bluuebunny/crossref_metadata_2025 huggingface dataset:
Abiotic Sequence‐Coded Oligomers as Efficient In Vivo Taggants for the Identification of Implanted Materials
Authors: Karamessini Denise , Simon‐Yarza Teresa , Poyer Salomé , Konishcheva Evgeniia , Charles Laurence , Letourneur Didier , Lutz Jean‐François
Published: June 2018

Sequence‐defined oligourethanes were tested as in vivo taggants for implant identification. The oligomers were prepared in an orthogonal solid‐phase iterative approach and thus contained a coded monomer sequence that can be unequivocally identified by tandem mass spectrometry (MS/MS). The oligomers were then included in small amounts (1 wt %) in square‐centimeter‐sized crosslinked poly(vinyl alcohol) (PVA) model films, which were intramuscularly and subcutaneously implanted in the abdomen of rats. After one week, one month, or three months of implantation, the PVA films were explanted. The rat tissues exposed to the implants did not exhibit any adverse reactions, which suggested that the taggants are not harmful and probably not leaching out from the films. Furthermore, the explanted films were immersed in methanol, as a solvent for oligourethanes, and the liquid extract was analyzed by mass spectrometry. In all cases, the oligourethane taggant was detected, and its sequence was identified by MS/MS.
Correlating the Surface Basicity of Metal Oxides with Photocatalytic Hydroxylation of Boronic Acids to Alcohols
Authors: Leow Wan Ru , Yu Jiancan , Li Bin , Hu Benhui , Li Wei , Chen Xiaodong
Published: June 2018

Photoredox catalysis provides opportunities in harnessing clean and green resources such as sunlight and O2, while the acid and base surface sites of metal oxides are critical for industrial catalysis such as oil cracking. The contribution of metal oxide surfaces towards photocatalytic aerobic reactions was elucidated, as demonstrated through the hydroxylation of boronic acids to alcohols. The strength and proximity of the surface base sites appeared to be two key factors in driving the reaction; basic and amphoteric oxides such as MgO, TiO2, ZnO, and Al2O3 enabled high alcohol yields, while acidic oxides such as SiO2 and B2O3 gave only low yields. The reaction is tunable to different irradiation sources by merely selecting photosensitizers of compatible excitation wavelengths. Such surface complexation mechanisms between reactants and earth abundant materials can be effectively utilized to achieve a wider range of photoredox reactions.
A Fluorooxosilicophosphate with an Unprecedented SiO2F4 Species
Authors: Han Guopeng , Lei Bing‐Hua , Yang Zhihua , Wang Ying , Pan Shilie
Published: June 2018

The large number and structural beauty of silicates are largely due to the variety of connection mode of SiO4 tetrahedra. SiO6 and SiF6 octahedra are also known and give rise for structural versatility of inorganic silicates. However, to date, the crystal structure of inorganic fluorooxosilicates with oxofluoride SiOxF4−x or SiOxF6−x species are unknown. Now, fluorine was successfully introduced into the silicophosphates, and the first fluorooxosilicophosphate K4Si3P2O7F12 with an unprecedented SiO2F4 species was synthesized. The existence of Si−F bonds was verified by comprehensively experimental and theoretical work. Using ab initio and bond valence calculations, the oxofluoride SiOxF6−x species is shown to be stable when oxygen atoms connect to other atoms with strong covalent interactions. This work will contribute to the structural diversity of silicate chemistry by the exploration of the new fluorooxosilicates.
Effects of Temperature and Heating Time on the Formation of Four Toxic α,β‐Unsaturated‐4‐Hydroxyaldehydes in Vegetable Oils
Authors: Liu Xiaoyu , Shoeman Don W. , Yuan Jieyao , Csallany A. Saari
Published: June 2018

The formation of four α,β‐unsaturated hydroxyaldehydes, 4‐hydroxy‐2‐trans‐hexenal (HHE), 4‐hydroxy‐2‐trans‐octenal (HOE), 4‐hydroxy‐2‐trans‐nonenal (HNE), and 4‐hydroxy‐2‐trans‐decenal (HDE), was detected in commercial corn, soybean, peanut, and canola oils heated for 1, 3, and 5 hours at 145, 165, and 185 °C. These four toxic aldehydes were investigated using high‐performance liquid chromatography (HPLC). These oils were selected based upon different degrees of unsaturations, especially their linoleic and linolenic acid concentrations. To select the appropriate conditions of temperatures and heating times, preliminary experiments were conducted using the thiobarbituric acid assay, which detects the formation of secondary‐oxidation products such as aldehydes and related carbonyl compounds. After various heat treatments, the formation of HHE, HOE, HNE, and HDE was detected as 2,4‐dinitrophenyl hydrazine derivatives using HPLC. In general, HHE, HOE, HNE, and HDE formation increased in all four oils with higher temperatures, longer heating times, and higher concentrations of linoleic and linolenic acids in the oils. The formation of HNE in the oils was mostly much higher than the other three 4‐hydroxyaldehyde isomers under the same conditions.
Brief Report: Interleukin‐17 Blockade With Secukinumab in Peripheral Spondyloarthritis Impacts Synovial Immunopathology Without Compromising Systemic Immune Responses
Authors: van Mens Leonieke J. J. , van de Sande Marleen G. H. , Menegatti Silvia , Chen Sijia , Blijdorp Iris C. J. , de Jong Henriette M. , Fluri Inka A. , Latuhihin Talia E. , van Kuijk Arno W. R. , Rogge Lars , Yeremenko Nataliya G. , Baeten Dominique L. P.
Published: June 2018

Objective

Secukinumab (anti–interleukin‐17A [anti–IL‐17A]) is an effective therapy for ankylosing spondylitis and psoriatic arthritis, the prototypical forms of spondyloarthritis (SpA). We undertook this study to determine whether secukinumab modulates the immunopathology of target lesions without blunting systemic immune responses, using peripheral SpA as a model.

