bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced flux pinning in YBCO multilayer films with BCO nanodots and segmented BZO nanorods
Authors: Malmivirta Mika , Rijckaert Hannes , Paasonen Ville , Huhtinen Hannu , Hynninen Teemu , Jha Rajveer , Awana Veerpal Singh , Van Driessche Isabel , Paturi Petriina
Published: October 2017

The flux pinning properties of the high temperature superconductor YBa2Cu3O7−δ
(YBCO) have been conventionally improved by creating both columnar and dot-like pinning centres into the YBCO matrix. To study the effects of differently doped multilayer structures on pinning, several samples consisting of a multiple number of individually BaZrO3 (BZO) and BaCeO3 (BCO) doped YBCO layers were fabricated. In the YBCO matrix, BZO forms columnar and BCO dot-like defects. The multilayer structure improves pinning capability throughout the whole angular range, giving rise to a high critical current density, Jc. However, the BZO doped monolayer reference still has the most isotropic Jc. Even though BZO forms nanorods, in this work the samples with multiple thin layers do not exhibit a c axis peak in the angular dependence of Jc. The angular dependencies and the approximately correct magnitude of Jc were also verified using a molecular dynamics simulation.
Modes of carbon fixation in an arsenic and CO2-rich shallow hydrothermal ecosystem
Authors: Callac Nolwenn , Posth Nicole R. , Rattray Jayne E. , Yamoah Kweku K. Y. , Wiech Alan , Ivarsson Magnus , Hemmingsson Christoffer , Kilias Stephanos P. , Argyraki Ariadne , Broman Curt , Skogby Henrik , Smittenberg Rienk H. , Fru Ernest Chi
Published: October 2017

The seafloor sediments of Spathi Bay, Milos Island, Greece, are part of the largest arsenic-CO2-rich shallow submarine hydrothermal ecosystem on Earth. Here, white and brown deposits cap chemically distinct sediments with varying hydrothermal influence. All sediments contain abundant genes for autotrophic carbon fixation used in the Calvin-Benson-Bassham (CBB) and reverse tricaboxylic acid (rTCA) cycles. Both forms of RuBisCO, together with ATP citrate lyase genes in the rTCA cycle, increase with distance from the active hydrothermal centres and decrease with sediment depth. Clustering of RuBisCO Form II with a highly prevalent Zetaproteobacteria 16S rRNA gene density infers that iron-oxidizing bacteria contribute significantly to the sediment CBB cycle gene content. Three clusters form from different microbial guilds, each one encompassing one gene involved in CO2 fixation, aside from sulfate reduction. Our study suggests that the microbially mediated CBB cycle drives carbon fixation in the Spathi Bay sediments that are characterized by diffuse hydrothermal activity, high CO2, As emissions and chemically reduced fluids. This study highlights the breadth of conditions influencing the biogeochemistry in shallow CO2-rich hydrothermal systems and the importance of coupling highly specific process indicators to elucidate the complexity of carbon cycling in these ecosystems.
miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome
Authors: Wohlfarth Carolin , Schmitteckert Stefanie , Härtle Janina D. , Houghton Lesley A. , Dweep Harsh , Fortea Marina , Assadi Ghazaleh , Braun Alexander , Mederer Tanja , Pöhner Sarina , Becker Philip P. , Fischer Christine , Granzow Martin , Mönnikes Hubert , Mayer Emeran A. , Sayuk Gregory , Boeckxstaens Guy , Wouters Mira M. , Simrén Magnus , Lindberg Greger , Ohlsson Bodil , Schmidt Peter Thelin , Dlugosz Aldona , Agreus Lars , Andreasson Anna , D’Amato Mauro , Burwinkel Barbara , Bermejo Justo Lorenzo , Röth Ralph , Lasitschka Felix , Vicario Maria , Metzger Marco , Santos Javier , Rappold Gudrun A. , Martinez Cristina , Niesler Beate
Published: October 2017

Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3′UTR binding sites. The novel isoform HTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.
The non-invasive exfoliated transcriptome (exfoliome) reflects the tissue-level transcriptome in a mouse model of NSAID enteropathy
Authors: Whitfield-Cargile Canaan M. , Cohen Noah D. , He Kejun , Ivanov Ivan , Goldsby Jennifer S. , Chamoun-Emanuelli Ana , Weeks Brad R. , Davidson Laurie A. , Chapkin Robert S.
Published: October 2017

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used classes of medications in the world, yet they induce an enteropathy that is associated with high morbidity and mortality. A major limitation to better understanding the pathophysiology and diagnosis of this enteropathy is the difficulty of obtaining information about the primary site of injury, namely the distal small intestine. We investigated the utility of using mRNA from exfoliated cells in stool as a means to surveil the distal small intestine in a murine model of NSAID enteropathy. Specifically, we performed RNA-Seq on exfoliated cells found in feces and compared these data to RNA-Seq from both the small intestinal mucosa and colonic mucosa of healthy control mice or those exhibiting NSAID-induced enteropathy. Global gene expression analysis, data intersection, pathway analysis, and computational approaches including linear discriminant analysis (LDA) and sparse canonical correlation analysis (CCA) were used to assess the inter-relatedness of tissue (invasive) and stool (noninvasive) datasets. These analyses revealed that the exfoliated cell transcriptome closely mirrored the transcriptome of the small intestinal mucosa. Thus, the exfoliome may serve as a non-invasive means of detecting and monitoring NSAID enteropathy (and possibly other gastrointestinal mucosal inflammatory diseases).
Design and Computational Modeling of a Modular, Compliant Robotic Assembly for Human Lumbar Unit and Spinal Cord Assistance
Authors: Agarwal Gunjan , Robertson Matthew A. , Sonar Harshal , Paik Jamie
Published: October 2017

