bluuebunny/crossref_metadata_2025 huggingface dataset:
An Integrated Approach for Selection of Intercity Transport Schemes on Railway Networks
Authors: Stoilova Svetla Dimitrova
Published: September 2018

A major problem connected with planning the organization of trains on a railway network is the optimization of the scheme of movement, which determines the routing and the number of trains. In this paper, an integrated approach of fuzzy linear programming method and multi-criteria analysis including three steps is proposed. In the first step, we defined the schemes of transportation of intercity trains and optimized each scheme in terms of direct operating costs by taking into account the uncertainty of passenger flows and utilization of train capacity using the fuzzy linear programming method. In the second step we determined the additional technological criteria to assess the variant schemes. The Fuzzy AHP method was applied to determine the weights of criteria. Using the results obtained from Fuzzy AHP, we prioritized the variant schemes of transportation by applying the PROMETHEE method. The third step presents the optimal choice of transportation of trains on a railway network based on minimum ratio of normalized costs and normalized PROMETHEE net outranking flow. In this step, the model uses the results obtained in the first and second steps. The practicability of the integrated approach is demonstratedthrough the case study of Bulgaria’s railway network, and nine schemes were investigated. The model results and the real situation were compared. It was found out that the optimal scheme of intercity train transportation improves the service and reduces direct operating costs.
Bleaching causes loss of disease resistance within the threatened coral species Acropora cervicornis
Authors: Muller Erinn M , Bartels Erich , Baums Iliana B
Published: September 2018

Determining the adaptive potential of foundation species, such as reef-building corals, is urgent as the oceans warm and coral populations decline. Theory predicts that corals may adapt to climate change via selection on standing genetic variation. Yet, corals face not only rising temperatures but also novel diseases. We studied the interaction between two major stressors affecting colonies of the threatened coral, Acropora cervicornis: white-band disease and high water temperature. We determined that 27% of A. cervicornis were disease resistant prior to a thermal anomaly. However, disease resistance was largely lost during a bleaching event because of more compromised coral hosts or increased pathogenic dose/virulence. There was no tradeoff between disease resistance and temperature tolerance; disease susceptibility was independent of Symbiodinium strain. The present study shows that susceptibility to temperature stress creates an increased risk in disease-associated mortality, and only rare genets may maintain or gain infectious disease resistance under high temperature. We conclude that A. cervicornis populations in the lower Florida Keys harbor few existing genotypes that are resistant to both warming and disease.
Sex-dependent effects of in utero cannabinoid exposure on cortical function
Authors: Bara Anissa , Manduca Antonia , Bernabeu Axel , Borsoi Milene , Serviado Michela , Lassalle Olivier , Murphy Michelle , Wager-Miller Jim , Mackie Ken , Pelissier-Alicot Anne-Laure , Trezza Viviana , Manzoni Olivier J
Published: September 2018

Cannabinoids can cross the placenta, thus may interfere with fetal endocannabinoid signaling during neurodevelopment, causing long-lasting deficits. Despite increasing reports of cannabis consumption during pregnancy, the protracted consequences of prenatal cannabinoid exposure (PCE) remain incompletely understood. Here, we report sex-specific differences in behavioral and neuronal deficits in the adult progeny of rat dams exposed to low doses of cannabinoids during gestation. In males, PCE reduced social interaction, ablated endocannabinoid long-term depression (LTD) and heightened excitability of prefrontal cortex pyramidal neurons, while females were spared. Group 1 mGluR and endocannabinoid signaling regulate emotional behavior and synaptic plasticity. Notably, sex-differences following PCE included levels of mGluR1/5 and TRPV1R mRNA. Finally, positive allosteric modulation of mGlu5 and enhancement of anandamide levels restored LTD and social interaction in PCE adult males. Together, these results highlight marked sexual differences in the effects of PCE and introduce strategies for reversing detrimental effects of PCE.
Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus
Authors: Jiménez-Zaragoza Manuel , Yubero Marina PL , Martín-Forero Esther , Castón Jose R , Reguera David , Luque Daniel , de Pablo Pedro J , Rodríguez Javier M
Published: September 2018

The functions performed by the concentric shells of multilayered dsRNA viruses require specific protein interactions that can be directly explored through their mechanical properties. We studied the stiffness, breaking force, critical strain and mechanical fatigue of individual Triple, Double and Single layered rotavirus (RV) particles. Our results, in combination with Finite Element simulations, demonstrate that the mechanics of the external layer provides the resistance needed to counteract the stringent conditions of extracellular media. Our experiments, in combination with electrostatic analyses, reveal a strong interaction between the two outer layers and how it is suppressed by the removal of calcium ions, a key step for transcription initiation. The intermediate layer presents weak hydrophobic interactions with the inner layer that allow the assembly and favor the conformational dynamics needed for transcription. Our work shows how the biophysical properties of the three shells are finely tuned to produce an infective RV virion.
Identification of cryptic subunits from an apicomplexan ATP synthase
Authors: Huet Diego , Rajendran Esther , van Dooren Giel G , Lourido Sebastian
Published: September 2018

The mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Modeling suggests that two of them, ICAP2 and ICAP18, are distantly related to mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.
Elucidating the mitochondrial proteome of Toxoplasma gondii reveals the presence of a divergent cytochrome c oxidase
Authors: Seidi Azadeh , Muellner-Wong Linden S , Rajendran Esther , Tjhin Edwin T , Dagley Laura F , Aw Vincent YT , Faou Pierre , Webb Andrew I , Tonkin Christopher J , van Dooren Giel G
Published: September 2018

