bluuebunny/crossref_metadata_2025 huggingface dataset:
Nationalisms, Modernisms and Masculinities: Strategies of Displacement in Vaughan Williams’s Reading of Walt Whitman
Authors: Collins Sarah
Published: November 2016

At the time of his death in 1892, the paradigmatic American poet Walt Whitman was more widely celebrated in Britain than in his own country, having received the vocal support of the likes of Tennyson, William Michael Rossetti, John Addington Symonds, Swinburne (for a time) and Edward Carpenter. For these writers, Whitman’s political egalitarianism – expressed through notions of ‘manly love’ and comradeship – presented a powerful alternative to prevailing Victorian forms of political and social relations. Whitman also provided significant inspiration for British composers at the turn of the twentieth century, with settings by Holst, Delius, Grainger, Scott, Gurney, Bridge, Stanford, Wood, Vaughan Williams and others. Yet while Whitman’s transatlantic literary reception has come to be seen as a moment of crystallization in the formation of contemporary notions of homosexuality, his reception among British composers is viewed as having been highly circumscribed, focusing more on the democratic and mystical implications of Whitman’s poetry.

This article suggests a different account of Vaughan Williams’s reading of Whitman, and explores the implications of this reading for our broader understanding of the relationship between several notions of nationalism, masculinity and modernism. This examination aims to complicate, inter alia, the narrative of rupture associated with the transition to modernism, by demonstrating how the continuity of intellectual concerns across aesthetic, national, and sexual spheres has been obscured by strategies of displacement.
Comparing the riskiness of dependent portfolios via nested L-statistics
Authors: Samanthi Ranadeera G.M. , Wei Wei , Brazauskas Vytaras
Published: November 2016

A non-parametric test based on nested L-statistics and designed to compare the riskiness of portfolios was introduced by Brazauskas et al. (2007). Its asymptotic and small-sample properties were primarily explored for independent portfolios, though independence is not a required condition for the test to work. In this paper, we investigate how performance of the test changes when insurance portfolios are dependent. To achieve that goal, we perform a simulation study where we consider three different risk measures: conditional tail expectation, proportional hazards transform, and mean. Further, three portfolios are generated from exponential, Pareto, and lognormal distributions, and their interdependence is modelled with the three-dimensional t and Gaussian copulas. It is found that the presence of strong positive dependence (comonotonicity) makes the test very liberal for all the risk measures under consideration. For types of dependence that are more common in an insurance environment, the effect of dependence is less dramatic but the results are mixed, i.e., they depend on the chosen risk measure, sample size, and even on the test’s significance level. Finally, we illustrate how to incorporate such findings into sensitivity analysis of the decisions. The risks we analyse represent tornado damages in different regions of the United States from 1890 to 1999.
Group cognitive behaviour therapy combining early intervention with an exclusive focus on single medication-resistant delusional beliefs: a service evaluation
Authors: Raune David , Last Anna , Towner Sarah , Domoney Jill , Georgiades Anna
Published: November 2016

Cognitive behaviour therapy (CBT) is now the psychological treatment of choice for psychosis but meta-analyses indicate a low effect size on delusions, so further innovations are clearly needed, and group CBT for psychosis (GCBTp) is an under-researched area. This study aimed to service-evaluate the feasibility, satisfaction, safety, and effectiveness of a CBT group specifically targeting medication-resistant single delusions in early psychosis patients (EI-GCBTp). Three separate EI-GCBTp groups were run resulting in a total of 11 medication-resistant early psychosis patients. A within-subjects design tested for group change across two time points: pre-baseline (4 weeks before treatment) to baseline (session 1 of treatment) and sessions 1–8 (the treatment period). Thirteen delusion dimensions were measured from three psychosis-specific questionnaires: The Psychotic Symptom Rating Scale (PSYRATS), Characteristics of Delusion Rating Scale, and the Belief Rating Scale. At least three patients attended each group, satisfaction scores were high, and no harm to patients was identified. With reference to effectiveness, the pre-baseline period showed virtually no change. In contrast, across the EI-GCBTp treatment period, the PSYRATS total demonstrated a statistically significant decrease in delusional severity (p < 0.01), a 31% symptom reduction, and a large effect size (Cohen's d = 1.2, 95% confidence interval = −2.53 to 0.05), statistically significant across four delusion dimensions. EI-GCBTp appears feasible, acceptable, safe, and preliminary uncontrolled effectiveness results suggest merit for larger-scale more rigorous testing of this treatment format for possible dimensional improvements of persistent delusions.
Psychometric Properties of the Online Arabic Versions of BDI-II,	HSCL-25, and PDS
Authors: Selmo Pirko , Koch Tobias , Brand Janine , Wagner Birgit , Knaevelsrud Christine
Published: November 2016

