bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible Cleavage/Formation of the Chromium–Chromium Quintuple Bond in the Highly Regioselective Alkyne Cyclotrimerization
Authors: Huang Yu‐Siang , Huang Gou‐Tao , Liu Yao‐Lun , Yu Jen‐Shiang K. , Tsai Yi‐Chou
Published: October 2017

Herein we report the employment of the quintuply bonded dichromium amidinates [Cr{κ2‐HC(N‐2,6‐iPr2C6H3)(N‐2,6‐R2C6H3)}]2 (R=iPr (1), Me (7)) as catalysts to mediate the [2+2+2] cyclotrimerization of terminal alkynes giving 1,3,5‐trisubstituted benzenes. During the catalysis, the ultrashort Cr−Cr quintuple bond underwent reversible cleavage/formation, corroborated by the characterization of two inverted arene sandwich dichromium complexes (μ‐η6:η6‐1,3,5‐(Me3Si)3C6H3)[Cr{κ2‐HC(N‐2,6‐iPr2C6H3)(N‐2,6‐R2C6H3)}]2 (R=iPr (5), Me (8)). In the presence of σ donors, such as THF and 2,4,6‐Me3C6H2CN, the bridging arene 1,3,5‐(Me3Si)3C6H3 in 5 and 8 was extruded and 1 and 7 were regenerated. Theoretical calculations were employed to disclose the reaction pathways of these highly regioselective [2+2+2] cylcotrimerization reactions of terminal alkynes.
Oxidation von organischen Substraten mit einem redoxaktiven Guanidinkatalysator
Authors: Wild Ute , Schön Florian , Himmel Hans‐Jörg
Published: October 2017

Hier wird über die ersten Beispiele für die Verwendung von redoxaktiven Guanidinen als Katalysatoren bei der grünen Oxidation von organischen Substraten mit Sauerstoff berichtet. In einer Halbreaktion wird die oxidierte Form des redoxaktiven Guanidins in die reduzierte, protonierte Form umgewandelt, wodurch eine oxidative Dehydrierung des Substrats (3,5‐Di‐tert‐butylcatechol→o‐Benzochinon, Benzoin→Benzil und 2,4‐Di‐tert‐butylphenol→Biphenol) stattfindet. In der anderen Halbreaktion wird eine effiziente Reoxidation des Guanidins in den oxidierten Zustand mit molekularem Sauerstoff in Gegenwart eines Kupfercokatalysators erreicht. Die Ergebnisse ebnen den Weg für eine breitere Verwendung von redoxaktiven Guanidinen als Oxidationskatalysatoren.
IrIII‐based Octahedral Metalloligands Derived Primitive Cubic Frameworks for Enhanced CO2/N2 Separation
Authors: Huang Sheng‐Li , Liu Naifang , Ling Yun , Luo He‐Kuan
Published: October 2017

We developed a metalloligand strategy to construct porous frameworks, viz. the combined use of IrIII‐based octahedral metalloligands and the linear unit [Ni(cyclam)] easily afforded two isostructural complexes 1 and 2 with primitive cubic frameworks. Both complexes show good CO2/N2 separation property.
Significance of aerosol radiative effect in energy balance control on global precipitation change
Authors: Suzuki Kentaroh , Stephens Graeme L. , Golaz Jean‐Christophe
Published: October 2017

Historical changes of global precipitation in the 20th century simulated by a climate model are investigated. The results simulated with alternate configurations of cloud microphysics are analyzed in the context of energy balance controls on global precipitation, where the latent heat changes associated with the precipitation change is nearly balanced with changes to atmospheric radiative cooling. The atmospheric radiative cooling is dominated by its clear‐sky component, which is found to correlate with changes to both column water vapor and aerosol optical depth (AOD). The water vapor‐dependent component of the clear‐sky radiative cooling is then found to scale with global temperature change through the Clausius–Clapeyron relationship. This component results in a tendency of global precipitation increase with increasing temperature at a rate of approximately 2%K−1. Another component of the clear‐sky radiative cooling, which is well correlated with changes to AOD, is also found to vary in magnitude among different scenarios with alternate configurations of cloud microphysics that controls the precipitation efficiency, a major factor influencing the aerosol scavenging process that can lead to different aerosol loadings. These results propose how different characteristics of cloud microphysics can cause different aerosol loadings that in turn perturb global energy balance to significantly change global precipitation. This implies a possible coupling of aerosol–cloud interaction with aerosol–radiation interaction in the context of global energy balance.
Analogous seasonal evolution of the South Atlantic SST dipole indices
Authors: Nnamchi Hyacinth C. , Kucharski Fred , Keenlyside Noel S. , Farneti Riccardo
Published: October 2017

Two variants of sea‐surface temperature (SST) dipole indices for the South Atlantic Ocean (SAO) has been previously described representing: (1) the South Atlantic subtropical dipole (SASD) supposedly peaking in austral summer and (2) the SAO dipole (SAOD) in winter. In this study, we present the analysis of observational data sets (1985–2014) showing the SASD and SAOD as largely constituting the same mode of ocean–atmosphere interaction reminiscent of the SAOD structure peaking in winter. Indeed, winter is the only season in which the inverse correlation between the northern and southern poles of both indices is statistically significant. The observed SASD and SAOD indices exhibit robust correlations (P ≤ 0.001) in all seasons and these are reproduced by 54 of the 63 different models of the Coupled Models Intercomparison Project analysed. Their robust correlations notwithstanding the SASD and SAOD indices appear to better capture different aspects of SAO climate variability and teleconnections.
Nitrogen‐doped carbon dots as a fluorescent probe for the highly sensitive detection of Ag+ and cell imaging
Authors: Li Junjian , Zuo Gancheng , Pan Xihao , Wei Wei , Qi Xiaoliang , Su Ting , Dong Wei
Published: October 2017