The mitochondrion of apicomplexan parasites is critical for parasite survival, although the full complement of proteins that localize to this organelle has not been defined. Here we undertake two independent approaches to elucidate the mitochondrial proteome of the apicomplexan Toxoplasma gondii. We identify approximately 400 mitochondrial proteins, many of which lack homologs in the animals that these parasites infect, and most of which are important for parasite growth. We demonstrate that one such protein, termed TgApiCox25, is an important component of the parasite cytochrome c oxidase (COX) complex. We identify numerous other apicomplexan-specific components of COX, and conclude that apicomplexan COX, and apicomplexan mitochondria more generally, differ substantially in their protein composition from the hosts they infect. Our study highlights the diversity that exists in mitochondrial proteomes across the eukaryotic domain of life, and provides a foundation for defining unique aspects of mitochondrial biology in an important phylum of parasites.
Tracing a protein’s folding pathway over evolutionary time using ancestral sequence reconstruction and hydrogen exchange
Authors: Lim Shion An , Bolin Eric Richard , Marqusee Susan
Published: September 2018

The conformations populated during protein folding have been studied for decades; yet, their evolutionary importance remains largely unexplored. Ancestral sequence reconstruction allows access to proteins across evolutionary time, and new methods such as pulsed-labeling hydrogen exchange coupled with mass spectrometry allow determination of folding intermediate structures at near amino-acid resolution. Here, we combine these techniques to monitor the folding of the ribonuclease H family along the evolutionary lineages of T. thermophilus and E. coli RNase H. All homologs and ancestral proteins studied populate a similar folding intermediate despite being separated by billions of years of evolution. Even though this conformation is conserved, the pathway leading to it has diverged over evolutionary time, and rational mutations can alter this trajectory. Our results demonstrate that evolutionary processes can affect the energy landscape to preserve or alter specific features of a protein’s folding pathway.
Growth under cold conditions in a wide perennial ryegrass panel is under tight physiological control
Authors: Förster Lena , Grant Jim , Michel Thibauld , Ng Carl , Barth Susanne
Published: September 2018

Background

Perennial ryegrass is a cool-season grass species from the family Poaceae and is widely cultivated in temperate regions because it exhibits rapid growth and establishment, and possesses high forage quality. The extension of the growing season in Ireland in spring and autumn is a breeding target to make farming more profitable since a grass-fed diet based on grazing is the cheapest way of nutrition for ruminants.

Methods

Fifty-seven perennial ryegrass accessions were screened for their ability to grow under typical Irish spring conditions as taken from long term temperature records in controlled climate chambers. They were grown in low temperature (8 °C/2 °C day/night) and control conditions (15 °C/8 °C day/night) in three consecutive independent experiments. Fresh weight, height, chlorophyll content and electrolyte leakage were measured, and these parameters were used to rank plant performance under low temperature growth conditions.

Results

The results showed that height, yield and electrolyte leakage are excellent measures for the impact of cold stress tolerance. Little variation in growth was seen under cold stress, but a wide variety of responses were observed under control conditions.

Discussion

Our results suggest that cold stress is under tight physiological control. Interestingly, the various genotypes responded differentially to more amenable control conditions, indicating that a quick response to more amenable growth conditions is a better target for breeding programmes.
Approach for an Analytical Description of the Failure Evolution of Continuous Steel and Carbon Fiber Hybrid Composites
Authors: Rehra Jan , Hannemann Benedikt , Schmeer Sebastian , Hausmann Joachim , Breuer Ulf P.
Published: September 2018

The integration of ductile continuous steel fibers into thermoset carbon fiber reinforced polymer (CFRP) enables significant enhancements of its damage tolerance and crashworthiness. Due to their high strain at failure, the embedded steel fibers provide alternative load paths after failure of the brittle carbon fibers. The resulting post damage performance of the hybrid composite depends on the proportions of the different types of reinforcing fibers, their individual properties, the laminate architecture, and particularly on the steel fiber resin adhesion. So far, common constitutive laws for fiber reinforced composites have very limited suitability for the complex interrelation between the nonlinear plastic behavior of steel fibers and the elastic behavior of the carbon fibers. For this reason, a novel analytical method is developed to predict the failure performance of fiber hybrid composites. In principle, the analytical approach is based on a structural dynamic analysis of the fracture gap formation during failure and thus unloading of the brittle carbon fibers. The present paper covers the derivation of this analytical approach and its exemplary application to a steel and carbon fiber reinforced hybrid composite. A final comparison with an experimentally obtained stress–strain curve validates the theoretical model introduced.
Frustrated Lewis Pairs Accelerating CO2 Reduction on Oxyhydroxide Photocatalysts with Surface Lattice Hydroxyls as a Solid‐State Proton Donor
Authors: Wang Xiaohui , Lu Lei , Wang Bing , Xu Zhe , Xin Zhenyu , Yan Shicheng , Geng Zhirong , Zou Zhigang
Published: September 2018

