bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Similar Binding Sites to Detect Distant Polypharmacology
Authors: Jalencas Xavier , Mestres Jordi 
Published: October 2013

AbstractThe ability of small molecules to interact with multiple proteins is referred to as polypharmacology. This property is often linked to the therapeutic action of drugs but it is known also to be responsible for many of their side effects. Because of its importance, the development of computational methods that can predict drug polypharmacology has become an important line of research that led recently to the identification of many novel targets for known drugs. Nowadays, the majority of these methods are based on measuring the similarity of a query molecule against the hundreds of thousands of molecules for which pharmacological data on thousands of proteins are available in public sources. However, similarity‐based methods are inherently biased by the chemical coverage offered by the active molecules present in those public repositories, which limits significantly their capacity to predict interactions with proteins structurally and functionally unrelated to any of the already known targets for drugs. It is in this respect that structure‐based methods aiming at identifying similar binding sites may offer an alternative complementary means to ligand‐based methods for detecting distant polypharmacology. The different existing approaches to binding site detection, representation, comparison, and fragmentation are reviewed and recent successful applications presented.
Extensions to In Silico Bioactivity Predictions Using Pathway Annotations and Differential Pharmacology Analysis: Application to Xenopus laevis Phenotypic Readouts
Authors: Liggi Sonia , Drakakis Georgios , Hendry Adam E. , Hanson Kimberley M. , Brewerton Suzanne C. , Wheeler Grant N. , Bodkin Michael J. , Evans David A. , Bender Andreas 
Published: October 2013

AbstractThe simultaneous increase of computational power and the availability of chemical and biological data have contributed to the recent popularity of in silico bioactivity prediction algorithms. Such methods are commonly used to infer the ‘Mechanism of Action’ of small molecules and they can also be employed in cases where full bioactivity profiles have not been established experimentally. However, protein target predictions by themselves do not necessarily capture information about the effect of a compound on a biological system, and hence merging their output with a systems biology approach can help to better understand the complex network modulation which leads to a particular phenotype. In this work, we review approaches and applications of target prediction, as well as their shortcomings, and demonstrate two extensions of this concept which are exemplified using phenotypic readouts from a chemical genetic screen in Xenopus laevis. In particular, the experimental observations are linked to their predicted bioactivity profiles. Predicted targets are annotated with pathways, which lead to further biological insight. Moreover, we subject the prediction to further machine learning algorithms, namely decision trees, to capture the differential pharmacology of ligand‐target interactions in biological systems. Both methodologies hence provide new insight into understanding the Mechanism of Action of compound activities from phenotypic screens.
Oscillating gradient spin‐echo (OGSE) diffusion tensor imaging of the human brain
Authors: Baron Corey A. , Beaulieu Christian 
Published: October 2013

PurposeThe dependence of diffusion tensor imaging (DTI) eigenvalues and fractional anisotropy (FA) on short diffusion times was investigated using oscillating gradient spin echo (OGSE) and pulsed gradient spin echo (PGSE) DTI in the human brain in vivo.Theory and MethodsDTI was performed in seven healthy volunteers at 4.7 Tesla (T) with b = 300 s/mm2 and diffusion times of 4.1 ms (OGSE 50 Hz), 7.4 ms (OGSE 25 Hz), 20 ms (PGSE), and 40 ms (PGSE). Eigenvalues and FA were compared in the corpus callosum body, splenium and genu, and the corticospinal, cingulum, inferior fronto‐occipital, superior and inferior longitudinal fasciculi using tractography, and the thalamus and putamen using region‐of‐interest.ResultsRelative to 40 ms, the 4.1 ms diffusion time led to significant increases in DTI eigenvalues in seven white matter tracts (6% to 20% parallel, 13% to 40% perpendicular) and both deep gray matter regions (16% parallel, 18% to 26% perpendicular), and reductions of FA (−9% to −12%) in four tracts.ConclusionDTI eigenvalues and FA depend on diffusion time in both white and gray matter in the human brain. The ability to target different length scales by means of the diffusion time may improve sensitivity to changes in tissue microstructure associated with pathology. Magn Reson Med 72:726–736, 2014. © 2013 Wiley Periodicals, Inc.
Improve myocardial T1 measurement in rats with a new regression model: Application to myocardial infarction and beyond
Authors: Zhang Haosen , Ye Qing , Zheng Jie , Schelbert Erik B. , Hitchens T. Kevin , Ho Chien 
Published: October 2013

