bluuebunny/crossref_metadata_2025 huggingface dataset:
Alleviating the Cadmium Toxicity and Growth‐Promotion in Paddy Rice by Photosynthetic Bacteria
Authors: Xiao Xian , Zhao Yuan , Zhou Qin , Wang Leyang , Zhang Xujie , Zhao Lihua , Zhang Sheng
Published: January 2019

Cadmium (Cd) accumulation in rice and its subsequent transfer to food chain has become a major environmental issue worldwide. Low growth in plants and high toxicity toward the living organism are major drawbacks associated with Cd contamination. Effective immobilization and reducing Cd uptake by rice grains can be promising strategies to minimize its toxicity. Here, the authors report an effective method for Cd immobilization by inoculating photosynthetic bacteria known as Rhodopseudomonas palustris (RP) in the soils, which is verified through pot and field experiments. The pot experiment indicated that high Cd contamination in control soils inhibited plant growth and decreased the biomass massively in paddy rice. Bacterial immobilization of Cd not only inhibited its uptake by plants but also increased fresh weight of rice seedlings under low Cd concentration (40 mg kg−1 soil). However, under high Cd concentration (80 mg kg−1), Bacillus subtilis enhanced the activity of RP for reducing the Cd uptake and subsequent accumulation in rice grains (from 0.65 to 0.19 mg Cd kg−1) to below the standard limits (0.2 mg kg−1). Field experiments showed that Cd prefers to accumulate in the root region, and the transmission process through roots, stems, and leaves are restricted for ultimately decreasing the Cd accumulation in rice grains. In natural soil with low Cd contamination, the rice grains can be safely edible. These findings will assist to minimize the Cd toxicity in human health and to address the food safety challenges of modern world.
Innovation in Regulatory Science Is Meeting Evolution of Clinical Evidence Generation
Authors: Lee Myrto , Ly Hoan , Möller Clemens C. , Ringel Michael S.
Published: January 2019

At the turn of the century, the pharmaceutical industry began a transition toward a focus on oncology, rare diseases, and other areas of high unmet need that required a new, more complex approach to drug development. For many of these disease states and novel approaches to therapy, traditional approaches to clinical trial design fall short, and a number of innovative trial designs have emerged. In light of these changes, regulators across the globe are implementing new programs to provide regular development program support, facilitate accelerated access, use real‐world data, and use digital tools to improve patients’ lives. Emerging market regulators are also focusing on simplifying their regulatory pathways via regional harmonization schemes with varying levels of ambition. These changes in the external environment imply that biopharma regulatory teams need to adapt and evolve, leveraging digital tools, data, and analytics, and positioning themselves as strategic advisors during development.
Model‐Informed Drug Development: Current US Regulatory Practice and Future Considerations
Authors: Wang Yaning , Zhu Hao , Madabushi Rajanikanth , Liu Qi , Huang Shiew‐Mei , Zineh Issam
Published: January 2019

Model‐informed drug development (MIDD) refers to the application of a wide range of quantitative models in drug development to facilitate the decision‐making process. MIDD was formally recognized in Prescription Drug User Fee Act (PDUFA) VI. There have been many regulatory applications of MIDD to address a variety of drug development and regulatory questions. These applications can be broadly classified into four categories: dose optimization, supportive evidence for efficacy, clinical trial design, and informing policy. Case studies, literature papers, and published regulatory documents are reviewed in this article to highlight some common features of these applications in each category. In addition to the further development and investment in these established domains of application, new technology, and areas, such as more mechanistic models, neural network models, and real‐world data/evidence, are gaining attention, and more submissions and experiences are being accumulated to expand the application of model‐based analysis to a wider scope.
Origins of abrupt change? Postfire subalpine conifer regeneration declines nonlinearly with warming and drying
Authors: Hansen Winslow D. , Turner Monica G.
Published: January 2019

Robust tree regeneration following high‐severity wildfire is key to the resilience of subalpine and boreal forests, and 21st century climate could initiate abrupt change in forests if postfire temperature and soil moisture become less suitable for tree seedling establishment. Using two widespread conifer species, lodgepole pine (Pinus contorta var. latifolia) and Douglas‐fir (Pseudotsuga menziesii var. glauca), we conducted complementary experiments to ask (1) How will projected early‐ to mid‐21st‐century warming and drying affect postfire tree seedling establishment and mortality? (2) How does early seedling growth differ between species and vary with warming and drying? With a four‐year in situ seed‐planting experiment and a one growing season controlled‐environment experiment, we explored effects of climate on tree seedling establishment, growth, and survival and identified nonlinear responses to temperature and soil moisture. In our field experiment, warmer and drier conditions, consistent with mid‐21st‐century projections, led to a 92% and 76% reduction in establishment of lodgepole pine and Douglas‐fir. Within three years, all seedlings that established under warmer conditions died, as might be expected at lower elevations and lower latitudes of species’ ranges. Seedling establishment and mortality also varied with aspect; approximately 1.7 times more seedlings established on mesic vs. xeric aspects, and fewer seedlings died. In the controlled‐environment experiment, soil temperatures were 2.0°–5.5°C cooler than the field experiment, and warming led to increased tree seedling establishment, as might be expected at upper treeline or higher latitudes. Lodgepole pine grew taller than Douglas‐fir and produced more needles with warming. Douglas‐fir grew longer roots relative to shoots, compared with lodgepole pine, particularly in dry soils. Differences in early growth between species may mediate climate change effects on competitive interactions, successional trajectories, and species distributions. This study demonstrates that climate following high‐severity fire exerts strong control over postfire tree regeneration in subalpine conifer forests. Climate change experiments, such as those reported here, hold great potential for identifying mechanisms that could underpin fundamental ecological change in 21st‐century ecosystems.
Effects of salinity on microbialite‐associated production in Great Salt Lake, Utah
Authors: Lindsay Melody R. , Johnston Rachel E. , Baxter Bonnie K. , Boyd Eric S.
Published: January 2019