Methods

Twenty patients with active peripheral SpA were included in a 12‐week open‐label trial with secukinumab (300 mg once weekly from baseline to week 4 and then every 4 weeks thereafter). Outcomes included clinical response, cytokine production by peripheral blood cells using TruCulture technology, and histologic and real‐time quantitative polymerase chain reaction analysis of synovial biopsy samples before and after treatment.

Results

All patients completed the 12‐week study without severe adverse events (AEs) or severe treatment‐related AEs. The efficacy end point, the number of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks, was achieved by 13 of the 20 patients, of whom 8 achieved an ACR50 response and 5 achieved an ACR70 response, with rapid and significant improvements in all clinical disease activity measures. Clinical improvement in joint counts was associated with a histologic decrease in synovial sublining macrophages (P = 0.028) and neutrophils (P = 0.004), both of which are sensitive synovial biomarkers of inflammatory response in peripheral SpA, as well as with decreased synovial expression of IL‐17A messenger RNA (mRNA) (P = 0.010) but not of tumor necrosis factor mRNA. Systemically, secukinumab treatment decreased the C‐reactive protein level and the erythrocyte sedimentation rate (both P < 0.01), and also decreased matrix metalloproteinase 3 production in the TruCulture system (P < 0.05). However, with the exception of IL‐17A itself, the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation with microbial antigens was not affected.

Conclusion

This mechanism‐of‐action study in peripheral SpA indicates that clinical improvement with secukinumab treatment is paralleled by immunomodulation of inflamed target tissues without compromising systemic immune responses.
Pharmacokinetics and Pharmacodynamics of Curcumin in regulating anti‐inflammatory and epigenetic gene expression
Authors: Boyanapalli Sarandeep S.S. , Huang Ying , Su Zhengyuan , Cheng David , Zhang Chengyue , Guo Yue , Rao Rohit , Androulakis Ioannis P. , Kong Ah‐Ng
Published: June 2018

Chronic inflammation is a key driver of cancer development. Nitrite levels, which are regulated by inducible nitric oxide synthase (iNOS), play a critical role in inflammation. While the anti‐oxidant and anti‐inflammatory effects of curcumin, a natural product present in the roots of Curcuma longa have been studied widely, the acute pharmacokinetics (PK) and pharmacodynamics (PD) of curcumin in suppressing pro‐inflammatory markers and epigenetic modulators remain unclear. This study evaluated the PK and PD of curcumin‐induced suppression of lipopolysaccharide (LPS)‐mediated inflammation in rat lymphocytes. LPS was administered intravenously either alone or with curcumin to female Sprague–Dawley rats. Plasma samples were analysed for curcumin concentration and mRNA expression was quantified in lymphocytes. The relative gene expression of several inflammatory and epigenetic modulators was analysed. To investigate the relationship between curcumin concentration and iNOS, TNF‐α, and IL‐6 gene expression, PK/PD modeling using Jusko's indirect response model (IDR) integrating transit compartments (TC) describing the delayed response was conducted. The concentration–time profile of curcumin exhibited a bi‐exponential decline, which was well described by a two‐compartmental pharmacokinetic model. Importantly the results demonstrate that LPS induced gene expression of pro‐inflammatory markers in lymphocytes, with peak expression at approximately 3 h and curcumin suppressed the gene expression in animals administered with LPS. These effects were well captured using the IDR model and an IDR model with the transit compartments. In summary, the PK/PD modeling approach could potentially provide a robust quantitative framework for evaluating the acute anti‐inflammatory and epigenetic effects of curcumin in future clinical trials.
Hunger and Satiety Signaling: Modeling Two Hypothalamomedullary Pathways for Energy Homeostasis
Authors: Nakamura Kazuhiro , Nakamura Yoshiko
Published: June 2018

The recent discovery of the medullary circuit driving “hunger responses” – reduced thermogenesis and promoted feeding – has greatly expanded our knowledge on the central neural networks for energy homeostasis. However, how hypothalamic hunger and satiety signals generated under fasted and fed conditions, respectively, control the medullary autonomic and somatic motor mechanisms remains unknown. Here, in reviewing this field, we propose two hypothalamomedullary neural pathways for hunger and satiety signaling. To trigger hunger signaling, neuropeptide Y activates a group of neurons in the paraventricular hypothalamic nucleus (PVH), which then stimulate an excitatory pathway to the medullary circuit to drive the hunger responses. In contrast, melanocortin‐mediated satiety signaling activates a distinct group of PVH neurons, which then stimulate a putatively inhibitory pathway to the medullary circuit to counteract the hunger signaling. The medullary circuit likely contains inhibitory and excitatory premotor neurons whose alternate phasic activation generates the coordinated masticatory motor rhythms to promote feeding.
Synapse Pruning: Mitochondrial ROS with Their Hands on the Shears
Authors: Cobley James N.
Published: June 2018

