duration of hospitalization (median 7.5 and 7.0 days for the control and intervention groups, respectively); however, Kaplan–Meier analysis revealed a strong tendency towards a shorter time to discharge in the intervention group (p = .06). No significant differences were found for the other outcome measures at time of discharge. No adverse events were reported. Within the intervention group, a significant reduction in RR adjusted for age was found.

Discussion

As no adverse events were reported, and AAD did not prolong hospitalization; AAD might be considered as safe and effective in young children with uncomplicated pneumonia. However, a larger multicentred RCT is warranted to determine the efficacy of AAD compared to standard nursing care.
Advanced Methods for Dose and Regimen Finding During Drug Development: Summary of the EMA/EFPIA Workshop on Dose Finding (London 4–5 December 2014)
Authors: Musuamba FT , Manolis E , Holford N , Cheung SYA , Friberg LE , Ogungbenro K , Posch M , Yates JWT , Berry S , Thomas N , Corriol‐Rohou S , Bornkamp B , Bretz F , Hooker AC , Van der Graaf PH , Standing JF , Hay J , Cole S , Gigante V , Karlsson K , Dumortier T , Benda N , Serone F , Das S , Brochot A , Ehmann F , Hemmings R , Rusten I Skottheim
Published: July 2017

Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late‐stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well‐established and regulatory‐acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4–5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP‐Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)‐based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well‐designed dose‐finding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale.
Slippage and immobilization detection for planetary exploration rovers via machine learning and proprioceptive sensing
Authors: Gonzalez Ramon , Apostolopoulos Dimi , Iagnemma Karl
Published: July 2017

This paper presents a new methodology where machine learning is used for detecting various levels of slip in the context of planetary exploration robotic missions. This methodology aims at employing proprioceptive rover sensor signals. Consequently, no operational complexity is added to the rover's commanding and it is independent of lighting conditions. Two supervised learning methods (Support Vector Machines and Artificial Neural Networks) are compared to two unsupervised learning approaches (K‐means and Self‐Organizing Maps (SOM)). Physical experiments using a single‐wheel testbed equipped with an MSL spare wheel and a real planetary exploration rover validate the implemented methodology. Performance is evaluated in terms of well‐known metrics both considering single data points and subsets of consecutive data points (moving median filter). Computation time and storage requirements are also examined. One of the SOM‐based algorithms, semantic SOM method, demonstrates a proper balance between the benefits of supervised learning algorithms (high success rate, >96%) and the advantages of unsupervised learning methods (low storage requirements, 5 kb, and no need of manually‐labeled training data). This paper also addresses the most convenient placement of IMU sensors on the rover chassis such that slippage detection is maximized.
Frequency recovery techniques for TM/TC satellite modem in critical scenarios
Authors: Fanfani Alessio , Morosi Simone , Ronga Luca , Del Re Enrico
Published: July 2017

Reliability and effectiveness are essential features of satellite transceivers for telemetry and telecommand applications. Modem performance has a strong impact on the success of a satellite mission, in particular, during critical scenarios as the early operation phase, the disposal of a satellite at the end of its life, or the deep‐space missions. In these specific mission critical scenarios, fast and correct data reception is even more important than high channel capacity. An unknown and fast variable channel condition, which can be caused by uncertain spacecraft attitude and large Doppler shift with respect to the data rate, requires efficient and innovative receiver architecture. This paper introduces a complete digital implementation of a transceiver for TM/TC application in low Earth orbit mission that is perfectly compliant with aforementioned requirements. Particular attention is dedicated to the definition and selection of the most appropriate frequency recovery technique; 2 open‐loop techniques that are derived from ML optimal estimator are presented and compared. Additionally, the performance of the proposed receiver is extensively studied and compared with an incoherent technique that is based on the double differential PSK modulation and is known to be suitable for sat‐com in critical scenarios.
Estimating population effects of vaccination using large, routinely collected data
Authors: Halloran M Elizabeth , Hudgens Michael G.
Published: July 2017

Vaccination in populations can have several kinds of effects. Establishing that vaccination produces population‐level effects beyond the direct effects in the vaccinated individuals can have important consequences for public health policy. Formal methods have been developed for study designs and analysis that can estimate the different effects of vaccination. However, implementing field studies to evaluate the different effects of vaccination can be expensive, of limited generalizability, or unethical. It would be advantageous to use routinely collected data to estimate the different effects of vaccination. We consider how different types of data are needed to estimate different effects of vaccination. The examples include rotavirus vaccination of young children, influenza vaccination of elderly adults, and a targeted influenza vaccination campaign in schools. Directions for future research are discussed. Copyright © 2017 John Wiley & Sons, Ltd.
Localized Defects on Copper Sulfide Surface for Enhanced Plasmon Resonance and Water Splitting
Authors: Ren Kaixv , Yin Pengfei , Zhou Yuzhu , Cao Xingzhong , Dong Cunku , Cui Lan , Liu Hui , Du Xiwen
Published: July 2017