Light‐driven CO2 reduction into high value‐added product is a potential route to convert and store solar energy. Here, using the hydroxyls on an oxyhydroxide photocatalyst, CoGeO2(OH)2, as solid‐state proton source to reduce the CO2 into CH4 is proposed. It is found that under irradiation, the lattice hydroxyls on surface of CoGeO2(OH)2 are oxidized by photogenerated holes, resulting in the generation of oxygen vacancies (OVs) and protons. The photoinduced OVs (Lewis acid) and its proximal surface hydroxyls (Lewis base) are more likely to form the frustrated Lewis acid–base pairs, which can capture, activate, and reduce CO2 with the assistance of protons into CH4. The surface lattice hydroxyls are able to regenerate when the catalyst is exposed to the water molecule–containing atmosphere, thus achieving a sustainable CO2 conversion. The proposed CO2 reduction by self‐breathing surface hydroxyls may open a new avenue to use photocatalysis for energy conversion.
Mass transfer around bubbles, drops, and particles in uniaxial and biaxial nonlinear extensional flows
Authors: Favelukis Moshe
Published: September 2018

Mass transfer around spherical bubbles, drops, and solid particles in uniaxial and biaxial nonlinear extensional creeping flows at large Peclet numbers is the subject of this theoretical report. The fluid mechanics problem is governed by the viscosity ratio (λ) and the nonlinear intensity of the flow (E). The flow outside such bodies reveals a different picture than the linear case (E = 0) such as separating surfaces or closed circulations. There is a range: −1.04 < E < 0 (bubbles and drops) and −0.490 < E < 0 (particles) where the mass transfer rate is lower than the linear case. Outside these ranges, the mass transfer rate is higher than the linear case and in general it increases as |E| increases. Same mass transfer rates are expected in uniaxial and biaxial flows, except in the presence of external closed circulations where the biaxial flow overcomes the uniaxial flow. © 2018 American Institute of Chemical Engineers AIChE J, 65: 398–408, 2019
An Alternative to Lithium Metal Anodes: Non‐dendritic and Highly Reversible Sodium Metal Anodes for Li–Na Hybrid Batteries
Authors: Zhang Qiu , Lu Yanying , Miao Licheng , Zhao Qing , Xia Kexin , Liang Jing , Chou Shu‐Lei , Chen Jun
Published: September 2018

Highly reversible, stable, and non‐dendritic metal anode (Li, Na etc.) is a crucial requirement for next‐generation high‐energy batteries. Herein, we have built a Li–Na hybrid battery (LNHB) based on Na plating/stripping, which features a high and stable coulombic efficiency of 99.2 % after 100 cycles, low voltage hysteresis (42 mV at 2 mA cm−2), and fast charge transfer. As a result of the Li+ electrostatic shield layer, the Na deposition showed cubic morphology rather than dendritic, even at high current density of 5 mA cm−2. The solvation/desolvation of Li+ and Na+ were modelled by density functional theory calculations, demonstrating the fast desolvation kinetics of Na+. Owing to the superior performance of the Na metal anode, the LNHB coupled with LiFePO4 cathode exhibited low voltage hysteresis and stable cycling performance that demonstrates its feasibility in practical applications.
Molecular identification of sterol regulatory element‐binding protein‐1c from Helicoverpa armigera pheromone gland
Authors: Zhang Yunhui , Ma Nana , Yin Letong , Wei Jizhen , Xi Yuqiang , Zhao Xincheng , Du Mengfang , An Shiheng
Published: September 2018

Sterol regulatory element‐binding protein‐1c (SREBP‐1c) is a basic helix‐loop‐helix type transcription factor that regulates the fatty acid and cholesterol biosynthesis. Lepidoptera sex pheromone is a product of fatty acid biosynthesis followed by carbon chain modifications. However, the role of SREBP‐1c on sex pheromone biosynthesis remains elusive. In the present study, Helicoverpa armigera was used as a model to investigate the role of SREBP‐1c on sex pheromone biosynthesis (HaSREBP‐1c). Sequence analysis demonstrated that the open reading frame of HaSREBP‐1c consists of 3201 bp nucleotides that encode 1066 amino acid residues. Blast searches based on amino acid sequences demonstrated that HaSREBP‐1c shares higher amino acid identity with lepidopteran homologues. Development expression profiles demonstrated that HaSREBP‐1c transcript could be detected at 72 hr before adult emergence, then gradually increased, and finally reached its peak at 24 hr after adult emergence. The spatial expression pattern demonstrated that HaSREBP‐1c was ubiquitously expressed in all examined tissues. The decrease of HaSREBP‐1c messenger RNA (mRNA) levels as shown by RNA interference caused significant decreases in acetyl‐coA carboxylase (ACC) mRNA levels and subsequent sex pheromone production. Behavior analysis demonstrated that the decrease of HaSREBP‐1c mRNA level caused a significant decrease in the female’s ability to attract males. Altogether our results demonstrated that HaSREBP‐1c acts as a transcription factor to regulate ACC mRNA expression and, therefore, to influence female sex pheromone biosynthesis.
Xantphos Doped POPs‐PPh3 as Heterogeneous Ligand for Cobalt‐Catalyzed Highly Regio‐ and Stereoselective Hydrosilylation of Alkynes
Authors: Li Ren‐Hao , Zhang Guo‐Liang , Dong Jia‐Xing , Li Ding‐Chang , Yang Ying , Pan Ying‐Ming , Tang Hai‐Tao , Chen Li , Zhan Zhuang‐Ping
Published: September 2018

