bluuebunny/crossref_metadata_2025 huggingface dataset:
A Sliding Mode Control Using Brain Limbic System Control Strategy for a Robotic Manipulator
Authors: Yi Hak
Published: November 2015

This paper presents a robust bio-inspired sliding mode control approach, designed to achieve a favourable tracking performance in a class of robotic manipulators with uncertainties. To this end, brain emotional learning-based intelligent control (BELBIC) is applied, to adaptively adjust the control input law in the sliding mode control. The combined form provides an adjustment of the control input law that effectively alleviates the chattering effects of the sliding mode control. Specifically, the online parameters computed from the parameter uncertainties and external disturbances help to improve the system robustness. The simulation results demonstrate that the proposed bio-inspired control strategy is very successful at tracking the given trajectories with less chattering as compared to both the conventional and fuzzy sling mode control schemes.
Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons
Authors: Martinez-Espinosa Pedro L , Wu Jianping , Yang Chengtao , Gonzalez-Perez Vivian , Zhou Huifang , Liang Hongwu , Xia Xiao-Ming , Lingle Christopher J
Published: November 2015

Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na+-dependent K+ (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations.
Networks of reader and country status: an analysis of Mendeley reader statistics
Authors: Haunschild Robin , Bornmann Lutz , Leydesdorff Loet
Published: November 2015

The number of papers published in journals indexed by the Web of Science core collection is steadily increasing. In recent years, nearly two million new papers were published each year; somewhat more than one million papers when primary research papers are considered only (articles and reviews are the document types where primary research is usually reported or reviewed). However, who reads these papers? More precisely, which groups of researchers from which (self-assigned) scientific disciplines and countries are reading these papers? Is it possible to visualize readership patterns for certain countries, scientific disciplines, or academic status groups? One popular method to answer these questions is a network analysis. In this study, we analyze Mendeley readership data of a set of 1,133,224 articles and 64,960 reviews with publication year 2012 to generate three different networks: (1) The network based on disciplinary affiliations of Mendeley readers contains four groups: (i) biology, (ii) social sciences and humanities (including relevant computer sciences), (iii) bio-medical sciences, and (iv) natural sciences and engineering. In all four groups, the category with the addition “miscellaneous” prevails. (2) The network of co-readers in terms of professional status shows that a common interest in papers is mainly shared among PhD students, Master’s students, and postdocs. (3) The country network focusses on global readership patterns: a group of 53 nations is identified as core to the scientific enterprise, including Russia and China as well as two thirds of the OECD (Organisation for Economic Co-operation and Development) countries.
Recent (Late Amazonian) enhanced backweathering rates on Mars: Paracratering evidence from gully alcoves
Authors: de Haas Tjalling , Conway Susan J. , Krautblatter Michael
Published: November 2015

Mars is believed to have been exposed to low planet‐wide weathering and denudation since the Noachian. However, the widespread occurrence of alcoves at the rim of pristine impact craters suggests locally enhanced recent backweathering rates. Here we derive Late Amazonian backweathering rates from the alcoves of 10 young equatorial and midlatitude craters. The enhanced Late Amazonian Martian backweathering rates (10−4–10−1 mm yr−1) are approximately 1 order of magnitude higher than previously reported erosion rates and are similar to terrestrial rates inferred from Meteor crater and various Arctic and Alpine rock faces. Alcoves on initially highly fractured and oversteepened crater rims following impact show enhanced backweathering rates that decline over at least 101–102 Myr as the crater wall stabilizes. This “paracratering” backweathering decline with time is analogous to the paraglacial effect observed in rock slopes after deglaciation, but the relaxation timescale of 101–102 Myr compared to 10 kyr of the Milankovitch‐controlled interglacial duration questions whether a paraglacial steady state is reached on Earth. The backweathering rates on the gullied pole‐facing alcoves of the studied midlatitude craters are much higher (∼2–60 times) than those on slopes with other azimuths and those in equatorial craters. The enhanced backweathering rates on gullied crater slopes may result from liquid water acting as a catalyst for backweathering. The decrease in backweathering rates over time might explain the similar size of gullies in young (<1 Ma) and much older craters, as alcove growth and sediment supply decrease to low‐background rates over time.
Neuroprotective effects of deep hypothermia in refractory status epilepticus
Authors: Niquet Jerome , Gezalian Michael , Baldwin Roger , Wasterlain Claude G.
Published: November 2015

Objective

Pharmacoresistance develops quickly during repetitive seizures, and refractory status epilepticus (RSE) remains a therapeutic challenge. The outcome of RSE is poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (20°C) is used clinically during reconstructive cardiac surgery and neurosurgery, and has proved safe and effective in those indications. We tested the hypothesis that deep hypothermia reduces RSE and its long‐term consequences.

Methods

We used a model of SE induced by lithium and pilocarpine and refractory to midazolam. Several EEG measures were recorded in both hypothermic (n = 17) and normothermic (n = 20) animals. Neuronal injury (by Fluoro‐Jade B), cell‐mediated inflammation, and breakdown of the blood–brain barrier (BBB) (by immunohistochemistry) were studied 48 h following SE onset.

Results

Normothermic rats in RSE seized for 4.1 ± 1.1 h, and at 48 h they displayed extensive neuronal injury in many brain regions, including hippocampus, dentate gyrus, amygdala, entorhinal and pyriform cortices, thalamus, caudate/putamen, and the frontoparietal neocortex. Deep hypothermia (20°C) of 30 min duration terminated RSE within 12 min of initiation of hypothermia, reduced EEG power and seizure activity upon rewarming, and eliminated SE‐induced neuronal injury in most animals. Normothermic rats showed widespread breakdown of the BBB, and extensive macrophage infiltration in areas of neuronal injury, which were completely absent in animals treated with hypothermia.