Abstract

Microbialites, organosedimentary carbonate structures, cover approximately 20% of the basin floor in the south arm of Great Salt Lake, which ranges from ~12 to 15% salinity. Photosynthetic microbial mats associated with these benthic mounds contribute biomass that supports secondary production in the ecosystem, including that of the brine shrimp, Artemia franciscana. However, the effects of predicted increases in the salinity of the lake on the productivity and composition of these mats and on A. franciscana fecundity is not well documented. In the present study, we applied molecular and microcosm‐based approaches to investigate the effects of changing salinity on (1) the primary productivity, abundance, and composition of microbialite‐associated mats of GSL, and (2) the fecundity and survivability of the secondary consumer, A. franciscana. When compared to microcosms incubated closest to the in situ measured salinity of 15.6%, the abundance of 16S rRNA gene templates increased in microcosms with lower salinities and decreased in those with higher salinities following a 7‐week incubation period. The abundance of 16S rRNA gene sequences affiliated with dominant primary producers, including the cyanobacterium Euhalothece and the diatom Navicula, increased in microcosms incubated at decreased salinity, but decreased in microcosms incubated at increased salinity. Increased salinity also decreased the rate of primary production in microcosm assays containing mats incubated for 7 weeks and decreased the number of A. franciscana cysts that hatched and survived. These results indicate that an increase in the salinity of GSL is likely to have a negative impact on the productivity of microbialite communities and the fecundity and survivability of A. franciscana. These observations suggest that a sustained increase in the salinity of GSL and the effects this has on primary and secondary production could have an upward and negative cascading effect on higher‐trophic‐level ecological compartments that depend on A. franciscana as a food source, including a number of species of migratory birds.
Multiple temperature effects on phenology and body size in wild butterflies predict a complex response to climate change
Authors: Davies W. James
Published: January 2019

Temperature‐induced alterations in phenology and body size are the cumulative outcome of sequential effects impacting development and are universal responses to climate change. Most studies have so far focused on phenological responses to warming in multiple taxa across space and time, or the ontogenetic effects of temperature in the laboratory. I here complement this work by investigating shifts in phenology and body size (wing length) attributable to temperature changes operating over the entire lifespan of the univoltine orange‐tip butterfly Anthocharis cardamines in a single wild population over 14 generations. Phenology was affected by temperatures during three discrete periods in the year prior to emergence, corresponding to late larval/early pupal life, the onset of the chilling period required to break pupal diapause, and postdiapause pupal development prior to eclosion. Higher temperatures during late larval/early pupal life and postdiapause pupal development advanced the subsequent emergence of the butterflies, whereas higher temperatures at the onset of the chilling period retarded it. The synchronization of the butterflies' emergence schedule increased when pupae were exposed to milder midwinter temperatures. Wing length increased with warmer temperatures at distinct points in the early and midpupal periods; such direct effects of temperature on body size could complement season length effects in explaining the reversal of the temperature–size rule in univoltine insects. The periods during which temperature affected the phenology of the butterfly only partially overlapped those affecting the first flowering date of its host plants lady's smock (Cardamine pratensis) and garlic mustard (Alliaria petiolata). Observed thermal effects on flowering time, emergence timing, and emergence synchronization indicate that phenological convergence as well as phenological mismatching could affect host‐plant availability and diet breadth; thermal effects on body size imply that important population‐level processes could be impacted through correlated changes in fecundity and dispersal rate. In general, the combined effects of phenological and ontogenetic responses to temperature changes across the whole lifespan will likely be important in modeling the demographic responses of interacting species to climate change.
Intraguild predation enhances biodiversity and functioning in complex food webs
Authors: Wang Shaopeng , Brose Ulrich , Gravel Dominique
Published: January 2019

