bluuebunny/crossref_metadata_2025 huggingface dataset:
“Click” generation of a conjugated polymer library for SWNT dispersion
Authors: Li Kelvin , Kardelis Vladimir , Adronov Alex
Published: August 2018

Noncovalent functionalization of single‐walled carbon nanotubes (SWNTs) with conjugated polymers enhances SWNT processability and allows for selective dispersion of various SWNT species. Selective dispersions can be obtained by tuning the nature of the polymer, which can involve using various polymer backbones or side‐chains. However, a clear understanding of selectivity determinants is elusive, as the degree of polymerization (DP) has a large effect on SWNT selectivity. Additionally, preparing libraries of conjugated polymers with varying functionality while keeping DP consistent is difficult. Here, we report the utilization of a strained cyclooctyne‐containing conjugated polymer that serves as a versatile scaffold, enabling systematic preparation of a small library of conjugated polymers with different side‐chain functionality, while maintaining a consistent DP. The resulting polymers were used as dispersants for SWNTs, forming supramolecular polymer‐SWNT complexes that were characterized by UV‐Vis‐NIR absorption and Raman spectroscopy. In the series of polymers, we were able to probe the effect of small changes within the side chains, such as the incorporation of a carbonyl group or an aromatic unit, on the quality of the polymer‐SWNT dispersion. The results of these studies provide new insight into the factors that dictate the ability of a polymer to form strong interactions with SWNTs. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2053–2058
Visible‐light induced RAFT polymerization of styrenic monomers with aromatic aldehydes as organophotoredox catalysts
Authors: Yang Qian , Zhang Xianhong , Ma Yuhong , Chen Dong , Yang Wantai
Published: August 2018

A photoinduced electron transfer‐reversible addition‐fragmentation chain transfer (PET‐RAFT) polymerization of p‐methylstyrene (p‐MS) and styrene (St) with 2‐(dodecylthiocarbonothioylthio)‐2‐methylpropionic acid as the chain transfer agent (CTA) and aromatic aldehydes, including 4‐cyanobenzaldehyde (PC1), 2,4‐dimethoxy benzaldehyde, and 4‐methoxy benzaldehyde, as organic photocatalysts has been demonstrated via irradiation with 23 W compact fluorescent lamps. The kinetics of the polymerizations shows first order with respect to monomer conversions. Linear evolution of the Mn of the produced polymers with the monomer conversion is observed. Meanwhile, the as‐prepared polymers are of relatively narrow polydispersity (PDI = Mw/Mn). For instance, the polymerization of p‐MS shows living polymerization features using PC1 within a range of solvents. Especially, the Mn of PpMS increased from about 2100 to 12,700 g/mol with the monomer conversion from 8% to 52% in tetrahydrofuran. The controlled polymerization of St is also observed under optimal reaction conditions. However, the Mn discrepancy between the experimental readings and theoretical calculations is greater at the monomer conversions greater than 40% and the PDI increased gradually over the monomer conversion. This is probably because that CTA is strongly sensitive to the light irradiation with wave range around its characteristic absorption wavelength, leading to significant decomposition of CTA moieties during the RAFT polymerization. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2072–2079
pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogels via aza‐michael addition for anticancer drug delivery
Authors: Patil Sachin S. , Shinde Vishnu S. , Misra R. Devesh K.
Published: August 2018

A pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogel containing “acetals” as pH‐sensitive groups and “disulfides” as reducible linkages was designed and synthesized via aza‐Michael addition reaction between PAMAM and PEGDA diacrylates. The pore size and swelling ratio of hydrogels was varied from 14 ± 3 to 19 ± 4 μm and 214 ± 13 to 300 ± 19 μm, respectively, with varying ethylene glycol repeating units in diacrylates. The swelling ratio of PEGDA/PAMAM network hydrogel increased with increase in the molecular weight of PEG and with decrease in pH. The presence of different cationizable amino‐functionalities in PEGDA/PAMAM network hydrogel helped to enhance the swelling ability of hydrogel under the acidic conditions. The continuous increase in metabolically active live HeLa cells with time in MTT assay implied biocompatibility/noncytotoxicity of the synthesized PEGDA/PAMAM injectable network hydrogel. Furthermore, the prepared PEGDA/PAMAM hydrogel showed higher degradation at lower pH and at higher concentration of DTT. The burst release of doxorubicin from PEGDA/PAMAM hydrogel under the environment of the lower pH and in presence of DTT compared to the release at normal physiological pH and in absence of DTT suggested the potential ability of this model hydrogel system for targeted and selective anticancer drug release at tumor tissues. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2080–2095
Biology and management of methicillin resistantStaphylococcus aureusin cystic fibrosis
Authors: Akil Nour , Muhlebach Marianne S.
Published: August 2018