No overarching hypotheses tie the basic mechanisms of mitochondrial reactive oxygen species (ROS) production to activity dependent synapse pruning—a fundamental biological process in health and disease. Neuronal activity divergently regulates mitochondrial ROS: activity decreases whereas inactivity increases their production, respectively. Placing mitochondrial ROS as innate synaptic activity sentinels informs the novel hypothesis that: (1) at an inactive synapse, increased mitochondrial ROS production initiates intrinsic apoptosis dependent pruning; and (2) at an active synapse, decreased mitochondrial ROS production masks intrinsic apoptosis dependent pruning. Immature antioxidant defense may enable the developing brain to harness mitochondrial ROS to prune weak synapses. Beyond development, endogenous antioxidant defense constrains mitochondrial (ROS) to mask pruning. Unwanted age‐related synapse loss may arise when mitochondrial ROS aberrantly recapitulate developmental pruning. Placing mitochondrial ROS with their hands on the shears is beneficial in early but deleterious in later life.
Understanding Immune Tolerance of Cancer: Re‐Purposing Insights from Fetal Allografts and Microbes
Authors: Barnet Megan B. , Blinman Prunella , Cooper Wendy , Boyer Michael J. , Kao Steven , Goodnow Christopher C.
Published: June 2018

Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis. Broadening the efficacy and durability of checkpoint inhibitors focuses on reversing tolerance and stimulating immunogenicity in the cancer, host, and environment. Two examples of important physiological states of tolerance that may inform tolerance of cancer are microbial infection and placental reproduction. These states of tolerance result from bilateral shaping of host and non‐self, akin to immunoediting in cancer, and offer reliable models to study the immune tolerance paradigm.
Ultrastructural Imaging of Salmonella–Host Interactions Using Super‐resolution Correlative Light‐Electron Microscopy of Bioorthogonal Pathogens
Authors: van Elsland Daphne M. , Pujals Sílvia , Bakkum Thomas , Bos Erik , Oikonomeas‐Koppasis Nikolaos , Berlin Ilana , Neefjes Jacques , Meijer Annemarie H. , Koster Abraham J. , Albertazzi Lorenzo , van Kasteren Sander I.
Published: June 2018

The imaging of intracellular pathogens inside host cells is complicated by the low resolution and sensitivity of fluorescence microscopy and by the lack of ultrastructural information to visualize the pathogens. Herein, we present a new method to visualize these pathogens during infection that circumvents these problems: by using a metabolic hijacking approach to bioorthogonally label the intracellular pathogen Salmonella Typhimurium and by using these bioorthogonal groups to introduce fluorophores compatible with stochastic optical reconstruction microscopy (STORM) and placing this in a correlative light electron microscopy (CLEM) workflow, the pathogen can be imaged within its host cell context Typhimurium with a resolution of 20 nm. This STORM‐CLEM approach thus presents a new approach to understand these pathogens during infection.
Blistering eruptions with tissue eosinophilia in a child with IgA vasculitis
Authors: Watanabe Toru , Tsukano Shinya
Published: June 2018

Key Clinical Message

We present a child with bullous IgA vasculitis. Because skin biopsy showed epidermal vesicles with neutrophil infiltration and leukocytoclastic vasculitis in all layers of the dermis, with IgA deposits and tissue eosinophilia, extensive dermal infiltration of neutrophils may have led to both blistering eruptions and tissue eosinophilia in our patient.
General Airbrush‐Spraying/Electrospinning Strategy for Ultrahigh Areal‐Capacity LiFePO4‐Based Cathodes
Authors: Huang Hui , Ju Xiaokang , Deng Pan , Li Shengyang , Qu Baihua , Wang Taihong
Published: June 2018

A versatile electrode fabrication strategy based on electrospinning combined with airbrush–spraying (ECAS) is developed for the preparation of composite paper electrodes. The LiFePO4 paper electrodes (ca. 13 mg cm−2) display good cycling stability with a capacity decay of only 15 % over 300 cycles at 1 C for lithium‐ion batteries. It is also demonstrated that the ECAS technique can obtain ultrahigh areal capacities of 12.3 mAh cm−2 using electrodes with an extra‐high areal loading of LiFePO4 paper (>75 mg cm−2). A full cell is constructed with ECAS LiFePO4 paper as the cathode and ECAS Li4Ti5O12 paper as the anode.
(Co, Ni)Sn0.5 Nanoparticles Supported on Hierarchical Carbon Nitride‐Graphene‐Based Electrocatalysts for the Oxygen Reduction Reaction
Authors: Negro Enrico , Nale Angeloclaudio , Vezzù Keti , Pagot Gioele , Herve Bang Yannick , Polizzi Stefano , Colombo Massimo , Prato Mirko , Crociani Laura , Bonaccorso Francesco , Di Noto Vito
Published: June 2018

The synthesis of new “Pt‐free” electrocatalysts (ECs) for the oxygen reduction reaction (ORR) is reported. The ECs are characterized by a hierarchical “core‐shell” morphology; the “core” is made of graphene, that is covered by a cratered, microporous carbon nitride (CN) “shell”. The latter supports nanoparticles of M1 and Sn metals (M1=Co; Ni) in “coordination nests”. The latter are holes in the CN matrix, whose walls consist of N‐ and C‐ligands. Two groups of ECs are studied: (i) “pristine” ECs; and (ii) “activated” ECs, that are obtained from the “pristine” ECs by means of a suitable activation process (A) aimed at improving the performance in the ORR. Here, the interplay existent between (i) the chemical composition, morphology, structure and A; and (ii) the ORR performance and mechanism is investigated. The resulting insights improve the fundamental understanding of this family of ECs and open the door to the devising of new preparations of “Pt‐free” ECs for the ORR, which: (i) are stabilized by a CN matrix and; (ii) exhibit an improved performance.
Enhanced oil recovery assignment using a new strategy for clustering oil reservoirs: Application of fuzzy logics
Authors: Khojastehmehr Mohsen , Naderifar Abbas , Aminshahidy Babak
Published: June 2018