Abstract

Intraguild predation (IGP), that is, feeding interaction between two consumers that share the same resource species, is commonly observed in natural food webs. IGP expands vertical niche space and slows down energy flows from lower to higher trophic levels, which potentially affects the diversity and dynamics of food webs. Here, we use food‐web models to investigate the effects of IGP on species diversity and ecosystem functioning. We first simulate a five‐species food‐web module with different strengths of IGP at the herbivore and/or carnivore level. Results show that as the strength of IGP within a trophic level increases, the biomass of its resource level increases because of predation release; this increased biomass in turn alters the energy fluxes and biomass of other trophic levels. These results are then extended by subsequent simulations of more diverse food webs. As the strength of IGP increases, simulated food webs maintain (1) higher species diversity at different trophic levels, (2) higher total biomasses at different trophic levels, and (3) larger energy fluxes across trophic levels. Our results challenge the intuitive hypothesis that food‐web structure should maximize the efficiency of energy transfer across trophic levels; instead, they suggest that the assembly of food webs should be governed by a balance between efficiency (of energy transfer) and persistence (i.e., the maintenance of species and biomasses). Our simulations also show that the relationship between biodiversity and ecosystem functioning (e.g., total biomass or primary production) is much stronger in the presence of IGP, reconciling the contrast from recent studies based on food‐chain and food‐web models. Our findings shed new light on the functional role of IGP and contribute to resolving the debate on structure, diversity and functioning in complex food webs.
Cardiac contractility modulation improves long‐term survival and hospitalizations in heart failure with reduced ejection fraction
Authors: Anker Stefan D. , Borggrefe Martin , Neuser Hans , Ohlow Marc‐Alexander , Röger Susanne , Goette Andreas , Remppis Bjoern A. , Kuck Karl‐Heinz , Najarian Kevin B. , Gutterman David D. , Rousso Benny , Burkhoff Daniel , Hasenfuss Gerd
Published: January 2019

Aims

Cardiac contractility modulation (CCM) improves symptoms and exercise tolerance and reduces heart failure (HF) hospitalizations over 6‐month follow‐up in patients with New York Heart Association (NYHA) class III or IV symptoms, QRS < 130 ms and 25% ≤ left ventricular ejection fraction (LVEF) ≤ 45% (FIX‐HF‐5C study). The current prospective registry study (CCM‐REG) aimed to assess the longer‐term impact of CCM on hospitalizations and mortality in real‐world experience in this same population.

Methods and results

A total of 140 patients with 25% ≤ LVEF ≤ 45% receiving CCM therapy (CCM‐REG25‐45) for clinical indications were included. Cardiovascular and HF hospitalizations, Minnesota Living with Heart Failure Questionnaire (MLHFQ) and NYHA class were assessed over 2 years. Mortality was tracked through 3 years and compared with predictions by the Seattle Heart Failure Model (SHFM). A separate analysis was performed on patients with 35% ≤ LVEF ≤ 45% (CCM‐REG35‐45) and 25% ≤ LVEF < 35% (CCM‐REG25‐34). Hospitalizations decreased by 75% (from 1.2/patient‐year the year before, to 0.35/patient‐year during the 2 years following CCM, P < 0.0001) in CCM‐REG25‐45 and by a similar amount in CCM‐REG35‐45 (P < 0.0001) and CCM‐REG25‐34. MLHFQ and NYHA class improved in all three cohorts, with progressive improvements over time (P < 0.002). Three‐year survival in CCM‐REG25‐45 (82.8%) and CCM‐REG24‐34 (79.4%) were similar to those predicted by SHFM (76.7%, P = 0.16; 78.0%, P = 0.81, respectively) and was better than predicted in CCM‐REG35‐45 (88.0% vs. 74.7%, P = 0.046).

Conclusion

In real‐world experience, CCM produces results similar to those of previous studies in subjects with 25% ≤ LVEF ≤ 45% and QRS < 130 ms; cardiovascular and HF hospitalizations are reduced and MLHFQ and NYHA class are improved. Overall mortality was comparable to that predicted by the SHFM but was lower than predicted in patients with 35% ≤ LVEF ≤ 45%.
The Niecke Biradicals and Their Congeners – The Journey from Stable Biradicaloids to Their Utilization for the Design of Nonlinear Optical Properties
Authors: Schoeller Wolfgang W.
Published: January 2019

Biradicals within organic chemistry are known to be of fleeting existence. They can be traced only by femtosecond spectroscopy and/or corresponding trapping experiments. The conceptual understanding of a biradical originates mainly from gas phase experiments. These shaped the biradicals as highly unstable species, their lifetimes determined by reactions, which are merely entropy controlled. On the other hand, biradicals in π‐systems of non‐Kekule type, lead to species, which either have distinct singlet or triplet ground states. Yet they are still species confined to spectroscopic investigations. The matter changed by the introduction of sterically protecting groups into chemistry, in order to stabilize hitherto highly reactive compounds. With the new growing field of phosphorus organic chemistry, both fields merged and the concept of a stable biradical came to light. The concept matured in subsequent years and it is now a flowering field with promising aspects in materials science. The Niecke‐type biradicaloid, which is a basic unit in this area, owes its stability by protection of the phosphorus position with sterically demanding substituents, in particular with the “super‐mesityl” (Mes*) group. The electron withdrawing TMS groups at the carbon positions enhance the singlet stability. On this basis it was possible to isolate and structurally characterize these non‐Kekule type structures. The description of these systems as biradicals or biradicaloids is determined by their high reactivity and they offer versatility for a variety of chemical reactions. From the point of theory this refers to small energy gaps between adiabatic singlet and triplet states. However, the understanding as biradicals is different to the Doering concept of a biradical vs. a biradicaloid, as anticipated in the transition state of the Cope automerization. In the Niecke‐type biradicaloid a corresponding biradical structure is promoted with enhanced pyramidalization at the phosphorus atoms or in more general by a decrease of the Lewis basicity of the lone pairs. The Niecke‐type biradical can be converted into a Bertrand‐type biradical with trans‐annular bonding. This requires changing the donor‐ability at the phosphorus centers. This prediction could be proven by either addition with Lewis acids or complexation with transition metal fragments. In the last part of this article, it is briefly shown how biradicals can be utilized as units for building extended π‐systems. They feature an interesting target for the design of interesting materials for nonlinear optics.
Inelastic Neutron Scattering of Lanthanoid Complexes and Single‐Molecule Magnets
Authors: Dunstan Maja A. , Mole Richard A. , Boskovic Colette
Published: January 2019