Staphylococcus aureusis one of the earliest bacteria isolated from the respiratory tract in people with cystic fibrosis (CF). Its methicillin resistant form, MRSA, has gained attention due to the rapid increase in the last decades and worse outcomes with chronic infection. In the United States, prevalence of MRSA in CF is around 27%, but is much lower (3‐18%) in most other countries. Methicillin is typically genetically encoded by themecA gene, which encodes for an alternative penicillin binding protein (PRBa). This PRBa has low affinity to β‐lactams, thereby enabling growth ofS. aureusin the presence of penicillinase resistant penicillins and most other β‐lactams. Non‐mecA positive strains of MRSA, so‐called borderline resistant (BORSA) have also been described. In addition to production of toxins, the virulence ofS. aureusis conferred by its adaptability allowing persistence in face of antibiotic therapies and host defense. These adaptive growth mechanisms include small colony variants, biofilms, and growth under anaerobic conditions. Several reports have described successful eradication of MRSA, yet only two randomized trials of eradication during early infection have been conducted. A list of MRSA specific antibiotics with dosing relevant to CF patients is presented here. Many of these require special dosing in people with CF. Novel antibiotics are in trials for skin and soft tissue infections and it is unclear if and when those might be available for lung infections. Thus the best strategies for MRSA would be primary prevention.
The CaspBase: a curated database for evolutionary biochemical studies of caspase functional divergence and ancestral sequence inference
Authors: Grinshpon Robert D. , Williford Anna , Titus‐McQuillan James , Clay Clark A.
Published: August 2018

Sequence databases are powerful tools for the contemporary scientists’ toolkit. However, most functional annotations in public databases are determined computationally and are not verified by a human expert. While hypotheses generated from computational studies are now amenable to experimentation, the quality of the results relies on the quality of input data. We developed the CaspBase to expedite high‐quality dataset compilation of annotated caspase sequences, to maximize phylogenetic signal, and to reduce the noise contributed from public databanks. We describe our methods of curation for the CaspBase and how researchers can acquire sequences from CaspBase.org. Our immediate goal for developing the CaspBase was to optimize the ancestral protein reconstruction (APR) of caspases, and we demonstrate the utility of the CaspBase in APR studies. We also developed the Common Position (CP) system for comparing human caspase family paralogs and suggest the CP system as an update to current reporting methods of caspase amino acid positions. We present a standardized multiple sequence alignment (MSA) for the CP system and show the advantage of using large databases such as the CaspBase in defining structural positions in proteins. Although the results described here pertain to caspase evolution and structure–function studies, the methods can be adapted to any gene family.
Testosterone regulates myosin II isoforms expression and functional activity in the rat prostate
Authors: Chen Ping , Xiao He , Huang Wei , Xu De‐Qiang , Guo Yu‐Ming , Wang Xiao , Wang Xing‐Huan , DiSanto Michael E. , Zhang Xin‐Hua
Published: August 2018

Background

Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and prostatic volume. At the molecular level, SM myosin II (SMM II) and non‐muscle myosin II (NMM II) mediate SM tone and cell proliferation while testosterone (T) plays a permissive role in the development of BPH.

Aims

The novel objective of this study was to elucidate the effects of T on the proliferation and apoptosis of rat prostatic cells and SM contractility as well as related regulatory signaling pathways.

Materials and Methods

Briefly, 36 male rats were divided into three groups (sham‐operated, surgically castrated, and castrated with T supplementation). In vitro organ bath studies, competitive RT‐PCR, Western‐blotting analysis, Masson's trichrome staining, and immunofluorescence staining were performed.

Results

Our data showed that castration dramatically increased prostatic SM contractility and SM MHC immunostaining revealed a relatively increased SM cell numbers in the stroma. T deprivation altered prostate SMM II isoform composition with upregulation of SM‐B and SM2 but downregulation of LC17a, favoring a faster more phasic‐type contraction. Moreover, protein expressions of MLCK, p‐MLCP, RhoB, ROCK1, and ROCK2 increased in castrated rats. Meanwhile NMM II heavy chain isoforms A, B, and C (NMMHC‐A, B, and C isoforms) were altered by castration which may be linked to decreased cell proliferation and increased apoptosis.

Conclusion

Our novel data demonstrated T regulates SMM II and NMM II and their functional activities in rat prostate and T ablation not only decreases prostate size (static component) but also changes the prostatic SM tone (dynamic component).
Omega‐3 fatty acids decrease prostate cancer progression associated with an anti‐tumor immune response in eugonadal and castrated mice
Authors: Gevariya Nikunj , Besançon Marjorie , Robitaille Karine , Picard Valérie , Diabaté Lamoussa , Alesawi Anwar , Julien Pierre , Fradet Yves , Bergeron Alain , Fradet Vincent
Published: August 2018

Background

Several lines of evidence suggest effects of dietary fat on prostate cancer (PCa) development and progression. Targeting omega (ω)‐3:ω6 fatty acids (FA) ratio could be beneficial against PCa by favorably modulating inflammation. Here, we studied the effects of ω3‐ and ω6‐enriched diets on prostate tumor growth and inflammatory response in androgen‐deprived and non‐deprived conditions.

Methods

Immune‐competent eugonadal and castrated C57BL/6 mice were injected with TRAMP‐C2 prostate tumor cells and daily fed with ω3‐ or ω6‐enriched diet. FA and cytokine profiles were measured in blood and tumors using gas chromatography and multiplex immunoassay, respectively. Immune cell infiltration in tumors was profiled by multicolor flow cytometry.

Results

ω3‐enriched diet decreased prostate TRAMP‐C2 tumor growth in immune‐competent eugonadal and castrated mice. Cytokines associated with Th1 immune response (IL‐12 [p70], IFN‐γ, GM‐CSF) and eosinophil recruitment (eotaxin‐1, IL‐5, and IL‐13) were significantly elevated in tumors of ω3‐fed mice. Using in vitro experiments, we confirmed ω3 FA‐induced eotaxin‐1 secretion by tumor cells and that eotaxin‐1 secretion was regulated by androgens. Analysis of immune cell infiltrating tumors showed no major difference of immune cells’ abundance between ω3‐ and ω6‐enriched diets.