A Co(acac)2/POL‐Xantphos@10PPh3‐catalyzed hydrosilylation of unsymmetrical internal alkynes with Ph2SiH2 has been developed for the synthesis of highly selective syn‐α‐vinylsilane products. Furthermore, terminal alkynes were also used and gave the products with excellent regioselectivity and a wide functional group tolerance. Because this porous organic polymer combines the selectivity and activity merits of Xantphos with the stability advantage derived from the high concentration of PPh3, the Co(acac)2/POL‐Xantphos@10PPh3 can be recycled multiple times without loss of activity and selectivity. This heterogeneous catalyst is expected to find promising applications in industrial synthesis.
Spectroscopic and metal binding properties of a de novo metalloprotein binding a tetrazinc cluster
Authors: Chino Marco , Zhang Shao‐Qing , Pirro Fabio , Leone Linda , Maglio Ornella , Lombardi Angela , DeGrado William F.
Published: September 2018

De novo design provides an attractive approach, which allows one to test and refine the principles guiding metalloproteins in defining the geometry and reactivity of their metal ion cofactors. Although impressive progress has been made in designing proteins that bind transition metal ions including iron–sulfur clusters, the design of tetranuclear clusters with oxygen‐rich environments remains in its infancy. In previous work, we described the design of homotetrameric four‐helix bundles that bind tetra‐Zn2+ clusters. The crystal structures of the helical proteins were in good agreement with the overall design, and the metal‐binding and conformational properties of the helical bundles in solution were consistent with the crystal structures. However, the corresponding apo‐proteins were not fully folded in solution. In this work, we design three peptides, based on the crystal structure of the original bundles. One of the peptides forms tetramers in aqueous solution in the absence of metal ions as assessed by CD and NMR. It also binds Zn2+ in the intended stoichiometry. These studies strongly suggest that the desired structure has been achieved in the apo state, providing evidence that the peptide is able to actively impart the designed geometry to the metal cluster.
Interactions of ethanol and caffeine on apoptosis in the rat cerebellum (voluntary ethanol consumers)
Authors: Martinez Marcelo , Rossetto Isabela M. U. , Neto Fermino Sanches Lizarte , Tirapelli Luiz F. , Tirapelli Daniela P. C. , Chuffa Luiz Gustavo A. , Cagnon Valeria H. A. , Martinez Francisco E.
Published: September 2018

Ethanol alters motricity, learning, cognition, and cellular metabolism in the cerebellum. The combination of ethanol with caffeine by consuming “energy drinks” is becoming increasingly popular among young people. We analyzed the use of ethanol and caffeine on apoptosis in the cerebellum of UChB rats. The adult rats were divided into three groups (n = 14/group): UChB group: rats fed with 1:10 (v/v) ethanol ad libitum (free choice for water or ethanol) drinking from >1.9 mL of ethanol/kg body weight/day, Control group and UChB/caffeine group (free choice for water or ethanol + caffeine 300 mg/L). The treatments occurred from Day 100 till Day 150, totalizing 50 days of ethanol/caffeine ingestion. Cerebellar sections were subjected to immunohistochemistry and gene expression for Real Time‐PCR (RT‐PCR) for Caspase‐3, XIAP, and insulin‐like growth factor 1‐receptor (IGF‐1R). The results showed a significant increase in the gene expression of Caspase‐3 and XIAP in UChB group. On the other hand, the animals of the UChB/caffeine group showed similar results to the Controls. Regarding IGFR‐1, there was greater expression in the UChB groups with strong labeling in Purkinje cells. Ethanol produces neuronal and glial neurodegeneration on the cerebellum of UChB rats. The simultaneous ingestion of ethanol and caffeine reversed the ethanol damages acting caffeine with a neuroprotective effect.
Family separation policy reminds all parents how important you are
Authors: Knopf Alison
Published: September 2018

The horrific policy of separating families at the border — now stopped, but with devastating results for the affected parents and children — is a reminder to everyone that the most important thing in your child's life isn't school, therapy, medications, or money: it's you, the parents.
Determination of Molybdenum Species Evolution during Non‐Oxidative Dehydroaromatization of Methane and its Implications for Catalytic Performance
Authors: Agote‐Arán Miren , Kroner Anna B. , Islam Husn U. , Sławiński Wojciech A. , Wragg David S. , Lezcano‐González Inés , Beale Andrew M.
Published: September 2018

Mo/H‐ZSM‐5 has been studied using a combination of operando X‐ray absorption spectroscopy and High Resolution Powder Diffraction in order to study the evolution of Mo species and their location within the zeolite pores. The results indicate that after calcination the majority of the species present are isolated Mo‐oxo species, attached to the zeolite framework at the straight channels. During reaction, Mo is first partially carburized to intermediate MoCxOy species. At longer reaction times Mo fully carburizes detaching from the zeolite and aggregates forming initial Mo1.6C3 clusters; this is coincident with maximum benzene production. The Mo1.6C3 clusters are then observed to grow, predominantly on the outer zeolite surface and this appears to be the primary cause of catalyst deactivation. The deactivation is not only due to a decrease in the amount of active Mo surface but also due to a loss in shape‐selectivity which leads to an increased carbon deposition at the outer shell of the zeolite crystals and eventually to pore blockage.
Incorporating Heavy Alkanes in Metal–Organic Frameworks for Optimizing Adsorbed Natural Gas Capacity
Authors: Fang Yu , Banerjee Sayan , Joseph Elizabeth A. , Day Gregory S. , Bosch Mathieu , Li Jialuo , Wang Qi , Drake Hannah , Ozdemir Osman K. , Ornstein Jason M. , Wang Ye , Lu Tong‐Bu , Zhou Hong‐Cai
Published: September 2018