PurposeTo improve myocardial and blood T1 measurements with a multi‐variable T1 fitting model specifically modified for a segmented multi‐shot FLASH sequence.MethodsThe proposed method was first evaluated in a series of phantoms simulating realistic tissues, and then in healthy rats (n = 8) and rats with acute myocardial infarction (MI) induced by coronary artery ligation (n = 8).ResultsBy taking into account the saturation effect caused by sampling α‐train pulses, and the longitudinal magnetization recovery between readouts, our model provided more accurate T1 estimate than the conventional three‐parameter fit in phantoms under realistic gating procedures (error of −0.42 ± 1.73% versus −3.40 ± 1.46%, respectively, when using the measured inversion efficiency, β). The baseline myocardial T1 values in healthy rats was 1636.3 ± 23.4 ms at 7 Tesla. One day postligation, the T1 values in the remote and proximal myocardial areas were 1637.5 ± 62.6 ms and 1740.3 ± 70.5 ms, respectively. In rats with acute MI, regional differences in myocardial T1 values were observed both before and after the administration of gadolinium.ConclusionThe proposed method has improved T1 estimate as validated in phantoms and could advance applications in rodents using quantitative myocardial T1 mapping. Magn Reson Med 72:737–748, 2014. © 2013 Wiley Periodicals, Inc.
Successful treatment of severe myasthenia gravis developed after allogeneic hematopoietic stem cell transplantation with plasma exchange and rituximab
Authors: Unal Sule , Sag Erdal , Kuskonmaz Baris , Kesici Selman , Bayrakci Benan , Ayvaz Deniz C. , Tezcan Ilhan , Yalnızoglu Dilek , Uckan Duygu 
Published: October 2013

AbstractMyasthenia gravis is among the rare complications after allogeneic hematopoietic stem cell transplantation and is usually associated with chronic GVHD. Herein, we report a 2‐year and 10 months of age female with Griscelli syndrome, who developed severe myasthenia gravis at post‐transplant +22nd month and required respiratory support with mechanical ventilation. She was unresponsive to cyclosporine A, methylprednisolone, intravenous immunoglobulin, and mycophenolate mofetil and the symptoms could only be controlled after plasma exchange and subsequent use of rituximab, in addition to cyclosporine A and mycophenolate mofetil maintenance. She is currently asymptomatic on the 6th month of follow‐up. Pediatr Blood Cancer 2014;61:928–930. © 2013 Wiley Periodicals, Inc.
Natural killer cell therapy and aerosol interleukin‐2 for the treatment of osteosarcoma lung metastasis
Authors: Guma Sergei R. , Lee Dean A. , Yu Ling , Gordon Nancy , Hughes Dennis , Stewart John , Wang Wei Lien , Kleinerman Eugenie S. 
Published: October 2013

AbstractBackgroundSurvival of patients with osteosarcoma lung metastases has not improved in 20 years. We evaluated the efficacy of combining natural killer (NK) cells with aerosol interleukin‐2 (IL‐2) to achieve organ‐specific NK cell migration and expansion in the metastatic organ, and to decrease toxicity associated with systemic IL‐2.ProcedureFive human osteosarcoma cell lines and 103 patient samples (47 primary and 56 metastatic) were analyzed for NKG2D ligand (NKG2DL) expression. Therapeutic efficacy of aerosol IL‐2 + NK cells was evaluated in vivo compared with aerosol IL‐2 alone and NK cells without aerosol IL‐2.ResultsOsteosarcoma cell lines and patient samples expressed various levels of NKG2DL. NK‐mediated killing was NKG2DL‐dependent and correlated with expression levels. Aerosol IL‐2 increased NK cell numbers in the lung and within metastatic nodules but not in other organs. Therapeutic efficacy, as judged by tumor number, size, and quantification of apoptosis, was also increased compared with NK cells or aerosol IL‐2 alone. There were no IL‐2‐associated systemic toxicities.ConclusionAerosol IL‐2 augmented the efficacy of NK cell therapy against osteosarcoma lung metastasis, without inducing systemic toxicity. Our data suggest that lung‐targeted IL‐2 delivery circumvents toxicities induced by systemic administration. Combining aerosol IL‐2 with NK cell infusions, may be a potential new therapeutic approach for patients with osteosarcoma lung metastasis. Pediatr Blood Cancer 2014;61:618–626. © 2013 Wiley Periodicals, Inc.
Myoepithelial carcinoma treatment in children: A report from the TREP project
Authors: Bisogno Gianni , Tagarelli Arianna , Schiavetti Amalia , Scarzello Giovanni , Ferrari Andrea , Cecchetto Giovanni , Alaggio Rita 
Published: October 2013