Conclusions

ω3‐enriched diet reduces prostate tumor growth independently of androgen levels. ω3 FA can inhibit tumor cell growth and induce a local anti‐tumor inflammatory response. These findings warrant further examination of dietary ω3's potential to slow down the progression of androgen‐sensitive and castrate‐resistant PCa by modulating immune cell function in tumors.
A new slow‐release formulation of methyl salicylate optimizes the alternative control of Sitobion avenae (Fabricius) (Hemiptera: Aphididae) in wheat fields
Authors: Wang Kang , Liu Jiahui , Zhan Yidi , Liu Yong
Published: August 2018

BACKGROUND

Some defects, such as the short persistence and lower release stability of methyl salicylate (MeSA), must be resolved before efficient field application. To enhance the utilization efficacy of MeSA, a slow‐release MeSA alginate bead was designed and tested to measure its release rate in a laboratory environment and to obtain insights into its ecological effects in wheat fields.

RESULTS

In laboratory tests, both the 2.5 and 10 mL formulations of MeSA alginate beads (hereafter referred to as MeSA 2.5 and MeSA 10) release stably and continuously for at least 15 days, whereas pure MeSA does so for only ∼ 7 days. In field experiments, both the MeSA 2.5 bead and the MeSA 10 bead reduce the abundance of Sitobion avenae significantly and attract Metasyrphus corollae compared with the control. In addition, the effect of MeSA 10 beads is significantly greater than that of MeSA 2.5.

CONCLUSION

The MeSA alginate bead we manufactured could be an efficient slow‐release formulation. The MeSA 10 bead had a significantly greater effect on S. avenae population suppression, partly by attracting M. corollae in fields. © 2018 Society of Chemical Industry
Morphology‐Controllable Synthesis of Cubic‐Structured In2O3 Particles with Enhanced NO2 Gas Sensitivity
Authors: Lu Bin , Chen Pen , Zou Jie , Yao Bin , Chen Hongbing
Published: August 2018

A hydrated basic sulfate precursor for In2O3 is facilely prepared from the mixed indium nitrate and ammonium sulfate solutions via means of single‐step hydrolysis precipitation at a relatively low synthetic temperature of ≈60 °C, which subsequently converts to an oxide powder via pyrolyzing. The morphologies of the precursor and oxide can be controlled via adjusting volume fractions of ethanol‐water solvents. The pure water solvent in the reaction system leads to a thick two‐dimension plate‐like precursor and its oxide generally retains the original shape, while the addition of ethanol up to the volume fraction of 75% in the mother liquor is able to effectively reduce the thickness of the plates to result in well‐dispersed oxide powder with round morphology via partial split, full collapse, and particle growth processes. The as‐prepared In2O3 gas sensors have rapid response and recovery time to trace NO2 and the In2O3 gas sensor derived from the well‐dispersed oxide powder has a rather higher sensitivity than the agglomerated one.
The Four‐Band Spin‐Less Kane Model in Curvilinear Coordinates
Authors: Gravesen Jens , Willatzen Morten
Published: August 2018

The possibility to fabricate complicated nanostructure geometries with novel topological effects so as to tailor physical properties makes it adamant to develop advanced analytical and numerical methods. The first multiband k · p model in general curvilinear coordinates based on Kane's four‐band spin‐less model for the upper conduction and valence band states is developed. The model captures the combined effects of electron and light‐hole bandstructure coupling and curvature effects. The formulation in curvilinear coordinates allows to obtain a simple set of equations, displaying directly the influence of the local curvature, and the explicit equation sets in the cases of a torus and a helix‐shaped nanowire structure with a square cross section are given. The presented derivation can be generalized to other types of k · p multiband models.
Altered clozapine concentrations associated with electronic cigarettes
Authors: Lam Y. W. Francis
Published: August 2018

The atypical antipsychotic clozapine has unique efficacy in patients with treatment‐resistant schizophrenia. However, its pharmacokinetic profile is highly variable and can be altered by changes in metabolic capacity as a result of cytochrome‐P450‐mediated drug‐drug interactions. In addition, smoking can increase the metabolic capacity of patients treated with clozapine, possibly resulting in lower clozapine concentrations. A recent report documented changes in clozapine concentration in a patient who was a smoker and who transitioned from traditional cigarettes to electronic cigarettes.
Lofexidine: Less than meets the eye
Authors: Price Lawrence H.
Published: August 2018

This month's issue of The Update includes coverage of the press release issued by the Food and Drug Administration (FDA) on May 16 announcing approval of lofexidine as “the first non‐opioid treatment for management of opioid withdrawal symptoms in adults” (see page 8). The announcement drew widespread media coverage that, while not abysmal, was seriously deficient in failing to provide context. But that deficiency followed directly from the way in which the FDA phrased its announcement. So here is some context, as well as some speculation as to what the FDA might have been up to.
Tetrel bonds between PhSiF3/PhTH3(T = Si, Ge, Sn) and H3ZO (Z = N, P, As): A pentacoordinate silicon (IV) complex
Authors: Xu Hui‐Li , Cheng Jian‐Bo , Li Hai‐Bei , Yang Xin , Li Qing‐Zhong
Published: August 2018