An easy hydrothermal synthesis strategy was applied to synthesize green‐yellow emitting nitrogen‐doped carbon dots (N‐CDs) using 1,2‐diaminobenzene as the carbon source, and dicyandiamide as the dopant. The nitrogen‐doped CDs resulted in improvement in the electronic characteristics and surface chemical activities. N‐CDs exhibited bright fluorescence emission and could response to Ag+ selectively and sensitively. Other ions produced nearly no interference. A N‐CDs based fluorescent probe was then applied to sensitively determine Ag+ with a detection limit of 5 × 10−8 mol/L. The method was applied to the determination of Ag+ dissolved in water. Finally, negligibly cytotoxic, excellently biocompatibile, and highly fluorescent carbon dots were applied for HepG2 cell imaging and the quenched fluorescence by adding Ag+, which indicated its potential applications.
Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches
Authors: Costa Elisabete C. , de Melo‐Diogo Duarte , Moreira André F. , Carvalho Marco P. , Correia Ilídio J.
Published: October 2017

Scalable and reproducible production of 3D cellular spheroids is highly demanded, by pharmaceutical companies, for drug screening purposes during the pre‐clinical evaluation phase. These 3D cellular constructs, unlike the monolayer culture of cells, can mimic different features of human tissues, including cellular organization, cell–cell and cell‐extracellular matrix (ECM) interactions. Up to now, different techniques (scaffold‐based and ‐free) have been used for spheroids formation, being the Liquid Overlay Technique (LOT) one of the most explored methodologies, due to its low cost and easy handling. Additionally, during the last few decades, this technique has been widely investigated in order to enhance its potential for being applied in high‐throughput analysis. Herein, an overview of the LOT advances, practical approaches, and troubleshooting is provided for those researchers that intend to produce spheroids using LOT, for drug screening purposes. Moreover, the advantages of the LOT over the other scaffold‐free techniques used for the spheroids formation are also addressed.

Highlights

• 2D cell culture drawbacks are summarized;

• spheroids mimic the features of human tissues;

• scaffold‐based and scaffold‐free technologies for spheroids production are discussed;

• advantages of LOT over other scaffold‐free techniques are highlighted;

• LOT advances, practical approaches and troubleshooting are underlined.
Synthetische Biologie
Authors: Becker Anke , Erb Tobias J. , Fritz Georg , Kellmann Jan‐W. , Sourjik Victor , Waldminghaus Torsten
Published: October 2017

Das Ausstatten und Erzeugen von Zellen mit neuen Eigenschaften im „Baukastenverfahren“ stellt einen komplett neuen Ansatz in der Biologie dar, der sich von den bisherigen analytisch‐deskriptiven Methoden stark unterscheidet. Durch die Synthetische Biologie werden die Wissenschaftlerinnen und Wissenschaftler zu Designern von Lebensprozessen, einzelnen Molekülen und ganzen Zellen. Dabei ist der Begriff „synthetisch“ dehnbar und vielfältig: Das Einbringen eines am DNA‐Synthesizer künstlich hergestellten Erbmoleküls wird ebenso wie eine am Reißbrett vorab modellierte und nachfolgend künstlich im Labor erzeugte Enzymreaktion, die beispielsweise der Biosynthese neuartiger Wirkstoffe und Materialien dienen kann, als Synthetische Biologie bezeichnet. Die Wissenschaftlerinnen und Wissenschaftler des Marburger LOEWE‐Zentrums für Synthetische Mikrobiologie (www.synmikro.com) widmen sich verschiedenen Forschungsansätzen, deren Schwerpunkte im Bereich der Mikroben und Mikroorganismen liegen.
Zur Biologie der Relationen
Authors: Haszprunar Gerhard
Published: October 2017

Die Größe von Organismen ist ein vielschichtiges Phänomen, welches bei allen biologischen Überlegungen zu funktionellen Fragen nicht ignoriert werden sollte, sei es nun bezüglich des Organismus selbst (Funktionsmorphologie, Physiologie, Reproduktionsbiologie), seiner Umwelt (Autökologie) oder aber zum Verständnis der Evolution.
Nachrichten des Verbandes Biologie, Biowissenschaften & Biomedizin in Deutschland
Authors: Klaproth‐Förster Silke
Published: October 2017

Im Gespräch

Arbeitskreise

Fotowettbewerb

Wissenschaft & Gesellschaft

Access and Benefit Sharing (ABS)

Landesverbände

Berlin‐Brandenburg

Veranstaltungen
Occurrence of overt seizures in comatose survivor patients treated with targeted temperature
Authors: Eilam Anda , Samogalskyi Volodymyr , Bregman Gennady , Eliner‐Avishai Sarit , Gilad Ronit
Published: October 2017

Background

Unconscious patients after out‐of‐hospital cardiac arrest have a high risk of death. Therapeutic hypothermia is recommended by international resuscitation guidelines in order to attenuate secondary destructive physiological processes such as reperfusion injury, apoptosis, and cerebral edema. The target temperature to reach ranges between 32 and 34°C for at least 24 hr. Hypothermia can induce metabolic disturbances. There are some reports in the literature indicating the presence of seizures during targeted temperature management. On the other hand, postanoxic seizures are a sign of unfavorable neurological outcome. The purpose of this study was to evaluate the occurrence of overt seizures in comatose survivor patients treated with targeted temperature in respect to overt seizures in a normal temperature group of comatose patients.