Wearable soft robotic systems are enabling safer human-robot interaction and are proving to be instrumental for biomedical rehabilitation. In this manuscript, we propose a novel, modular, wearable robotic device for human (lumbar) spine assistance that is developed using vacuum driven, soft pneumatic actuators (V-SPA). The actuators can handle large, repetitive loads efficiently under compression. Computational models to capture the complex non-linear mechanical behavior of individual actuator modules and the integrated assistive device are developed using the finite element method (FEM). The models presented can predict system behavior at large values of mechanical deformations and allow for rapid design iterations. It is shown that a single actuator module can be used to obtain a variety of different motion and force profiles and yield multiple degrees of freedom (DOF) depending on the module loading conditions, resulting in high system versatility and adaptability, and efficient replication of the targeted motion range for the human spinal cord. The efficacy of the finite element model is first validated for a single module using experimental results that include free displacement and blocked-forces. These results are then extended to encompass an extensive investigation of bio-mechanical performance requirements from the module assembly for the human spine-assistive device proposed.
Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient
Authors: Saxena Abhishek , Stevens Jo , Cetin Hakan , Koneczny Inga , Webster Richard , Lazaridis Konstantinos , Tzartos Socrates , Vrolix Kathleen , Nogales-Gadea Gisela , Machiels Barbie , Molenaar Peter C. , Damoiseaux Jan , De Baets Marc H. , Simon-Keller Katja , Marx Alexander , Vincent Angela , Losen Mario , Martinez-Martinez Pilar
Published: October 2017

We report here the sequence and functional characterization of a recombinantly expressed autoantibody (mAb 131) previously isolated from a myasthenia gravis patient by immortalization of thymic B cells using Epstein-Barr virus and TLR9 activation. The antibody is characterized by a high degree of somatic mutations as well as a 6 amino acid insertion within the VHCDR2. The recombinant mAb 131 is specific for the γ-subunit of the fetal AChR to which it bound with sub-nanomolar apparent affinity, and detected the presence of fetal AChR on a number of rhabdomyosarcoma cell lines. Mab 131 blocked one of the two α-bungarotoxin binding sites on the fetal AChR, and partially blocked the binding of an antibody (mAb 637) to the α-subunit of the AChR, suggesting that both antibodies bind at or near one ACh binding site at the α/γ subunit interface. However, mAb 131 did not reduce fetal AChR ion channel currents in electrophysiological experiments. These results indicate that mAb 131, although generated from an MG patient, is unlikely to be pathogenic and may make it a potentially useful reagent for studies of myasthenia gravis, rhabdomyosarcoma and arthrogryposis multiplex congenita which can be caused by fetal-specific AChR-blocking autoantibodies.
Indian Ocean corals reveal crucial role of World War II bias for twentieth century warming estimates
Authors: Pfeiffer M. , Zinke J. , Dullo W.-C. , Garbe-Schönberg D. , Latif M. , Weber M. E.
Published: October 2017

The western Indian Ocean has been warming faster than any other tropical ocean during the 20th century, and is the largest contributor to the global mean sea surface temperature (SST) rise. However, the temporal pattern of Indian Ocean warming is poorly constrained and depends on the historical SST product. As all SST products are derived from the International Comprehensive Ocean-Atmosphere dataset (ICOADS), it is challenging to evaluate which product is superior. Here, we present a new, independent SST reconstruction from a set of Porites coral geochemical records from the western Indian Ocean. Our coral reconstruction shows that the World War II bias in the historical sea surface temperature record is the main reason for the differences between the SST products, and affects western Indian Ocean and global mean temperature trends. The 20th century Indian Ocean warming pattern portrayed by the corals is consistent with the SST product from the Hadley Centre (HadSST3), and suggests that the latter should be used in climate studies that include Indian Ocean SSTs. Our data shows that multi-core coral temperature reconstructions help to evaluate the SST products. Proxy records can provide estimates of 20th century SST that are truly independent from the ICOADS data base.
Chromatin interaction networks revealed unique connectivity patterns of broad H3K4me3 domains and super enhancers in 3D chromatin
Authors: Thibodeau Asa , Márquez Eladio J. , Shin Dong-Guk , Vera-Licona Paola , Ucar Duygu
Published: October 2017