Interpretation

These results suggest that deep hypothermia may open a new therapeutic avenue for the treatment of RSE and for the prevention of its long‐term consequences.
Efficacy, Tolerability, and Safety of Cannabinoid Treatments in the Rheumatic Diseases: A Systematic Review of Randomized Controlled Trials
Authors: Fitzcharles Mary‐Ann , Ste‐Marie Peter A. , Häuser Winfried , Clauw Daniel J. , Jamal Shahin , Karsh Jacob , Landry Tara , Leclercq Sharon , Mcdougall Jason J. , Shir Yoram , Shojania Kam , Walsh Zach
Published: November 2015

Objective

To assess the efficacy, tolerability, and safety of cannabinoids (phyto‐ and syntheto‐) in the management of rheumatic diseases.

Methods

Multiple databases, including Medline, Embase, and CENTRAL, were searched. Randomized controlled trials with outcomes of pain, sleep, quality of life, tolerability (dropouts due to adverse events), and safety (serious adverse events), with comparison of cannabinoids with any type of control, were included. Study methodology quality was evaluated with the Cochrane risk of bias tool.

Results

In 4 short‐term studies comprising 203 patients (58 with rheumatoid arthritis, 71 with fibromyalgia, and 74 with osteoarthritis [OA]), cannabinoids had a statistically significant effect on pain in 2, sleep in 2, and improved quality of life in 1, with the OA study prematurely terminated due to futility. The risk of bias was high for all 3 completed studies. Dizziness, cognitive problems, and drowsiness, as well as nausea, were reported for almost half of the patients. No serious adverse events were reported for cannabinoids during the study duration. No studies of herbal cannabis were identified.

Conclusion

Extremely small sample sizes, short study duration, heterogeneity of rheumatic conditions and products, and absence of studies of herbal cannabis allow for only limited conclusions for the effects of cannabinoids in rheumatic conditions. Pain relief and effect on sleep may have some potential therapeutic benefit, but with considerable mild to moderate adverse events. There is currently insufficient evidence to recommend cannabinoid treatments for management of rheumatic diseases pending further study.
Nanoporous Substrate‐Infiltrated Hydrogels: a Bioinspired Regenerable Surface for High Load Bearing and Tunable Friction
Authors: Ma Shuanhong , Scaraggi M. , Wang Daoai , Wang Xiaolong , Liang Yongmin , Liu Weimin , Dini Daniele , Zhou Feng
Published: November 2015

Nature has successfully combined soft matter and hydration lubrication to achieve ultralow friction even at relatively high contact pressure (e.g., articular cartilage). Inspired by this, hydrogels are used to mimic natural aqueous lubricating systems. However, hydrogels usually cannot bear high load because of solvation in water environments and are, therefore, not adopted in real applications. Here, a novel composite surface of ordered hydrogel nanofiber arrays confined in anodic aluminum oxide (AAO) nanoporous template based on a soft/hard combination strategy is developed. The synergy between the soft hydrogel fibers, which provide excellent aqueous lubrication, and the hard phase AAO, which gives high load bearing capacity, is shown to be capable of attaining very low coeffcient of friction (<0.01) under heavy load (contact pressures ≈2 MPa). Interestingly, the composite synthetic material is very stable, cannot be peeled off during sliding, and exhibits desirable regenerative (self‐healing) properties, which can assure long‐term resistance to wear. Moreover, the crosslinked polymethylacrylic acid hydrogels are shown to be able to promptly switch between high friction (>0.3) and superlubrication (≈10−3) when their state is changed from contracted to swollen by means of acidic and basic actuation. The mechanisms governing ultralow and tunable friction are theoretically explained via an in‐depth study of the chemomechanical interactions responsible for the behavior of these substrate‐infiltrated hydrogels. These findings open a promising route for the design of ultra‐slippery and smart surface/interface materials.
Nanoionic Resistive Switching Memories: On the Physical Nature of the Dynamic Reset Process
Authors: Marchewka Astrid , Roesgen Bernd , Skaja Katharina , Du Hongchu , Jia Chun‐Lin , Mayer Joachim , Rana Vikas , Waser Rainer , Menzel Stephan
Published: November 2015

Resistive switching memories based on the valence change mechanism have attracted great attention due to their potential use in future nanoelectronics. The working principle relies on ion migration in an oxide matrix and subsequent nanoscale redox processes leading to a resistance change. While switching from a low resistive to a high resistive state, different intermediate resistance levels can be programmed by changing the maximum applied voltage, making resistive switches highly interesting for multibit data storage and neuromorphic applications. To date, this phenomenon, which is known as gradual reset, has been reported in various experimental studies, but a comprehensive physical understanding of this key phenomenon is missing. Here, a combined experimental and numerical modeling approach is presented to address these issues. Time‐resolved pulse measurements are performed to study the reset kinetics in TaOx‐based nano‐crossbar structures. The results are analyzed using a 2D dynamic model of nonisothermal drift–diffusion transport in the mixed electronic–ionic conducting oxide including the effect of contact potential barriers. The model accurately describes the experimental data and provides physical insights into the processes determining the gradual reset. The gradual nature can be attributed to the temperature‐accelerated oxygen‐vacancy motion being governed by drift and diffusion processes approaching an equilibrium situation.
Hierarchisch strukturierte Nanomaterialien für die elektrochemische Energieumwandlung
Authors: Trogadas Panagiotis , Ramani Vijay , Strasser Peter , Fuller Thomas F. , Coppens Marc‐Olivier
Published: November 2015