Metal–organic frameworks (MOFs) as methane adsorbents are highly promising materials for applications such as methane‐powered vehicles, flare gas capture, and field natural gas separation. Pre‐ and post‐synthetic modification of MOFs have been known to help improve both the overall methane uptake as well as the working capacity. Here, a post‐synthetic modification strategy to non‐covalently modify MOF adsorbents for the enhancement of the natural gas uptake for the MOF material is introduced. In this study, PCN‐250 adsorbents were doped with C10 alkane and C14 fatty acid and their impact on the methane uptake capabilities was investigated. It was found that even trace amounts of heavy hydrocarbons could considerably enhance the raw methane uptake of the MOF while still being regenerable. The doped hydrocarbons are presumably located at the mesoporous defects of PCN‐250, thus optimizing the framework–methane interactions. These findings reveal a general approach that can be used to modify the MOF absorbents, improving their ability to be sustainable and renewable natural gas adsorption platforms.
Cubane‐Type [Mo3S4M] Clusters with First‐Row Groups 4–10 Transition‐Metal Halides Supported by C5Me5 Ligands on Molybdenum
Authors: Ohki Yasuhiro , Uchida Keisuke , Hara Ryota , Kachi Mami , Fujisawa Mayu , Tada Mizuki , Sakai Yoichi , Sameera W. M. C.
Published: September 2018

A synthetic protocol was developed for a series of cubane‐type [Mo3S4M] clusters that incorporate halides of first‐row transition metals (M) from Groups 4–10. This protocol is based on the anionic cluster platform [Cp*3Mo3S4]− ([1]−; Cp*=η5‐C5Me5), which crystallizes when K(18‐crown‐6) is used as the counter cation. Treatment of in situ‐generated [1]− with such transition‐metal halides led to the formation of [Mo3S4M] clusters, in which the M/halide ratio gradually changes from 1:2 to 1:1.5 and to 1:1, when moving from early to late transition metals. This trend suggests a tendency for early transition metals to tolerate higher oxidation states and adopt larger ionic radii relative to late transition metals. The properties of the [Mo3S4Fe] cluster 6 a were investigated in detail by using 57Fe Mössbauer spectroscopy and computational methods.
Catalyst‐Free Hydroboration of CO2 With a Nucleophilic Diborane(4)
Authors: Frick Markus , Horn Julian , Wadepohl Hubert , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: September 2018

Hydroboration generally requires the presence of a catalyst to lower the barrier for hydride transfer. This work reports on the first catalyst‐free CO2 hydroboration with a neutral boron compound, the nucleophilic diborane [HB(hpp)]2, 1 (hpp=1,3,4,6,7,8‐hexahydro‐2H‐pyrimido[1,2‐a]pyrimidinate). Further hydroboration reactions to bis(boryl)acetals are possible. In acetonitrile, but not in dichloromethane solutions, hydroboration of a first CO2 is followed by hydroboration of a second CO2 molecule. Detailed kinetic measurements for both hydroboration steps were carried out and the influence of the solvent and the addition of a Lewis base on the rate constants analyzed. In contrast to catalyst‐free hydroboration of CO2, hydroboration of the less electrophilic acetone requires the presence of an activating Lewis acid.
Proton Exchange Membrane Water Electrolysis Modeling for System Simulation and Degradation Analysis
Authors: Gößling Sönke , Stypka Sebastian , Bahr Matthias , Oberschachtsiek Bernd , Heinzel Angelika
Published: September 2018

This paper presents a numeric model for proton exchange membrane electrolysis, which describes the current‐voltage dependency. Besides physical constants and parameters characterizing material properties, it also contains parameters that cannot be measured ex situ, e.g., charge transfer coefficients and exchange current densities. To determine these parameters, the model includes an automated parameter calibration procedure that is able to find the best parameter combinations. An exemplary integration of the model in MATLAB/Simulink is presented, including a validation with dynamic measurement data.
Gold(I)–Coumarin–Caffeine‐Based Complexes as New Potential Anti‐Inflammatory and Anticancer Trackable Agents
Authors: Trommenschlager Audrey , Chotard Florian , Bertrand Benoît , Amor Souheila , Richard Philippe , Bettaïeb Ali , Paul Catherine , Connat Jean‐Louis , Le Gendre Pierre , Bodio Ewen
Published: September 2018

Three new gold(I)–coumarin‐based trackable therapeutic complexes and two non‐trackable analogues have been synthesised and fully characterised. They all display anti‐proliferative properties on several types of cancer cell lines, including those of colon, breast, and prostate. Two complexes displayed significant anti‐inflammatory effects; one displayed pro‐inflammatory behaviour; this highlights the impact of the position of the fluorophore on the caffeine scaffold. Additionally, the three coumarin derivatives could be visualised in vitro by two‐photon microscopy.
Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4‐year follow‐up and analysis of relative progression‐free survival from the randomized ELOQUENT‐2 trial
Authors: Dimopoulos Meletios A. , Lonial Sagar , Betts Keith A. , Chen Clara , Zichlin Miriam L. , Brun Alexander , Signorovitch James E. , Makenbaeva Dinara , Mekan Sabeen , Sy Oumar , Weisel Katja , Richardson Paul G.
Published: September 2018

Background

The randomized phase 3 ELOQUENT‐2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab plus lenalidomide and dexamethasone (ELd) versus lenalidomide and dexamethasone (Ld) in relapsed/refractory multiple myeloma (RRMM), and to date, has the longest follow‐up of any monoclonal antibody in patients with RRMM.