Methods

This was a retrospective study of unconscious adults post cardiopulmonary resuscitation, hospitalized in the intensive care unit during the years 2008–2015. The patients were divided into two groups: those treated with hypothermia and those with normal body temperature. Both groups were evaluated for the appearance of overt seizures during their hospitalization which was the primary outcome of the study.

Results

The data of 88 consecutive unconscious patients after out‐of‐hospital cardiac arrest were collected. Twenty‐six patients were treated with targeted temperature (32–34°C) and 62 patients with normal temperature. In the hypothermic group, 6 (23%) patients developed overt seizures during hospitalization compared to 11 (17%) in the normothermic group. The mortality rate was similar in both groups, 16 (61%) in the hypothermic group and 38 (61%) in the conservative group. According to the present study, overt seizures were more common in the group treated with hypothermia.
ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR
Authors: Müller Bent , Schaadt Gesa , Boltze Johannes , Emmrich Frank ,   LEGASCREEN Consortium, Skeide Michael A. , Neef Nicole E. , Kraft Indra , Brauer Jens , Friederici Angela D. , Kirsten Holger , Wilcke Arndt
Published: October 2017

Background

Dyslexia is a specific learning disorder affecting reading and spelling abilities. Its prevalence is ~5% in German‐speaking individuals. Although the etiology of dyslexia largely remains to be determined, comprehensive evidence supports deficient phonological processing as a major contributing factor. An important prerequisite for phonological processing is auditory discrimination and, thus, essential for acquiring reading and spelling skills. The event‐related potential Mismatch Response (MMR) is an indicator for auditory discrimination capabilities with dyslexics showing an altered late component ofMMRin response to auditory input.

Methods

In this study, we comprehensively analyzed associations of dyslexia‐specific lateMMRs with genetic variants previously reported to be associated with dyslexia‐related phenotypes in multiple studies comprising 25 independent single‐nucleotide polymorphisms (SNPs) within 10 genes.

Results

First, we demonstrated validity of theseSNPs for dyslexia in our sample by showing that additional inclusion of a polygenic risk score improved prediction of impaired writing compared with a model that usedMMRalone. Secondly, a multifactorial regression analysis was conducted to uncover the subset of the 25SNPs that is associated with the dyslexia‐specific late component ofMMR. In total, four independentSNPs withinDYX1C1andATP2C2 were found to be associated withMMRstronger than expected from multiple testing. To explore potential pathomechanisms, we annotated these variants with functional data including tissue‐specific expression analysis andeQTLs.

Conclusion

Our findings corroborate the late component ofMMRas a potential endophenotype for dyslexia and support tripartite relationships between dyslexia‐relatedSNPs, the late component ofMMRand dyslexia.
Beryllium and Copper‐Beryllium Alloys
Authors: Nagel Nikolaus
Published: October 2017

The light metal beryllium is a comparatively rare element, which nowadays is primarily derived from bertrandite. It is mainly used as pure metal or in the form of copper‐beryllium alloys, e.g., in automotive industry, aerospace, and electrical components. The wide range of applications is mainly attributed to the extremely high rigidity/density ratio. An overview of the history of the metal, its production and recycling as well as the properties of CuBe alloys are given.
Sol–Gel Autocombustion Combined Carbothermal Synthesis of Iron‐Based Catalysts for the Fischer–Tropsch Reaction
Authors: Xue Yingying , Zhai Yongbiao , Chen Zheng , Zhang Juan , Sun Jiaqiang , Abbas Mohamed , Chen Yilong , Chen Jiangang
Published: October 2017

A new combined method of sol–gel autocombustion with carbothermal reduction has been developed to synthesize Fe‐based Fischer–Tropsch synthesis (FTS) catalysts. The effect of the glucose content on the structure and texture of the Fe phase is investigated. The glucose is employed as a reducing and carburizing agent to control the phase transformation of the Fe precursors. The reducibility of the synthesized iron oxide increases with the increase of the proportion of glucose. Meanwhile, iron oxide is converted completely into iron carbide in the presence of abundant glucose. The addition of glucose to the precursor is conducive to construct active sites before the FTS reaction. However, excess glucose results in carbon deposition and a poor FTS performance. Iron carbide also could be synthesized by this new method and will be applied directly to the FTS reaction in further research.
Atomic/Molecular Layer Deposition of s‐Block Metal Carboxylate Coordination Network Thin Films
Authors: Penttinen Jenna , Nisula Mikko , Karppinen Maarit
Published: October 2017

We present novel atomic/molecular layer deposition (ALD/MLD) processes for the fabrication of crystalline inorganic–organic coordination network thin films with different s‐block elements. Terephthalic acid is employed as the organic precursor. Such thin films could enable for example, next‐generation battery, sensor and gas‐storage technologies. The deposition processes fulfill the basic principles of ALD/MLD‐type growth including the sequential self‐saturated gas‐surface reactions and atomic/molecular‐level control for the film thickness, and yield crystalline thin films in a wide deposition temperature range. Structural characterization of the films is performed by grazing incidence X‐ray diffraction (GIXRD) and Fourier‐transform infrared (FTIR) spectroscopy. The data do not unambiguously prove but also do not rule out the crystal structures previously reported for the corresponding bulk samples. We moreover demonstrate the growth of crystalline thin films of a new terephthalate material with La as the metal component. Upon humidity treatments the Li, Na, K, Ba, and La terephthalate films remain unaffected while the Mg, Ca, and Sr terephthalate films reversibly absorb water molecules forming well‐defined crystalline water‐derivative phases.
Quantitative Analysis of Self‐Assembly Process of a Pd2L4 Cage Consisting of Rigid Ditopic Ligands
Authors: Kai Shumpei , Martí‐Centelles Vicente , Sakuma Yui , Mashiko Takako , Kojima Tatsuo , Nagashima Umpei , Tachikawa Masanori , Lusby Paul J. , Hiraoka Shuichi
Published: October 2017