Single‐molecule magnets (SMMs) are discrete metal complexes that retain their magnetisation below a certain temperature, with possible applications in quantum information processing, molecular spintronics and high‐density data storage. Complexes of lanthanoid(III) ions have proven highly successful in the field, some exhibiting magnetic hysteresis at liquid nitrogen temperatures. Inelastic neutron scattering (INS), widely used for the study of the crystal field splitting engendered by the coordination environment of metal centres, can afford a wealth of information when applied to the study of these molecular nanomagnets, as the SMM properties arise from the electronic structure of the lanthanoid(III) ions. Although relatively underutilised to date, INS can be employed alongside crystal field analysis, and/or ab initio calculations, to understand how subtle structural changes impact SMM behaviour. In this Minireview we discuss the application of INS to the study of lanthanoid complexes, to elucidate both crystal field splitting and exchange coupling in coupled metal‐radical and metal‐metal SMMs.
Antioxidant Capacity, Phenolic Composition and Physicochemical Characteristics of Whole Olive Stone Oil Extracted from Different Olive Varieties Grown in Iran
Authors: Khadem Samineh , Rashidi Ladan , Homapour Masoud
Published: January 2019

In this study, the physicochemical properties and bioactive contents of whole olive stone oils (WOSOs) extracted from six olive varieties, including Zard, Roughani, Mari, Shengeh, Koroneiki, and Manzanilla, cultivated in the city of Fasa, Iran, are investigated. Therefore, fatty acids (FAs), sterols, and triacylglycerols (TAGs) contents, equivalent carbon number (ECN), saponification, iodine, and unsaponifiable matter values, and phenolic contents of each WOSO are analyzed. The lowest and highest fat content of six WOS varieties are obtained as 2.41 and 5.41%, respectively. The results from saponification value, iodine value, and unsaponifiable matter tests on different varieties of WOSO are respectively ranged from 192.27 to 192.30 (mg KOH/g fat), from 82.80 to 93.35 (mg I2/g fat) and from 0.03 to 0.32 (%). β‐sitosterol is found as the predominant sterol in the WOSO. TAGs with one FA, triolein (OOO, 19.29–28.12%), followed by TAGs with two FAs, oleic‐oleic‐linoleic (OOL, 17.36–23.93%), and then those with three FAs, palmitic‐linoleic‐oleic (PLO, 8.36–11.73%), are the predominant TAGs in the WOSO. Oleic acid and ferulic acid are respectively found as the predominant FA and phenolic compounds in the WOSO. The influence of the olive variety on physicochemical properties and bioactive contents of the WOSO is observed.

Practical Applications: The main outcome of this study shows that the determination of FA, sterol, and TAG compositions of WOSO can be applied for the differentiation of olive variety. In addition, determination of the main parameters of chemical properties and bioactive contents of WOSO can be of importance for its further application in different industries, including the food industry, cosmetics, animal food, etc. Results show that this oil can be used as a natural source of polar phenol compounds for human consumption. Using WOSO for human consumption or the pharmaceutical industry can help to reduce waste disposal problems.

The whole olive stone (WOS) is known as an important byproduct generated in the olive oil extraction. Special physicochemical properties of whole olive stone oil (WOSO) are shown that this oil is a rich source of polar phenol and bioactive compounds. Results are shown that fatty acids, sterols, and triacylglycerols composition of WOSO depend on the olive cultivar. WOSO has similar the physicochemical properties and bioactive content as olive oil.
Ruthenium‐Catalyzed Regioselective Direct Ortho‐Acyloxylation of Azoarenes with Carboxylic Acids via C–H Bond Activation
Authors: Kianmehr Ebrahim , Nasab Sepideh Bahrami
Published: January 2019

A RuII‐catalyzed highly regioselective C–H acyloxylation of azoarenes with inexpensive alkyl and aryl carboxylic acids as an acyloxylation agent is described. The reaction demonstrates a broad substrate scope and good functional group tolerance. This method provides a facile procedure to synthesize ortho‐acyloxylated azoarene derivatives.
Transformations of meso‐Iminofunctionalized Pd(II) and Ni(II)‐Complexes of β‐Alkylsubstituted Porphyrins
Authors: Erzina Dina R. , Zamilatskov Ilya A. , Stanetskaya Nadezhda M. , Tyurin Vladimir S. , Kozhemyakin Grigory L. , Ponomarev Gelii V. , Chernyshev Vladimir V. , Fitch Andrew N.
Published: January 2019