Abstract. The Beck Depression Inventory (BDI-II), Hopkins Symptom Checklist (HSCL-25), and Posttraumatic Diagnostic Scale (PDS) are three widely applied clinical instruments for assessing depression, anxiety, and posttraumatic stress symptoms, respectively. Use of online-based psychological help and assessment is rapidly growing which necessitates the need for the validation of online assessment. To address these needs, data from 1,544 Arabic mother tongue treatment-seeking participants, who filled in the Arabic versions of these instruments online, was analyzed in two steps. In the first step, exploratory structural equation modeling (ESEM) was used to scrutinize factorial validity and eliminate items. In the second step, we examined the interrelationships between the latent factors (dimensions) using confirmatory factor analysis (CFA) of multitrait-multimethod (MTMM) data. Results show an acceptable to good fit of the hypothesized model, providing some first insights into the factorial and construct validity of the Arabic versions of BDI-II, HSCL-25, and PDS under consideration of cultural-specific aspects. Present evidence speaks for construct validity of the three instruments and the reliability and usefulness of online assessment.
A Need for Cognition Scale for Children and	Adolescents
Authors: Keller Ulrich , Strobel Anja , Wollschläger Rachel , Greiff Samuel , Martin Romain , Vainikainen Mari-Pauliina , Preckel Franzis
Published: November 2016

Abstract. Need for Cognition (NFC) signifies “the tendency for an individual to engage in and enjoy thinking” ( Cacioppo & Petty, 1982, p. 116 ). Up to now, no scale of sufficient psychometric quality existed to assess NFC in children. Using data from three independent, diverse cross-sectional samples from Germany, Luxembourg, and Finland, we examined the psychometric properties of a new NFC scale intended to fill in this gap. In all samples, across grade levels ranging from 1 to 9, confirmatory factor analysis confirmed the hypothesized nested factor structure based on Mussel’s (2013) Intellect model, with one general factor Think influencing all items and two specific factors Seek and Conquer each influencing a subset of items. At least partial scalar measurement invariance with regard to grade level and sex could be demonstrated. The scale exhibited good psychometric properties and showed convergent and discriminant validity with an established NFC scale and other noncognitive traits such as academic self-concept and interests. It incrementally predicted mostly statistically significant but relatively small portions of academic achievement variance over and above academic self-concept and interest. Implications for research on the development of NFC and its role as an investment trait in intellectual development are discussed.
A New Model to Improve Gravity Models
Authors: Hall Shannon
Published: November 2016

Data from the Gravity Recovery and Climate Experiment (GRACE) mission gets a new and improved look.
Systems-level metabolism of the altered Schaedler flora, a complete gut microbiota
Authors: Biggs Matthew B , Medlock Gregory L , Moutinho Thomas J , Lees Hannah J , Swann Jonathan R , Kolling Glynis L , Papin Jason A
Published: November 2016

The altered Schaedler flora (ASF) is a model microbial community with both in vivo and in vitro relevance. Here we provide the first characterization of the ASF community in vitro, independent of a murine host. We compared the functional genetic content of the ASF to wild murine metagenomes and found that the ASF functionally represents wild microbiomes better than random consortia of similar taxonomic composition. We developed a chemically defined medium that supported growth of seven of the eight ASF members. To elucidate the metabolic capabilities of these ASF species—including potential for interactions such as cross-feeding—we performed a spent media screen and analyzed the results through dynamic growth measurements and non-targeted metabolic profiling. We found that cross-feeding is relatively rare (32 of 3570 possible cases), but is enriched between Clostridium ASF356 and Parabacteroides ASF519. We identified many cases of emergent metabolism (856 of 3570 possible cases). These data will inform efforts to understand ASF dynamics and spatial distribution in vivo, to design pre- and probiotics that modulate relative abundances of ASF members, and will be essential for validating computational models of ASF metabolism. Well-characterized, experimentally tractable microbial communities enable research that can translate into more effective microbiome-targeted therapies to improve human health.
An enduring rapidly moving storm as a guide to Saturn’s Equatorial jet’s complex structure
Authors: Sánchez-Lavega A. , García-Melendo E. , Pérez-Hoyos S. , Hueso R. , Wong M. H. , Simon A. , Sanz-Requena J. F. , Antuñano A. , Barrado-Izagirre N. , Garate-Lopez I. , Rojas J. F. , del Río-Gaztelurrutia T. , Gómez-Forrellad J. M. , de Pater I. , Li L. , Barry T.
Published: November 2016

Saturn has an intense and broad eastward equatorial jet with a complex three-dimensional structure mixed with time variability. The equatorial region experiences strong seasonal insolation variations enhanced by ring shadowing, and three of the six known giant planetary-scale storms have developed in it. These factors make Saturn’s equator a natural laboratory to test models of jets in giant planets. Here we report on a bright equatorial atmospheric feature imaged in 2015 that moved steadily at a high speed of 450 ms−1 not measured since 1980–1981 with other equatorial clouds moving within an ample range of velocities. Radiative transfer models show that these motions occur at three altitude levels within the upper haze and clouds. We find that the peak of the jet (latitudes 10° N to 10° S) suffers intense vertical shears reaching +2.5 ms−1 km−1, two orders of magnitude higher than meridional shears, and temporal variability above 1 bar altitude level.
Random synaptic feedback weights support error backpropagation for deep learning
Authors: Lillicrap Timothy P. , Cownden Daniel , Tweed Douglas B. , Akerman Colin J.
Published: November 2016