Enhanced Oil Recovery (EOR) aims at producing more oil from low productive reservoirs. EOR is a costly process due to the time and expenses required to allocate a suitable EOR method to an oil reservoir. For this purpose, this work presents a systematic approach to incorporate past experiences into a compact system to assign the EOR process to oil reservoirs. Because the number of clusters within the reservoirs data is not known, the method proposes a novel validity index to calculate optimal number of clusters copt. Then, the data are clustered to coptcompact clusters according to their similarities, dissimilarities, rock, and fluid properties using fuzzy clustering algorithm. To decide on the EOR process to be applied to a new reservoir, this reservoir is assigned to one of the copt clusters based on similarity, and then the EOR method is chosen based on that cluster. This approach is used for available reservoirs data from different oil fields, and its effectiveness and superiority over previous methods are confirmed.
Life's Biological Chemistry: A Destiny or Destination Starting from Prebiotic Chemistry?
Authors: Krishnamurthy Ramanarayanan
Published: June 2018

Research into understanding the origins—and evolution—of life has long been dominated by the concept of taking clues from extant biology and extrapolating its molecules and pathways backwards in time. This approach has also guided the search for solutions to the problem of how contemporary biomolecules would have arisen directly from prebiotic chemistry on early earth. However, the continuing difficulties in finding universally convincing solutions in connecting prebiotic chemistry to biological chemistry should give us pause, and prompt us to rethink this concept of treating extant life's chemical processes as the sole end goal and, therefore, focusing only, and implicitly, on the respective extant chemical building blocks. Rather, it may be worthwhile “to set aside the goal” and begin with what would have been plausible prebiotic reaction mixtures (which may have no obvious or direct connection to life's chemical building blocks and processes) and allow their chemistries and interactions, under different geochemical constraints, to guide and illuminate as to what processes and systems can emerge. Such a conceptual approach gives rise to the prospect that chemistry of life‐as‐we‐know‐it is not the only result (not a “destiny”), but one that has emerged among many potential possibilities (a “destination”). This postulate, in turn, could impact the way we think about chemical signatures and criteria used in the search for alternative and extraterrestrial “life”. As a bonus, we may discover the chemistries and pathways naturally that led to the emergence of life as we know it.
Hierarchical MoS2/Carbon Composite Microspheres as Advanced Anodes for Lithium/Sodium‐Ion Batteries
Authors: Tang Wangjia , Wang Xiuli , Zhong Yu , Xie Dong , Zhang Xuqing , Xia Xinhui , Wu Jiangbo , Gu Changdong , Tu Jiangping
Published: June 2018

It is crucial to design advanced electrodes with large Li/Na‐ion storage capacities for the development of next‐generation battery systems. Herein, hierarchical MoS2/C composite microspheres were constructed by facile template‐free self‐assembly sulfurization plus post‐carbonization. Cross‐linked MoS2 nanosheets and outer carbon layer are organically combined together to form composite microspheres with diameters of 400–500 nm. Due to enhanced electrical conductivity and good structural stability, the MoS2/C composite microspheres exhibit substantially improved Li/Na‐ion storage performance. Compared to unmodified MoS2, MoS2/C composite microspheres deliver higher Li/Na‐ion storage capacity (Li+: 1017 mA h g−1 at 100 mA g−1 and Na+: 531 mA h g−1 at 100 mA g−1), as well as better rate capability (Li+: 434 mA h g−1 at 1 Ag−1 and Na+: 102 mA h g−1 at 1 Ag−1) and capacity retention (Li+: 902 mA h g−1 after 200 cycles and Na+: 342 mA h g−1 over 100 cycles). The superior Li/Na‐ion storage performance is mainly attributed to the unique porous microsphere architecture with increased electrode/electrolyte interfaces and more diffusion paths for Li/Na ion insertion. Additionally, the carbon coating can not only improve the electronic conductivity, but also suppress the shuttle effect of polysulfides.
High prevalence of occult heart disease in normotensive patients with rheumatoid arthritis
Authors: Cioffi Giovanni , Ognibeni Federica , Dalbeni Andrea , Giollo Alessandro , Orsolini Giovanni , Gatti Davide , Rossini Maurizio , Viapiana Ombretta
Published: June 2018

Background

Due to chronic inflammatory status, rheumatoid arthritis (RA) patients are exposed to changes in left ventricular (LV) geometry and function. We assessed prevalence, factors associated with, and prognostic role of concentric LV geometry and systolic dysfunction (LVSD) detected by echocardiography in a large cohort of patients with RA and normal blood pressure.

Hypothesis

Changes in LV geometry and function are widely detectable in normotensive patients with RA analyzed in primary prevention.

Methods

We prospectively analyzed 194 normotensive RA patients without overt cardiac disease recruited between March 2014 and May 2016, compared with 194 non‐RA matched controls. Relative wall thickness >0.43 defined concentric LV geometry. LVSD was defined as impaired global longitudinal strain (GLS). The prespecified study endpoints were all‐cause hospitalization and hospitalization for cardiovascular cause.