Hierarchische Nanomaterialien eignen sich hervorragend als Elektrokatalysatoren und Träger von Elektrokatalysatoren in Systemen für die elektrochemische Energieumwandlung. Die intrinsische Kinetik eines Elektrokatalysators wird von der Nanostruktur der aktiven Phasen und des Trägers bestimmt, während die Gesamteigenschaften auch von der Mesostruktur abhängen. Eine Kontrolle über diese beiden Strukturen ist demzufolge nötig. Es werden eine vergleichende Übersicht über die modernsten Katalysatoren und Träger sowie eine detaillierte Beschreibung von Synthesemethoden gegeben. Weitergehende Designverbesserungen bei hierarchischen Nanomaterialien erfordern die tiefgründige Erforschung des Zusammenhangs zwischen der Architektur der Materialien und ihrer Reaktions‐ sowie Transportkinetik. Dafür können Vorbilder aus der Natur genutzt werden, die viele sehr effektive hierarchische Strukturen hervorgebracht hat. Die grundlegenden Kenntnis darüber, wie die begehrten Eigenschaften biologischer Systeme und ihre hierarchischen Architektur zusammenhängen, kann eine Basis für die Entwicklung neuartiger katalytischer Nanomaterialien und elektrochemischer Systeme nach dem Vorbild der Natur sein.
Selective Extraction and In Situ Reduction of Precious Metal Salts from Model Waste To Generate Hybrid Gels with Embedded Electrocatalytic Nanoparticles
Authors: Okesola Babatunde O. , Suravaram Sindhu K. , Parkin Alison , Smith David K.
Published: November 2015

A hydrogel based on 1,3:2,4‐dibenzylidenesorbitol (DBS), modified with acyl hydrazides which extracts gold/silver salts from model waste is reported, with preferential uptake of precious heavy metals over other common metals. Reduction of gold/silver salts occurs spontaneously in the gel to yield metal nanoparticles located on the gel nanofibers. High nanoparticle loadings can be achieved, endowing the gel with electrochemical activity. These hybrid gels exhibit higher conductances than gels doped with carbon nanotubes, and can be used to modify electrode surfaces, enhancing electrocatalysis. We reason this simple, industrially and environmentally relevant approach to conducting materials is of considerable significance.
New Norcantharidin Analogs: Synthesis and Anticancer Activity
Authors: Pachuta‐Stec Anna , Szuster‐Ciesielska Agnieszka
Published: November 2015

The reaction of direct condensation between S‐ethyl‐N‐(7‐oxabicyclo‐[2.2.1]heptane‐2,3‐dicarbonyl)isothiosemicarbazide (1) and primary amines was used for synthesizing new N‐substituted amides of 3‐(3‐ethylthio‐1,2,4‐triazol‐5‐yl)‐7‐oxabicyclo‐[2.2.1]heptane‐2‐carboxylic acid (2–12) as norcantharadin analogs. Moreover, the anticancer activity of the obtained compounds was studied. Among all compounds, the N‐3‐methylbutyl amide of 3‐(3‐ethylthio‐1,2,4‐triazol‐5‐yl)‐7‐oxabicyclo‐[2.2.1]heptane‐2‐carboxylic acid (4) presented selective in vitro toxic and antiproliferative effects against the human hepatoma cell line Hep3B, without affecting normal human liver stellate cells (LX‐2 cell line).
Ambiguity Attitudes over Time
Authors: Liu Yuanyuan , Onculer Ayse
Published: November 2015

Previous research demonstrates that individuals exhibit a stronger level of ambiguity aversion for high probabilities than for low probabilities. Given that risky and ambiguous prospects are often unresolved until a future date (e.g., investment decisions, new product launches, and medical interventions), this study examines the impact of time on ambiguity preferences at different probability levels. Our experimental results indicate that although ambiguity preferences for low‐probability events remain constant, a robust effect of time occurs for high‐probability events. More specifically, temporal distance mitigates ambiguity aversion. This effect is consistent for different elicitation methods (preference rating and probability–ambiguity trade‐off tasks). We propose a dual‐process model (affective versus cognitive processing styles) to explain our results. Affective processing for high‐probability lotteries resolved in the current period increases ambiguity aversion, while cognitive processing leads to less ambiguity‐averse choices for future lotteries. Copyright © 2015 John Wiley & Sons, Ltd.
Dynamic metabolic flux analysis using a convex analysis approach: Application to hybridoma cell cultures in perfusion
Authors: Fernandes de Sousa Sofia , Bastin Georges , Jolicoeur Mario , Vande Wouwer Alain
Published: November 2015