Broad domain promoters and super enhancers are regulatory elements that govern cell-specific functions and harbor disease-associated sequence variants. These elements are characterized by distinct epigenomic profiles, such as expanded deposition of histone marks H3K27ac for super enhancers and H3K4me3 for broad domains, however little is known about how they interact with each other and the rest of the genome in three-dimensional chromatin space. Using network theory methods, we studied chromatin interactions between broad domains and super enhancers in three ENCODE cell lines (K562, MCF7, GM12878) obtained via ChIA-PET, Hi-C, and Hi-CHIP assays. In these networks, broad domains and super enhancers interact more frequently with each other compared to their typical counterparts. Network measures and graphlets revealed distinct connectivity patterns associated with these regulatory elements that are robust across cell types and alternative assays. Machine learning models showed that these connectivity patterns could effectively discriminate broad domains from typical promoters and super enhancers from typical enhancers. Finally, targets of broad domains in these networks were enriched in disease-causing SNPs of cognate cell types. Taken together these results suggest a robust and unique organization of the chromatin around broad domains and super enhancers: loci critical for pathologies and cell-specific functions.
Enzalutamide inhibits testosterone-induced growth of human prostate cancer xenografts in zebrafish and can induce bradycardia
Authors: Melong Nicole , Steele Shelby , MacDonald Morgan , Holly Alice , Collins Colin C. , Zoubeidi Amina , Berman Jason N. , Dellaire Graham
Published: October 2017

The zebrafish has become a popular human tumour xenograft model, particularly for solid tumours including prostate cancer (PCa). To date PCa xenotransplantation studies in zebrafish have not been performed in the presence of testosterone, even when employing androgen-dependent cell models, such as the LNCaP cell line. Thus, with the goal of more faithfully modelling the hormonal milieu in which PCa develops in humans, we sought to determine the effects of exogenous testosterone on the growth of LNCaP, or androgen-independent C4-2 cells xenografted into zebrafish embryos. Testosterone significantly increased engrafted LNCaP proliferation compared to control xenografts, which could be inhibited by co-administration of the anti-androgen receptor drug, enzalutamide. By contrast, C4-2 cell growth was not affected by either testosterone or enzalutamide. Enzalutamide also induced bradycardia and death in zebrafish embryos in a dose-dependent manner and strongly synergized with the potassium-channel blocking agent, terfenadine, known to induce long QT syndrome and cardiac arrhythmia. Together, these data not only indicate that testosterone administration should be considered in all PCa xenograft studies in zebrafish but also highlights the unique opportunity of this preclinical platform to simultaneously evaluate efficacy and toxicity of novel therapies and/or protective agents towards developing safer and more effective PCa treatments.
Gravel bars are sites of increased CO2 outgassing in stream corridors
Authors: Boodoo Kyle S. , Trauth Nico , Schmidt Christian , Schelker Jakob , Battin Tom J.
Published: October 2017

Streams are significant sources of CO2to the atmosphere. Estimates of CO2evasion fluxes (fCO2) from streams typically relate to the free flowing water but exclude geomorphological structures within the stream corridor. We found that gravel bars (GBs) are important sources of CO2to the atmosphere, with on average more than twice as highfCO2as those from the streamwater, affectingfCO2at the level of entire headwater networks. Vertical temperature gradients resulting from the interplay between advective heat transfer and mixing with groundwater within GBs explained the observed variation infCO2from the GBs reasonably well. We propose that increased temperatures and their gradients within GBs exposed to solar radiation stimulate heterotrophic metabolism therein and facilitate the venting of CO2from external sources (e.g. downwelling streamwater, groundwater) within GBs. Our study shows that GBfCO2increasedfCO2from stream corridors by [median, (95% confidence interval)] 16.69%, (15.85–18.49%); 30.44%, (30.40–34.68%) and 2.92%, (2.90–3.0%), for 3rd, 4thand 5thorder streams, respectively. These findings shed new light on regional estimates offCO2from streams, and are relevant given that streamwater thermal regimes change owing to global warming and human alteration of stream corridors.
Surface reactivity of amphibole asbestos: a comparison between crocidolite and tremolite
Authors: Andreozzi Giovanni B. , Pacella Alessandro , Corazzari Ingrid , Tomatis Maura , Turci Francesco
Published: October 2017

Among asbestos minerals, fibrous riebeckite (crocidolite) and tremolite share the amphibole structure but largely differ in terms of their iron content and oxidation state. In asbestos toxicology, iron-generated free radicals are largely held as one of the causes of asbestos malignant effect. With the aim of clarifying i) the relationship between Fe occurrence and asbestos surface reactivity, and ii) how free-radical generation is modulated by surface modifications of the minerals, UICC crocidolite and fibrous tremolite from Maryland were leached from 1 day to 1 month in an oxidative medium buffered at pH 7.4 to induce redox alterations and surface rearrangements that may occur in body fluids. Structural and chemical modifications and free radical generation were monitored by HR-TEM/EDS and spin trapping/EPR spectroscopy, respectively. Free radical yield resulted to be dependent on few specific Fe2+ and Fe3+ surface sites rather than total Fe content. The evolution of reactivity with time highlighted that low-coordinated Fe ions primarily contribute to the overall reactivity of the fibre. Current findings contribute to explain the causes of the severe asbestos-induced oxidative stress at molecular level also for iron-poor amphiboles, and demonstrate that asbestos have a sustained surface radical activity even when highly altered by oxidative leaching.
Entropy production selects nonequilibrium states in multistable systems
Authors: Endres Robert G.
Published: October 2017