AbstractBackgroundMyoepithelial carcinoma (MC) of soft tissues is an aggressive tumor that rarely affects children, for whom no established treatment protocols exist. As part of the TREP (Tumori Rari in Età Pediatrica) project – an Italian network dedicated to children and adolescents with very rare tumors – we present a series of patients with MC, who were treated homogeneously and achieved a satisfactory outcome.ProcedureFrom 2005 to 2012, seven patients (age 0.5–9.2 years) with a diagnosis of MC were registered in the TREP study. After one patient treated with ifosfamide, cisplatin, and etoposide showed tumor shrinkage and experienced long‐term disease remission, all subsequent patients were treated with the same chemotherapy regimen. All patients also received radiotherapy.ResultsInitial surgical management involved a biopsy in three cases and tumor resection in 4. Response to initial chemotherapy was evaluable in four patients: two had a partial remission, one a minor response and one stable disease. Four patients received external‐beam radiotherapy and three had brachytherapy. Overall, six patients are alive in first complete remission with a median follow‐up of 2.5 years (0.9–5.1 years).ConclusionsThough our experience is limited to a small number of patients, our treatment strategy for patients with MC is appears clinically useful and demonstrates how cooperation within the TREP project has enabled enough data to be collected to propose treatment recommendations for pediatric patients with this very rare tumor. Pediatr Blood Cancer 2014;61:643–646. © 2013 Wiley Periodicals, Inc.
Predictors of posttraumatic growth in women with breast cancer
Authors: Danhauer Suzanne C. , Case L. Douglas , Tedeschi Richard , Russell Greg , Vishnevsky Tanya , Triplett Kelli , Ip Edward H. , Avis Nancy E. 
Published: October 2013

AbstractObjectivePosttraumatic growth (PTG) is defined as ‘positive psychological change experienced as a result of a struggle with highly challenging life circumstances’. The current study examined change in PTG over 2 years following breast cancer diagnosis and variables associated with PTG over time.MethodsWomen recently diagnosed with breast cancer completed surveys within 8 months of diagnosis and 6, 12, and 18 months later. Linear mixed effects models were used to assess the longitudinal effects of demographic, medical, and psychosocial variables on PTG as measured by the Posttraumatic Growth Inventory (PTGI).ResultsA total of 653 women were accrued (mean age = 54.9, SD = 12.6). Total PTGI score increased over time mostly within the first few months following diagnosis. In the longitudinal model, greater PTGI scores were associated with education level, longer time since diagnosis, greater baseline level of illness intrusiveness, and increases in social support, spirituality, use of active–adaptive coping strategies, and mental health. Findings for the PTGI domains were similar to those for the total score except for the Spiritual Change domain.ConclusionPTG develops relatively soon after a breast cancer diagnosis and is associated with baseline illness intrusiveness and increases in social support, spirituality, use of active–adaptive coping strategies, and mental health. Copyright © 2013 John Wiley & Sons, Ltd.
Floating‐bridge structure of graphene with ionic‐liquid gate
Authors: Yamashiro Yusuke , Ohno Yasuhide , Maehashi Kenzo , Inoue Koichi , Matsumoto Kazuhiko 
Published: October 2013

AbstractFloating‐bridge structures of graphene with ionic‐liquid gate have been fabricated. After removing the SiO2 layer under the graphene channel and introduction of ionic liquid, the ionic liquid under the suspended‐graphene channel contacts with an exposed back‐gate electrode, resulting in formation of the floating‐bridge structures. Owing to elimination of the interaction with SiO2 layers and the electrical double layer in the ionic liquid, the floating‐bridge bilayer graphene devices have the on/off ratio of 20 in a conductance when the back‐gate voltage of only 2 V was applied. The floating‐bridge structures of graphene on the ionic liquid operate with high performance by small gate voltage. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Current conduction mechanisms and breakdown fields of AlxTiyO/n‐GaAs(001) metal‐insulator‐semiconductor structures
Authors: Ui Toshimasa , Kudo Masahiro , Suzuki Toshi‐kazu 
Published: October 2013