Methods

In this extended 4‐year follow‐up of the ELOQUENT‐2 trial, the coprimary endpoints of progression‐free survival (PFS) and overall response rate as well as the secondary endpoint of overall survival were assessed. In the absence of head‐to‐head trials comparing Ld‐based triplet regimens to guide treatment selection, 4 randomized controlled trials—ELOQUENT‐2, ASPIRE, TOURMALINE‐MM1, and POLLUX—were indirectly compared to provide insight into the relative efficacy of these regimens in RRMM.

Results

Data at 4 years were consistent with 2‐ and 3‐year follow‐up data: ELd reduced the risk of disease progression/death by 29% versus Ld (hazard ratio, 0.71) while maintaining safety. The greatest PFS benefit among the assessed subgroups was observed in patients at the median time or further from diagnosis (≥3.5 years) with 1 prior line of therapy, who had a 44% reduction in the risk of progression/death, and in patients in the high‐risk category, who had a 36% reduction in favor of ELd. This regimen also showed a relative PFS benefit that was maintained beyond 50 months.

Conclusions

The sustained PFS benefit and long‐term safety of ELd at 4 years, similar to those observed at 2 and 3 years, support ELd as a valuable therapeutic option for the long‐term treatment of patients with RRMM.
GNAS, GNAQ,andGNA11alterations in patients with diverse cancers
Authors: Parish Austin J. , Nguyen Vi , Goodman Aaron M. , Murugesan Karthikeyan , Frampton Garrett M. , Kurzrock Razelle
Published: September 2018

Background

Advances in deep sequencing technology have uncovered a widespread, protumorigenic role of guanine nucleotide‐binding (G protein) α (GNA) subunits, particularly GNA subunits Gs (GNAS), Gq (GNAQ), and G11 (GNA11) (GNA*), in a diverse collection of malignancies. The objectives of the current study were: 1) to determineGNA*aberration status in a cohort of 1348 patients with cancer and 2) to examine tumor mutational burden, overall survival rates, and treatment outcomes in patients withGNA*‐positive tumors versus those with tumors that had wild‐typeGNA*.

Methods

For each patient, clinical and genomic data were collected from medical records. Next‐generation sequencing was performed for each patient (range, 182‐236 genes).

Results

Aberrations ofGNA*genes were identified in a subset of patients who had 8 of the 12 cancer types examined, and a significant association was observed for appendiceal cancer and ocular melanoma (P< .0001 for both; multivariate analysis). Overall, 4.1% of the cancer population was affected.GNA*abnormalities were associated with higher numbers of co‐alterations in univariate (but not multivariate) analysis and were most commonly accompanied by Aurora kinase A (AURKA), Cbl proto‐oncogene (CBL), and LYN proto‐oncogene (LYN) co‐alterations (allP< .0001; multivariate analysis).GNA*alterations were correlated with a trend toward lower median overall survival (P= .085). The median tumor mutational burden was 4 mutations per megabase in bothGNA*‐altered andGNA*wild‐type tumors. For this limited sample ofGNA*‐positive patients, longer survival was not correlated with any specific treatment regimens.

Conclusions

In the current sample, the genesGNAS,GNAQ, andGNA11were widely altered across cancer types, and these alterations often were accompanied by specific genomic abnormalities inAURKA,CBL, andLYN. Therefore, targetingGNA*alterations may require drugs that address the GNA* signal and important co‐alterations.Cancer 2018;00:000‐000.© 2018 American Cancer Society.
Improved diagnostic precision of urine cytology by implementation of The Paris System and the use of cell blocks
Authors: Chan Emily , Balassanian Ronald , Tabatabai Z. Laura , Lou Hubing , Vohra Poonam
Published: September 2018

Background

The Paris System for Reporting Urinary Cytology (TPS) published in 2016 provides a standardized approach to evaluating urine cytology. In the authors’ practice, a TPS‐like approach was adopted in 2012 using similarly defined cytologic criteria and correlating cystoscopic findings, and they also began incorporating the use of cell block (CB) material. The objective of the current study was to assess whether this TPS‐like approach with the use of CB, as well as direct implementation of TPS, improved the diagnostic value of urine cytology.

Methods

In total, 188 consecutive urine cytology specimens from 2010 through 2016 that had concurrent or subsequent histologic specimens available were retrospectively analyzed for diagnostic correlation. Urine cytology performance was compared between the periods 2010 to 2012 (pre–TPS‐like), 2013 to 2016 (TPS‐like), and after TPS reclassification, including blind review by a cytopathologist. The contribution of available CB material to final diagnoses also was assessed.

Results

Both the TPS‐like approach and TPS reclassification resulted in significantly lowering the rate of atypical urothelial cells (AUC) diagnosis from 48%, to 21%, to 9% (from pre‐TPS, to TPS‐like, to after TPS reclassification, respectively; P < 0.01) while increasing the positive predictive value of an AUC diagnosis for high‐grade urothelial carcinoma from 21%, to 43%, to 83%, respectively. The use of CBs contributed to a definitive final diagnosis in 24 of 36 cases (66.7%).