The nature of the complexes PhTH3H3ZO and PhSiF3H3ZO (T = Si, Ge, and Sn; Z = N, P, and As) has been investigated at the MP2/aug’‐cc‐pVTZ(PP) level. These complexes are primarily stabilized by one T···O tetrel bond. Interaction energies of these complexes vary from 11 to 220 kJ/mol, and T···O separations from 1.89 to 3.09 Å. Charge transfer from the O lone pair into the CT and TH σ* antibonding orbitals leads to the stabilization of these complexes. The T···O tetrel bond between PhTH3/PhSiF3and H3NO exhibits a significant degree of covalence, characterized by the large interaction energy, negative energy density, and large charge transfer. Furthermore, a pentacoordinate silicon (IV) complex is formed in PhSiF3H3NO with the Si···O distance almost close to the length of SiO bond. This indicates that the oxygen atom in N‐oxides shows a strong affinity to the silicon atom in organosilicon compounds.
Quinone‐based switches for candidate building blocks of molecular junctions with QTAIM and the stress tensor
Authors: Xu Tianlv , Wang Lingling , Ping Yang , van Mourik Tanja , Früchtl Herbert , Kirk Steven R. , Jenkins Samantha
Published: August 2018

The current work investigates candidate building blocks based on molecular junctions from hydrogen transfer tautomerization in the benzoquinone‐like core of an azophenine molecule with QTAIM and the recently introduced stress tensor trajectory analysis. We find that in particular the stress tensor trajectories are well suited to describe the mechanism of the switching process. The effects of an Fe‐dopant atom coordinated to the quinone ring, as well as F and Cl substitution of different ring‐hydrogens, are investigated and the new QTAIM and stress tensor analysis is used to draw conclusions on the effectiveness of such molecules as molecular switches in nanosized electronic circuits. We find that the coordinated Fe‐dopant greatly improves the switching properties, both in terms of the tautomerization barrier that has to be crossed in the switching process and the expected conductance behavior, while the effects of hydrogen substitution are more subtle. The absence of the Fe‐dopant atom led to impaired functioning of the switch “OFF” mechanism as well as coinciding with the formation of closed‐shell H—H bond critical points that indicated a strained or electron deficient environment. Our analysis demonstrates promise for future use in design of molecular electronic devices.
Stable oxygen isotopes in water of concentrated liquid foodstuffs: Are the commonly determined values accurate?
Authors: Iacumin Paola , Di Matteo Antonietta , Selmo Enricomaria , Venturelli Giampiero
Published: August 2018

Rationale

Oxygen isotope analysis of water molecules of liquid foodstuffs is commonly performed under isotopic equilibrium between water in the solution and the vapour water, assuming that the liquid water activity is equal to unity and that liquid water is an ideal mixture of H2O isotopologues. A priori this behaviour is not realistic for all foodstuffs, which frequently are very concentrated solutions. In this paper we mainly consider “balsamic vinegar” with the aim of defining an appropriate procedure of oxygen isotope ratio analysis of water molecules in these concentrated solutions.

Methods

Isotope ratio mass spectrometry (IRMS) measurements of the oxygen isotope ratios (δ18O values) were carried out on CO2 equilibrated with water molecules at 22 ± 0.1°C. Three independently calibrated, very low salinity waters were used as standards.

Results

For grape must and wine vinegar (density < 1.15 g/cm3) the δ18O values for water determined directly on these solutions are “true” values. On the contrary, for balsamic vinegar with density higher than 1.15–1.20 g/cm3, the δ18O values obtained directly on the solutions are systematically different from those obtained on water produced by distillation of the same samples at 70°C under vacuum.

Conclusions

In the case of balsamic vinegar with density higher than 1.15–1.20 g/cm3, to avoid severe systematic errors, the isotopic analyses must be carried out on water obtained by distillation under stirring.
A novel laser desorption/ionization method using through hole porous alumina membranes
Authors: Naito Yasuhide , Kotani Masahiro , Ohmura Takayuki
Published: August 2018

Rationale

A novel matrix‐free laser desorption/ionization method based on porous alumina membranes was developed. The porous alumina membranes have a two‐dimensional (2D) ordered structure consisting of closely aligned straight through holes of sub‐micron in diameter that are amenable to mass production by industrial fabrication processes.

Methods

Considering a balance between the ion generating efficiency and the mechanical strength of the membranes, the typical values for the hole diameter, open aperture ratio and membrane thickness were set to 200 nm, 50% and 5 μm, respectively. The membranes were coated with platinum on a single side that was exposed to the laser. Evaluation experiments were conducted on the feasibility of this membrane structure for an ionization method using a single peptide and mixed peptides and polyethylene glycol samples and a commercial matrix‐assisted laser desorption/ionization (MALDI) time‐of‐flight mass spectrometer in the positive ion mode.

Results

Results showed a softness of ionization and no sweet spot nature. The capillary action of the through holes with very high aspect ratio enables several loading protocols including sample impregnation from the surface opposite to the laser exposure side.