Far-from-equilibrium thermodynamics underpins the emergence of life, but how has been a long-outstanding puzzle. Best candidate theories based on the maximum entropy production principle could not be unequivocally proven, in part due to complicated physics, unintuitive stochastic thermodynamics, and the existence of alternative theories such as the minimum entropy production principle. Here, we use a simple, analytically solvable, one-dimensional bistable chemical system to demonstrate the validity of the maximum entropy production principle. To generalize to multistable stochastic system, we use the stochastic least-action principle to derive the entropy production and its role in the stability of nonequilibrium steady states. This shows that in a multistable system, all else being equal, the steady state with the highest entropy production is favored, with a number of implications for the evolution of biological, physical, and geological systems.
Language and music phrase boundary processing in Autism Spectrum Disorder: An ERP study
Authors: DePriest John , Glushko Anastasia , Steinhauer Karsten , Koelsch Stefan
Published: October 2017

Autism spectrum disorder (ASD) is frequently associated with communicative impairment, regardless of intelligence level or mental age. Impairment of prosodic processing in particular is a common feature of ASD. Despite extensive overlap in neural resources involved in prosody and music processing, music perception seems to be spared in this population. The present study is the first to investigate prosodic phrasing in ASD in both language and music, combining event-related brain potential (ERP) and behavioral methods. We tested phrase boundary processing in language and music in neuro-typical adults and high-functioning individuals with ASD. We targeted an ERP response associated with phrase boundary processing in both language and music – i.e., the Closure Positive Shift (CPS). While a language-CPS was observed in the neuro-typical group, for ASD participants a smaller response failed to reach statistical significance. In music, we found a boundary-onset music-CPS for both groups during pauses between musical phrases. Our results support the view of preserved processing of musical cues in ASD individuals, with a corresponding prosodic impairment. This suggests that, despite the existence of a domain-general processing mechanism (the CPS), key differences in the integration of features of language and music may lead to the prosodic impairment in ASD.
Transition state-based ST6Gal I inhibitors: Mimicking the phosphodiester linkage with a triazole or carbamate through an enthalpy-entropy compensation
Authors: Montgomery Andrew P. , Skropeta Danielle , Yu Haibo
Published: October 2017

Human β-galactoside α-2,6-sialyltransferase I (ST6Gal I) catalyses the synthesis of sialylated glycoconjugates. Overexpression of ST6Gal I is observed in many cancers, where it promotes metastasis through altered cell surface sialylation. A wide range of sialyltransferase inhibitors have been developed, with analogues structurally similar to the transition state exhibiting the highest inhibitory activity. To improve synthetic accessibility and pharmacokinetics of previously reported inhibitors, the replacement of the charged phosphodiester linker with a potential neutral isostere such as a carbamate or a 1,2,3-triazole has been investigated. Extensive molecular dynamics simulations have demonstrated that compounds with the alternate linkers could maintain key interactions with the human ST6Gal I active site, demonstrating the potential of a carbamate or a 1,2,3-triazole as a phosphodiester isostere. Free energy perturbation calculations provided energetic evidence suggesting that the carbamate and 1,2,3-triazole were slightly more favourable than the phosphodiester. Further exploration with free energy component, quasi-harmonic and cluster analysis suggested that there is an enthalpy-entropy compensation accounting for the replacement of the flexible charged phosphodiester with a neutral and rigid isostere. Overall, these simulations provide a strong rationale for the use of a carbamate or 1,2,3-triazole as a phosphodiester isostere in the development of novel inhibitors of human ST6Gal I.
Heparin at physiological concentration can enhance PEG-free in vitro infection with human hepatitis B virus
Authors: Choijilsuren Gansukh , Jhou Ren-Shiang , Chou Shu-Fan , Chang Ching-Jen , Yang Hwai-I , Chen Yang-Yuan , Chuang Wan-Long , Yu Ming-Lung , Shih Chiaho
Published: October 2017

Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field. Surprisingly, we found that heparin at physiological concentration can enhance HBV infection in a PreS1-peptide sensitive, NTCP-dependent manner in both HepaRG and HepG2-NTCP-AS cells. O-sulfation of heparin is more important for the infection enhancement than N-sulfation. This system based on the HepG2-NTCP-AS cells can support in vitro infection with HBV genotypes B and C, as well as using serum samples from HBeAg positive and negative chronic carriers. In summary, our study provides a PEG-free infection system closely resembling human natural infection. In addition, it points to a future research direction for heparin and heparin-binding host factor(s) in the blood, which are potentially involved in viral entry. To our knowledge, this is the first soluble and circulatory host factor which can enhance HBV in vitro infection.
Graph theory reveals amygdala modules consistent with its anatomical subdivisions
Authors: Caparelli Elisabeth C. , Ross Thomas J. , Gu Hong , Liang Xia , Stein Elliot A. , Yang Yihong
Published: October 2017