The brain processes information through multiple layers of neurons. This deep architecture is representationally powerful, but complicates learning because it is difficult to identify the responsible neurons when a mistake is made. In machine learning, the backpropagation algorithm assigns blame by multiplying error signals with all the synaptic weights on each neuron’s axon and further downstream. However, this involves a precise, symmetric backward connectivity pattern, which is thought to be impossible in the brain. Here we demonstrate that this strong architectural constraint is not required for effective error propagation. We present a surprisingly simple mechanism that assigns blame by multiplying errors by even random synaptic weights. This mechanism can transmit teaching signals across multiple layers of neurons and performs as effectively as backpropagation on a variety of tasks. Our results help reopen questions about how the brain could use error signals and dispel long-held assumptions about algorithmic constraints on learning.
Record of massive upwellings from the Pacific large low shear velocity province
Authors: Madrigal Pilar , Gazel Esteban , Flores Kennet E. , Bizimis Michael , Jicha Brian
Published: November 2016

Large igneous provinces, as the surface expression of deep mantle processes, play a key role in the evolution of the planet. Here we analyse the geochemical record and timing of the Pacific Ocean Large Igneous Provinces and preserved accreted terranes to reconstruct the history of pulses of mantle plume upwellings and their relation with a deep-rooted source like the Pacific large low-shear velocity Province during the Mid-Jurassic to Upper Cretaceous. Petrological modelling and geochemical data suggest the need of interaction between these deep-rooted upwellings and mid-ocean ridges in pulses separated by ∼10–20 Ma, to generate the massive volumes of melt preserved today as oceanic plateaus. These pulses impacted the marine biota resulting in episodes of anoxia and mass extinctions shortly after their eruption.
Origin and structure of polar domains in doped molecular crystals
Authors: Meirzadeh E. , Azuri I. , Qi Y. , Ehre D. , Rappe A. M. , Lahav M. , Kronik L. , Lubomirsky I.
Published: November 2016

Doping is a primary tool for the modification of the properties of materials. Occlusion of guest molecules in crystals generally reduces their symmetry by the creation of polar domains, which engender polarization and pyroelectricity in the doped crystals. Here we describe a molecular-level determination of the structure of such polar domains, as created by low dopant concentrations (<0.5%). The approach comprises crystal engineering and pyroelectric measurements, together with dispersion-corrected density functional theory and classical molecular dynamics calculations of the doped crystals, using neutron diffraction data of the host at different temperatures. This approach is illustrated using centrosymmetric α-glycine crystals doped with minute amounts of different L-amino acids. The experimentally determined pyroelectric coefficients are explained by the structure and polarization calculations, thus providing strong support for the local and global understanding of how different dopants influence the properties of molecular crystals.
DNA evidence of bowhead whale exploitation by Greenlandic Paleo-Inuit 4,000 years ago
Authors: Seersholm Frederik Valeur , Pedersen Mikkel Winther , Søe Martin Jensen , Shokry Hussein , Mak Sarah Siu Tze , Ruter Anthony , Raghavan Maanasa , Fitzhugh William , Kjær Kurt H. , Willerslev Eske , Meldgaard Morten , Kapel Christian M.O. , Hansen Anders Johannes
Published: November 2016

The demographic history of Greenland is characterized by recurrent migrations and extinctions since the first humans arrived 4,500 years ago. Our current understanding of these extinct cultures relies primarily on preserved fossils found in their archaeological deposits, which hold valuable information on past subsistence practices. However, some exploited taxa, though economically important, comprise only a small fraction of these sub-fossil assemblages. Here we reconstruct a comprehensive record of past subsistence economies in Greenland by sequencing ancient DNA from four well-described midden deposits. Our results confirm that the species found in the fossil record, like harp seal and ringed seal, were a vital part of Inuit subsistence, but also add a new dimension with evidence that caribou, walrus and whale species played a more prominent role for the survival of Paleo-Inuit cultures than previously reported. Most notably, we report evidence of bowhead whale exploitation by the Saqqaq culture 4,000 years ago.
Aurora A Kinase Inhibitor AKI603 Induces Cellular Senescence in Chronic Myeloid Leukemia Cells Harboring T315I Mutation
Authors: Wang Le-Xun , Wang Jun-Dan , Chen Jia-Jie , Long Bing , Liu Ling-Ling , Tu Xi-Xiang , Luo Yu , Hu Yuan , Lin Dong-Jun , Lu Gui , Long Zi-Jie , Liu Quentin
Published: November 2016

The emergence of resistance to imatinib mediated by mutations in the BCR-ABL has become a major challenge in the treatment of chronic myeloid leukemia (CML). Alternative therapeutic strategies to override imatinib-resistant CML are urgently needed. In this study, we investigated the effect of AKI603, a novel small molecule inhibitor of Aurora kinase A (AurA) to overcome resistance mediated by BCR-ABL-T315I mutation. Our results showed that AKI603 exhibited strong anti-proliferative activity in leukemic cells. AKI603 inhibited cell proliferation and colony formation capacities in imatinib-resistant CML cells by inducing cell cycle arrest with polyploidy accumulation. Surprisingly, inhibition of AurA by AKI603 induced leukemia cell senescence in both BCR-ABL wild type and T315I mutation cells. Furthermore, the induction of senescence was associated with enhancing reactive oxygen species (ROS) level. Moreover, the anti-tumor effect of AKI603 was proved in the BALB/c nude mice KBM5-T315I xenograft model. Taken together, our data demonstrate that the small molecule AurA inhibitor AKI603 may be used to overcome drug resistance induced by BCR-ABL-T315I mutation in CML.
A Novel Insulin/Glucose Model after a Mixed-Meal Test in Patients with Type 1 Diabetes on Insulin Pump Therapy
Authors: Marchetti Luca , Reali Federico , Dauriz Marco , Brangani Corinna , Boselli Linda , Ceradini Giulia , Bonora Enzo , Bonadonna Riccardo C. , Priami Corrado
Published: November 2016