Results

The 194 normotensive subjects (mean age, 54 years; 63% female; RA duration 13 years) had a prevalence of LV concentric geometry 5‐fold higher and LVSD 5‐fold higher than non‐RA matched controls. Body mass index, LVSD, and diastolic dysfunction were associated with concentric LV geometry, while worsening renal function and older age were associated with LVSD. LVSD was independently related to the study endpoints (HR 2.37 [1.24‐4.53], p = 0.009, for all‐causes hospitalization and HR 6.60 [1.47‐29.72], p = 0.01 for cardiovascular hospitalization).

Conclusions

Despite normotensive status, a consistent proportion of RA patients analyzed in primary prevention have cardiac abnormalities detectable by echocardiography. LVSD is a strong prognosticator of adverse outcome at midterm period in these patients.
Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure–Degradation Relationships
Authors: Burslem George M. , Ottis Philipp , Jaime‐Figueroa Saul , Morgan Alicia , Cromm Philipp M. , Toure Momar , Crews Craig M.
Published: June 2018

The immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small‐molecule‐induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one‐pot synthesis without purification that provides rapid access to a multitude of IMiD analogues. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure–activity relationship with only a few compounds showing sub‐micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti‐proliferative activity as well as Aiolos degradation could be identified for two IMiD analogues. This study provides useful insight into the structure–degradation relationships for molecules of this type as well as a rapid and robust method for IMiD synthesis.
Non‐Coding RNA Analysis Using the Rfam Database
Authors: Kalvari Ioanna , Nawrocki Eric P. , Argasinska Joanna , Quinones‐Olvera Natalia , Finn Robert D. , Bateman Alex , Petrov Anton I.
Published: June 2018

Rfam is a database of non‐coding RNA families in which each family is represented by a multiple sequence alignment, a consensus secondary structure, and a covariance model. Using a combination of manual and literature‐based curation and a custom software pipeline, Rfam converts descriptions of RNA families found in the scientific literature into computational models that can be used to annotate RNAs belonging to those families in any DNA or RNA sequence. Valuable research outputs that are often locked up in figures and supplementary information files are encapsulated in Rfam entries and made accessible through the Rfam Web site. The data produced by Rfam have a broad application, from genome annotation to providing training sets for algorithm development. This article gives an overview of how to search and navigate the Rfam Web site, and how to annotate sequences with RNA families. The Rfam database is freely available at http://rfam.org. © 2018 by John Wiley & Sons, Inc.
Amenamevir: Studies of Potential CYP2C8‐ and CYP2B6‐Mediated Pharmacokinetic Interactions With Montelukast and Bupropion in Healthy Volunteers
Authors: Dennison Jeremy , Puri Adeep , Warrington Steven , Endo Takamasa , Adeloye Temitope , Johnston Atholl
Published: June 2018

Amenamevir (formerly ASP2151) induces cytochrome P450 (CYP)2B6 and CYP3A4 and inhibits CYP2C8.  We conducted 2 studies, 1 using montelukast as a probe to assess CYP2C8 and the other bupropion to assess CYP2B6.  The montelukast study examined the effect of amenamevir on the pharmacokinetics of montelukast in 24 healthy men: each subject received montelukast 10 mg alone, followed by montelukast 10 mg with amenamevir 400 mg, or vice versa after a washout period.  In the bupropion study, 24 subjects received a single dose of 150 mg bupropion on days 1, 15, 22, and 29, and repeated once‐daily doses of 400 mg amenamevir on days 6‐15.  Amenamevir increased peak concentration and area under the concentration‐time curve of montelukast by about 22% (ratio 121.7%, 90%CI [114.8, 129.1]; 121% [116.2, 128.4], respectively) with a similar increase in hydroxymontelukast (ratio 121.4%, 90%CI [106.4, 138.5]; 125.6 % [111.3, 141.7]).  Amenamevir reduced peak concentration and area under the concentration‐time curve of bupropion by 16% (84.29%, 90%CI [78.00, 91.10]; 84.07%, 90%CI [78.85, 89.63]), with recovery after 1 week; the pharmacokinetics of the primary metabolite hydroxybupropion was unaffected.  Thus, amenamevir increased plasma concentrations of montelukast and decreased those of bupropion, but it did not do so enough to require dose adjustment of coadministered substrates of either CYP2C8 or CYP2B6.
Pharmacokinetics of Perampanel in Healthy Korean, White, and Japanese Adult Subjects
Authors: Tabuchi Hiroko , Shiba Sari , Yasuda Sanae , Ohnishi Akihiro , Shin Jae‐Gook
Published: June 2018

Perampanel is a highly selective, orally active, noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor antagonist that has been approved in many countries as a treatment for partial‐onset seizures and primary generalized tonic‐clonic seizures. The pharmacokinetics (PK) of perampanel following multiple doses in healthy Korean, white, and Japanese male subjects were assessed in 3 studies. Noncompartmental PK parameters were derived from plasma concentration‐time data. At steady state of perampanel 2‐, 4‐, and 6‐mg oral multiple administration, perampanel was rapidly absorbed, as plasma perampanel concentration reached maximum concentration after 0.55–1 hour (median) after dosing in all 3 ethnic groups. The elimination was slow, with terminal elimination phase half‐life values ranging from 63.9–129 hours (mean) for doses of 2–6 mg; there was no specific tendency suggesting a dose‐related effect, and perampanel PK were linear in Korean subjects. There were no clinically relevant ethnic differences in PK following multiple doses of perampanel 2 and 4 mg between Korean, white, or Japanese subjects. Perampanel was well tolerated by all 3 ethnic groups. This outcome indicates that with respect to PK, the dosing regimens established in white and Japanese patients are applicable to Korean patients.
Kinetics, Assembling, and Conformation Control of L‐Cysteine Adsorption on Pt Investigated by in situ FTIR Spectroscopy and QCM‐D
Authors: Dourado André H. B. , Silva Rubens A. , Torresi Roberto M. , Sumodjo Paulo T. A. , Arenz Matthias , Cordoba de Torresi Susana I.
Published: June 2018