The meso‐imino derivatives of the palladium (II) and nickel (II) complexes of coproporphyrins I and II and β‐octaethylporphyrin were obtained by the Vilsmeier formylation followed by interaction with amines. The metal complexes of the azomethines obtained were transformed to the corresponding complexes of cyclopentane and cyclopentane‐pyrrolidone fused porphyrin derivatives by thermolysis. The plausible mechanism of such transformations was suggested and substantiated with quantum chemical calculations. Meso‐cyano‐, meso‐hydroxy‐, and meso‐aminocarbonyl derivatives of β‐octaethylporphyrin were obtained by treatment of the corresponding meso‐imino derivatives with bases. Demetalation of the nickel complex of the meso‐ hydroxy‐β‐octaethylporphyrin led to formation of the free base derivative. The structures of new types of the porphyrin derivatives were determined via X‐ray powder diffraction analysis. The obtained types of porphyrins are promising candidates to use as photosensitizers in medicine applications due to their longer wave absorption combined with high stability.
Ruthenium‐Catalysed Olefin Metathesis in Environmentally Friendly Solvents: 2‐Methyltetrahydrofuran Revisited
Authors: Smoleń Michał , Marczyk Anna , Kośnik Wioletta , Trzaskowski Bartosz , Kajetanowicz Anna , Grela Karol
Published: January 2019

Application profiles of a set of popular second‐generation ruthenium catalysts were experimentally investigated in an environmentally friendly solvent, 2‐methyltetrahydrofuran (2‐MeTHF), and compared with the activity of the same catalysts in toluene, a popular solvent used in industrial olefin metathesis. It was found that a catalyst containing a 2‐isopropoxy‐5‐nitrobenzylidene moiety and a symmetrical N‐heterocyclic (NHC) ligand with 2,6‐diisopropylphenyl substituents (SIPr) exhibits the highest catalytic activity in 2‐MeTHF also at a lower temperature (30 °C).Ab initiostudies showed that initiation rates of Ru catalysts bearing NHC ligands in 2‐MeTHF can be correlated with partial charges and bond lengths between selected crucial atoms in the studied ruthenium complexes. The results demonstrate that aromatic or chlorinated solvents, typically used in metathesis reactions, can be successfully replaced in many cases by 2‐MeTHF.
Effect of the Cathode Catalyst Layer Thickness on the Performance in Direct Methanol Fuel Cells
Authors: Glass Dean E. , Prakash G. K. Surya
Published: January 2019

Catalyst deposition control is one of the overlooked areas of fuel cell fabrication and research that can affect the overall performance and cost of the fuel cell to manufacture for mass production. The effect of the different individual catalyst layer thicknesses and loadings of the cathode compartment of a direct methanol fuel cell (DMFC) was investigated. The drawdown method was performed at thicknesses varying from 1 mil to 8 mils with platinum loadings ranging from 0.25 mg cm−2 to 2.0 mg cm−2. The membrane electrode assemblies (MEAs) with thicker individual layers (8 mil and 4 mil) performed better overall compared to the ones prepared with thinner individual layers (1 mil). The power density maxima for the different loading levels followed an exponential decrease of platinum utilization at the higher loading levels. The painted MEAs tended to display the similar performance characteristics as the drawdown MEA layers closest to the thickness at the respective loadings.
Nanomolar Level Acetaminophen Sensor Based on Novel Polypyrrole Hydrogel Derived N‐doped Porous Carbon
Authors: Wang Meiling , Zhong Laijin , Cui Mingzhu , Liu Weifeng , Liu Xuguang
Published: January 2019

This study develops a novel approach to morphology‐controlled N‐doped porous carbons (NPC) derived from supramolecular crosslinked polypyrrole hydrogel (PPy‐gel) with tetra‐functional tetrakis(4‐carboxyphenyl)porphyrin as dopant and cross‐linker. Both optimized PPy‐gel and NPC realize acetaminophen determination at nanomolar level, displaying record‐low respective detection limits of 3.0 and 1.0 nM (S/N=3). The optimized NPC demonstrates necklace‐like structure with more edge pyridinic N, revealing better electronic conductivity and higher electrochemically active surface area, and consequently higher sensitivity and selectivity. Even in the presence of three interferences (ascorbic acid, dopamine and uric acid), NPC based electrochemical sensor also shows the ultra‐low detection limit (1.2 nM). The promising application potential of the sensor is proved by the high consistence between measurements in pharmaceutical sample and established acetaminophen standard curve. Moreover, the determination results of acetaminophen in human urine sample obtained by this sensor were in a good agreement with the reference values assayed by HPLC.
Quantification of controlled release leuprolide and triptorelin in rabbit plasma using electromembrane extraction coupled with HPLC–UV
Authors: Hosseiny Davarani Saied Saeed , Pourahadi Ahmad , Ghasemzadeh Peivand
Published: January 2019

An electromembrane extraction followed by HPLC–UV technique was developed and validated for quantification of leuprolide and triptorelin in rabbit plasma. The influencing parameters on the extraction efficiency were optimized using experimental design methodology. The optimized conditions were found to be; supported liquid membrane: a mixture of 1‐octanol and 2‐ethyl hexanol (1:1) containing 10% v/v di(2‐ethylhexyl) phosphate, applied voltage: 5 V, extraction time: 5 min, pH of the donor phase: 4.5 and pH of the acceptor phase: 1.0. The optimized method was validated for linearity, intraday and interday precision, and accuracy in rabbit plasma. The range of quantification for both peptides was 0.5–1000 ng/mL with regression coefficients higher than 0.994. Relative recoveries of leuprolide and triptorelin were found to be 80.3 and 75.5%, respectively. Limits of quantification and detection for both peptides were found to be 0.5 and 0.15 ng/mL, respectively. The validated method was successfully applied to pharmacokinetic study of the 1‐month depot formulations of each peptide after subcutaneous administration to rabbits.
MoFe‐Codoped Ni3S2/Ni(OH)2 Nanosheets with Large Sample Size toward High‐Performance Oxygen Evolution
Authors: Xie Liu , Tong Rui , Zhang Wen , Wang Dejian , Liu Tao , Li Qi , Peng Xiaoniu , Wang Xina
Published: January 2019