Conclusions

The feasibility study indicates that the through hole porous alumina membranes have several advantages in terms of usefulness over the conventional surface‐assisted laser desorption ionization (SALDI) methods. The proposed novel ionization method is termed Desorption Ionization Using Through Hole Alumina Membrane (DIUTHAME).
Cluster ion beam generation from a wetted needle emitter for organic secondary ion mass spectrometry (organic SIMS) using a protic ionic liquid, propylammonium nitrate
Authors: Fujiwara Yukio , Saito Naoaki
Published: August 2018

Rationale

Propylammonium nitrate (PAN, [C3H7NH3][NO3]), a protic ionic liquid, has an active proton in its molecular structure, so that it can promote protonation. In addition, PAN has high aggregability, so that it tends to form large aggregated (or cluster) ions. These features will be desirable for cluster ion beams in secondary ion mass spectrometry (SIMS) of organic materials. The aggregability may enable us to generate a cluster ion beam from a needle tip wetted with PAN by electrospray in vacuum. For these reasons, cluster ion beam generation was investigated using an externally wetted needle emitter.

Methods

A sharpened glass rod was used as a needle emitter. PAN was electrosprayed in vacuum using the needle emitter to generate a cluster ion beam. Beam characteristics were investigated with an apparatus for measuring transient responses of a beam current. SIMS experiments were also performed using the cluster ion beam as a primary ion beam; arginine and polyethylene glycol (PEG300) were analyzed.

Results

A stable cluster ion beam was generated from the needle emitter wetted with PAN. The ion beam consisted of mixed cluster ions whose m/z ranged from about 180 to 5000 or higher. The cluster ion beam successfully produced protonated molecules [M + H]+ (M denotes arginine and PEG molecules) with relatively little fragmentation. Adduct ions [M + C3H7NH3]+ formed by propylammonium‐attachment reaction were also detected for PEG.

Conclusions

It has been demonstrated that a needle emitter wetted with PAN can generate a cluster ion beam that includes massive cluster ions. The cluster ion beam proved to be helpful in producing molecular secondary ions and suitable for a primary ion beam in organic SIMS.
Mono(2‐ethylhexyl) phthalate (MEHP) and mono(2‐ethyl‐5‐oxohexyl) phthalate (MEOHP) but not di(2‐ethylhexyl) phthalate (DEHP) bind productively to the peroxisome proliferator‐activated receptor γ
Authors: Kratochvil Isabel , Hofmann Tommy , Rother Sandra , Schlichting Rita , Moretti Rocco , Scharnweber Dieter , Hintze Vera , Escher Beate I. , Meiler Jens , Kalkhof Stefan , von Bergen Martin
Published: August 2018

Rationale

The most frequently occurring phthalate, di(2‐ethylhexyl) phthalate (DEHP), causes adverse effects on glucose homeostasis and insulin sensitivity in several cell models and epidemiological studies. However, thus far, there is no information available on the molecular interaction of phthalates and one of the key regulators of the metabolism, the peroxisome proliferator‐activated receptor gamma (PPARγ). Since the endogenous ligand of PPARγ, 15‐deoxy‐delta‐12,14‐prostaglandin J2 (15Δ‐PGJ2), features structural similarity to DEHP and its main metabolites produced in human hepatic metabolism, mono(2‐ethylhexyl) phthalate (MEHP) and mono(2‐ethyl‐5‐oxohexyl) phthalate (MEOHP), we tested the hypothesis of direct interactions between PPARγ and DEHP or its transformation products.

Methods

Hydrogen/deuterium exchange mass spectrometry (HDX‐MS) and docking were conducted to obtain structural insights into the interactions and surface plasmon resonance (SPR) analysis to reveal information about binding levels. To confirm the activation of PPARγ upon ligand binding on the cellular level, the GeneBLAzer® bioassay was performed.

Results

HDX‐MS and SPR analyses demonstrated that the metabolites MEHP and MEOHP, but not DEHP itself, bind to the ligand binding pocket of PPARγ. This binding leads to typical activation‐associated conformational changes, as observed with its endogenous ligand 15Δ‐PGJ2. Furthermore, the reporter gene assay confirmed productive interaction. DEHP was inactive up to a concentration of 14 μM, while the metabolites MEHP and MEOHP were active at low micromolar concentrations.

Conclusions

In summary, this study gives structural insights into the direct interaction of PPARγ with MEHP and MEOHP and shows that the DEHP transformation products may modulate the lipid metabolism through PPARγ pathways.
Fractionation of otolith nitrogen stable isotopes measured by peroxodisulfate oxidation‐bacterial conversion and isotope ratio mass spectrometry
Authors: Cheng Li‐Chi , Shiao Jen‐Chieh , Hsiao Silver Sung‐Yun , Wang Pei‐Ling
Published: August 2018

Rationale

Otoliths are usually used to estimate the age of fish and the chemical composition such as nitrogen stable isotope ratios (δ15N values) may record environmental information and ecological role of the fish. However, the isotopic fractionation of δ15N values between diets and otoliths has rarely been investigated and remains unclear.

Methods

Nitrogen isotopic fractionation between five different diets (δ15Ndiet values) and otoliths (δ15Noto values) were elucidated in tilapia Oreochromis mossambica reared in controlled feeding experiments. The otoliths were dissolved with hydrogen chloride and peroxodisulfate was used to oxidize the total organic materials to nitrate, which was further converted into N2O gas by denitrification bacteria before the measurement of δ15Noto values by isotope ratio mass spectrometry. The δ15N values of muscles, gills, scales and livers of the tilapias were also measured by isotope ratio mass spectrometry.

Results

The peroxodisulfate oxidation‐bacterial conversion method reduced the minimum mass of the otoliths required for analysis to as low as 2 mg, unlike past methods, which have required masses of 8–155 mg. The δ15Noto values were not significantly different from the δ15Ndiet values of the five diets. Furthermore, the somatic growth rate had no effect on the δ15Noto values. Nevertheless, the δ15N values of metabolically active tissues were significantly different from each other and higher than the δ15Ndiet values, due to the deamination of these tissues.