A quartz crystal microbalance method with dissipation (QCM−D) and attenuated total reflection Fourier‐transform infrared (ATR‐FTIRS) spectroscopy were used to study the adsorption of L‐cysteine (L–Cys) on Pt. Through QCM−D, it was possible to verify that the viscoelastic properties of the adsorbed species play an important role in the adsorption, rendering Sauerbrey's equation inapplicable. The modelling of QCM−D data exposed two different processes for the adsorption reaction. The first one had an activation time and is fast, whereas the second is slow. These processes were also resolved by ATR‐FTIRS and identified to be water and anion adsorption preceded by L–Cys adsorption. Both techniques reveal that the degree of surface coverage is pH dependent. Spectroscopic data indicate that the conformation of L–Cys(ads) changes with pH and that the structures do not fully agree with those proposed in literature for other metallic surfaces. The assembling of the adsorbed monolayer appeared to be very fast, and it was not possible to determine or quantify this kinetics. The conformation is also controlled by applied potential, and the anion adsorption and interfacial water depends on the conformation of the adsorbed molecules.
An Effective Recombinant Protein Expression and Purification System in Saccharomyces cerevisiae
Authors: Xie Ying , Han Xiao , Miao Yansong
Published: June 2018

The expression and purification of recombinant proteins using bacterial vectors is a mature and preferred system to obtain folded and stable proteins. However, functional post‐translational protein modifications, such as glycosylation or phosphorylation, can only be achieved using eukaryotic expression systems. In addition, insolubility is another challenge when using proteins expressed in Escherichia coli, such as certain intrinsically disordered proteins, which are more prone to aggregation than folded proteins. Eukaryotic protein expression systems, including human cells, baculovirus/insect cells, and yeast, have become indispensable for the production of functional eukaryotic proteins. This article describes a detailed protocol for performing cytosolic protein expression, protein purification, and protein characterization using the budding yeast Saccharomyces cerevisiae. The introduced protein expression and purification system in yeast are advantageous due to the low cost, high yield, high protein solubility, and minimal expertise required. © 2018 by John Wiley & Sons, Inc.
Iron‐Catalyzed Graphitic Carbon Materials from Biomass Resources as Anodes for Lithium‐Ion Batteries
Authors: Gomez‐Martin Aurora , Martinez‐Fernandez Julian , Ruttert Mirco , Heckmann Andreas , Winter Martin , Placke Tobias , Ramirez‐Rico Joaquin
Published: June 2018

Graphitized carbon materials from biomass resources were successfully synthesized with an iron catalyst, and their electrochemical performance as anode materials for lithium‐ion batteries (LIBs) was investigated. Peak pyrolysis temperatures between 850 and 2000 °C were covered to study the effect of crystallinity and microstructural parameters on the anodic behavior, with a focus on the first‐cycle Coulombic efficiency, reversible specific capacity, and rate performance. In terms of capacity, results at the highest temperatures are comparable to those of commercially used synthetic graphite derived from a petroleum coke precursor at higher temperatures, and up to twice as much as that of uncatalyzed biomass‐derived carbons. The opportunity to graphitize low‐cost biomass resources at moderate temperatures through this one‐step environmentally friendly process, and the positive effects on the specific capacity, make it interesting to develop more sustainable graphite‐based anodes for LIBs.
X‐ray micrographic imaging system based on COTS CMOS sensors
Authors: Alcalde Bessia Fabricio , Pérez Martin , Lipovetzky José , Piunno Natalia Alejandra , Mateos Horacio , Sidelnik Iván , Blostein Juan Jerónimo , Sofo Haro Miguel , Gómez Berisso Mariano
Published: June 2018

This paper presents the use of commercial off the shelf CMOS image sensors for the acquisition of X‐ray images with high spatial resolution. The X‐ray images, with application in biology, electronic components inspection, and paleontology research, are obtained with 8‐keV photons from a Cu tube. The quantum efficiency of the detector is estimated using attenuation lengths of photons in the sensor and compared to traditional scintillator conversion layers. The spatial resolution observed with the sensor is limited by the charge redistribution produced after photon interaction with Si.
The Template‐Free Synthesis of CuO@CeO2 Nanospheres: Facile Strategy, Structure Optimization, and Enhanced Catalytic Activity toward CO Oxidation
Authors: Su Yunfei , Yuan Shanshan , Ning Dandan , Zhang Qingwen , Han Weiliang , Wang Yi
Published: June 2018