In recent years, dynamic metabolic flux analysis (DMFA) has been developed in order to evaluate the dynamic evolution of the metabolic fluxes. Most of the proposed approaches are dedicated to exactly determined or overdetermined systems. When an underdetermined system is considered, the literature suggests the use of dynamic flux balance analysis (DFBA). However the main challenge of this approach is to determine an appropriate objective function, which remains valid over the whole culture. In this work, we propose an alternative dynamic metabolic flux analysis based on convex analysis, DMFCA, which allows the determination of bounded intervals for the fluxes using the available knowledge of the metabolic network and information provided by the time evolution of extracellular component concentrations. Smoothing splines and mass balance differential equations are used to estimate the time evolution of the uptake and excretion rates from this experimental data. The main advantage of the proposed procedure is that it does not require additional constraints or objective functions, and provides relatively narrow intervals for the intracellular metabolic fluxes. DMFCA is applied to experimental data from hybridoma HB58 cell perfusion cultures, in order to investigate the influence of the operating mode (batch and perfusion) on the metabolic flux distribution. Biotechnol. Bioeng. 2016;113: 1102–1112. © 2015 Wiley Periodicals, Inc.
High throughput determination of cleaning solutions to prevent the fouling of an anion exchange resin
Authors: Elich Thomas , Iskra Timothy , Daniels William , Morrison Christopher J.
Published: November 2015

Effective cleaning of chromatography resin is required to prevent fouling and maximize the number of processing cycles which can be achieved. Optimization of resin cleaning procedures, however, can lead to prohibitive material, labor, and time requirements, even when using milliliter scale chromatography columns. In this work, high throughput (HT) techniques were used to evaluate cleaning agents for a monoclonal antibody (mAb) polishing step utilizing Fractogel® EMD TMAE HiCap (M) anion exchange (AEX) resin. For this particular mAb feed stream, the AEX resin could not be fully restored with traditional NaCl and NaOH cleaning solutions, resulting in a loss of impurity capacity with resin cycling. Miniaturized microliter scale chromatography columns and an automated liquid handling system (LHS) were employed to evaluate various experimental cleaning conditions. Cleaning agents were monitored for their ability to maintain resin impurity capacity over multiple processing cycles by analyzing the flowthrough material for turbidity and high molecular weight (HMW) content. HT experiments indicated that a 167 mM acetic acid strip solution followed by a 0.5 M NaOH, 2 M NaCl sanitization provided approximately 90% cleaning improvement over solutions containing solely NaCl and/or NaOH. Results from the microliter scale HT experiments were confirmed in subsequent evaluations at the milliliter scale. These results identify cleaning agents which may restore resin performance for applications involving fouling species in ion exchange systems. In addition, this work demonstrates the use of miniaturized columns operated with an automated LHS for HT evaluation of chromatographic cleaning procedures, effectively decreasing material requirements while simultaneously increasing throughput. Biotechnol. Bioeng. 2016;113: 1251–1259. © 2015 Wiley Periodicals, Inc.
Host cell protein impurities in chromatographic polishing steps for monoclonal antibody purification
Authors: Levy Nicholas E. , Valente Kristin N. , Lee Kelvin H. , Lenhoff Abraham M.
Published: November 2015

Downstream purification of monoclonal antibodies (mAbs) is normally performed using a platform process that is empirically tuned to optimize impurity removal for each new product. A more fundamental understanding of impurities and the product itself would provide insights into the rational design of efficient downstream processes. This work examines the chromatographic properties of Chinese hamster ovary host cell protein (HCP) impurities in non‐affinity chromatographic resins commonly used in polishing steps for monoclonal antibody purification: ion‐exchange, hydrophobic interaction, and multimodal. Using proteomic analysis, the specific HCP impurities that elute close to mAb products are identified for these resins at typical downstream processing conditions. Additionally, the interactions of HCP impurities with mAb products are profiled to determine the total extent of product association and the specific HCP species that form associative complexes under conditions encountered in polishing columns. Product association and co‐elution were both identified as viable mechanisms of HCP retention for the non‐affinity resins tested here. A relatively large sub‐population of HCP impurities was found to co‐elute or associate with mAbs in each polishing column, but only a small population of HCPs—including lipoprotein lipase, chrondroitin sulfate proteoglycan 4, nidogen‐1, and SPARC—were identified as difficult to remove across an entire downstream mAb process. Biotechnol. Bioeng. 2016;113: 1260–1272. © 2015 Wiley Periodicals, Inc.
Rh(III)‐catalyzed ortho‐Alkylation of N‐Benzyltriflamides with Diazo Compounds
Authors: Han Sang Hoon , Mishra Neeraj Kumar , Kim In Su
Published: November 2015

The rhodium(III)‐catalyzed ortho‐CH functionalization of N‐benzyltriflamides with α‐diazo compounds is described. This transformation provides the facile construction of C2‐alkylated N‐benzyltriflamides in the absence of external oxidants under mild reaction conditions.
Adults’ Detection of Deception in Children: Effect of Coaching and Age for Children's True and Fabricated Reports of Injuries
Authors: Warren Kelly L. , Bakhtiar Aishah , Mulrooney Brent , Raynor Graham , Dodd Elyse , Peterson Carole
Published: November 2015

A total of 1,074 undergraduates judged the truthfulness of children's interviews (from verbatim transcripts) about experiencing injuries serious enough to require hospital emergency room treatment. Ninety‐six children (three age groups: 5–7, 8–10, and 11–14 years, 50% girls) were interviewed. At each age, 16 children told truthful accounts of actual injury experiences and 16 fabricated their reports, with half of each group coached by parents for the previous 4 days. Lies by 5‐ to 7‐year‐olds, whether coached or not, were detected at above‐chance levels. In contrast, 8‐ to 10‐year‐olds’ accounts that were coached, whether true or not, were more likely to be believed. For 11‐ to 14‐year‐olds, adults were less likely to accurately judge lies if they were coached. The believability of children aged 8 or above who were coached to lie is particularly disturbing in light of the finding that participants were more confident in the accuracy of their veracity decisions when judging coached reports. Copyright © 2015 John Wiley & Sons, Ltd.
Development of Fluorescent Protein Probes Specific for Parallel DNA and RNA G‐Quadruplexes
Authors: Dang Dung Thanh , Phan Anh Tuân
Published: November 2015