The self‐assembly process of a Pd2L4 cage complex consisting of rigid ditopic ligands, in which two 3‐pyridyl groups are connected to a benzene ring through acetylene bonds and PdII ions was revealed by a recently developed quantitative analysis of self‐assembly process (QASAP), with which the self‐assembly process of coordination assemblies can be investigated by monitoring the evolution with time of the average composition of all the intermediates. QASAP revealed that the rate‐determining steps of the cage formation are the intramolecular ligand exchanges in the final stage of the self‐assembly: [Pd2L4Py*2]4+→[Pd2L4Py*1]4++Py* and [Pd2L4Py*1]4+→[Pd2L4]4++Py* (Py*: 3‐chloropyridine, which was used as a leaving ligand on the metal source). The energy barriers for the two reactions were determined to be 22.3 and 21.9 kcal mol−1, respectively. DFT calculations of the transition‐state (TS) structures for the two steps indicated that the distortion of the trigonal‐bipyramidal PdII center at the TS geometries increases the activation free energy of the two steps.
First Structure of a Designed Minor Groove Binding Heterocyclic Cation that Specifically Recognizes Mixed DNA Base Pair Sequences
Authors: Harika Narinder K. , Germann Markus W. , Wilson W. David
Published: October 2017

The high‐resolution NMR structure of the first heterocyclic, non‐amide, organic cation that strongly and selectively recognizes mixed AT/GC bp (bp=base pair) sequences of DNA in a 1:1 complex is described. Compound designs of this type provide essential methods for control of functional, non‐genomic DNA sequences and have broad cell uptake capability, based on studies from animals to humans. The high‐resolution structural studies described in this report are essential for understanding the molecular basis for the sequence‐specific binding as well as for new ideas for additional compound designs for sequence‐specific recognition. The molecular features, in this report, explain the mechanism of recognition of both A⋅T and G⋅C bps and are an interesting molecular recognition story. Examination of the experimental structure and the NMR restrained molecular dynamics model suggests that recognition of the G⋅C base pair involves two specific H‐bonds. The structure illustrates a wealth of information on different DNA interactions and illustrates an interfacial water molecule that is a key component of the complex.
Assembly of Coordination Polymers Using Thioether‐Functionalized Octasilsesquioxanes: Occurrence of (CuX)n Clusters (X=Br and I) within 3D‐POSS Networks
Authors: Raghuvanshi Abhinav , Strohmann Carsten , Tissot Jean‐Baptiste , Clément Sébastien , Mehdi Ahmad , Richeter Sébastien , Viau Lydie , Knorr Michael
Published: October 2017

For the first time, POSS‐based coordination polymers (CPs) have been structurally characterized. These CPs were obtained in high yield via self‐assembly reactions of thioether‐functionalized polysilsesquioxanes with CuI salts under mild conditions. Single crystal analyses revealed the formation of 3D networks incorporating different secondary building units (SBUs) as connection nodes. The nature of the ‐SAr functionality allows a fine‐tuning of the cluster nuclearity, that is, butterfly‐shaped Cu2X2 or closed cubane‐type Cu4I4 cores. As such, the resulting hybrid materials exhibit a combination of high thermal stability arising from the inorganic POSS core along with interesting luminescent properties conferred by the cubane cluster core. Furthermore, the occurrence of channels has been shown crystallographically in the case of the Cu4I4 cluster containing CP.
Effects of the Protonation State of Titratable Residues and the Presence of Water Molecules on Nocodazole Binding to β‐Tubulin
Authors: Guzmán‐Ocampo Dulce C. , Aguayo‐Ortiz Rodrigo , Cano‐González Lucia , Castillo Rafael , Hernández‐Campos Alicia , Dominguez Laura
Published: October 2017

Regulation of microtubule assembly by antimitotic agents is a potential therapeutic strategy for the treatment of cancer, parasite infections, and neurodegenerative diseases. One of these agents is nocodazole (NZ), which inhibits microtubule polymerization by binding to β‐tubulin. NZ was recently co‐crystallized in Gallus gallus tubulin, providing new information about the features of interaction for ligand recognition and stability. In this work, we used state‐of‐the‐art computational approaches to evaluate the protonation effects of titratable residues and the presence of water molecules in the binding of NZ. Analysis of protonation states showed that residue E198 has the largest modification in its pKa value. The resulting E198 pKa value, calculated with pH‐REMD methodology (pKa=6.21), was higher than the isolated E amino acid (pKa=4.25), thus being more likely to be found in its protonated state at the binding site. Moreover, we identified an interaction between a water molecule and C239 and G235 as essential for NZ binding. Our results suggest that the protonation state of E198 and the structural water molecules play key roles in the binding of NZ to β‐tubulin.
Dendritic Core‐Frame and Frame Multimetallic Rhombic Dodecahedra: A Comparison Study of Composition and Structure Effects on Electrocatalysis of Methanol Oxidation
Authors: Mathurin Leanne E. , Tao Jing , Xin Huolin , Li Jun , Zhu Yimei , Chen Jingyi
Published: October 2017