Efficient, stable, and scalable oxygen evolution reaction (OER) electrocatalysts are highly needed for industrial hydrogen production. Herein, MoFe‐codoped Ni3S2/Ni(OH)2 nanosheets with a sample size area of 200 cm2 are established on Ni foam via a facial hydrothermal method. It is found that Fe3+ and MoO42− are effectively doped into the Ni3S2/Ni(OH)2 nanosheets that are composed by heazlewoodite Ni3S2 and β‐Ni(OH)2 nanocrystals. Based on the systematic study on the non‐, Fe‐, Mo‐, and MoFe‐doped Ni3S2/Ni(OH)2 composites, it is revealed that Fe3+ and MoO42− play important roles in reducing the interfacial charge transfer and increasing the electrochemical active surface area, respectively. When doping at a MoFe molar ratio of 5/3, the synergistic effect of Fe and Mo leads to an optimum OER property with low overpotentials of η100 (263 mV) and η500 (301 mV), Tafel plot of 52 mV  dec−1, and long durability for at least 24 h. An effective strategy for high‐efficiency, long‐durability, and nonprecious OER electrocatalysts with promising applications is provided.
Carbonation of BOF Slag in a Rotary Kiln Reactor in View of the Scale‐Up of the Wet Route Process
Authors: Librandi Paola , Costa Giulia , Stendardo Stefano , Baciocchi Renato
Published: January 2019

Carbonation of alkaline residues represents a potentially interesting technique for permanently storing in solid form CO2 contained in flue gas, syngas or biogas, as well as for the valorization of the residues. In particular, the wet carbonation route requires a low amount of water, does not generate wastewater and can be exploited to produce aggregates. The efficacy of this route has been demonstrated at laboratory scale. In view of its scale‐up, this study was aimed at evaluating the performance of a wet‐route carbonation process applied to Basic Oxygen Furnace (BOF) steel slag employing an operating procedure that could be adopted also at demonstrative or full scale. Dry residues were directly fed by a loading hopper into a rotary kiln reactor, in which gas containing 40% CO2 and steam were flown through. During the experiments, the flow and composition of the gas phase were continuously monitored, allowing to calculate the amount of CO2 captured from the gas phase and to compare it with the CO2 uptake of the solid product. In addition, the leaching behavior of the treated slag was assessed. The results of the tests were close to those obtained in previous experiments performed with pre‐humidified BOF slag, both with the same reactor used in this study and at laboratory scale; this suggests that this more automated wet‐route process could be employed for demonstration or full scale tests. The set up still needs to be optimized to obtain a product with physical and technical properties suitable for use as aggregate. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13140, 2019
Opportunistic multiple access (OMA) for crowdsensing networks with sparse activation
Authors: Moosavi Seyede Nazanin , Pourahmadi Vahid
Published: January 2019

For gathering data in a crowdsensing network, we need to support the connectivity of a massive number of low power devices. In this paper, a new multiple access technique is proposed for such networks with a large number of devices/sensors/users where we have taken advantage of the fact that these devices usually do not become active at the same time, which we refer to as sparse activation property. In this scheme, each device uses a specific spreading code which is changing at symbol level. Symbol‐level change of the spreading code and the random nature of user activation are the two building blocks that provide opportunistic low interference between data transmitted by devices, which are activated in a specific time slot. We also discuss how the proposed scheme can be used in grant free schemes which eliminate the need for heavy signaling before data transmission. The performance of the proposed scheme has been evaluated in different scenarios, and the block error rates are compared with a few other multiple access schemes.
Multivariate morphometrics, quantitative genetics, and neutral theory: Developing a “modern synthesis” for primate evolutionary morphology
Authors: von Cramon‐Taubadel Noreen
Published: January 2019

Anthropologists are increasingly turning to explicit model‐bound evolutionary approaches for understanding the morphological diversification of humans and other primate lineages. Such evolutionary morphological analyses rely on three interconnected conceptual frameworks; multivariate morphometrics for quantifying similarity and differences among taxa, quantitative genetics for modeling the inheritance and evolution of morphology, and neutral theory for assessing the likelihood that taxon diversification is due to stochastic processes such as genetic drift. Importantly, neutral theory provides a framework for testing more parsimonious explanations for observed morphological differences before considering more complex adaptive scenarios. However, the consistency with which these concepts are applied varies considerably, which mirrors some of the theoretical obstacles faced during the “modern synthesis” of classical population genetics in the early 20th century. Here, each framework is reviewed and some potential stumbling blocks to the full conceptual integration of multivariate morphometrics, quantitative genetics, and neutral theory are considered.
Regime switching rough Heston model
Authors: Alfeus Mesias , Overbeck Ludger , Schlögl Erik
Published: January 2019

This model combines two important stylized features of volatility, the rough behavior consistent with a Hurst parameter less than , and the regime switching property consistent with more long‐term economic considerations. It is nevertheless highly tractable in the sense of semianalytic formulae for European options, and permits a partial Monte Carlo method of similar computational speed as the semianalytic formula (at an appropriate number of Monte Carlo simulations). While option prices are relatively insensitive to the choice of Hurst parameter, introducing rough volatility allows for a better fit to the at‐the‐money skew.
Valuation and applications of compound basket options
Authors: Bae Kwangil
Published: January 2019