We have developed fluorescent protein probes specific for parallel G‐quadruplexes by attaching cyan fluorescent protein to the G‐quadruplex‐binding motif of the RNA helicase RHAU. Fluorescent probes containing RHAU peptide fragments of different lengths were constructed, and their binding to G‐quadruplexes was characterized. The selective recognition and discrimination of G‐quadruplex topologies by the fluorescent protein probes was easily detected by the naked eye or by conventional gel imaging.
Pigmented perianal macules
Authors: Rallis Efstathios , Tsibouris Panagiotis
Published: November 2015

Key Clinical Message

Primary mucosal melanoma occurs in under 2% of melanomas. Anorectal melanoma is a rare disorder, approximately accounting for 1% of all anorectal carcinomas. Primary anorectal melanoma presents predominantly in women, in the 4th–6th decade of life. Typical clinical manifestations include rectal bleeding and tenesmus. The prognosis remains poor.
Cell‐free DNA testing in a trisomy 21 pregnancy with confined placental mosaicism for a cell line with trisomy for both chromosomes 18 and 21
Authors: Crooks Kristy , Edwardsen Ginger , O'Connor Siobhan , Powell Cynthia , Vargo Diane , Vora Neeta , Kaiser‐Rogers Kathleen
Published: November 2015

Key Clinical Message

NIPT (noninvasive prenatal testing) detected trisomy for two chromosomes. One trisomy reflected the fetal karyotype, and the other resulted from CPM (confined placental mosaicism). This case illustrates that extensive cytogenetic analysis can be required to identify CPM, and that patients should be counseled regarding the possibility of discordant NIPT results.
A case of neurolymphomatosis caused by follicular lymphoma successfully treated with bendamustine
Authors: Umeda Masayuki , Kondo Tadakazu , Nishikori Momoko , Kitano Toshiyuki , Hishizawa Masakatsu , Kadowaki Norimitsu , Takaori‐Kondo Akifumi
Published: November 2015

Key Clinical Message

Currently, there is no standard treatment for neurolymphomatosis because of the scarcity of clinical studies. Here, we report the successful treatment of neurolymphomatosis caused by follicular lymphoma with bendamustine, which could be an effective treatment option for this condition.
Anhydrous Amorphous Calcium Oxalate Nanoparticles from Ionic Liquids: Stable Crystallization Intermediates in the Formation of Whewellite
Authors: Gehl Aaron , Dietzsch Michael , Mondeshki Mihail , Bach Sven , Häger Tobias , Panthöfer Martin , Barton Bastian , Kolb Ute , Tremel Wolfgang
Published: November 2015

The mechanisms by which amorphous intermediates transform into crystalline materials are not well understood. To test the viability and the limits of the classical crystallization, new model systems for crystallization are needed. With a view to elucidating the formation of an amorphous precursor and its subsequent crystallization, the crystallization of calcium oxalate, a biomineral widely occurring in plants, is investigated. Amorphous calcium oxalate (ACO) precipitated from an aqueous solution is described as a hydrated metastable phase, as often observed during low‐temperature inorganic synthesis and biomineralization. In the presence of water, ACO rapidly transforms into hydrated whewellite (monohydrate, CaC2O4⋅H2O, COM). The problem of fast crystallization kinetics is circumvented by synthesizing anhydrous ACO from a pure ionic liquid (IL‐ACO) for the first time. IL‐ACO is stable in the absence of water at ambient temperature. It is obtained as well‐defined, non‐agglomerated particles with diameters of 15–20 nm. When exposed to water, it crystallizes to give (hydrated) COM through a dissolution/recrystallization mechanism.
Effect of the Metal on Disulfide/Thiolate Interconversion: Manganese versus Cobalt
Authors: Gennari Marcello , Brazzolotto Deborah , Yu Shengying , Pécaut Jacques , Philouze Christian , Rouzières Mathieu , Clérac Rodolphe , Orio Maylis , Duboc Carole
Published: November 2015

It has recently been proposed that disulfide/thiolate interconversion supported by transition‐metal ions is involved in several relevant biological processes. In this context, the present contribution represents a unique investigation of the effect of the coordinated metal (M) on the Mn+disulfide/M(n+1)+thiolate switch properties. Like its isostructural CoII‐based parent compound, CoII2SS (Angew. Chem. Int. Ed.­ 2014, 53, 5318), the new dinuclear disulfide‐bridged MnII complex MnII2SS can undergo an MIIdisulfide/MIIIthiolate interconversion, which leads to the first disulfide/thiolate switch based on Mn. The coordination of iodide to the metal ion stabilizes the oxidized form, as the disulfide is reduced to the thiolate. The reverse process, which involves the reduction of MIII to MII with the concomitant oxidation of the thiolates, requires the release of iodide. The MnII2SS complex slowly reacts with Bu4NI in CH2Cl2 to afford the mononuclear MnIIIthiolate complex MnIIII. The process is much slower (ca. 16 h) and much less efficient (ca. 30 % yield) with respect to the instantaneous and quantitative conversion of CoII2SS into CoIIII under similar conditions. This distinctive behavior can be rationalized by considering the different electrochemical properties of the involved Co and Mn complexes and the DFT‐calculated driving force of the disulfide/thiolate conversion. For both Mn and Co systems, MIIdisulfide/MIIIthiolate interconversion is reversible. However, when the iodide is removed with Ag+, the MII2SS complexes are regenerated, albeit much slower for Mn than for Co systems.
A Combined NMR and Computational Approach to Determine the RGDechi‐hCit‐αvβ3 Integrin Recognition Mode in Isolated Cell Membranes
Authors: Farina Biancamaria , de Paola Ivan , Russo Luigi , Capasso Domenica , Liguoro Annamaria , Gatto Annarita Del , Saviano Michele , Pedone Paolo V. , Di Gaetano Sonia , Malgieri Gaetano , Zaccaro Laura , Fattorusso Roberto
Published: November 2015