The composition and structure of multimetallic nanostructures can be tailored to enhance electrocatalytic properties. This work reports a seed‐mediated synthesis of novel multimetallic dendritic core‐frame and frame nanostructures with a rhombic dodecahedral shape for enhanced methanol oxidation reaction (MOR). The synthesis involves in situ formation of Cu seeds and the subsequent selective deposition of Pt and Ru on the edges and vertices of the Cu seeds to generate CuPt and CuPtRu dendritic core‐frame nanostructures. The core‐frame nanostructures undergo a post acetic acid etching process to form the frame nanostructures. While transmission electron microscopy reveals the morphology and elemental distribution of the nanostructures, X‐ray diffraction patterns confirm the alloy compositions of dendritic frames for both the core‐frame and frame nanostructures. Compared to the bimetallic CuPt nanostructures, the trimetallic CuPtRu nanostructures lower the onset potential and completely suppress the peak current in the reverse scan for MOR. The CuPtRu alloyed frame nanostructures are the best to prevent Ru leaching compared to the CuPtRu core‐frame nanostructures and PtRu catalysts. X‐ray photoelectron spectroscopy reveals that all three elements become more electron rich in the frame nanostructures. Further refining the composition ratio of the CuPtRu alloyed dendritic frame nanostructures can lead to more efficient catalysts at a lower cost for MOR.
The relationship between container colors and the beauty benefits of skin care products
Authors: Liao Ching‐Chih , Lee Wen‐Yuan , Lai Yu‐Husan , Wang Li‐Ying
Published: October 2017

This study explored the best color selections to match the benefits of beauty products based on rankings obtained from an experimental perception of different skin care product containers. Gender (64 males, 75 females) and cultural (76 Taiwanese, 63 Malaysians) differences were also compared, aiming to explore color associations and emotional bonding by using psychophysical testing methods. A survey of 205 market samples showed that nearly half of the existing skin care product containers had a white body color. White appeared frequently on containers for skin whitening, firming, exfoliating, antiaging, and antiacne products. However, skin moisturizing products used an equal amount of white and blue on their containers. The psychophysical experiment results showed that participants felt that white best matched skin whitening products, red matched skin firming and antiaging products, blue matched skin moisturizing products, black matched exfoliating products, and green matched antiacne products. Neither gender nor cultural differences were found to be significant. Comparing the results with color emotion studies, it was found that (1) for color emotion weight, firming products were related to heaviness, whereas whitening products were connected to lightness; (2) for color emotion heat, whitening, moisturizing, exfoliating and antiacne products were aligned with coolness; and (3) for color emotion activity, product container colors were not related, except slightly for firming products. These findings suggest that psychological responses to color meaning are context‐ and experience‐dependent, meaning that selection of colors to match beauty benefits is based more on people's expectations of the products than their color emotion response.
Absolute Bioavailability of Bosutinib in Healthy Subjects From an Open‐Label, Randomized, 2‐Period Crossover Study
Authors: Hsyu Poe‐Hirr , Pignataro Daniela Soriano , Matschke Kyle
Published: October 2017

This study evaluated the absolute bioavailability of bosutinib and assessed its safety and tolerability after single‐dose oral and intravenous administration. In this phase 1 open‐label, 2‐sequence, 2‐period crossover study, healthy, fed subjects aged 18−55 years were randomized to 1 of 2 treatment sequences (n = 7/sequence): oral bosutinib (100 mg × 5) followed by intravenous bosutinib (120 mg in approximately 240 mL over 1 hour), with a ≥14‐day washout, or intravenous bosutinib and then oral bosutinib. Results of plasma pharmacokinetics analyses demonstrated that exposure to intravenous bosutinib was 3‐fold higher than for oral bosutinib (16.2 and 5.5 ng·h/mL/mg, respectively), and mean terminal half‐life was similar (35.5 and 31.7 hours). The ratio of adjusted geometric means (90%CI) for the dose‐normalized area under the plasma concentration–time profile (AUC0−∞/D) was 33.85% (30.65%‒37.38%). Most treatment‐emergent adverse events (AEs) were mild in severity. Gastrointestinal (GI) AEs occurred in 9 of 13 subjects given oral bosutinib, whereas no subjects given intravenous bosutinib experienced GI AEs, suggesting bosutinib present in the GI tract had an effect. Bosutinib exhibited an absolute bioavailability of 33.85% based on the ratio of AUC0−∞/D. Both oral and intravenous bosutinib were safe and well tolerated in healthy, fed adult subjects.
The Selective Role of Long‐Range Forces in the Stereodynamics of Ion–Molecule Reactions: The He++Methyl Formate Case From Guided‐Ion‐Beam Experiments
Authors: Cernuto Andrea , Pirani Fernando , Martini Luca Matteo , Tosi Paolo , Ascenzi Daniela
Published: October 2017

Long‐range intermolecular forces play a crucial role in controlling the outcome of ion–molecule chemical reactions, such as those determining the disappearance of organic or inorganic “complex” molecules recently detected in various regions of the interstellar medium due to collisions with abundant interstellar atomic ions (e.g. H+ and He+). Theoretical treatments, for example, based on simple capture models, are nowadays often adopted to evaluate the collision‐energy dependence of reactive cross sections and the temperature dependent rate coefficients of many ion–molecule reactions. The obtained results are widely used for the modelling of phenomena occurring in different natural environments or technological applications such as astrophysical and laboratory plasmas. Herein it is demonstrated, through a combined experimental and theoretical investigation on a prototype ion–molecule reaction (He++methyl formate), that the dynamics, investigated in detail, shows some intriguing features that can lead to rate coefficients at odds with the expectations (e.g. Arrhenius versus anti‐Arrhenius behaviour). Therefore, this study casts light on some new and general guidelines to be properly taken into account for a suitable evaluation of rate coefficients of ion–molecule reactions.
Bioluminescence Resonance Energy Transfer Assay to Characterize Gi‐Like G Protein Subtype‐Dependent Functional Selectivity
Authors: Yano Hideaki , Sánchez‐Soto Marta , Ferré Sergi
Published: October 2017