This study investigates compound basket options, which are options on portfolios of options. Although they may be new to financial markets, they are available as equity basket options, equity spread options, stocks of holding companies, and collateralized debt obligations. Using moments of portfolio values, we provide formulas for pricing compound basket options. According to numerical analysis, a lower bound and a weighted average of bounds yield relatively small errors. Additionally, ignoring the compound feature increases the pricing error of equity basket options because the feature captures the capital structure and leverage effect of stock prices.
A fully adjusted two‐stage procedure for rank‐normalization in genetic association studies
Authors: Sofer Tamar , Zheng Xiuwen , Gogarten Stephanie M. , Laurie Cecelia A. , Grinde Kelsey , Shaffer John R. , Shungin Dmitry , O’Connell Jeffrey R. , Durazo‐Arvizo Ramon A. , Raffield Laura , Lange Leslie , Musani Solomon , Vasan Ramachandran S. , Cupples L. Adrienne , Reiner Alexander P. ,   NHLBI Trans‐Omics for Precision Medicine (TOPMed) Consortium, Laurie Cathy C. , Rice Kenneth M.
Published: January 2019

When testing genotype–phenotype associations using linear regression, departure of the trait distribution from normality can impact both Type I error rate control and statistical power, with worse consequences for rarer variants. Because genotypes are expected to have small effects (if any) investigators now routinely use a two‐stage method, in which they first regress the trait on covariates, obtain residuals, rank‐normalize them, and then use the rank‐normalized residuals in association analysis with the genotypes. Potential confounding signals are assumed to be removed at the first stage, so in practice, no further adjustment is done in the second stage. Here, we show that this widely used approach can lead to tests with undesirable statistical properties, due to both combination of a mis‐specified mean–variance relationship and remaining covariate associations between the rank‐normalized residuals and genotypes. We demonstrate these properties theoretically, and also in applications to genome‐wide and whole‐genome sequencing association studies. We further propose and evaluate an alternative fully adjusted two‐stage approach that adjusts for covariates both when residuals are obtained and in the subsequent association test. This method can reduce excess Type I errors and improve statistical power.
Pressure‐temperature‐time evolution of ultrahigh‐temperature granulites from the Trivandrum Block, southern India: Implications for long‐lived high‐grade metamorphism
Authors: Kadowaki Hikaru , Tsunogae Toshiaki , He Xiao‐Fang , Santosh M. , Takamura Yusuke , Shaji E. , Tsutsumi Yukiyasu
Published: January 2019

The Southern Granulite Terrane in India comprises a number of Archean to Neoproterozoic magmatic arcs and supracrustal units that underwent latest Neoproterozoic to Cambrian high‐grade metamorphism. Here, we present a new petrological and geochronological data from khondalites in the western part of the Trivandrum Block and discuss pressure‐temperature‐time (P–T–t) path of the block for unravelling the duration and heat source of high‐grade metamorphism. Phase equilibria modelling of the khondalite indicates peak P–T condition of 920°C–1,030°C and 6.0–7.6 kbar, suggesting ultrahigh‐temperature (UHT) metamorphism. Prograde and retrograde P–T conditions of ~750°C/~7 kbar and ~750°C/~4 kbar, respectively, were also obtained, based on which a clockwise P–T path with geotherm‐parallel slow cooling is inferred. Zircon and monazite U–Pb geochronology and rare‐earth elements (REE) patterns suggest that heavy rare‐earth elements (HREE)‐depleted zircons grew together with garnet during prograde partial melting at >810°C or during fluid activity at around 582 ± 17 Ma, which was followed by peak UHT metamorphism at 555.1 ± 8.1 Ma as inferred from the dominant monazite ages. Relatively HREE‐enriched zircons (527.3 ± 8.0 Ma) and monazites (501.9 ± 8.5 Ma) were probably formed by garnet breakdown during retrograde metamorphism. The growth of HREE‐enriched zircons at 489 ± 12 Ma might be related to later fluid infiltration and hydration of garnet to form biotite at <770°C/~4 kbar. Our results suggest that high‐grade metamorphism continued at least 90 Myr, from 582 to 489 Ma, suggesting a long‐lived thermal event possibly related to the input of radiogenic heat from the crust and/or magmatic heat from syntectonic to post‐tectonic intrusions.
Research on high‐precision gravity scratch analysis and structure features of Yili Basin, north‐west China
Authors: Mei Yanhui , Ren Shoumai , Zhang Pingchuan , Ma Yanyan , Ma Yongsheng , Fu Yu
Published: January 2019