The template‐free construction of hollow multiporous materials with hierarchically multiporous walls, unique morphologies, and functionalities remains a great challenge in materials science. Here, we describe a facile template‐free approach to synthesize hollow multiporous‐walled CeO2 (HMW‐CeO2) nanospheres. The HMW‐CeO2 nanosphere possesses a hierarchically multiporous wall, with pore sizes ranging from micropores to mesopores, centered at 0.43, 4.2, and 14.3 nm. The CuO loaded HMW‐CeO2 support (HMW‐CuO@CeO2) is evaluated for its catalytic activity in a CO oxidation reaction. The HMW‐CuO@CeO2 support exhibits a higher catalytic activity than all of the other CeO2 catalysts. The results show a low T100 of about 60 °C (the temperature at which 100 % CO conversion has been achieved) and high stability, with negligible decrease in the CO conversion during 12 h of reaction. Overall, it provides a simple, low‐cost and mass‐productive method for the preparation of highly active catalysts for CO oxidation.
An Approach to One‐Pot Regioselective Synthesis of Indenones through Palladium‐Catalyzed Annulation in Water
Authors: Ramesh Karu , Satyanarayana Gedu
Published: June 2018

A one‐pot synthesis of indenones is presented. The process involves palladium‐catalyzed annulation of ortho‐halobenzaldehydes with internal alkynes. Notably, it proceeded successfully in water as the sole, and green, solvent. Significantly, unlike in earlier reports, this protocol showed excellent regioselectivity with unsymmetrical alkylarylacetylenes. Further, the strategy was extended to a one‐pot synthesis of a neolignan natural product.
One‐Pot Synthesis of 3‐Aryl‐5‐amino‐1,2,4‐thiadiazoles from Imidates and Thioureas by I2‐Mediated Oxidative Construction of the N–S Bond
Authors: Chai Ling , Lai Zhenzhen , Xia Qiangqiang , Yuan Jiangpei , Bian Qilong , Yu Mingjian , Zhang Wenkai , Xu Yuanqing , Xu Hao
Published: June 2018

A simple and practical method for the one‐pot synthesis of 3‐aryl‐5‐amino‐1,2,4‐thiadiazoles from imidates and thioureas has been developed. The protocol proceeds through sequential base‐mediated nucleophilic addition‐elimination reactions and an I2‐mediated oxidative coupling for the N–S bond formation. The approach employes readily available and nontoxic substrates and a simple workup to provide 3‐aryl‐5‐amino‐1,2,4‐thiadiazoles that have a free or substituted amino group.
Multicomponent Synthesis of Structurally Diverse Imidazoles Featuring Azirines, Amines and Aldehydes
Authors: Rossa Thaís A. , Fantinel Mariane , Bortoluzzi Adailton J. , Sá Marcus M.
Published: June 2018

A novel and efficient method for the synthesis of structurally diverse imidazoles through a multicomponent reaction involving an azirine, an amine, and an aldehyde is described. The method is simple and environmentally benign, producing multifunctionalized imidazoles in moderate‐to‐good yields and in a regioselective manner, which was demonstrated by NMR experiments and X‐ray analysis. A mechanism is proposed in which the amine participates not only as a reactant, but also as a nucleophilic reaction promoter.
Forensic ancestry analysis in two Chinese minority populations using massively parallel sequencing of 165 ancestry‐informative SNPs
Authors: He Guanglin , Wang Zheng , Wang Mengge , Luo Tao , Liu Jing , Zhou You , Gao Bo , Hou Yiping
Published: June 2018

Ancestry inference based on SNPs with marked allele frequency differences in diverse populations (called ancestry‐informative SNP (AISNP)) is rapidly developed with the technology advancements of massively parallel sequencing. Despite the decade of exploration and broad public interest in the peopling of East‐Asians, the genetic landscape of Chinese Silk Road populations based on the AISNPs is still little known. In this work, 206 unrelated individuals from Chinese Uyghur and Hui populations were firstly genotyped by 165 AISNPs (The Precision ID Ancestry Panel) using the Ion Torrent Personal Genome Machine system. The ethnic origin of two investigated populations and population structures and genetic relationships were subsequently investigated. The 165 AISNPs panel not only can differentiate Uyghur and Hui populations but also has potential applications in individual identification. Comprehensive population comparisons and admixture estimates demonstrated a predominantly higher European‐related ancestry (36.30%) in Uyghurs than Huis (3.66%). Overall, the Precision ID Ancestry Panel can provide good resolution at the intercontinental level, but has limitations on the genetic homogeneous populations, such as the Hui and Han. Additional population‐specific AISNPs remain necessary to get better‐scale resolution within geographically proximate populations in East Asia.
A lumped parameter model for time‐domain inertial soil‐structure interaction analysis of structures on pile foundations
Authors: Carbonari Sandro , Morici Michele , Dezi Francesca , Leoni Graziano
Published: June 2018

The paper presents a lumped parameter model for the approximation of the frequency‐dependent dynamic stiffness of pile group foundations. The model can be implemented in commercial software to perform linear or nonlinear dynamic analyses of structures founded on piles taking into account the frequency‐dependent coupled roto‐translational, vertical, and torsional behaviour of the soil‐foundation system. Closed‐form formulas for estimating parameters of the model are proposed with reference to pile groups embedded in homogeneous soil deposits. These are calibrated with a nonlinear least square procedure, based on data provided by an extensive non‐dimensional parametric analysis performed with a model previously developed by the authors. Pile groups with square layout and different number of piles embedded in soft and stiff soils are considered. Formulas are overall well capable to reproduce parameters of the proposed lumped system that can be straightforwardly incorporated into inertial structural analyses to account for the dynamic behaviour of the soil‐foundation system. Some applications on typical bridge piers are finally presented to show examples of practical use of the proposed model. Results demonstrate the capability of the proposed lumped system as well as the formulas efficiency in approximating impedances of pile groups and the relevant effect on the response of the superstructure.
Moving beyond run‐off calibration—Multivariable optimization of a surface–subsurface–atmosphere model
Authors: Stisen Simon , Koch Julian , Sonnenborg Torben O. , Refsgaard Jens Christian , Bircher Simone , Ringgaard Rasmus , Jensen Karsten H.
Published: June 2018