Similarities on the cellular and neurochemical composition of the amygdaloid subnuclei suggests their clustering into subunits that exhibit unique functional organization. The topological principle of community structure has been used to identify functional subnetworks in neuroimaging data that reflect the brain effective organization. Here we used modularity to investigate the organization of the amygdala using resting state functional magnetic resonance imaging (rsfMRI) data. Our goal was to determine whether such topological organization would reliably reflect the known neurobiology of individual amygdaloid nuclei, allowing for human imaging studies to accurately reflect the underlying neurobiology. Modularity analysis identified amygdaloid elements consistent with the main anatomical subdivisions of the amygdala that embody distinct functional and structural properties. Additionally, functional connectivity pathways of these subunits and their correlation with task-induced amygdala activation revealed distinct functional profiles consistent with the neurobiology of the amygdala nuclei. These modularity findings corroborate the structure–function relationship between amygdala anatomical substructures, supporting the use of network analysis techniques to generate biologically meaningful partitions of brain structures.
Determination on the Coefficient of Thermal Expansion in High-Power InGaN-based Light-emitting Diodes by Optical Coherence Tomography
Authors: Lee Ya-Ju , Chou Chun-Yang , Huang Chun-Ying , Yao Yung-Chi , Haung Yi-Kai , Tsai Meng-Tsan
Published: October 2017

The coefficient of thermal expansion (CTE) is a physical quantity that indicates the thermal expansion value of a material upon heating. For advanced thermal management, the accurate and immediate determination of the CTE of packaging materials is gaining importance because the demand for high-power lighting-emitting diodes (LEDs) is currently increasing. In this study, we used optical coherence tomography (OCT) to measure the CTE of an InGaN-based (λ = 450 nm) high-power LED encapsulated in polystyrene resin. The distances between individual interfaces of the OCT images were observed and recorded to derive the instantaneous CTE of the packaged LED under different injected currents. The LED junction temperature at different injected currents was established with the forward voltage method. Accordingly, the measured instantaneous CTE of polystyrene resin varied from 5.86 × 10−5 °C−1 to 14.10 × 10−5 °C−1 in the junction temperature range 25–225 °C and exhibited a uniform distribution in an OCT scanning area of 200 × 200 μm. Most importantly, this work validates the hypothesis that OCT can provide an alternative way to directly and nondestructively determine the spatially resolved CTE of the packaged LED device, which offers significant advantages over traditional CTE measurement techniques.
Anti-obesity effect of a traditional Chinese dietary habit—blending lard with vegetable oil while cooking
Authors: Wang Ji , Yan Sisi , Xiao Haisi , Zhou Huijuan , Liu Shuiping , Zeng Yu , Liu Biying , Li Rongfang , Yuan Zhihang , Wu Jing , Yi Jine , Razack Yarou Bao Sero , Wen Lixin
Published: October 2017

Obesity, which is associated with dietary habits, has become a global social problem and causes many metabolic diseases. In China, both percentages of adult obesity and overweight are far lower compared to western countries. It was designed to increase the two levels of daily intake in human, namely 3.8% and 6.5%, which are recommendatory intake (25 g/d) and Chinese citizens’ practical intake (41.4 g/d), respectively. The mice were respectively fed with feeds added with soybean oil, lard or the oil blended by both for 12 weeks. In the mice fed with diet containing 3.8% of the three oils or 6.5% blended oil, their body weight, body fat rate, cross-sectional area of adipocytes, adipogenesis and lipogenesis in adipose were decreased, whereas hydrolysis of triglyserides in adipose was increased. This study demonstrated that the oil mixture containing lard and soybean oil had a remarkable anti-obesity effect. It suggests that the traditional Chinese dietary habits using oils blended with lard and soybean oil, might be one of the factors of lower percentages of overweight and obesity in China, and that the increasing of dietary oil intake and the changing of its component resulted in the increasing of obesity rate in China over the past decades.
Projective simulation with generalization
Authors: Melnikov Alexey A. , Makmal Adi , Dunjko Vedran , Briegel Hans J.
Published: October 2017

The ability to generalize is an important feature of any intelligent agent. Not only because it may allow the agent to cope with large amounts of data, but also because in some environments, an agent with no generalization capabilities cannot learn. In this work we outline several criteria for generalization, and present a dynamic and autonomous machinery that enables projective simulation agents to meaningfully generalize. Projective simulation, a novel, physical approach to artificial intelligence, was recently shown to perform well in standard reinforcement learning problems, with applications in advanced robotics as well as quantum experiments. Both the basic projective simulation model and the presented generalization machinery are based on very simple principles. This allows us to provide a full analytical analysis of the agent’s performance and to illustrate the benefit the agent gains by generalizing. Specifically, we show that already in basic (but extreme) environments, learning without generalization may be impossible, and demonstrate how the presented generalization machinery enables the projective simulation agent to learn.
Novel Benzylidene Thiazolidinedione Derivatives as Partial PPARγ Agonists and their Antidiabetic Effects on Type 2 Diabetes
Authors: Yasmin Sabina , Capone Fabio , Laghezza Antonio , Piaz Fabrizio Dal , Loiodice Fulvio , Vijayan Viswanathan , Devadasan Velmurugan , Mondal Susanta K. , Atlı Özlem , Baysal Merve , Pattnaik Ashok K. , Jayaprakash Venkatesan , Lavecchia Antonio
Published: October 2017