Current closed-loop insulin delivery methods stem from sophisticated models of the glucose-insulin (G/I) system, mostly based on complex studies employing glucose tracer technology. We tested the performance of a new minimal model (GLUKINSLOOP 2.0) of the G/I system to characterize the glucose and insulin dynamics during multiple mixed meal tests (MMT) of different sizes in patients with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion, CSII). The GLUKINSLOOP 2.0 identified the G/I system, provided a close fit of the G/I time-courses and showed acceptable reproducibility of the G/I system parameters in repeated studies of identical and double-sized MMTs. This model can provide a fairly good and reproducible description of the G/I system in T1D patients on CSII, and it may be applied to create a bank of “virtual” patients. Our results might be relevant at improving the architecture of upcoming closed-loop CSII systems.
Length-free near infrared measurement of newborn malnutrition
Authors: Mustafa Fatin Hamimi , Bek Emily J. , Huvanandana Jacqueline , Jones Peter W. , Carberry Angela E. , Jeffery Heather E. , Jin Craig T. , McEwan Alistair L.
Published: November 2016

Under-nutrition in neonates can cause immediate mortality, impaired cognitive development and early onset adult disease. Body fat percentage measured using air-displacement-plethysmography has been found to better indicate under-nutrition than conventional birth weight percentiles. However, air-displacement-plethysmography equipment is expensive and non-portable, so is not suited for use in developing communities where the burden is often the greatest. We proposed a new body fat measurement technique using a length-free model with near-infrared spectroscopy measurements on a single site of the body - the thigh. To remove the need for length measurement, we developed a model with five discrete wavelengths and a sex parameter. The model was developed using air-displacement-plethysmography measurements in 52 neonates within 48 hours of birth. We identified instrumentation required in a low-cost LED-based screening device and incorporated a receptor device that can increase the amount of light collected. This near-infrared method may be suitable as a low cost screening tool for detecting body fat levels and monitoring nutritional interventions for malnutrition in neonates and young children in resource-constrained communities.
Involvement of eIF6 in external mechanical stretch–mediated murine dermal fibroblast function via TGF-β1 pathway
Authors: Shu Qin , Tan Jianglin , Ulrike Van Daele , Zhang Xiaorong , Yang Jiacai , Yang Sisi , Hu Xiaohong , He Weifeng , Luo Gaoxing , Wu Jun
Published: November 2016

External mechanical loading on a wound commonly increases fibrosis. Transforming growth factor-β1 (TGF-β1) has been implicated in fibrosis in various models, including the mechanical force model. However, the underlying mechanism is unclear. Our previous experiments suggested that eukaryotic initiation factor 6 (eIF6) acted as a regulator of TGF-β1 expression, and negatively impact on collagen synthesis. Our current results showed that external mechanical stretching significantly increased COL1A1, TGF-β1 and eIF6 expression as well as dermal fibroblasts proliferation, both in vitro and in vivo. eIF6 –deficient (eIF6+/−) cells exhibited significantly higher levels of COL1A1, and these levels increased further with external mechanical stretching, suggesting that mechanical stretching plays a synergistic role in promoting COL1A1 expression in eIF6+/− cells. Inhibition of TGFβR I/II by LY2109761 decreased COL1A1 protein expression in eIF6+/− dermal fibroblasts in a cell stretching model, and attenuated granulation tissue formation in partial thickness wounds of eIF6+/− mice. These data suggest that mechanical stretching has a synergistic role in the expression of COL1A1 in eIF6+/− cells, and is mediated by activation of TGFβRI/II. Taken together, our results indicate that eIF6 may be involved in external mechanical force-mediated murine dermal fibroblast function at least partly through the TGF-β1 pathway.
Establishing the limits of efficiency of perovskite solar cells from first principles modeling
Authors: Grånäs Oscar , Vinichenko Dmitry , Kaxiras Efthimios
Published: November 2016

The recent surge in research on metal-halide-perovskite solar cells has led to a seven-fold increase of efficiency, from ~3% in early devices to over 22% in research prototypes. Oft-cited reasons for this increase are: (i) a carrier diffusion length reaching hundreds of microns; (ii) a low exciton binding energy; and (iii) a high optical absorption coefficient. These hybrid organic-inorganic materials span a large chemical space with the perovskite structure. Here, using first-principles calculations and thermodynamic modelling, we establish that, given the range of band-gaps of the metal-halide-perovskites, the theoretical maximum efficiency limit is in the range of ~25–27%. Our conclusions are based on the effect of level alignment between the perovskite absorber layer and carrier-transporting materials on the performance of the solar cell as a whole. Our results provide a useful framework for experimental searches toward more efficient devices.
RETRACTED ARTICLE: Sulforaphane Improves Ischemia-Induced Detrusor Overactivity by Downregulating the Enhancement of Associated Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in Rat Bladder
Authors: Tai Huai-Ching , Chung Shiu-Dong , Chien Chiang-Ting , Yu Hong-Jeng
Published: November 2016