G protein–coupled receptors (GPCRs) comprise the single most targeted protein class in pharmacology. G protein signaling transduces extracellular stimuli such as neurotransmitters into cellular responses. Although preference for a specific GPCR among different G protein families (e.g., Gs‐, Gi‐, or Gq‐like proteins) is often well studied, preference for a specific G protein subtype (e.g., Gi1, Gi2, Gi3, Go1, and Go2) has received little attention. Due to tissue expression differences and potentially exploitable functional differences, G protein subtype‐dependent functional selectivity is an attractive framework to expand GPCR drug development. Herein we present a bioluminescence resonance energy transfer (BRET)‐based method to characterize functional selectivity among Gi‐like protein subtypes. © 2017 by John Wiley & Sons, Inc.
A 12‐bit 10‐MS/s SAR ADC with a binary‐window DAC switching scheme in 180‐nm CMOS
Authors: Chung Yung‐Hui , Yen Chia‐Wei , Tsai Pei‐Kang
Published: October 2017

This paper presents an energy‐efficient 12‐bit successive approximation‐register A/D converter (ADC). The D/A converter (DAC) plays a crucial role in ADC linearity, which can be enhanced by using larger capacitor arrays. The binary‐window DAC switching scheme proposed in this paper effectively reduces DAC nonlinearity and switching errors to improve both the spurious‐free dynamic range and signal‐to‐noise‐and‐distortion ratio. The ADC prototype occupies an active area of 0.12 mm2 in the 0.18‐μm CMOS process and consumes a total power of 0.6 mW from a 1.5‐V supply. The measured peak differential nonlinearity and integral nonlinearity are 0.57 and 0.73 least significant bit, respectively. The ADC achieves a 64.7‐dB signal‐to‐noise‐and‐distortion ratio and 83‐dB spurious‐free dynamic range at a sampling rate of 10 MS/s, corresponding to a peak figure‐of‐merit of 43 fJ/conversion‐step.
Intraspecific and interspecific competition induces density‐dependent habitat niche shifts in an endangered steppe bird
Authors: Tarjuelo Rocío , Morales Manuel B. , Arroyo Beatriz , Mañosa Santiago , Bota Gerard , Casas Fabián , Traba Juan
Published: October 2017

Interspecific competition is a dominant force in animal communities that induces niche shifts in ecological and evolutionary time. If competition occurs, niche expansion can be expected when the competitor disappears because resources previously inaccessible due to competitive constraints can then be exploited (i.e., ecological release). Here, we aimed to determine the potential effects of interspecific competition between the little bustard (Tetrax tetrax) and the great bustard (Otis tarda) using a multidimensional niche approach with habitat distribution data. We explored whether the degree of niche overlap between the species was a density‐dependent function of interspecific competition. We then looked for evidences of ecological release by comparing measures of niche breadth and position of the little bustard between allopatric and sympatric situations. Furthermore, we evaluated whether niche shifts could depend not only on the presence of great bustard but also on the density of little and great bustards. The habitat niches of these bustard species partially overlapped when co‐occurring, but we found no relationship between degree of overlap and great bustard density. In the presence of the competitor, little bustard's niche was displaced toward increased use of the species' primary habitat. Little bustard's niche breadth decreased proportionally with great bustard density in sympatric sites, in consistence with theory. Overall, our results suggest that density‐dependent variation in little bustard's niche is the outcome of interspecific competition with the great bustard. The use of computational tools like kernel density estimators to obtain multidimensional niches should bring novel insights on how species' ecological niches behave under the effects of interspecific competition in ecological communities.
High‐stakes steeplechase: a behavior‐based model to predict individual travel times through diverse migration segments
Authors: Crozier Lisa G. , Bowerman Tracy E. , Burke Brian J. , Keefer Matthew L. , Caudill Christopher C.
Published: October 2017

Many migratory species traverse highly heterogeneous landscapes, often including habitats that have been altered by human activities. Modeling migration dynamics is challenging because individual variability in behavior at multiple spatial and temporal scales can produce complex, multi‐modal distributions in migration travel times. Moreover, behavioral responses to conditions encountered en route can affect habitat‐specific migration rates which then influence bioenergetic costs and mortality risk over the entire migration. To quantify impacts of conditions within migration corridors, refined analyses of behavior are needed. In this study, we developed a behavior‐based simulation model that predicts individual adult salmon migration duration over 24 distinct river reaches totaling 922 km, including eight hydropower dams. The study population, threatened Snake River spring/summer Chinook salmon (Oncorhynchus tshawytscha), had observed migration durations ranging from 23 to 108 d. In a novel application of N‐dimensional mixture models, which can account for subpopulations that behave differently, we simulated “fast” vs. “slow” travel through migration reaches. The proportion of migrants in each category was determined by diel, seasonal, and proximate river conditions, which captured the temporally shifting bimodal patterns in the data. We fit reach‐specific models with data from 2188 tagged salmon migrating in 2000–2013 and validated the cumulative model with additional data through 2015. By accounting for multiple behaviors in this way, the model successfully recreated the breadth and variability in total travel times to within 3% of observed durations throughout the 5th–95th quantiles. En route mortality appeared to account for the loss of the slowest fish that encountered record‐breaking high temperatures in 2015. For Chinook salmon, this combined reach and cumulative travel‐time model provides an opportunity to link high‐resolution behavioral data to individual fitness and population‐level impacts on viability. More generally, the N‐dimensional modeling approach offers a framework for assessing the cumulative impacts of alternative behaviors at small spatial and temporal scales. Improved accounting of changes in migration rate in response to local conditions will aid recovery efforts for species of concern traversing complex migration corridors.
An Assessment Framework for Benefit Sharing Mechanisms to Reduce Emissions from Deforestation and Forest Degradation within a Forest Policy Mix
Authors: Wong Grace Yee , Loft Lasse , Brockhaus Maria , Yang Anastasia Lucy , Pham Thu Thuy , Assembe‐Mvondo Samuel , Luttrell Cecilia
Published: October 2017