Peroxisome proliferator-activated receptor γ (PPARγ) has received significant attention as a key regulator of glucose and lipid homeostasis. In this study, we synthesized and tested a library of novel 5-benzylidene-thiazolidin-2,4-dione (BTZD) derivatives bearing a substituent on nitrogen of TZD nucleus (compounds 1a-1k, 2i-10i, 3a, 6a, and 8a-10a). Three compounds (1a, 1i, and 3a) exhibited selectivity towards PPARγ and were found to be weak to moderate partial agonists. Surface Plasmon Resonance (SPR) results demonstrated binding affinity of 1a, 1i and 3a towards PPARγ. Furthermore, docking experiments revealed that BTZDs interact with PPARγ through a distinct binding mode, forming primarily hydrophobic contacts with the ligand-binding pocket (LBD) without direct H-bonding interactions to key residues in H12 that are characteristic of full agonists. In addition, 1a, 1i and 3a significantly improved hyperglycemia and hyperlipidaemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats at a dose of 36 mg/kg/day administered orally for 15 days. Histopathological investigations revealed that microscopic architecture of pancreatic and hepatic cells improved in BTZDs-treated diabetic rats. These findings suggested that 1a, 1i and 3a are very promising pharmacological agents by selectively targeting PPARγ for further development in the clinical treatment of type 2 diabetes mellitus.
High throughput discovery of influenza virus neutralizing antibodies from phage-displayed synthetic antibody libraries
Authors: Chen Ing-Chien , Chiu Yi-Kai , Yu Chung-Ming , Lee Cheng-Chung , Tung Chao-Ping , Tsou Yueh-Liang , Huang Yi-Jen , Lin Chia-Lung , Chen Hong-Sen , Wang Andrew H.-J. , Yang An-Suei
Published: October 2017

Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to human society. Passive immunotherapy with recombinant neutralizing antibodies can potentially mitigate the threats of IAV infection. With a high throughput neutralizing antibody discovery platform, we produced artificial anti-hemagglutinin (HA) IAV-neutralizing IgGs from phage-displayed synthetic scFv libraries without necessitating prior memory of antibody-antigen interactions or relying on affinity maturation essential for in vivo immune systems to generate highly specific neutralizing antibodies. At least two thirds of the epitope groups of the artificial anti-HA antibodies resemble those of natural protective anti-HA antibodies, providing alternatives to neutralizing antibodies from natural antibody repertoires. With continuing advancement in designing and constructing synthetic scFv libraries, this technological platform is useful in mitigating not only the threats of IAV pandemics but also those from other newly emerging viral infections.
85% internal quantum efficiency of 280-nm AlGaN multiple quantum wells by defect engineering
Authors: Wang Tzu-Yu , Tasi Chi-Tsung , Lin Chia-Feng , Wuu Dong-Sing
Published: October 2017

In this study, high internal-quantum-efficiency (IQE) AlGaN multiple quantum wells (MQWs) were successfully demonstrated on low-defect-density AlN templates with nano-patterned sapphire substrates. These templates consisted of AlN structures with 0∼30 periods superlattices (SLs) by alternating high (100) and low (25) V/III ratios under a low growth temperature (1130 °C). Compared to conventional high crystal-quality AlN epilayers achieved at temperatures ≥1300 °C, lower thermal budget can reduce the production cost and wafer warpage. Via optimization of the SL period, the AlN crystallinity was systematically improved. Strong dependence of SL period number on the X-ray full-width-at-half-maximum (FWHM) of the AlN epilayer was observed. The AlN template with 20-period SLs exhibited the lowest FWHM values for (0002) and (10ī2), namely 331 and 652 arcsec, respectively, as well as an ultra-low etching pit density of 1 × 105 cm−2. The relative IQE of 280 nm AlGaN MQWs exhibited a dramatically increase from 22.8% to 85% when the inserted SL increased from 0 to 20 periods. It has hardly ever been reported for the AlGaN MQW sample. The results indicate that the engineered AlN templates have high potential applications in deep ultraviolet light emitters.
Design of Reduction Process of SnO2 by CH4 for Efficient Sn Recovery
Authors: Ha Hyunwoo , Yoo Mi , An Hyesung , Shin Kihyun , Han Taeyang , Sohn Youhan , Kim Sangyeol , Lee Sang-Ro , Han Jun Hyun , Kim Hyun You
Published: October 2017

We design a novel method for the CH4 reduction of SnO2 for the efficient recovery of Sn from SnO2 through a study combining theory and experiment. The atomic-level process of CH4-SnO2 interaction and temperature-dependent reduction behavior of SnO2 were studied with a combination of a multi-scale computational method of thermodynamic simulations and density functional theory (DFT) calculations. We found that CH4 was a highly efficient and a versatile reducing agent, as the total reducing power of CH4 originates from the carbon and hydrogen of CH4, which sequentially reduce SnO2. Moreover, as a result of the CH4 reduction of SnO2, a mixture of CO and H2 was produced as a gas-phase product (syngas). The relative molar ratio of the produced gas-phase product was controllable by the reduction temperature and the amount of supplied CH4. The laboratory-scale experimental study confirmed that CH4 actively reduces SnO2, producing 99.34% high-purity Sn and H2 and CO. Our results present a novel method for an efficient, green, and economical recycling strategy for Sn with economic value added that is held by the co-produced clean energy source (syngas).
Microgel assisted Lab-on-Fiber Optrode
Authors: Aliberti A. , Ricciardi A. , Giaquinto M. , Micco A. , Bobeico E. , La Ferrara V. , Ruvo M. , Cutolo A. , Cusano A.
Published: October 2017