Surficial defects in semiconductor can induce high density of carriers and cause localized surface plasmon resonance which is prone to light harvesting and energy conversion, while internal defects may cause serious recombination of electrons and holes. Thus, it is significant to precisely control the distribution of defects, although there are few successful examples. Herein, an effective strategy to confine abundant defects within the surface layer of Cu1.94S nanoflake arrays (NFAs) is reported, leaving a perfect internal structure. The Cu1.94S NFAs are then applied in photoelectrochemical (PEC) water splitting. As expected, the surficial defects give rise to strong LSPR effect and quick charge separation near the surface; meanwhile, they provide active sites for catalyzing hydrogen evolution. As a result, the NFAs achieve the top PEC properties ever reported for CuxS‐based photocathodes.
Porous Carbon Nanofibers Encapsulated with Peapod‐Like Hematite Nanoparticles for High‐Rate and Long‐Life Battery Anodes
Authors: Xia Guanglin , Gao Qili , Sun Dalin , Yu Xuebin
Published: July 2017

Fe2O3 is regarded as a promising anode material for lithium‐ion batteries (LIBs) and sodium‐ion batteries (SIBs) due to its high specific capacity. The large volume change during discharge and charge processes, however, induces significant cracking of the Fe2O3 anodes, leading to rapid fading of the capacity. Herein, a novel peapod‐like nanostructured material, consisting of Fe2O3 nanoparticles homogeneously encapsulated in the hollow interior of N‐doped porous carbon nanofibers, as a high‐performance anode material is reported. The distinctive structure not only provides enough voids to accommodate the volume expansion of the pea‐like Fe2O3 nanoparticles but also offers a continuous conducting framework for electron transport and accessible nanoporous channels for fast diffusion and transport of Li/Na‐ions. As a consequence, this peapod‐like structure exhibits a stable discharge capacity of 1434 mAh g−1 (at 100 mA g−1) and 806 mAh g−1 (at 200 mA g−1) over 100 cycles as anode materials for LIBs and SIBs, respectively. More importantly, a stable capacity of 958 mAh g−1 after 1000 cycles and 396 mAh g−1 after 1500 cycles can be achieved for LIBs and SIBs, respectively, at a large current density of 2000 mA g−1. This study provides a promising strategy for developing long‐cycle‐life LIBs and SIBs.
Rice starch biotechnology: Rice endosperm as a model of cereal endosperms
Authors: Nakamura Yasunori
Published: July 2017

During the last couple of decades, rapid progress has been made in increasing our understanding of the specific contributions of the most important enzymes to starch biosynthesis in cereal endosperms, particularly in rice endosperm. Now, we can basically predict how and to what extent the starch‐related phenotypes can be modified in the endosperm in accordance with alterations of activities of single or simultaneously multiple starch biosynthetic isozymes. Thus, starch bioengineering in planta is now a most particularly promising field of plant biotechnology. Here, an overview of the present status of biochemical, molecular, and genetic research is presented, regarding starch biosynthesis and its engineering for the generation of new cultivars with improved cooking or novel functional properties of starch in rice endosperm. A huge number and variety of cultivars have been developed and cultivated mainly in paddy fields of Asian countries because rice is the most important staple food grain there. The availability of such invaluable genetic resources, as well as databases for various types of mutants, complete genome sequences, and omics tools should ensure further progress in the rice starch biotechnology research field.
β‐mangostin suppresses human hepatocellular carcinoma cell invasion through inhibition of MMP‐2 and MMP‐9 expression and activating the ERK and JNK pathways
Authors: Huang Chien‐Feng , Teng Ying‐Hock , Lu Fung‐Jou , Hsu Wen‐Hung , Lin Chia‐Liang , Hung Chia‐Chen , Tung Jai‐Nien , Hsieh Yi‐Hsien , Liu Chung‐Jung
Published: July 2017

β‐mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of β‐mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that β‐mangostin did not induce cytotoxicity in human HCC cells (SK‐Hep‐1, Huh‐7 and HA22T/VGH cells). β‐mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, β‐mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)‐2 and MMP‐9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways. Furthermore, using specific inhibitor for ERK1/2 (PD98059) and JNK1/2 (JNKII) significantly restored the expression of MMP‐2/‐9 and invasion by β‐mangostin treatment in Huh‐7 cells. In addition, β‐mangostin effectively restored the protein levels and transcription activity of MMP‐2 and MMP‐9 in siERK or siJNK‐transfected Huh‐7 cells, concomitantly with promotion on cell migration and invasion. Taken together, these findings are the first to demonstrate the antimetastatic activity of β‐mangostin against human HCC cells, which may act as a promising therapeutic agent for the treatment of HCC.
QSAR modeling, docking and ADMET studies for exploration of potential anti-malarial compounds against Plasmodium falciparum
Authors: Qidwai Tabish
Published: July 2017

Development of resistance in thePlasmodium falciparumto Artemisinin, the most effective anti-malarial compound, threatens malaria elimination tactics. To gain more efficacious Artemisinin derivatives, QSAR modeling and docking was performed. In the present study, 2D-QSAR model and molecular docking were used to evaluate the Artemisinin compounds and to reveal their binding modes and structural basis of inhibitory activity. Moreover, ADMET-related descriptors have been calculated to predict the pharmacokinetic properties of the effective compounds. The correlation expressed as coefficient of determination (r2) and prediction accuracy expressed in the form of cross-validated r2(q2) of QSAR model are found 0.9687 and 0.9586, respectively. Total 239 descriptors have been included in the study as independent variables. The four chemical descriptors, namely radius of gyration, mominertia Z, SssNH count and SK Average have been found to be well correlated with anti-malarial activities. The model was statistically robust and has good predictive power which could be employed for virtual screening of proposed anti-malarial compounds. QSAR and docking results revealed that studied compounds exhibit good anti-malarial activities and binding affinities. The outcomes could be useful for the design and development of the potent inhibitors which after optimization can be potential therapeutics for malaria.