The critical role of integrins in tumor progression and metastasis has stimulated intense efforts to identify pharmacological agents that can modulate integrin function. In recent years, αvβ3 and αvβ5 integrin antagonists were demonstrated to be effective in blocking tumor progression. RGDechi‐hCit, a chimeric peptide containing a cyclic RGD motif linked to an echistatin C‐terminal fragment, is able to recognize selectively αvβ3 integrin both in vitro and in vivo. High‐resolution molecular details of the selective αvβ3 recognition of the peptide are certainly required, nonetheless RGDechi‐hCit internalization limited the use of classical in cell NMR experiments. To overcome such limitations, we used WM266 isolated cellular membranes to accomplish a detailed NMR interaction study that, combined with a computational analysis, provides significant structural insights into αvβ3 molecular recognition by RGDechi‐hCit. Remarkably, on the basis of the identified molecular determinants, we design a RGDechi‐hCit mutant that is selective for αvβ5 integrin.
Molecular Engineering of Pyrido[3,4‐b]pyrazine‐Based Donor–Acceptor–π‐Acceptor Organic Sensitizers: Effect of Auxiliary Acceptor in Cobalt‐ and Iodine‐Based Electrolytes
Authors: Liu Bo , Giordano Fabrizio , Pei Kai , Decoppet Jean‐David , Zhu Wei‐Hong , Zakeeruddin Shaik M. , Grätzel Michael
Published: November 2015

Due to the ease of tuning its redox potential, the cobalt‐based redox couple has been extensively applied for highly efficient dye‐sensitized solar cells (DSSCs) with extraordinarily high photovoltages. However, a cobalt electrolyte needs particular structural changes in the organic dye components to obtain such high photovoltages. To achieve high device performance, specific requirements in the molecular tailoring of organic sensitizers still need to be met. Besides the need for large electron donors, studies of the auxiliary acceptor segment of donor–acceptor–π‐acceptor (D‐A‐π‐A) organic sensitizers are still rare in molecular optimization in the context of cobalt electrolytes. In this work, two novel organic D‐A‐π‐A‐type sensitizers (IQ13 and IQ17) have been developed and exploited in cobalt‐ and iodine‐based redox electrolyte DSSCs, specifically to provide insight into the effect of π‐bridge modification in different electrolytes. The investigation has been focused on the additional electron‐withdrawing acceptor capability with grafted long alkoxy chains. Optoelectronic transient measurements have indicated that IQ17 containing a pyrido[3,4‐b]pyrazine moiety bearing long alkoxyphenyl chains is more suitable for application in cobalt‐based DSSCs.
Rhodium‐Catalyzed Intramolecular C−H Bond Activation with Triazoles: Preparation of Stereodefined Pyrrolidines and Other Related Cyclic Compounds
Authors: Senoo Masato , Furukawa Ayana , Hata Takeshi , Urabe Hirokazu
Published: November 2015

On treatment of triazoles having an N‐sulfonyl‐protected benzylamine moiety with [Rh2(C7H15CO2)4], intramolecular C−H bond insertion takes place at the benzylic position to give cis‐N‐sulfonyl‐2‐aryl‐3‐[(sulfonylimino)methyl]pyrrolidines in good yields and with highly stereoselectivities. Analogously, the similar treatment of triazoles having an ether or even an alkyl moiety affords 2‐alkyl‐ or 2‐aryl‐3‐[(sulfonylimino)methyl]tetrahydrofurans or a 2‐alkyl‐3‐[(sulfonylimino)methyl]cyclopentane in good yields.
Aerobic Dimerization of Enediyne Compounds: Construction of Naphthalene Frameworks
Authors: Wang Dongxu , Ling Fei , Liu Xiang , Li Zexiang , Ma Cheng
Published: November 2015

The first bimolecular oxygenative annulation of enediyne compounds leading to naphthalene frameworks has been developed by using Pd(OAc)2 as the catalyst in the presence of NaI under O2 (1 atm). This reaction provided efficient access to a class of symmetric core‐annulated naphthalenes by the homoannulation of enediyne–imides. Intriguingly, the crossover annulation of enediyne–imides and other functionalized enediynes could also be achieved by the same catalytic system, resulting in the formation of several unsymmetrical naphthalene derivatives. Preliminary mechanistic investigation using 18O isotopic labelling and radical scavengers indicated that radical oxygen incorporation cascades might be involved in this conversion.
The Radical Anion of Cyclopentasilane‐Fused Hexasilabenzvalene
Authors: Tsurusaki Akihiro , Kyushin Soichiro
Published: November 2015