Precision medicine is continuously demanding for novel point of care systems, potentially exploitable also for in-vivo analysis. Biosensing probes based on Lab-On-Fiber Technology have been recently developed to meet these challenges. However, devices exploiting standard label-free approaches (based on ligand/target molecule interaction) suffer from low sensitivity in all cases where the detection of small molecules at low concentrations is needed. Here we report on a platform developed through the combination of Lab-On-Fiber probes with microgels, which are directly integrated onto the resonant plasmonic nanostructure realized on the fiber tip. In response to binding events, the microgel network concentrates the target molecule and amplifies the optical response, leading to remarkable sensitivity enhancement. Moreover, by acting on the microgel degrees of freedom such as concentration and operating temperature, it is possible to control the limit of detection, tune the working range as well as the response time of the probe. These unique characteristics pave the way for advanced label-free biosensing platforms, suitably reconfigurable depending on the specific application.
Antibodies against peripheral nerve antigens in chronic inflammatory demyelinating polyradiculoneuropathy
Authors: Querol Luis , Siles Ana M , Alba-Rovira Roser , Jáuregui Agustín , Devaux Jérôme , Faivre-Sarrailh Catherine , Araque Josefa , Rojas-Garcia Ricard , Diaz-Manera Jordi , Cortés-Vicente Elena , Nogales-Gadea Gisela , Navas-Madroñal Miquel , Gallardo Eduard , Illa Isabel
Published: October 2017

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous disease in which diverse autoantibodies have been described but systematic screening has never been performed. Detection of CIDP-specific antibodies may be clinically useful. We developed a screening protocol to uncover novel reactivities in CIDP. Sixty-five CIDP patients and 28 controls were included in our study. Three patients (4.6%) had antibodies against neurofascin 155, four (6.2%) against contactin-1 and one (1.5%) against the contactin-1/contactin-associated protein-1 complex. Eleven (18.6%) patients showed anti-ganglioside antibodies, and one (1.6%) antibodies against peripheral myelin protein 2. No antibodies against myelin protein zero, contactin-2/contactin-associated protein-2 complex, neuronal cell adhesion molecule, gliomedin or the voltage-gated sodium channel were detected. In IgG experiments, three patients (5.3%) showed a weak reactivity against motor neurons; 14 (24.6%) reacted against DRG neurons, four of them strongly (7.0%), and seven (12.3%) reacted against Schwann cells, three of them strongly (5.3%). In IgM experiments, six patients (10.7%) reacted against DRG neurons, while three (5.4%) reacted against Schwann cells. However, results were not statistically significant when compared to controls. Immunoprecipitation experiments identified CD9 and L1CAM as potential antigens, but reactivity could not be confirmed with cell-based assays. In summary, we describe a diverse autoantibody repertoire in CIDP patients, reinforcing the hypothesis of CIDP’s pathophysiological heterogeneity.
HLA-DMB restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG7 acetylation
Authors: Wang Jie , Song Di , Liu Yanzi , Lu Guangjian , Yang Shuai , Liu Lu , Gao Zhitao , Ma Lingling , Guo Zhixiang , Zhang Chenguang , Wang Hui , Yang Bo
Published: October 2017

The roles of autophagy in viral infection are complicated. While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it. The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation. Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection. Immunoblot and real-time PCR assays demonstrated that overexpression of DMB decreased HTLV-1 protein expression while the knockdown of DMB increased HTLV-1 protein expression. Immunoblot and confocal microscopy assays indicated that overexpression of DMB decreased HTLV-1 induced autophagosome accumulation while the knockdown of DMB yielded the opposite effects. Coimmunoprecipitation and immunoprecipitation experiments suggested DMB interacted with autophagy-related gene (ATG) 7 and increased the acetylation of ATG7. Taken together, these results suggested DMB modulated HTLV-1 protein expression through regulation of autophagosome accumulation and our findings suggested a new mechanism by which the host cells defended against HTLV-1 infection.
Combating virulence of Gram-negative bacilli by OmpA inhibition
Authors: Vila-Farrés Xavier , Parra-Millán Raquel , Sánchez-Encinales Viviana , Varese Monica , Ayerbe-Algaba Rafael , Bayó Nuria , Guardiola Salvador , Pachón-Ibáñez María Eugenia , Kotev Martin , García Jesús , Teixidó Meritxell , Vila Jordi , Pachón Jerónimo , Giralt Ernest , Smani Younes
Published: October 2017

Preventing the adhesion of pathogens to host cells provides an innovative approach to tackling multidrug-resistant bacteria. In this regard, the identification of outer membrane protein A (OmpA) as a key bacterial virulence factor has been a major breakthrough. The use of virtual screening helped us to identify a cyclic hexapeptide AOA-2 that inhibits the adhesion of Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli to host cells and the formation of biofilm, thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. Inhibition of OmpA offers a strategy as monotherapy to address the urgent need for treatments for infections caused by Gram-negative bacilli.
Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole
Authors: Campos Mônica C. , Phelan Jody , Francisco Amanda F. , Taylor Martin C. , Lewis Michael D. , Pain Arnab , Clark Taane G. , Kelly John M.
Published: October 2017