Conclusions

In support of the new TPS recommendations, the application of stringent “TPS‐like” and TPS criteria improves the value of an AUC diagnosis for clinicians and patients by lowering the AUC rate and increasing the positive predictive value of AUC for high‐grade urothelial carcinoma. CBs can be used to help resolve problematic cases for more definitive diagnostic categorization.
Photodynamics and Luminescence of Mono‐ and Tri‐Nuclear Lanthanide Complexes in the Gas Phase and in Solution
Authors: Liedy Florian , Bäppler Florian , Waldt Eugen , Nosenko Yevgeniy , Imanbaew Dimitri , Bhunia Asamanjoy , Yadav Munendra , Diller Rolf , Kappes Manfred M. , Roesky Peter W. , Schooss Detlef , Riehn Christoph
Published: September 2018

Lanthanide ions (DyIII, EuIII) are stabilized by coordination with two Schiff base ligands in compounds [Dy{H3L}2](NO3)(EtOH)(H2O)8 (1) and [Eu{H3L}2](NO3)(H2O)8 (3) (H4L, 2,2′‐{[(2‐aminoethyl)imino]bis[2,1‐ethanediyl‐nitriloethylidyne]}bis‐2‐hydroxy‐benzoic acid). The latter is reported here for the first time. Both luminescence and ultrafast photodynamics after photoexcitation via a ligand absorption band (∼400 nm) have been studied. In solution, only the [Eu{H3L}2]+ ([3]+) complex displays the typical lanthanide emission lines, whereas in gas phase both, [Dy{H3L}2]+ ([1]+) and [3]+, show their corresponding transitions depending on excitation energy. The ultrafast excited state dynamics, obtained in gas phase and in solution, are assigned to excited state intramolecular proton transfer processes in the ligands. The antenna ligand moiety of these complexes provides pockets for stabilization of two MnII ions so that we additionally investigated the photophysical behavior of the corresponding tri‐nuclear (NHEt3)2[Ln{MnL}2](ClO4)(H2O)2 (Ln=DyIII, EuIII) compounds (2, 4). Interestingly, the related complexes do not show lanthanide emission, neither in solution nor in gas phase. Transient data in solution and gas phase suggests an efficient quenching of the ligand's electronically excited state by strong interaction with the MnII ions. This effect could possibly be developed further into a design principle for luminescence‐based sensing devices for metal cations.
Polar Effects Control the Gas‐Phase Reactivity of para‐Benzyne Analogs
Authors: Sheng Huaming , Ma Xin , Lei Hao‐Ran , Milton Jacob , Tang Weijuan , Jin Chunfen , Gao Jinshan , Wittrig Ashley M. , Archibold Enada F. , Nash John J. , Kenttämaa Hilkka I.
Published: September 2018

We report herein a gas‐phase reactivity study on a para‐benzyne cation and its three cyano‐substituted, isomeric derivatives performed using a dual‐linear quadrupole ion trap mass spectrometer. All four biradicals were found to undergo primary and secondary radical reactions analogous to those observed for the related monoradicals, indicating the presence of two reactive radical sites. The reactivity of all biradicals is substantially lower than that of the related monoradicals, as expected based on the singlet ground states of the biradicals. The cyano‐substituted biradicals show substantially greater reactivity than the analogous unsubstituted biradical. The greater reactivity is rationalized by the substantially greater (calculated) electron affinity of the radical sites of the cyano‐substituted biradicals, which results in stabilization of their transition states through polar effects. This finding is in contrast to the long‐standing thinking that the magnitude of the singlet‐triplet splitting controls the reactivity of para‐benzynes.
Dual‐Channel Photostimulation for Independent Excitation of Two Populations
Authors: Hooks Bryan M.
Published: September 2018

Manipulation of defined neurons using excitatory opsins, including channelrhodopsin, enables studies of connectivity and the functional role of these circuit components in the brain. These techniques are vital in the neocortex, where diverse neurons are intermingled, and stimulation of specific cell types is difficult without the spatial, temporal, and genetic control available with optogenetic approaches. Channelrhodopsins are effective for mapping excitatory connectivity from one input type to its target. Attempts to use multiple opsins to simultaneously map multiple inputs face the challenge of partially overlapping light spectra for different opsins. This protocol describes one strategy to independently stimulate two comingled inputs in the same brain area to assess convergence and interaction of pathways in neural circuits. This is highly relevant in the neocortex, where pyramidal neurons integrate excitatory inputs from multiple local cell types and long‐range corticocortical and thalamocortical projections. © 2018 by John Wiley & Sons, Inc.
Using the primary process emotional–behavioural system to better meet patient needs in psychotherapy
Authors: Kuei Tien , Tsai Mavis , McLeod Hamish J. , White Ross G. , Kanter Jonathan
Published: September 2018

In order to increase therapeutic impact by enhancing awareness of clients' nonverbal communications, this article operationalizes the therapeutic alliance as a needs‐satisfaction process. The client's competence as a needs seeker and the therapist assisting with the client's expression and satiation of basic social needs are proposed as being key mechanisms of change.