Conclusions

These results suggest that diet was the main source of amino acids for the otolith organic matrix and there was no biochemical transamination during the assimilation of dietary amino acids to otoliths. The δ15Noto value can be used as a proxy of nitrogen sources of fishes and may have potential application in ecological studies such as the detection of diet shift, migration, trophic levels and environmental changes experienced by the fish population.
The funnel pre‐compensator
Authors: Berger Thomas , Reis Timo
Published: August 2018

We introduce the funnel pre‐compensator as a novel and simple adaptive pre‐compensator of “high‐gain type”. We show that this pre‐compensator is feasible for a large class of signal pairs, which satisfy a certain relationship. We show that the funnel pre‐compensator guarantees prescribed transient behavior of the compensator error, it is of low complexity and inherently robust since its design is model‐free. As an application in adaptive control of nonlinear systems, a cascade of funnel pre‐compensators is exploited to obtain an artificial output with explicitly known derivatives, which tracks the system output with prescribed transient behavior. In some important cases the interconnection of the system with the pre‐compensator cascade is shown to have input‐to‐state stable internal dynamics. This guarantees feasibility of a novel funnel controller that consists of a funnel pre‐compensator cascade in conjunction with a recently developed funnel controller for systems with arbitrary relative degree. We illustrate the application of this interconnection for some mechanical systems.
Quantization effects and convergence properties of rigid formation control systems with quantized distance measurements
Authors: Sun Zhiyong , Garcia de Marina Hector , Anderson Brian D. O. , Cao Ming
Published: August 2018

In this paper, we discuss quantization effects in rigid formation control systems when target formations are described by interagent distances. Because of practical sensing and measurement constraints, we consider in this paper distance measurements in their quantized forms. We show that under gradient‐based formation control, in the case of uniform quantization, the distance errors converge locally to a bounded set whose size depends on the quantization error, while in the case of logarithmic quantization, all distance errors converge locally to zero. A special quantizer involving the signum function is then considered with which all agents can only measure coarse distances in terms of binary information. In this case, the formation converges locally to a target formation within a finite time. Lastly, we discuss the effect of asymmetric uniform quantization on rigid formation control.
Fish assemblage change following the structural restoration of a degraded stream
Authors: Favata Carl A. , Maia Anabela , Pant Manisha , Nepal Vaskar , Colombo Robert E.
Published: August 2018

Decades of anthropogenic pressure have harmed riverscapes throughout North America by degrading habitats and water quality and can result in the extirpation of sensitive aquatic taxa. Local stream restoration projects have increased in frequency, but monitoring is still infrequent. In 2010, Kickapoo Creek in East Central Illinois was subjected to a stream restoration project that included implementation of artificial riffles, riprap, scouring keys, and riparian vegetation. We monitored the restoration efforts for 6 years after the restoration through annual sampling efforts at restored and reference sites to determine changes in habitat and fish assemblage using standard habitat sampling and electrofishing techniques. We observed distinct temporal and spatial shifts in physico‐chemical parameters along with changes in fish community structure. Although biotic integrity remained moderately low in reference assemblages, restored reaches showed 3‐year delay in response to restoration, with biotic integrity positively linked to additional instream habitat and altered channel morphology. Larger substrate sizes, submerged terrestrial vegetation, and newly formed scour pools along with reduced siltation were found in the restored sites, in contrast to the reference sites. These changes resulted in increased species diversity, reduced number of opportunistic species and consequently an overall increase in health of fish communities. We also observed recruitment of habitat specialists and increase in species with reproductive strategies that rely on complex substrates. The results of this study highlight some of the complex dynamics driving reach‐scale restoration projects. We demonstrate the usefulness of structural restoration as a management tool to increase biotic integrity through long‐term alteration of critical habitat. The delay in the response of species to the restoration efforts emphasizes the need for long‐term continuous temporal and spatial monitoring.
Human Spinal Oligodendrogenic Neural Progenitor Cells Promote Functional Recovery After Spinal Cord Injury by Axonal Remyelination and Tissue Sparing
Authors: Nagoshi Narihito , Khazaei Mohamad , Ahlfors Jan-Eric , Ahuja Christopher S. , Nori Satoshi , Wang Jian , Shibata Shinsuke , Fehlings Michael G.
Published: August 2018

Cell transplantation therapy utilizing neural precursor cells (NPCs) is a conceptually attractive strategy for traumatic spinal cord injury (SCI) to replace lost cells, remyelinate denuded host axons and promote tissue sparing. However, the number of mature oligodendrocytes that differentiate from typical NPCs remains limited. Herein, we describe a novel approach to bias the differentiation of directly reprogrammed human NPCs (drNPCs) toward a more oligodendrogenic fate (oNPCs) while preserving their tripotency. The oNPCs derived from different lines of human NPCs showed similar characteristics in vitro. To assess the in vivo efficacy of this approach, we used oNPCs derived from drNPCs and transplanted them into a SCI model in immunodeficient Rowett Nude (RNU) rats. The transplanted cells showed significant migration along the rostrocaudal axis and proportionally greater differentiation into oligodendrocytes. These cells promoted perilesional tissue sparing and axonal remyelination, which resulted in recovery of motor function. Moreover, after transplantation of the oNPCs into intact spinal cords of immunodeficient NOD/SCID mice, we detected no evidence of tumor formation even after 5 months of observation. Thus, biasing drNPC differentiation along an oligodendroglial lineage represents a promising approach to promote tissue sparing, axonal remyelination, and neural repair after traumatic SCI.
Sliding wear‐induced nano‐tribofilm formation from EP/AW agent on copper foil against ferroalloy counterparts under high load
Authors: Xiong Sang , Sun Jianlin
Published: August 2018