Spatially distributed hydrological models are traditionally calibrated and evaluated against few spatially aggregated observations such as river discharge. This model evaluation approach does not enable an assessment of the model predictive capabilities of other hydrological states and fluxes nor does it give any insight into the model ability to mimic the spatial patterns within a catchment. The current study explores a multivariable optimization of a complex coupled surface–subsurface–atmosphere model at the catchment scale in an attempt to move beyond simple run‐off calibration. The model is evaluated against five independent observational data sets of discharge (Q), hydraulic head (h), actual evapotranspiration (ET), soil moisture (SM), and remotely sensed land surface temperature (LST). It is shown that a balanced optimization can be achieved where errors on objective functions for all five observation data sets can be reduced simultaneously. Additionally, the multivariable calibration proved more robust, compared with calibration against Q and h only, during the validation period, even for Q and h. The current parameterization and calibration framework was mainly suitable for reducing model biases and allowed only limited improvements in the spatio‐temporal patterns of the model simulations. This points towards development of better parametrization schemes that will allow simulated spatial patterns to adjust during calibration. Additionally, analysis showed that systematic spatial patterns in the errors of the LST maps could be a very valuable diagnostic tool for assessing deficiencies in the model structure, spatial parameterization, or process description.
Divergence over conformity: Change in immigration attitudes after the electoral success of an anti‐immigration populist party in the Finnish 2015 parliamentary elections
Authors: Lönnqvist Jan‐Erik , Mannerström Rasmus , Leikas Sointu
Published: June 2018

The populist, anti‐immigration‐oriented Finns Party was considered the winner of the Finnish 2015 parliamentary elections. In a representative sample of young adults (N = 606), a longitudinal pre‐ post‐election design revealed that attitudes towards immigration became more favourable among those disappointed by the outcome and those who did not vote for the Finns Party. Among the latter, both supporting the green‐red rival parties and disliking the Finns Party independently predicted increased support for migration. Other attitudes did not change. The results highlight the importance of social processes and identity concerns, particularly self‐categorization, as drivers of attitude change. While previous work has focused on conformity dynamics, our results suggest that diverging from an unwanted identity may be associated with attitude change.
Critical issues in genotoxicity assessment of TiO2 nanoparticles by human peripheral blood mononuclear cells
Authors: Andreoli Cristina , Leter Giorgio , De Berardis Barbara , Degan Paolo , De Angelis Isabella , Pacchierotti Francesca , Crebelli Riccardo , Barone Flavia , Zijno Andrea
Published: June 2018

In the last years, a number of in vitro studies have been performed to assess the genotoxic activity of titanium dioxide (TiO2). To resolve the contradictory results, in this study, we investigated the genotoxic activity of commercial TiO2 nanoparticles (NPs) and microparticles of different forms (anatase, rutile and mix of both). We evaluated micronucleus formation in stimulated lymphocytes, as well as DNA strand breaks and 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine in peripheral blood mononuclear cells (PBMCs), a mixed population of lymphocytes and monocytes. Different responses to TiO2 exposure were obtained depending on the assay. Both TiO2 NPs and microparticles and all the crystalline forms elicited a significant increase in 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine and DNA strand breaks in the whole PBMC population, without a concurrent increase of micronuclei in proliferating lymphocytes. The distribution of DNA damage in PBMCs, detected by the comet assay, that measures DNA damage at level of single cells, indicated the presence of a more susceptible cell subpopulation. The measurement of side scatter signals by flow cytometry highlighted the preferential physical interaction of TiO2 particles with monocytes that also displayed higher reactive oxygen species generation, providing a mechanistic explanation for the different responses observed in genotoxicity assays with PBMCs and lymphocytes. This study confirmed the suitability of human PBMCs as multi‐cell model to investigate NP‐induced DNA damage, but suggested some caution in the use of stimulated lymphocytes for the assessment of NP clastogenicity.
Long noncoding RNA FAM83H‐AS1 exerts an oncogenic role in glioma through epigenetically silencing CDKN1A (p21)
Authors: Bi Yong‐Yan , Shen Gang , Quan Yong , Jiang Wei , Xu Fulin
Published: June 2018

Gliomas are the commonest and most aggressive primary malignant tumor in the central nervous system. Long noncoding RNAs (lncRNAs) have been identified to act as crucial regulators in multiple biological processes, including tumorigenesis. FAM83H antisense RNA1 (FAM83H‐AS1) has been uncovered to be dysregulated in several cancers. However, the biological role of FAM83H‐AS1 in glioma still needs to be investigated. Currently, our findings indicated that FAM83H‐AS1 was upregulated in glioma tissues and cell lines and high level of FAM83H‐AS1 was associated with poor prognosis of glioma. Loss‐of‐function assays demonstrated that silenced FAM83H‐AS1 obviously suppressed cell proliferation via regulating the cell‐cycle distribution and cell apoptosis rate, and mechanistic experiments revealed that FAM83H‐AS1 could epidemically silence CDKN1A expression through recruiting EZH2 to the promoter of CDKN1A, thereby influencing the cell cycle and proliferation. Collectively, our findings suggested that FAM83H‐AS1 participated in the progression of glioma and might act as a potential therapeutic target and prognosis biomarker for human glioma.