Policy instruments for implementing the Reducing Emissions from Deforestation and Forest Degradation and the enhancement of forest carbon stocks (REDD+) mechanism operate within an orchestra of policy mixes that affect the forest and other land sectors. How will policymakers choose between the myriad of options for distributing REDD+ benefits, and be able to evaluate its potential effectiveness, efficiency and equity (3Es)? This is a pressing issue given the results‐based aspect of REDD+. We present here a three‐element assessment framework for evaluating the outcomes and performance of REDD+ benefit sharing mechanisms, using the criteria of effectiveness, efficiency and equity: (1) the structures (objective and policies) of a REDD+ benefit sharing mechanism; (2) the broader institutional and policy contexts underlying forest governance; (3) outcomes of REDD+ including emission reductions, ecosystem service provision and poverty alleviation. A strength of the assessment framework is its flexible design to incorporate indicators relevant to different contexts; this helps to generate a shared working understanding of what is to be evaluated in the different REDD+ benefit sharing mechanisms (BSMs) across complex socio‐political contexts. In applying the framework to case studies, the assessment highlights trade‐offs among the 3Es, and the need to better manage access to information, monitoring and evaluation, consideration of local perceptions of equity and inclusive decisionmaking processes. The framework does not aim to simplify complexity, but rather serves to identify actionable ways forward towards a more efficient, effective and equitable implementation and re‐evaluation of REDD+ BSMs as part of reflexive policymaking. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Synthesis of Disubstituted Pyrazino‐Oxazine Derivatives with Controlled Stereochemistry
Authors: Ručilová Veronika , Králová Petra , Soural Miroslav
Published: October 2017

Herein, we report a simple synthesis of disubstituted pyrazino‐oxazines with controlled stereochemistry using readily available building blocks: N‐Fmoc‐protected α‐amino acids and 2‐bromo ketones. The convenient solid‐phase synthesis afforded polymer‐supported derivatives of N‐alkylated N‐acylated tert‐butylserine, which were subjected to spontaneous cyclative cleavage to yield the corresponding pyrazine intermediates. The target 1,7,8,9a‐tetrahydropyrazino[2,1‐c][1,4]oxazine‐6,9‐diones were obtained in two steps by acid‐mediated cleavage of the tert‐butyl group followed by cyclization of the oxazine scaffold.
Experiments on the morphological controls of velocity inversions in bedrock canyons
Authors: Hunt Brendan , Venditti Jeremy G. , Kwoll Eva
Published: October 2017

A better understanding of bedrock incision mechanisms and processes is essential to the study of long‐term landscape evolution. Yet, little is known about flow dynamics in bedrock rivers, limiting our ability to make realistic predictions of local bedrock incision rates. A recent investigation of flow through bedrock canyons of the Fraser River revealed that plunging flows, defined by the downward‐directed movement of near surface flow toward the channel bed, occur in channels that have low width‐to‐depth ratios. Plunging flows occur into deep scour pools, which are often coincident with lateral constrictions and channel spanning submerged ridges (sills). A phenomenological investigation was undertaken to reproduce the flow fields observed in the Fraser canyons and to explore morphological controls on the occurrence and relative strength of plunging flow in bedrock canyons. Our observations show that the plunging flow structure can be produced along a scour pool entrance slope by accelerating the flow at the canyon entrance either over submerged sills or through lateral constrictions. Plunging flow appears to be a function of convective deceleration into a scour pool which can be enhanced by sill height, the amount of the channel width that is constricted, pool entrance slope, discharge, and a reduction in channel width‐to‐depth ratio. Plunging flow greatly enhances the potential for incision to occur along the channel bed and is an extreme departure from the assumptions of steady, uniform flow in bedrock incision models, highlighting the need for improved formulations that account for fluid flow. Copyright © 2017 John Wiley & Sons, Ltd.
Modeling the effects of thiamethoxam on Midwestern farm ponds and emergent wetlands
Authors: Bartell Steven M. , Nair Shyam K. , Grant Shanique , Brain Richard A.
Published: October 2017

Potential toxic effects of thiamethoxam on nontarget organisms and the community structure of a generic Midwestern farm pond and emergent wetland were assessed using 2 versions of the comprehensive aquatic system model: CASMGFP, a generic farm pond model, and CASMGWL, a generic wetland model. The CASMGFP and CASMGWL are integrated bioenergetics-based and habitat quality models that describe the daily biomass values of selected producer and consumer populations representative of generalized Midwestern farm ponds and emergent wetlands. The CASMGFP demonstrated the ability to reproduce values of population biomass reported for Midwestern (and other) pond ecosystems; the CASMGWL provided a similar modeling capability for Midwestern emergent wetlands. Lethal and sublethal effects of thiamethoxam were modeled as extrapolations of laboratory toxicity assays using the CASMGFP and the CASMGWL. Time series of daily environmental concentrations of thiamethoxam constructed for 6 regional pesticide applications across the United States failed to produce any calculated impacts on modeled population biomass or changes in community structure of modeled trophic guilds in the CASMGFP or the CASMGWL. However, evaluation of systematically increased daily concentrations demonstrated the ability of both models to simulate direct and indirect toxic effects of this pesticide. The present model study suggests that process-based food web/ecosystem models can be used to characterize the potential ecological effects of thiamethoxam on generalized farm pond and emergent wetland ecosystems. Environ Toxicol Chem 2018;37:738–754. © 2017 SETAC
Experimental evaluation of carbonated waterflooding: A practical process for enhanced oil recovery and geological CO2 storage
Authors: Bakhshi Puyan , Kharrat Riyaz , Hashemi Abdolnabi , Zallaghi Mehdi
Published: October 2017