AbstractWe investigated AlxTiyO/n‐GaAs(001) metal‐insulator‐semiconductor (MIS) structures, in which Alx TiyO thin films as high‐k dielectric were obtained by atomic layer deposition, utilizing alternative supply of Al2O3 and TiO2 precursors. Using X‐ray photoelectron spectroscopy, we obtained atomic composition ratios of Al and Ti in the Alx TiyO thin films. It is shown that the breakdown field of the AlxTiyO increases with increase in the Al composition.Based on temperature‐dependent current density‐voltage (J ‐V) characteristics, we elucidated that dominant conduction mechanisms are thermionic emission, Fowler‐Nordheim tunneling, and Poole‐Frenkel conduction, depending on the composition. From the Poole‐Frenkel current, we estimated dielectric constants of the AlxTiyO, which increase with decrease in the Al composition. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Measurements of electromagnetic surface wave propagation in the cut‐off frequency region
Authors: Watanabe Osamu 
Published: October 2013

AbstractElectromagnetic surface wave propagation on a corrugated metal plate is confirmed by a cold test in the X‐band. The measured cut‐off frequency is almost in agreement with the theoretical cut‐off frequency. The propagation is damped at a frequency region higher than the cut‐off frequency. The periodicity of the propagation power to the frequency is confirmed. For the confirmation of these characteristics, it is necessary that the corrugated metal plate is enclosed within a microwave absorber. © 2013 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Formaldehyde exposure induces autophagy in testicular tissues of adult male rats
Authors: Han Shui‐Ping , Zhou Dang‐Xia , Lin Pu , Qin Zhen , An Lu , Zheng Lie‐Rui , Lei Li 
Published: October 2013

ABSTRACTFormaldehyde, a ubiquitous environmental pollutant, has long been suspected of causing adverse male reproductive effects. However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of autophagy in male reproductive injuries induced by formaldehyde exposure, by which we can further understand the molecular mechanism of spermatogenesis and develop new targets for prevention and treatment of male infertility. In this study, electron microscopy, Western blot, and RT‐PCR analysis were used to detect autophagy in testicular tissues. Moreover, testicular weights, histopathology, and morphometry were used to evaluate the reproductive injuries of formaldehyde exposure. We found that formaldehyde exposure‐induced autophagy in testicular tissues was dose dependent. Increasing autophagosomes in spermatogenetic cells was observed by electron microscopy in formaldehyde exposure group. In addition, RT‐PCR and Western blot analysis showed the transcription levels of the LC3‐II, as well as the conversion from LC3‐I to LC3‐II, an indicator of autophagy, significantly increased in testicular tissue of formaldehyde exposure group in a dose dependent manner when compared with those in control group. Furthermore, the alterations of autophage were basically consistent with the changes in testicular weight and morphologic findings. In summary, formaldehyde exposure triggered autophagy, and autophagy may be a scathing factor responsible for male reproductive impairment induced by formaldehyde. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 323–331, 2015.
β‐Naphthoflavone induces oxidative stress in the intertidal copepod, Tigriopus japonicus
Authors: Rhee Jae‐Sung , Lee Young‐Mi , Kim Bo‐Mi , Leung Kenneth Mei Yee , Kim Il‐Chan , Yim Joung Han , Lee Jae‐Seong 
Published: October 2013

ABSTRACTβ‐Naphtoflavone (β‐NF) is a flavonoid and enhances oxidative stress in vertebrates with little information from aquatic invertebrates as yet. In this study, we investigated the effects of β‐NF on the antioxidant defense systems of the intertidal copepod Tigriopus japonicus. To measure the β‐NF‐triggered changes in oxidative stress markers, such as intracellular reactive oxygen species (ROS), glutathione (GSH) concentration, residual glutathione S‐transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and superoxide dismutase (SOD) activity, T. japonicus were exposed to β‐NF (0.5 and 1 mg/L) for 72 h. Significant (P < 0.05) induction of the intracellular ROS content (%) was observed in 1 mg/L of β‐NF exposed T. japonicus, compared to the negative control and H2O2‐exposed group. The GSH levels were significantly increased in the 0.5 mg/L of β‐NF‐exposed group for 12 h and 1 mg/L of β‐NF‐exposed groups for 12–24 h. GPx, GST, and GR activities showed a significant increase in the 1 mg/L β‐NF‐exposed group, indicating that β‐NF induces oxidative stress in T. japonicus. To understand the effects of β‐NF at the level of transcript expression, a 6K microarray analysis was employed. Transcript profiles of selected antioxidant‐related genes were modulated after 72 h exposure to 1 mg/L of β‐NF. From microarray data, 10 GST isoforms, GR, GPx, PH‐GPx, and Se‐GPx were chosen for a time‐course test by real‐time RT‐PCR. T. japonicus GST‐S, GST‐O, GST‐M, and GST‐D1 were significantly increased in a 1 mg/L β‐NF‐exposed group. T. japonicus GPx, GR, and Se‐GPx mRNA levels were also significantly increased at both concentrations. Our results revealed that oxidative stress was induced by β‐NF exposure in T. japonicus. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 332–342, 2015.
Climate change and visual imagery
Authors: O'Neill Saffron J. , Smith Nicholas 
Published: October 2013