The radical anion of cyclopentasilane‐fused hexasilabenzvalene was synthesized by the reduction of the corresponding neutral compound. X‐ray crystallographic analysis showed a more trans‐bent structure of the disilene moiety than the neutral compound. Theoretical calculations showed that the highly trans‐bent structure is attributed to the hexasilabenzvalene structure. The EPR spectrum showed that an unpaired electron exists mainly at the disilene moiety. In the UV/Vis spectrum, a large bathochromic shift was observed compared with the neutral compound.
Sorption equilibrium and kinetics for cyclohexane, toluene, and water on Athabasca oil sands solids
Authors: Tan Xiaoli , Vagi Lisa , Liu Qi , Choi Phillip , Gray Murray R.
Published: November 2015

The sorption of solvents from the vapour phase to solid substrates is important in producing heavy oil and bitumen, particularly from the oil sands. We investigated the sorption and desorption equilibrium and kinetics of cyclohexane, toluene, and water on kaolinite, fine solids, and organic‐rich fine solids isolated from Athabasca oil sands over a wide range of solvent vapour concentrations using a gravimetric method. The isotherms for both adsorption and desorption of solvent vapour were determined, and the Brunauer‐Emmett‐Teller equation was used to fit the experimental data. The initial kinetic rate constants for the adsorption and desorption of solvent vapour were determined with the linear driving force model. The results were compared and discussed in terms of the type of solvent, the content of organic materials, and the surface area of the solid substrates. The results suggest that, in addition to the adsorption of solvent on mineral surfaces, the contribution from solvent partitioning in the organic materials and the porosity resulting from high amounts of organic materials are significant factors for solvent uptake and kinetic rate constants. In mixed solvent vapours, the competitive sorption of water and cyclohexane was observed in the solid substrates. However, the degree of competitiveness decreased with an increase in the content of organic materials in the substrates.
Structural Determinants of the Selectivity of 3‐Benzyluracil‐1‐acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10
Authors: Ruiz Francesc X. , Cousido‐Siah Alexandra , Porté Sergio , Domínguez Marta , Crespo Isidro , Rechlin Chris , Mitschler André , de Lera Ángel R. , Martín María Jesús , de la Fuente Jesús Ángel , Klebe Gerhard , Parés Xavier , Farrés Jaume , Podjarny Alberto
Published: November 2015

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.
Assessment of DNA double‐strand breaks induced by intravascular iodinated contrast media following in vitro irradiation and in vivo, during paediatric cardiac catheterization
Authors: Gould Richard , McFadden Sonyia L. , Horn Simon , Prise Kevin M. , Doyle Philip , Hughes Ciara M.
Published: November 2015

Paediatric cardiac catheterizations may result in the administration of substantial amounts of iodinated contrast media and ionizing radiation. The aim of this work was to investigate the effect of iodinated contrast media in combination with in vitro and in vivo X‐ray radiation on lymphocyte DNA. Six concentrations of iodine (15, 17.5, 30, 35, 45, and 52.5 mg of iodine per mL blood) represented volumes of iodinated contrast media used in the clinical setting. Blood obtained from healthy volunteers was mixed with iodinated contrast media and exposed to radiation doses commonly used in paediatric cardiac catheterizations (0 mGy, 70 mGy, 140 mGy, 250 mGy and 450 mGy). Control samples contained no iodine. For in vivo experimentation, pre and post blood samples were collected from children undergoing cardiac catheterization, receiving iodine concentrations of up to 51 mg of iodine per mL blood and radiation doses of up to 400 mGy. Fluorescence microscopy was performed to assess γH2AX‐foci induction, which corresponded to the number of DNA double‐strand breaks. The presence of iodine in vitro resulted in significant increases of DNA double‐strand breaks beyond that induced by radiation for ≥17.5 mg/mL iodine to blood. The in vivo effects of contrast media on children undergoing cardiac catheterization resulted in a 19% increase in DNA double‐strand breaks in children receiving an average concentration of 19 mg/mL iodine to blood. A larger investigation is required to provide further information of the potential benefit of lowering the amount of iodinated contrast media received during X‐ray radiation investigations. Copyright © 2015 John Wiley & Sons, Ltd.
A Cucurbit[7]uril Based Molecular Shuttle Encoded by Visible Room‐Temperature Phosphorescence
Authors: Gong Yifan , Chen Hui , Ma Xiang , Tian He
Published: November 2015

A visible room‐temperature phosphorescence (RTP) signal, generated by complexation of cururbit[7]uril (CB[7]) and bromo‐substituted isoquinoline in aqueous solution, is employed to address the shuttling of a pH‐controlling molecular shuttle fabricated by CB[7] and a phosphor 6‐bromoisoquinoline derivative IQC[5]. The CB[7] host shuttles along the axial guest under acidic conditions, accompanied by a weak RTP emission signal, while deprotonation of the guest IQC[5] makes the CB[7] wheel locate on the phosphor group, leading to intense RTP emission. The switching RTP emission of the molecular shuttle, via pH adjusting, can be visibly identified by the naked eye. This is the first CB‐based molecular shuttle with an RTP signal as the output address of its shuttling and conformation.
NET formation can occur independently of RIPK3 and MLKL signaling
Authors: Amini Poorya , Stojkov Darko , Wang Xiaoliang , Wicki Simone , Kaufmann Thomas , Wong Wendy Wei‐Lynn , Simon Hans‐Uwe , Yousefi Shida
Published: November 2015