Atherosclerosis-associated pelvic ischemia has been reported to be a risk factor for bladder dysfunction and subsequent lower urinary tract symptoms (LUTS) in the elderly population. However, the molecular mechanisms of this association remain unclear. We hypothesized that stress-induced cellular responses might play a role in the pathogenesis of ischemia-induced bladder dysfunction. In the present study, the animal model of bladder ischemia was induced by bilateral partial arterial occlusion (BPAO) in rats. We found that BPAO significantly induced the presence of detrusor overactivity (DO) and upregulated the expression of several molecular reactions, including biomarkers in endoplasmic reticulum stress (78 kDa glucose-regulated protein, GRP78 and C/EBP-homologous protein, CHOP), autophagy (Beclin-1, p62 and LC3 II) and apoptosis (caspase 3). BPAO also disturbed the Kelch-like ECH-associated protein 1–nuclear factor erythroid-2-related factor 2 (Keap1–Nrf2) pathways. These responses might collectively alter muscarinic and purinergic signaling and contribute to the presence of DO in the ischemic bladder. Therapeutically, treatment with neither a muscarinic nor purinergic receptor antagonist restored bladder function. Interestingly, sulforaphane effectively attenuated ischemia-enhanced endoplasmic reticulum stress, autophagy and apoptosis in the bladder, subsequently ameliorated ischemia-induced bladder dysfunction and might emerge as a novel strategy to protect the bladder against ischemia-induced oxidative damage.
Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells
Authors: Hodges Robin R. , Li Dayu , Shatos Marie A. , Serhan Charles N. , Dartt Darlene A.
Published: November 2016

Conjunctival goblet cells synthesize and secrete mucins which play an important role in protecting the ocular surface. Pro-resolution mediators, such as lipoxin A4 (LXA4), are produced during inflammation returning the tissue to homeostasis and are also produced in non-inflamed tissues. The purpose of this study was to determine the actions of LXA4 on cultured human conjunctival goblet cell mucin secretion and increase in intracellular [Ca2+] ([Ca2+]i) and on histamine-stimulated responses. LXA4 increased mucin secretion and [Ca2+]i, and activated ERK1/2 in human goblet cells. Addition of LXA4 before resolvin D1 (RvD1) decreased RvD1 responses though RvD1 did not block LXA4 responses. LXA4 inhibited histamine-stimulated increases in mucin secretion, [Ca2+]i, and ERK1/2 activation through activation of β-adrenergic receptor kinase 1. We conclude that conjunctival goblet cells respond to LXA4 through the ALX/FPR2 receptor to maintain homeostasis of the ocular surface and regulate histamine responses and could provide a new therapeutic approach for allergic conjunctivitis and dry eye diseases.
Modeling the development of the post-natal mouse thymus in the absence of bone marrow progenitors
Authors: Zaharie Daniela , Moleriu Radu D. , Mic Felix A.
Published: November 2016

Many mathematical models have been published with the purpose of explaining aspects of T-cell development in the thymus. In this manuscript we adapted a four-compartment model of the thymus and used a range of mathematical approaches with the aim of explaining the dynamics of the four main thymocyte populations in the mouse thymus, from the emergence of the first fetal thymocyte until the death of the animal. At various pre-natal and post-natal stages we investigated experimentally the number and composition of thymocytes populations, their apoptosis and proliferation, along with data from literature, to create and validate the model. In our model the proliferation processes are characterized by decreasing proliferation rates, which allows us to model the natural involution of the thymus. The best results were obtained when different sets of parameters were used for the fetal and post-natal periods, suggesting that birth may induce a discontinuity in the modeled processes. Our model is able to model the development of both pre-natal and post-natal thymocyte populations. Also, our findings showed that the post-natal thymus is able to develop in the absence of the daily input of bone marrow progenitors, providing more evidence to support the autonomous development of the post-natal thymus.
Trehalose prevents aggregation of exosomes and cryodamage
Authors: Bosch Steffi , de Beaurepaire Laurence , Allard Marie , Mosser Mathilde , Heichette Claire , Chrétien Denis , Jegou Dominique , Bach Jean-Marie
Published: November 2016

Exosomes are important mediators in intercellular communication. Released by many cell types, they transport proteins, lipids, and nucleic acids to distant recipient cells and contribute to important physiopathological processes. Standard current exosome isolation methods based on differential centrifugation protocols tend to induce aggregation of particles in highly concentrated suspensions and freezing of exosomes can induce damage and inconsistent biological activity. Trehalose is a natural, non-toxic sugar widely used as a protein stabilizer and cryoprotectant by the food and drug industry. Here we report that addition of 25 mM trehalose to pancreatic beta-cell exosome-like vesicle isolation and storage buffer narrows the particle size distribution and increases the number of individual particles per microgram of protein. Repeated freeze-thaw cycles induce an increase in particle concentration and in the width of the size distribution for exosome-like vesicles stored in PBS, but not in PBS 25 mM trehalose. No signs of lysis or incomplete vesicles were observed by cryo-electron tomography in PBS and trehalose samples. In macrophage immune assays, beta-cell extracellular vesicles in trehalose show consistently higher TNF-alpha cytokine secretion stimulation indexes suggesting improved preservation of biological activity. The addition of trehalose might be an attractive means to standardize experiments in the field of exosome research and downstream applications.
Extremely Sensitive Dependence of SnOx Film Properties on Sputtering Power
Authors: Li Yunpeng , Xin Qian , Du Lulu , Qu Yunxiu , Li He , Kong Xi , Wang Qingpu , Song Aimin
Published: November 2016