Many actors—including scientists, journalists, artists, and campaigning organizations—create visualizations of climate change. In doing so, they evoke climate change in particular ways, and make the issue meaningful in everyday discourse. While a diversity of climate change imagery exists, particular types of climate imagery appear to have gained dominance, promoting particular ways of knowing about climate change (and marginalizing others). This imagery, and public engagement with this imagery, helps to shape the cultural politics of climate change in important ways. This article critically reviews the nascent research area of the visual representations of climate change, and public engagement with visual imagery. It synthesizes a diverse body of research to explore visual representations and engagement across the news media, NGO communications, advertising, and marketing, climate science, art, and virtual reality systems. The discussion brings together three themes which occur throughout the review: time, truth, and power. The article concludes by suggesting fruitful directions for future research in the visual communication of climate change. WIREs Clim Change 2014, 5:73–87. doi: 10.1002/wcc.249This article is categorized under:

Perceptions, Behavior, and Communication of Climate Change > Communication
Multidimensional compressed sensing and their applications
Authors: Caiafa Cesar F. , Cichocki Andrzej 
Published: October 2013

Compressed sensing (CS) comprises a set of relatively new techniques that exploit the underlying structure of data sets allowing their reconstruction from compressed versions or incomplete information. CS reconstruction algorithms are essentially nonlinear, demanding heavy computation overhead and large storage memory, especially in the case of multidimensional signals. Excellent review papers discussing CS state‐of‐the‐art theory and algorithms already exist in the literature, which mostly consider data sets in vector forms. In this paper, we give an overview of existing techniques with special focus on the treatment of multidimensional signals (tensors). We discuss recent trends that exploit the natural multidimensional structure of signals (tensors) achieving simple and efficient CS algorithms. The Kronecker structure of dictionaries is emphasized and its equivalence to the Tucker tensor decomposition is exploited allowing us to use tensor tools and models for CS. Several examples based on real world multidimensional signals are presented, illustrating common problems in signal processing such as the recovery of signals from compressed measurements for magnetic resonance imaging (MRI) signals or for hyper‐spectral imaging, and the tensor completion problem (multidimensional inpainting). WIREs Data Mining Knowl Discov 2013, 3:355–380. doi: 10.1002/widm.1108This article is categorized under:

Algorithmic Development > Spatial and Temporal Data Mining
Algorithmic Development > Structure Discovery
Application Areas > Science and Technology
Sustaining Collective Action in Urbanizing China
Authors: Kuang Xianwen , Göbel Christian 
Published: October 2013

AbstractIn recent years there has been a proliferation of scholarship on protests and other forms of collective action in China. Important insights have been gained into how conflicts between social groups and local governments begin, which strategies and instruments protesters apply, and under which circumstances protests are likely to succeed or fail. However, comparatively little is known about the mobilizing structures and how such collective action can be sustained over a long period of time, in some instances over several years. Such perseverance would be remarkable even in a democracy, but it is more so in an authoritarian system where the risks of participating in collective action are higher and the chances to succeed much smaller. This article compares the development of public protests in two research locations and identifies four factors instrumental to overcoming the formidable challenges of sustaining collective action in China: the continuing existence of substantial grievances; the re-activation of strong social ties; the presence of unifying frames; and an adaptive protest leadership. The comparison shows that the last factor is particularly crucial: while the two villages were similar in all other respects, leadership in village B was far more adaptive than in village A, which goes a long way towards explaining why collective action could be sustained twice as long in village B.