Sliding friction of copper foil surface, which was exposed to bis (6‐acetyl‐1,3,6,2 ‐dioxazaborocan‐2‐yl) methyl phosphate (NEPB) as extreme‐pressure/antiwear agent in base oil while rubbing by a ferroalloy disk under high load, was explored in a multi‐specimen test machine to investigate the wear mechanism of NEPB on thin film lubrication. The results reveal that NEPB reduces the friction coefficient to ~0.16 at normal load of 200 N, and it has better antiwear and friction‐reducing property than the common copper oil. Ferroalloy against copper foil is along the Cu (111) direction, and the friction coefficient decrease relies on the spontaneous formation of chemically nanolayered tribofilm (approx. 30 nm) during sliding wear. The size of wear debris arranges from 6 nm to submicron. Decomposed borate esters and organic nitrides were adsorbed on the worn surface and P element of NEPB as extreme‐pressure/antiwear agent reacted with Cu and existed in the form of phosphates, both of which contributed to the formation of boundary lubricating film.
A validation sampling approach for consistent estimation of adverse drug reaction risk with misclassified right‐censored survival data
Authors: Gravel Christopher A. , Dewanji Anup , Farrell Patrick J. , Krewski Daniel
Published: August 2018

Patient electronic health records, viewed as continuous‐time right‐censored survival data, can be used to estimate adverse drug reaction risk. Temporal outcome misclassification may occur as a result of errors in follow‐up. These errors can be due to a failure to observe the incidence time of the adverse event of interest (due to misdiagnosis or nonreporting, etc) or an actual misdiagnosis of a competing adverse event. As the misclassifying event is often unobservable in the original data, we apply an internal validation sampling approach to produce consistent estimation in the presence of such errors. We introduce a univariate survival model and a cause‐specific hazards model in which misclassification may also manifest as a diagnosis of an alternate adverse health outcome other than that of interest. We develop a method of maximum likelihood estimation of the model parameters and establish consistency and asymptotic normality of the estimators using standard results. We also conduct simulation studies to numerically investigate the finite sample properties of these estimators and the impact of ignoring the misclassification error.
Optimal seamless phase 2/3 oncology trial designs based on Probability of Success (PoS)
Authors: Teng Zhaoyang , Liang Liang , Liu Guohui , Liu Yi
Published: August 2018

In recent years, there has been an increasing trend in conducting seamless phase 2/3 clinical trials for drug development in the pharmaceutical industry due to the visible advantages compared with traditional approaches for separate phase 2 and 3 development. Innovative study designs have been proposed for seamless phase 2/3 trials, which mainly focus on the traditional aspects of study design, such as how to control the Type I error rate, sample size re‐estimation after the phase 2 portion, and how to make treatment selection at the end of the phase 2 portion. However, there are still some questions unresolved such as how to determine the go/no‐go boundary and how to plan the phase 2 portion sample size. In this paper, we discuss how to determine the phase 2 portion and phase 3 portion sample sizes as well as the corresponding go/no‐go criteria for a seamless phase 2/3 oncology trial based on Probability of Success. In addition, we further expand the methodology to include designs with an interim look within the phase 2 portion to speed up the go/no‐go decision‐making process. In case of overwhelming efficacy, this design would further shorten the overall trial duration. In case of inefficacy, this design can stop the trial earlier without exposing more patients to inefficacious treatment.
Using marginal structural models to adjust for treatment drop‐in when developing clinical prediction models
Authors: Sperrin Matthew , Martin Glen P. , Pate Alexander , Van Staa Tjeerd , Peek Niels , Buchan Iain
Published: August 2018

Clinical prediction models (CPMs) can inform decision making about treatment initiation, which requires predicted risks assuming no treatment is given. However, this is challenging since CPMs are usually derived using data sets where patients received treatment, often initiated postbaseline as “treatment drop‐ins.” This study proposes the use of marginal structural models (MSMs) to adjust for treatment drop‐in. We illustrate the use of MSMs in the CPM framework through simulation studies that represent randomized controlled trials and real‐world observational data and the example of statin initiation for cardiovascular disease prevention. The simulations include a binary treatment and a covariate, each recorded at two timepoints and having a prognostic effect on a binary outcome. The bias in predicted risk was examined in a model ignoring treatment, a model fitted on treatment‐naïve patients (at baseline), a model including baseline treatment, and the MSM. In all simulation scenarios, all models except the MSM underestimated the risk of outcome given absence of treatment. These results were supported in the statin initiation example, which showed that ignoring statin initiation postbaseline resulted in models that significantly underestimated the risk of a cardiovascular disease event occurring within 10 years. Consequently, CPMs that do not acknowledge treatment drop‐in can lead to underallocation of treatment. In conclusion, when developing CPMs to predict treatment‐naïve risk, researchers should consider using MSMs to adjust for treatment drop‐in, and also seek to exploit the ability of MSMs to allow estimation of individual treatment effects.
Graphene‐Wrapped Nanoporous Nickel‐Cobalt Oxide Flakes for Electrochemical Supercapacitors
Authors: Azhar Alowasheeir , Zakaria Mohamed B. , Lin Jianjian , Chikyow Toyohiro , Martin Darren J. , Alghamdi Yousef Gamaan , Alshehri Abdulmohsen Ali , Bando Yoshio , Hossain Md. Shahriar A. , Wu Kevin C.‐W. , Kumar Nanjundan Ashok , Yamauchi Yusuke
Published: August 2018