An extremely sensitive dependence of the electronic properties of SnOx film on sputtering deposition power is discovered experimentally. The carrier transport sharply switches from n-type to p-type when the sputtering power increases by less than 2%. The best n-type carrier transport behavior is observed in thin-film transistors (TFTs) produced at a sputtering power just below a critical value (120 W). In contrast, at just above the critical sputtering power, the p-type behavior is found to be the best with the TFTs showing the highest on/off ratio of 1.79 × 104 and the best subthreshold swing among all the sputtering powers that we have tested. A further increase in the sputtering power by only a few percent results in a drastic drop in on/off ratio by more than one order of magnitude. Scanning electron micrographs, x-ray diffraction spectra, x-ray photoelectron spectroscopy, as well as TFT output and transfer characteristics are analyzed. Our studies suggest that the sputtering power critically affects the stoichiometry of the SnOx film.
Near-infrared spectroscopy (NIRS)-based eyes-closed brain-computer interface (BCI) using prefrontal cortex activation due to mental arithmetic
Authors: Shin Jaeyoung , Müller Klaus-R , Hwang Han-Jeong
Published: November 2016

We propose a near-infrared spectroscopy (NIRS)-based brain-computer interface (BCI) that can be operated in eyes-closed (EC) state. To evaluate the feasibility of NIRS-based EC BCIs, we compared the performance of an eye-open (EO) BCI paradigm and an EC BCI paradigm with respect to hemodynamic response and classification accuracy. To this end, subjects performed either mental arithmetic or imagined vocalization of the English alphabet as a baseline task with very low cognitive loading. The performances of two linear classifiers were compared; resulting in an advantage of shrinkage linear discriminant analysis (LDA). The classification accuracy of EC paradigm (75.6 ± 7.3%) was observed to be lower than that of EO paradigm (77.0 ± 9.2%), which was statistically insignificant (p = 0.5698). Subjects reported they felt it more comfortable (p = 0.057) and easier (p < 0.05) to perform the EC BCI tasks. The different task difficulty may become a cause of the slightly lower classification accuracy of EC data. From the analysis results, we could confirm the feasibility of NIRS-based EC BCIs, which can be a BCI option that may ultimately be of use for patients who cannot keep their eyes open consistently.
Rational Design and Synthesis of [5]Helicene-Derived Phosphine Ligands and Their Application in Pd-Catalyzed Asymmetric Reactions
Authors: Yamamoto Kosuke , Shimizu Takashi , Igawa Kazunobu , Tomooka Katsuhiko , Hirai Go , Suemune Hiroshi , Usui Kazuteru
Published: November 2016

A series of novel optically active [5]helicene-derived phosphine ligands (L1, with a 7,8-dihydro[5]helicene core structure- and L2, with a fully aromatic [5]helicene core structure) were synthesized. Despite their structural similarities, L1 and L2 exhibit particularly different characteristics in their use as chiral ligands. L1 was highly effective in the asymmetric allylation of indoles with 1,3-diphenylallyl acetate (up to 99% ee), and in the etherification of alcohols (up to 96% ee). In contrast, L2 was highly effective in the stereocontrol of helical chirality in Suzuki–Miyaura coupling (SMC) reaction (up to 99% ee). Density functional theory analysis was employed to propose a model that accounts for the origin of the enantioselectivity in these reactions.
Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity
Authors: Vardi Roni , Goldental Amir , Sardi Shira , Sheinin Anton , Kanter Ido
Published: November 2016

The increasing number of recording electrodes enhances the capability of capturing the network’s cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.
Identity of major sulfur-cycle prokaryotes in freshwater lake ecosystems revealed by a comprehensive phylogenetic study of the dissimilatory adenylylsulfate reductase
Authors: Watanabe Tomohiro , Kojima Hisaya , Fukui Manabu
Published: November 2016

Adenylylsulfate reductase is a heterodimeric complex of two subunits, AprB and AprA, and is a key enzyme in dissimilatory sulfate reduction and sulfur oxidation. Common use of aprA as a functional marker gene has revealed the diversity of sulfur-cycle prokaryotes in diverse environments. In this study, we established a comprehensive sequence set of apr genes and employed it to reanalyze apr phylogeny, evaluate the coverage of a widely used primer set (AprA-1-FW/AprA-5-RV), and categorize environmental aprA sequences. Phylogenetic tree construction revealed new members of Apr lineage II and several previously unrecognized lateral gene transfer events. Using the established phylogenetic tree, we classified all previously reported aprA sequences amplified from freshwater lakes with the primer pair AprA-1-FW/AprA-5-RV in addition to the aprA sequences newly retrieved from freshwater lakes; the obtained results were complemented by 16S rRNA clone library analysis. Apr-based classifications of some of operational taxonomic units were supported by 16S rRNA-based analysis. This study updates our knowledge on the phylogeny of aprBA and shows the identities of several sulfur-cycle bacteria, which could not be classified to a known taxa until now. The established apr sequence set is publicly available and can be applied to assign environmental sequences to known lineages.
Preservation of epithelial progenitor cells from collagenase-digested oral mucosa during ex vivo cultivation
Authors: Hsueh Yi-Jen , Huang Shiang-Fu , Lai Jui-Yang , Ma Shih-Chieh , Chen Hung-Chi , Wu Sung-En , Wang Tze-Kai , Sun Chi-Chin , Ma Kevin Sheng-Kai , Chen Jan-Kan , Lai Chyong-Huey , Ma David Hui-Kang
Published: November 2016