The rapid escalation of anthropogenic CO2 emissions at the same time as the growth in energy demand has brought the importance of CO2 enhanced oil recovery (EOR) into the spotlight. Nevertheless, fundamental problems with conventional CO2 injection have paved the way for practicing other strategies, such as carbonated waterflooding (CWF), i.e., flooding of CO2 dissolved in flood water through the reservoir. In this work, performance of CWF as a joint method of EOR and CO2 storage in an Iranian oil field is examined through sets of coreflooding experiments, conducted at a specified pressure and temperature condition on two different reservoir oil (light and heavy) and rock (carbonate and sandstone) samples from the investigated oil field. In summary, CWF improved the oil recovery as compared to waterflooding (WF). Average recovery factors (RFs) for CWG ranged from 6.4% to 13.6% when implemented as a secondary recovery technique and 4.2% to 4.8% when used as a tertiary recovery technique. This improvement was also higher in the carbonate rock than in the sandstone one, slightly higher with light oil than with heavy oil, and lower when a more saline brine was used for carbonated water preparation. CWF also showed to be more effective when implemented in a mixed‐wet system than in a water‐wet one. Moreover, considerable amounts (about 42‒60%) of the CO2 injected through the flooding brine were ultimately stored in the porous media. Finally, a co‐optimizing function was used as a standard for coupling CO2 EOR and storage. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd.
Benefit‐risk assessment for sofosbuvir/velpatasvir/voxilaprevir based on patient population and hepatitis C virus genotype: U. S. Food and Drug Administration's evaluation
Authors: Struble Kimberly , Chan‐Tack Kirk , Qi Karen , Naeger Lisa K. , Birnkrant Debra
Published: October 2017

On July 18, 2017, the U.S. Food and Drug Administration (FDA) approved sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed‐dose combination (FDC), an interferon‐free, complete regimen for adult patients with chronic hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis (Child‐Pugh A) who have:

• genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with an HCV regimen containing a nonstructural protein 5A (NS5A) inhibitor; and

• genotype 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.

Approval was based on an acceptable safety profile and high sustained virological response rates 12 weeks after the end of treatment (SVR12) in two phase 3 clinical trials in subjects previously treated with a direct‐acting antiviral (DAA) regimen. In POLARIS‐1, 96% of SOF/VEL/VOX‐treated subjects achieved SVR12. In POLARIS‐4, 98% of SOF/VEL/VOX‐treated subjects achieved SVR12. A key and challenging question in evaluating the data was determining the contribution of VOX to SOF/VEL and how this differed depending on the genotype and patient population. In this article, we provide our perspective on the issues considered in making these determinations, especially regarding the POLARIS‐4 data in subjects who have previously been treated with a chronic HCV regimen containing sofosbuvir without an NS5A inhibitor. Conclusion: We seek to provide context as to why a broad indication was given for NS5A inhibitor‐experienced patients (HCV genotypes 1‐6) while the indication for NS5A inhibitor‐ naïve patients was limited to HCV genotypes 1a and 3 only. (Hepatology 2018;67:482‐491).
Interferon regulatory factor 1–Rab27a regulated extracellular vesicles promote liver ischemia/reperfusion injury
Authors: Yang Mu‐qing , Du Qiang , Goswami Julie , Varley Patrick R. , Chen Bin , Wang Rong‐hua , Morelli Adrian E. , Stolz Donna B. , Billiar Timothy R. , Li Jiyu , Geller David A.
Published: October 2017

The role and regulators of extracellular vesicle (EV) secretion in hepatic ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF‐1) is a transcription factor that plays an important role in liver IR and regulates certain guanosine triphosphatases. However, the relationships among IRF‐1, Rab27a, and EV secretion are largely unknown. Here, we show induction of IRF‐1 and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and orthotopic liver transplantation livers. Interferon γ stimulation, IRF‐1 transduction, or IR promoted Rab27a expression and EV secretion. Meanwhile, silencing of IRF‐1 decreased Rab27a expression and EV secretion. Rab27a silencing decreased EV secretion and liver IR injury. Ten putative IRF‐1 binding motifs in the 1,692‐bp Rab27a promoter region were identified. Chromatin immunoprecipitation and electrophoretic mobility shift assay verified five functional IRF‐1 binding motifs, which were confirmed by a Rab27a promoter luciferase assay. IR‐induced EVs contained higher oxidized phospholipids (OxPL). OxPLs on the EV surface activated neutrophils through the toll‐like receptor 4 pathway. OxPL‐neutralizing E06 antibody blocked the effect of EVs and decreased liver IR injury. Conclusion: These findings provide a novel mechanism by which IRF‐1 regulates Rab27a transcription and EV secretion, leading to OxPL activation of neutrophils and subsequent hepatic IR injury. (Hepatology 2018;67:1056–1070)