It is of great importance to study the structural division of Yili Basin in north‐west China to guide oil and gas exploration. In this paper, high‐precision gravity area measurement is carried out, and the gravity scratch analysis method is employed to research the Northern Depression Belt of Yili Basin. Based on surface scratch recognition principles, the ridge coefficient and the edge coefficient of gravitational potential field are extracted. And a clearer understanding of fracture characteristics and structural boundaries is obtained. Faults F1, F2, F3, and F4 control the boundaries between Baishidun Sub‐Bulge and its peripheries; meanwhile, Faults F5 and F6 control the internal structural framework of Baishidun Sub‐Bulge and its hydrocarbon migration. Fault F4 is the structural boundary between Baishidun Sub‐Bulge and Gongliu Sub‐Sag. The result shows that the gravity scratch analysis method can get a good application in small‐scale structure recognization.
Radiation dose to the masseter and medial pterygoid muscle in relation to trismus after chemoradiotherapy for advanced head and neck cancer
Authors: Kraaijenga Sophie A. , Hamming‐Vrieze Olga , Verheijen Sonja , Lamers Emmy , van der Molen Lisette , Hilgers Frans J. , van den Brekel Michiel W. , Heemsbergen Wilma D.
Published: January 2019

Background

We studied the relationship between trismus (maximum interincisor opening [MIO] ≤35 mm) and the dose to the ipsilateral masseter muscle (iMM) and ipsilateral medial pterygoid muscle (iMPM).

Methods

Pretreatment and post‐treatment measurement of MIO at 13 weeks revealed 17% of trismus cases in 83 patients treated with chemoradiation and intensity‐modulated radiation therapy. Logistic regression models were fitted with dose parameters of the iMM and iMPM and baseline MIO (bMIO). A risk classification tree was generated to obtain optimal cut‐off values and risk groups.

Results

Dose levels of iMM and iMPM were highly correlated due to proximity. Both iMPM and iMM dose parameters were predictive for trismus, especially mean dose and intermediate dose volume parameters. Adding bMIO, significantly improved Normal Tissue Complication Probability (NTCP) models. Optimal cutoffs were 58 Gy (mean dose iMPM), 22 Gy (mean dose iMM) and 46 mm (bMIO).

Conclusions

Both iMPM and iMM doses, as well as bMIO, are clinically relevant parameters for trismus prediction.
Voice outcome after unilateral ELS type III or bilateral type II resections for T1‐T2 glottic carcinoma: Results after 1 year
Authors: van Loon Yda , Hendriksma Martine , Heijnen Bas J. , van de Kamp Vivienne A. H. , Hakkesteegt Marieke M. , Böhringer Stefan , Langeveld Ton P. M. , de Jong M. A. , Klop W. Martin C. , Baatenburg de Jong Robert J. , Sjögren Elisabeth V.
Published: January 2019

Background

Voice outcome was assessed in patients with extended T1 and limited T2 glottic carcinoma, treated with a unilateral type III or a bilateral type II resection according to the European Laryngological Society (ELS) classification.

Methods

Objective evaluation (acoustic and aerodynamic parameters), perceptual evaluation (GRBAS), and patients' self‐assessment (voice handicap index [VHI]) were performed before and 1 year after treatment. Results were evaluated according to ELS resection type and the involvement of the anterior commissure.

Results

The majority of voice parameters in all resection subgroups showed an improvement of the mean score 1 year postoperatively. Grade of dysphonia varied between 1.15 and 1.66 postoperatively and VHI score varied from 23.3 to 24.5.

Conclusion

Voice outcome after ELS unilateral type III or a bilateral type II resection for extended T1 and limited T2 glottic carcinoma is good with mild to very moderate perceptive dysphonia and low self‐reported voice impairment.
Survival of patients with head and neck cancer with metachronous multiple primary tumors is surprisingly favorable
Authors: Bugter Oisín , van Iwaarden Dirk L.P. , Dronkers Emilie A.C. , de Herdt Martine J. , Wieringa Marjan H. , Verduijn Gerda M. , Mureau Marc A.M. , ten Hove Ivo , van Meerten Esther , Hardillo José A. , Baatenburg de Jong Robert J.
Published: January 2019

Background

The objectives of this study are to determine the incidence and survival rate of patients with head and neck squamous cell carcinoma (HNSCC) with multiple primary tumors (MPT) in the HN‐region, lung, or esophagus.

Methods

Patient and tumor specific data of 1372 patients with HNSCC were collected from both the national cancer registry and patient records to ensure high‐quality double‐checked data.

Results

The total incidence of MPTs in the HN‐region, lung, and esophagus in patients with HNSCC was 11% (149/1372). Patients with lung MPTs and esophageal MPTs had a significant worse 5‐year survival than patients with HN‐MPTs (29%, 14%, and 67%, respectively, P < 0.001). The 5‐year survival rate for synchronous HN MPTs was only 25%, whereas it was surprisingly high for patients with metachronous HN MPT (85%, P < 0.001).

Conclusions

One of 10 patients with HNSCC develop MPTs in the HN‐region, lung, or esophagus. The 5‐year survival of patients with metachronous HN MPTs was surprisingly favorable.
The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes
Authors: Pavón Miguel Angel , Arroyo‐Solera Irene , León Xavier , Téllez‐Gabriel Marta , Virós David , Gallardo Alberto , Céspedes Maria Virtudes , Casanova Isolda , Lopez‐Pousa Antonio , Barnadas Agustí , Quer Miquel , Mangues Ramón
Published: January 2019

Background

We aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial‐like (EL) or mesenchymal‐like (ML) phenotypes.

Materials and methods

We analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival.

Results

EL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93‐gene expression signature between ML and EL cells was used to build a three‐gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA‐seq data of the TCGA‐HNSC project. Its prognostic value was confirmed in two independent cohorts.

Conclusion

EFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.