To avoid xenogeneic infection, we report a novel protocol for producing animal-derived component-free oral mucosal epithelial cells (OMECs) sheet for transplantation, in which collagenase was used to replace dispase II/trypsin-EDTA for digesting oral mucosal tissue, and human platelet-derived PLTMax to replace fetal bovine serum. The resulting epithelial aggregates were expanded on de-epithelialized amniotic membranes without 3T3 feeder cells, and serum-free EpiLife was used to reduce contamination by submucosal mesenchymal cells. The OMEC sheets thus generated showed similar positive keratin 3/76-positive and keratin 8-negative staining patterns compared with those generated by the original protocol. Colony formation efficiency assay, BrdU label retention assay, and p63 and p75NTR immunostaining results indicated that higher proliferative potentials and more progenitor cells were preserved by the modified protocol. TaqMan array analysis revealed that the transcription of integrin-linked kinase (ILK) was up-regulated along with an increase in β-catenin signaling and its downstream cell cycle modulators, cyclin D1 and p27KIP1. Furthermore, ILK silencing led to the inhibition of nuclear β-catenin accumulation, suppressed p63 expression, and reduced the expression of cyclin D1 and p27KIP1; these observations suggest that ILK/β-catenin pathway may be involved in cell proliferation regulation during the ex vivo expansion of OMECs for transplantation purposes.
Determinants of High Fasting Insulin and Insulin Resistance Among Overweight/Obese Adolescents
Authors: Ling Jerri Chiu Yun , Mohamed Mohd Nahar Azmi , Jalaludin Muhammad Yazid , Rampal Sanjay , Zaharan Nur Lisa , Mohamed Zahurin
Published: November 2016

Hyperinsulinaemia is the earliest subclinical metabolic abnormality, which precedes insulin resistance in obese children. An investigation was conducted on the potential predictors of fasting insulin and insulin resistance among overweight/obese adolescents in a developing Asian country. A total of 173 overweight/obese (BMI > 85th percentile) multi-ethnic Malaysian adolescents aged 13 were recruited from 23 randomly selected schools in this cross-sectional study. Waist circumference (WC), body fat percentage (BF%), physical fitness score (PFS), fasting glucose and fasting insulin were measured. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Adjusted stepwise multiple regression analysis was performed to predict fasting insulin and HOMA-IR. Covariates included pubertal stage, socioeconomic status, nutritional and physical activity scores. One-third of our adolescents were insulin resistant, with girls having significantly higher fasting insulin and HOMA-IR than boys. Gender, pubertal stage, BMI, WC and BF% had significant, positive moderate correlations with fasting insulin and HOMA-IR while PFS was inversely correlated (p < 0.05). Fasting insulin was primarily predicted by gender-girls (Beta = 0.305, p < 0.0001), higher BMI (Beta = −0.254, p = 0.02) and greater WC (Beta = 0.242, p = 0.03). This study demonstrated that gender, BMI and WC are simple predictors of fasting insulin and insulin resistance in overweight/obese adolescents.
Structural changes induced by acidic pH in human apolipoprotein B-100
Authors: Fernández-Higuero José A. , Benito-Vicente Asier , Etxebarria Aitor , Milicua José Carlos G. , Ostolaza Helena , Arrondo José L. R. , Martín Cesar
Published: November 2016

Acidification in the endosome causes lipoprotein release by promoting a conformational change in the LDLR allowing its recycling and degradation of LDL. Notwithstanding conformational changes occurring in the LDLR have expanded considerably, structural changes occurring in LDL particles have not been fully explored yet. The objectives of the present work were to study structural changes occurring in apoB100 by infrared spectroscopy (IR) and also LDL size and morphology by dynamic light scattering (DLS) and electron microscopy (EM) at both pH 7.4 and 5.0. We determined by IR that pH acidification from 7.4 to 5.0, resembling that occurring within endosomal environment, induces a huge reversible structural rearrangement of apoB100 that is characterized by a reduction of beta-sheet content in favor of alpha-helix structures. Data obtained from DLS and EM showed no appreciable differences in size and morphology of LDL. These structural changes observed in apoB100, which are likely implied in particle release from lipoprotein receptor, also compromise the apoprotein stability what would facilitate LDL degradation. In conclusion, the obtained results reveal a more dynamic picture of the LDL/LDLR dissociation process than previously perceived and provide new structural insights into LDL/LDLR interactions than can occur at endosomal low-pH milieu.
DDR1 promotes E-cadherin stability via inhibition of integrin-β1-Src activation-mediated E-cadherin endocytosis
Authors: Chen Hong-Ru , Yeh Yi-Chun , Liu Ching-Yi , Wu Yu-Ting , Lo Fang-Yu , Tang Ming-Jer , Wang Yang-Kao
Published: November 2016

Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase of collagen, is primarily expressed in epithelial cells. Activation of DDR1 stabilises E-cadherin located on the cell membrane; however, the detailed mechanism of DDR1-stabilised E-cadherin remains unclear. We performed DDR1 knockdown (Sh-DDR1) on Mardin-Darby canine kidney cells to investigate the mechanism of DDR1-stabilised E-cadherin. Sh-DDR1 decreased junctional localisation, increased endocytosis of E-cadherin, and increased physical interactions between E-cadherin and clathrin. Treatment of the dynamin inhibitor Dyngo 4a suppressed Sh-DDR1-induced E-cadherin endocytosis. In addition, the phosphorylation level of Src tyrosine 418 was increased in Sh-DDR1 cell junctions, and inhibition of Src activity decreased Sh-DDR1-induced E-cadherin endocytosis. To characterise the molecular mechanisms, blocking integrin β1 decreased Src activity and E-cadherin junctional localisation in Sh-DDR1 cells. Photoconversion results showed that inhibition of Src activity rescued E-cadherin membrane stability and that inhibition of integrin β1-Src signalling decreased stress fibres and rescued E-cadherin membrane stability in Sh-DDR1 cells. Taken together, DDR1 stabilised membrane localisation of E-cadherin by inhibiting the integrin β1-Src-mediated clathrin-dependent endocytosis pathway.
Detailed Analysis of Protein Topology of Extracellular Vesicles–Evidence of Unconventional Membrane Protein Orientation
Authors: Cvjetkovic Aleksander , Jang Su Chul , Konečná Barbora , Höög Johanna L. , Sihlbom Carina , Lässer Cecilia , Lötvall Jan
Published: November 2016

Extracellular vesicles (EVs) are important mediators of intercellular communication that change the recipient cell by shuttling lipids, RNA, or protein cargo between cells. Here, we investigate the topology of the protein cargo found in EVs, as this topology can fundamentally influence the biological effects of EVs. A multiple proteomics approach, combining proteinase treatment and biotin tagging, shows that many proteins of cytosolic origin are localized on the surface of EVs. A detailed analysis of the EV proteome at the peptide level revealed that a number of EV membrane proteins are present in a topologically reversed orientation compared to what is annotated. Two examples of such proteins, SCAMP3 and STX4, were confirmed to have a reversed topology. This reversed typology was determined using flow cytometry and fluorescent microscopy with antibodies directed toward their cytoplasmic epitopes. These results describe a novel workflow to define the EV proteome and the orientation of each protein, including membrane protein topology. These data are fundamentally important to understanding the EV proteome and required to fully explain EV biogenesis as well as biological function in recipient cells.
Boreal earliest Triassic biotas elucidate globally depauperate hard substrate communities after the end-Permian mass extinction
Authors: Zatoń Michał , Niedźwiedzki Grzegorz , Blom Henning , Kear Benjamin P.
Published: November 2016

The end-Permian mass extinction constituted the most devastating biotic crisis of the Phanerozoic. Its aftermath was characterized by harsh marine conditions incorporating volcanically induced oceanic warming, widespread anoxia and acidification. Bio-productivity accordingly experienced marked fluctuations. In particular, low palaeolatitude hard substrate communities from shallow seas fringing Western Pangaea and the Tethyan Realm were extremely impoverished, being dominated by monogeneric colonies of filter-feeding microconchid tubeworms. Here we present the first equivalent field data for Boreal hard substrate assemblages from the earliest Triassic (Induan) of East Greenland. This region bordered a discrete bio-realm situated at mid-high palaeolatitude (>30°N). Nevertheless, hard substrate biotas were compositionally identical to those from elsewhere, with microconchids encrustingClaraiabivalves and algal buildups on the sea floor. Biostratigraphical correlation further shows that Boreal microconchids underwent progressive tube modification and unique taxic diversification concordant with changing habitats over time. We interpret this as a post-extinction recovery and adaptive radiation sequence that mirrored coeval subequatorial faunas, and thus confirms hard substrate ecosystem depletion as a hallmark of the earliest Triassic interval globally.
Identification of Novel HLA-A*0201-Restricted CTL Epitopes in Chinese Vitiligo Patients
Authors: Cui Tingting , Yi Xiuli , Guo Sen , Zhou Fubo , Liu Ling , Li Chunying , Li Kai , Gao Tianwen
Published: November 2016

Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair. Recent studies suggested the key role of CD8+T lymphocytes for mediating immune response in vitiligo through melanocyte differentiation antigens, including tyrosinase, gp100 and MelanA/Mart-1. However, the specific epitopes of these auto-antigens are still unknown. In our study, we predicted the possible HLA-A*0201-restricted nonapeptides overlaying the full-length amino acid sequences of these three known antigens and investigated the lymphocytes reactivity to these nonapeptides by Elispot assay. In addition, we evaluated the abilities of these nonapeptides to activate CD8+T cells. We screened out 5 possible epitopes originated from tyrosinase and gp100, numbered P28, P41, P112, P118 and P119. Among these 5 epitopes, notably, P28 and P119 played the dominant role in activating CTLs, with a significant increase in proliferation rate and Interferon-γ (IFN-γ) production of CD8+T cells. Nevertheless, antigen-specific T cell reactivity was not detected in MelanA/Mart-1 peptides. Our studies identified two novel epitopes originated from proteins of gp100 and tyrosinase, which may have implications for the development of immunotherapies for vitiligo.