Functional model of primary emotions derived from Panksepp's seven primary emotional systems (care seeking, caretaking, lust, fear and anxiety, anger, play, seeking, plus dominance and disgust) is integrated with Functional Analytic Psychotherapy's emphasis on in‐session contingent natural reinforcement of clients' target behaviours. By identifying in‐the‐moment cues of underlying emotional–behavioural functions drawn from a categorization of clients' nonverbal communication can bridge the gap between client private events and therapist observables, in order to maximize therapist attunement and responsiveness to clients, and to increase the effectiveness of clinical interventions.
Generation and Fusion of Human Cortical and Medial Ganglionic Eminence Brain Organoids
Authors: Xiang Yangfei , Yoshiaki Tanaka , Patterson Benjamin , Cakir Bilal , Kim Kun‐Yong , Cho Yee Sook , Park In‐Hyun
Published: September 2018

Three‐dimensional brain organoid culture has become an essential tool for investigating human brain development and modeling neurological disorders during the past few years. Given specific regionalization during brain development, it is important to produce distinct brain organoids that represent different brain regions and their interactions. The authors recently established a platform to generate brain organoids resembling the medial ganglionic eminence (MGE), a specific brain region responsible for interneurogenesis, and found that when these organoids were fused with organoids resembling the cortex, the resulting organoids enabled modeling of interneuron migration in the brain. This unit describes four basic protocols that have been successfully applied by the authors, covering the generation of embryonic bodies with neuroectodermal fate, the production of human MGE organoids and cortical organoids, and the fusion of these two organoids. © 2018 by John Wiley & Sons, Inc.
Stimuli‐Responsive Tannin–FeIII Hybrid Microcapsules Demonstrated by the Active Release of an Anti‐Tuberculosis Agent
Authors: Bartzoka Elisavet D. , Lange Heiko , Poce Giovanna , Crestini Claudia
Published: September 2018

A simple and facile strategy for the creation of ferric tannin microcapsules around a liquid, non‐sacrificial core is described. The assembly of the capsules occurs rapidly once ferric tannin complexes are subjected to ultrasonic treatment. The driving forces for the rapid capsule assembly reside in the strategy of adding ferric ions into the initial emulsion, which promotes shell formation and stability through well‐known complexation effects. This is the first time that microcapsule assemblies of monomeric tannins like epigallocatechin‐3‐O‐gallate has been demonstrated, which are reportedly unable to form dispersing microcapsules in the absence of a templating metal. The efficacy of the approach is demonstrated by the complete release of a hydrophobic molecule that is active against M. tuberculosis by using Acacia tannin capsules. The release kinetics of the active molecule were of zeroth order over a 12 h time frame.
Updated protocols for the detection of Sotatercept and Luspatercept in human serum
Authors: Reichel Christian , Gmeiner Günter , Walpurgis Katja , Thevis Mario
Published: September 2018

We recently published two protocols for the detection of Sotatercept (ACE‐011, ACVR2A‐Fc) and Luspatercept (ACE‐536, ACVR2B‐Fc) in human serum. Both methods used covalently immobilized antibodies on agarose beads for immunoprecipitation and SAR‐PAGE/Western blotting for detection. Disadvantages were the relatively high amount of antibody required per sample (10 μg) and the need of a secondary antibody for the final detection. The updated protocols overcome these limitations by antigen–antibody complex formation in solution followed by capture of the complex with anti‐antibody‐coated magnetic beads. They also omit the secondary antibody incubation step by usage of biotinylated primary antibodies, which can be directly incubated with streptavidin‐HRP. Thus, the new protocols are faster, simpler, and cheaper and offer comparable sensitivities.
Shifting the conservation paradigm: a synthesis of options for renovating nature under climate change
Authors: Prober Suzanne M. , Doerr Veronica A. J. , Broadhurst Linda M. , Williams Kristen J. , Dickson Fiona
Published: September 2018

Changes in Earth's climate are accelerating, prompting increasing calls to ensure that investments in ecological restoration and nature conservation accommodate such changes. To acknowledge this need, we propose the term “ecological renovation” to describe ecological management and nature conservation actions that actively allow for environmental change. To evaluate and progress the development of ecological renovation and related intervention options in a climate change context, we reviewed the literature and established a typology of options that have been proposed. We explored how these options address emerging principles underpinning climate‐adapted conservation goals and whether the balance of approaches reflected in our typology is likely to be sufficient given expected rapid rates of climate change. Our typology recognizes a matrix of 23 intervention option types arranged on the basis of underpinning ecological mechanisms (“ameliorate changing conditions” or “build adaptive capacity”) on one axis, and the nature of the tools used to manipulate them (“low regrets” or “climate targeted”) on the other. Despite a burgeoning literature since 2008, we found that the majority of effort has consistently focused on low‐regrets adaptation approaches that aim to build adaptive capacity. This is in many ways desirable, but a paradigm shift enabling greater attention to climate‐targeted approaches is likely to be needed as climate change accelerates. When assessed against five emerging principles for setting nature conservation goals in a changing climate, only one option type could deliver to all five, and we identified a conflict between climate‐targeted options and “wildness” values that calls for deeper evaluation. Importantly, much of the inference in the 473 reviewed studies was drawn from ecological reasoning and modeling, with only 16% offering new empirical evidence. We also noted significant biases toward North America and Europe, forest ecosystems, trees, and vertebrates. To address these limitations and help shift the paradigm toward humans as “renovators” rather than “restorers” of a prior world, we propose that ecological researchers contribute by (1) informing societal discourse toward adapting nature conservation goals to climate change, (2) adjusting and upscaling conservation planning to accommodate this suite of climate‐adapted goals, and (3) reconceptualizing experimental approaches to increase empirical evidence and expedite innovation of tools to address change.