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects 5–8 million people in Latin America. Although the nitroheterocyclic compound benznidazole has been the front-line drug for several decades, treatment failures are common. Benznidazole is a pro-drug and is bio-activated within the parasite by the mitochondrial nitroreductase TcNTR-1, leading to the generation of reactive metabolites that have trypanocidal activity. To better assess drug action and resistance, we sequenced the genomes of T. cruzi Y strain (35.5 Mb) and three benznidazole-resistant clones derived from a single drug-selected population. This revealed the genome-wide accumulation of mutations in the resistant parasites, in addition to variations in DNA copy-number. We observed mutations in DNA repair genes, linked with increased susceptibility to DNA alkylating and inter-strand cross-linking agents. Stop-codon-generating mutations in TcNTR-1 were associated with cross-resistance to other nitroheterocyclic drugs. Unexpectedly, the clones were also highly resistant to the ergosterol biosynthesis inhibitor posaconazole, a drug proposed for use against T. cruzi infections, in combination with benznidazole. Our findings therefore identify the highly mutagenic activity of benznidazole metabolites in T. cruzi, demonstrate that this can result in multi-drug resistance, and indicate that vigilance will be required if benznidazole is used in combination therapy.
Molecular Dynamics Computer Simulations of Biological Systems
Authors: Carter James W. , Tascini Anna Sofia , Seddon John M. , Bresme Fernando
Published: October 2017

In this chapter, we discuss the application of molecular dynamics computer simulation to investigate biological molecules. Starting with the basics of molecular dynamics we discuss state-of-the-art force fields for biomolecular simulations, advanced simulation techniques for enhanced sampling, computation of free energies, investigation of rare events, and quantification of elastic properties of biological membranes. A critical discussion of current opportunities in the development of integrated experimental and simulation approaches in the area of NMR and scattering techniques is provided. We close the chapter with an overview of future directions for biomolecular simulations, and how these directions can build on our current ability to perform very large simulations of, for example, organelles and viruses.
Designing Chemical Tools with Computational Chemistry
Authors: Rinaldi Silvia , Colombo Giorgio
Published: October 2017

The continuous rise in computer power, improvements in algorithm design and the advent of big data are sparking the start of a new era in the discovery and design of small molecule chemicals with biological activities. In this chapter, we will present and discuss some of the most promising approaches in this field. The impacts and implications for future chemical biology are discussed.
Uncovering GPCR and G Protein Function by Protein Structure Network Analysis
Authors: Fanelli Francesca , Felline Angelo
Published: October 2017

Protein structure network (PSN) analysis is one of the graph theory-based approaches currently used for investigating structural communication in biomolecular systems. Information on the system's dynamics can be provided by atomistic molecular dynamics (MD) simulations or coarse grained elastic network models paired with normal mode analysis (ENM-NMA). This chapter reports on selected applications of PSN analysis to uncover the structural communication in G protein coupled receptors (GPCRs) and G proteins. Strategies to highlight changes in structural communication caused by mutations, ligand and protein binding are described. Conserved amino acids, sites of misfolding mutations, or ligands acting as functional switches tend to behave as hubs in the native structure networks. Densely linked regions in the protein structure graphs could be identified as playing central roles in protein stability and function. Changes in the communication pathway fingerprints depending on the bound ligand or following amino acid mutation could be highlighted as well. A bridge between misfolding and misrouting could be established in rhodopsin mutants linked to inherited blindness. The analysis of native network perturbations by misfolding mutations served to infer key structural elements of protein responsiveness to small chaperones with implications for drug discovery.
Deoxydehydration of vicinal diols and polyols catalyzed by pyridinium perrhenate salts
Authors: Morris Danny S. , van Rees Karlotta , Curcio Massimiliano , Cokoja Mirza , Kühn Fritz E. , Duarte Fernanda , Love Jason B.
Published: October 2017

Simple ammonium and pyridinium perrhenate salts were evaluated as catalysts for the deoxydehydration (DODH) of diols into alkenes.
Artificial macrocycles as IL-17A/IL-17RA antagonists
Authors: Wang Wenjia , Groves Matthew R. , Dömling Alexander
Published: October 2017

Interleukin 17(A) is a pro-inflammatory cytokine involved in several auto-immune and inflammatory diseases.
Two-dimensional transition-metal dichalcogenides-based ferromagnetic van der Waals heterostructures
Authors: Du Juan , Xia Congxin , Xiong Wenqi , Wang Tianxing , Jia Yu , Li Jingbo
Published: October 2017

TMDs-based vdW semiconducting heterostructures have stable ferromagnetic (FM) ground state, high Curie temperatures and electric field-tunable multi-band alignments.
Design, synthesis and ring-opening polymerization of a new iodinated carbonate monomer: a universal route towards ultrahigh radiopaque aliphatic polycarbonates
Authors: Ma Qian , Lei Kewen , Ding Jian , Yu Lin , Ding Jiandong
Published: October 2017

A universal route towards ultrahigh radiopaque aliphatic polycarbonates was developed based on a new iodinated carbonate monomer.
Diffusion ordered spectroscopy (DOSY) as applied to polymers
Authors: Groves Patrick
Published: October 2017

Optimization of Diffusion Ordered NMR Spectroscopy (DOSY) parameters for the improved and extended analysis of polymers.