The importance of neutrophil extracellular traps (NETs) in innate immunity is well established but the molecular mechanisms responsible for their formation are still a matter of scientific dispute. Here, we aim to characterize a possible role of the receptor‐interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain‐like (MLKL) signaling pathway, which are known to cause necroptosis, in NET formation. Using genetic and pharmacological approaches, we investigated whether this programmed form of necrosis is a prerequisite for NET formation. NETs have been defined as extracellular DNA scaffolds associated with the neutrophil granule protein elastase that are capable of killing bacteria. Neither Ripk3‐deficient mouse neutrophils nor human neutrophils in which MLKL had been pharmacologically inactivated, exhibited abnormalities in NET formation upon physiological activation or exposure to low concentrations of PMA. These data indicate that NET formation occurs independently of both RIPK3 and MLKL signaling.
The end of gating? An introduction to automated analysis of high dimensional cytometry data
Authors: Mair Florian , Hartmann Felix J. , Mrdjen Dunja , Tosevski Vinko , Krieg Carsten , Becher Burkhard
Published: November 2015

Ever since its invention half a century ago, flow cytometry has been a major tool for single‐cell analysis, fueling advances in our understanding of a variety of complex cellular systems, in particular the immune system. The last decade has witnessed significant technical improvements in available cytometry platforms, such that more than 20 parameters can be analyzed on a single‐cell level by fluorescence‐based flow cytometry. The advent of mass cytometry has pushed this limit up to, currently, 50 parameters. However, traditional analysis approaches for the resulting high‐dimensional datasets, such as gating on bivariate dot plots, have proven to be inefficient. Although a variety of novel computational analysis approaches to interpret these datasets are already available, they have not yet made it into the mainstream and remain largely unknown to many immunologists. Therefore, this review aims at providing a practical overview of novel analysis techniques for high‐dimensional cytometry data including SPADE, t‐SNE, Wanderlust, Citrus, and PhenoGraph, and how these applications can be used advantageously not only for the most complex datasets, but also for standard 14‐parameter cytometry datasets.
Efficient Cp*Ir Catalysts with Imidazoline Ligands for CO2 Hydrogenation
Authors: Xu Shaoan , Onishi Naoya , Tsurusaki Akihiro , Manaka Yuichi , Wang Wan‐Hui , Muckerman James T. , Fujita Etsuko , Himeda Yuichiro
Published: November 2015

We report newly developed iridium catalysts with electron‐donating imidazoline moieties as ligands for the hydrogenation of CO2 to formate in aqueous solution. Interestingly, these new complexes promote CO2 hydrogenation much more effectively than their imidazole analogues and exhibit a turnover frequency (TOF) of 1290 h–1 for the bisimidazoline complex compared to that of 20 h–1 for the bisimidazole complex at 1 MPa and 50 °C. In addition, the hydrogenation proceeds smoothly even under atmospheric pressure at room temperature. The TOF of 43 h–1 for the bisimidazoline complex is comparable to that of a dinuclear complex (70 h–1, highest TOF reported) [Nat. Chem. 2012, 4, 383], which incorporates proton‐responsive ligands with pendent‐OH groups in the second coordination sphere. The catalytic activity of the complex with an N‐methylated imidazoline moiety is much the same as that of the corresponding pyridylimidazoline analogue. This result and the UV/Vis titrations of the imidazoline complexes indicate that the high activity is not attributable to the deprotonation of NH on the imidazoline under the reaction conditions.
Self‐Assembly of Hexameric Macrocycles from PtII/Ferrocene Dimetallic Subunits – Synthesis, Characterization, Chemical Reactivity, and Oxidation Behavior
Authors: Giannetto Antonino , Puntoriero Fausto , Notti Anna , Parisi Melchiorre F. , Ielo Ileana , Nastasi Francesco , Bruno Giuseppe , Campagna Sebastiano , Lanza Santo
Published: November 2015

New compounds Ia–h of the form [(Me2SO)ClPt(HR2DTO κ‐S,S Pt)] (HR2DTO = secondary dithiooxamide, with R = methyl, ethyl, n‐propyl, n‐butyl, n‐decyl, isopropyl, (R)‐1‐phenylethyl, or (S)‐2‐hydroxypropyl; κ‐S,S Pt denotes the coordination of the DTO moiety to the Pt atom) have been prepared and used to synthesize platinum(II)/ferrocene dimetallic species IIa–h of formula [(dppf)Pt(HR2DTO κ‐S,S Pt)]Cl (dppf = 1,1′‐diphosphinoferrocene). Complexes IIa–e, bearing unbranched groups on the dithiooxamide moiety (i.e., R = methyl, ethyl, n‐propyl, n‐butyl, or n‐decyl groups), self‐assemble upon standing to form unprecedented hexameric macrocycles IIIa–e. Compounds IIa–e, IIIa–e, as well as IIf–h, have been characterized by a combination of 1H, 13C, 31P NMR spectroscopy and 2D‐ROESY and diffusion‐ordered NMR spectroscopy (DOSY) experiments; the latter experiments have been used to calculate the hydrodynamic radius of IIa–e and IIIa–e, assisted by the data provided by the X‐ray crystal structure of IIh. Compounds IIIa–e are characterized by the presence of six dppf bridging units occupying the inner rim of the macrocycles and exhibit interesting properties, for example, oxidation of IIIa–e occurs around +0.40 V versus saturated calomel electrode (SCE), whereas oxidation of the type II species occurs at potentials greater than +1.0 V. Oxidation of IIIa–e is explained through a delocalized orbital extending over the six dppf subunits. The reversibility of the self‐assembly process is finally demonstrated by alternate addition of acids and bases to the type III compounds.