A novel approach for hybridizing nanoporous NiCo oxide flakes with graphene sheets is reported. Positively charged cyano‐bridged CoNi coordination polymer flakes (CoNi‐CP) are mixed with graphene (G) suspension with negatively charged surface. Due to effective electrostatic interaction, both the materials are hybridized to form CoNi‐CP/G composite. The as‐prepared CoNi‐CP/G composite is thermally treated in air, to remove the organic components without affecting the integrity of the parent G sheets. Through the thermal treatment, the CoNi‐CP flakes wrapped into G sheets are converted to NiCo oxide, resulting in a new composite consisting of NiCo oxide flakes and G sheets. The NiCo‐oxide/G composite shows the high specific capacitance (∼ 199 F g‐1) at 5 mV/s, and features the good capacitance retention of ∼68% at 100 mV(∼ 135 F g−1).
Microwave‐Assisted Synthesis of Novel Symmetric Bis‐1,2,4‐triazolin‐3‐ones as Potent Inhibitors of CYP51: An Antifungal Activity Study
Authors: Somagond Shilpa M. , Kamble Ravindra R. , Shaikh Saba Kauser J. , Bayannavar Praveen K. , Joshi Shrinivas D.
Published: August 2018

Improvement of antifungal agents is a good solution to beat the drug‐resistance problems. In this context, a series of novel bis‐1,2,4‐triazolin‐3‐ones (5i‐t) were designed and synthesized by microwave irradiation (MWI), a convenient and efficient method. An effort was also made to get these bis‐1,2,4‐triazolin‐3‐ones (5i‐t) by one‐pot three‐component reaction (3CR) using 3‐aryl‐5‐methyl‐1,3,4‐oxadiazol‐2(3H)‐one (2a‐b), formamide and dibromo reagent (4c‐h) under microwave irradiation (MWI). In vitro antifungal activity was carried out against six pathogenic fungi. From the results it was observed that the newly synthesized bis‐1,2,4‐triazolin‐3‐ones (5i‐t) have shown excellent activity against all the tested pathogenic fungi with least MIC values in the range of 0.80 μg/ml to 0.20 μg/ml. Particularly, in comparison with the reference drug Fluconazole and mono‐1,2,4‐triazolin‐3‐ones (3a‐b) some of the bis‐1,2,4‐triazolin‐3‐ones (5i, 5j, 5 m, 5p and 5r) have shown broad spectrum of antifungal activity. Further, the molecular docking study has been performed for all the tested compounds with 14α‐demethylase (CYP51) as target enzyme and this study validated the experimental results. Thus, docking study has culminated in the identification of a new class of potent inhibitors of CYP51. The results provide significant information for the future design of more potent antifungal agents.
Fe3O4 @ PLGA‐PEG Nanocomposite for Improved Delivery of Methotrexate in Cancer Treatment
Authors: Basu Tanushree , Singh Satnam , Pal Bonamali
Published: August 2018

Magnetic Fe3O4 nanoparticles are gaining significance in drug delivery applications owing to their targeting capability. Surface modification of amphiphilic block polymers by Fe3O4 nanoparticles increases their properties. In this study, Fe3O4 @ PLGA‐PEG nanocomposite is prepared by double emulsion (w/o/w) method. A shift in the 2Θ values for the composite in XRD attributes to interaction between Fe3O4 and PLGA‐PEG. Also, a shift in the Fe‐O band in the FTIR spectrum of Fe3O4@PLGA‐PEG from 578 cm‐1 to 510 cm‐1 confirms the formation of nanocomposite. Surface morphology of the prepared nanocomposite is analyzed by TEM and AFM. Decrease in agglomeration due to electrostatic repulsion between the polymer chains and magnetic particles is observed while an increased surface area (61.0nm) confirms the formation of the nanocomposite. To determine the effectiveness of the prepared magnetically modified nanoparticles, methotrexate (anticancer drug) is encapsulated into the nanocomposite. High entrapment efficiency of 95% is observed when polymer:drug is 1:1. The in‐vitro release profile shows that pH of release medium plays a significant role. At physiological pH of 7.3 there is only 15% methotrexate release while nearly 86% of methotrexate release is observed at acidic pH of 4.6 over 72h. Korsemeyer‐Peppas model of drug release (R2‐0.9868) represents swelling controlled release of methotrexate. Further, the cytotoxic cell viability assay on SK‐BR‐3 (breast adinocarcinoma) cells showed that methotrexate loaded onto the nanocomposite showed higher cell viability as compared to free methotrexate after 96h of incubation. The fluorescent cell imaging also showed that methotrexate released slowly from the nanoparticles and diffused into the nucleus without losing its cytotoxic effect on the cancer cells. Based on these properties of the magnetically modified PLGA‐PEG nanoparticles they can be used as targeting drug delivery agents in treatment of cancer therapy.