bluuebunny/crossref_metadata_2025_split huggingface dataset:
EVEN ORPHEUS NEEDS A SYNTHI
Authors: Gardner James 
Published: April 2016

AbstractIn recent years there has been an increase in the quantity, if not necessarily the quality, of scholarly and popular writing on the histories of electronic music in Britain. In this literature, the contributions of Peter Zinovieff (b. 1933) and his computer-equipped electronic music studio to those histories have been variously exaggerated, underestimated and misreported. This article attempts to correct this misinformation, investigating Zinovieff's solo work and his collaborations with Harrison Birtwistle, Hans Werner Henze and others, through a critical discussion of two recent contributions to the discourse surrounding the compositions realised at Zinovieff's EMS studio in the 1960s and 70s.
Keeping your Friends Close: British Foreign Policy and the Nordic Economic Community, 1968–1972
Authors: BROAD MATTHEW 
Published: April 2016

AbstractThe Nordic Economic Community (Nordek) was a short-lived and ultimately unsuccessful attempt to strengthen cooperation between the four Nordic states. While the importance of the project to Britain has often been overlooked, this article suggests that Whitehall took considerable interest from the start. It demonstrates how, although officially neutral, London sought first to mitigate the effects of Nordek, then to undermine its establishment and, finally, in the wake of Nordek's collapse, to guard against its re-emergence. The aim throughout was to protect three central tenets of British foreign policy: EFTA unity in light of the second veto, Britain's own application for EEC membership and a cohesive Western Europe militarily integrated in NATO. However, the article highlights the absence of a coherent strategy towards tentative Nordic integration and the mixed success this brought, the interdependency of Anglo-Nordic relations in the pursuit and success of British foreign policy goals and the relative decline of the Britain's influence in the Nordic region.
NATO and the Environment: The Committee on the Challenges of Modern Society
Authors: RISSO LINDA 
Published: April 2016

AbstractLaunched with considerable fanfare in 1969, the Committee on the Challenges of Modern Society (CCMS) was supposed to bring new life to NATO by both re-energising public support and engaging with a variety of themes, issues and partners well beyond the alliance's traditional scope. The first aim of this article is to go beyond the careful media operation that surrounded the launch of the CCMS and to examine the scepticism and resistance of some European partners, particularly the British. The second aim is to demonstrate that NATO started to think in terms of crisis management, disaster relief and environmental disasters well before 1989. The sheer military strength of the alliance and of its partners did remain central – and notably came back to the forefront in 1979 – but the alliance did start to see itself as a geopolitical player and to consider engagement beyond its strictly defined geographical area as early as 1969.
Radiotherapy in sentinel node-positive breast cancer: results of an international survey
Authors: O’Sullivan Siobhra , Rock Kathy , ElBeltagi Nazmy 
Published: April 2016

AbstractPurposeThe purpose of this study was to assess the radiotherapy fields being offered to women with a positive sentinel lymph node (SLN) who have not had axillary lymph node dissection (ALND), based on the American College of Surgeons Oncology Group Z11 results.MethodsWe conducted a postal survey, addressed to radiation oncologists specialising in breast cancer treatment. In total, 179 cancer centres were contacted. Three hypothetical case scenarios were presented. In each case, the patient is clinically node negative but has a positive SLN following breast-conserving surgery, without further ALND. Respondents were asked what radiotherapy fields they would treat with in each scenario.ResultsWe received responses from 90 radiation oncologists from 73 centres in 11 countries. In the three scenarios (low, intermediate and high risk of further lymph node involvement), standard tangential beams would be used by only 27, 12 and 7%, respectively; high tangential beams by 33, 18 and 13%; tangents with full axillary/supraclavicular irradiation by 26, 51 and 61%; the remaining 14, 19 and 19% would use a nomogram to aid their decision.ConclusionThis survey describes the lack of consensus regarding the management of the axilla in patients with clinically node-negative breast cancer but a positive sentinel node and who have not had ALND.
Estimates for the number of visible galaxy-spanning civilizations and the cosmological expansion of life
Authors: Olson S. Jay 
Published: April 2016

AbstractIf advanced civilizations appear in the universe with an ability and desire to expand, the entire universe can become saturated with life on a short timescale, even if such expanders appear rarely. Our presence in an apparently untouched Milky Way thus constrains the appearance rate of galaxy-spanning Kardashev type III (K3) civilizations, if it is assumed that some fraction of K3 civilizations will continue their expansion at intergalactic distances. We use this constraint to estimate the appearance rate of K3 civilizations for 81 cosmological scenarios by specifying the extent to which humanity is a statistical outlier. We find that in nearly all plausible scenarios, the distance to the nearest visible K3 is cosmological. In searches for K3 galaxies where the observable range is limited, we also find that the most likely detections tend to be expanding civilizations who have entered the observable range from farther away. An observation of K3 clusters is thus more likely than isolated K3 galaxies.
THE MODULI SPACE OF TWISTED CANONICAL DIVISORS
Authors: Farkas Gavril , Pandharipande Rahul 
Published: April 2016

The moduli space of canonical divisors (with prescribed zeros and poles) on nonsingular curves is not compact since the curve may degenerate. We define a proper moduli space of twisted canonical divisors in $\overline{{\mathcal{M}}}_{g,n}$ which includes the space of canonical divisors as an open subset. The theory leads to geometric/combinatorial constraints on the closures of the moduli spaces of canonical divisors.In case the differentials have at least one pole (the strictly meromorphic case), the moduli spaces of twisted canonical divisors on genus $g$ curves are of pure codimension $g$ in $\overline{{\mathcal{M}}}_{g,n}$. In addition to the closure of the canonical divisors on nonsingular curves, the moduli spaces have virtual components. In the Appendix A, a complete proposal relating the sum of the fundamental classes of all components (with intrinsic multiplicities) to a formula of Pixton is proposed. The result is a precise and explicit conjecture in the tautological ring for the weighted fundamental class of the moduli spaces of twisted canonical divisors.As a consequence of the conjecture, the classes of the closures of the moduli spaces of canonical divisors on nonsingular curves are determined (both in the holomorphic and meromorphic cases).
Questions and controversies in innate immune research: what is the physiological role of NLRP3?
Authors: Coll RC , O’Neill LAJ , Schroder K 
Published: April 2016

AbstractThe NLRP3 inflammasome is a key component of the innate immune system that induces pro-inflammatory cytokine production and cell death. Although NLRP3 is activated by many pathogens, it only appears to be critical for host defense for a limited number of specific infections. NLRP3 is however strongly associated with the initiation and pathology of many inflammatory diseases. If NLRP3 function is largely redundant for host defense, but drives a number of inflammatory diseases, this raises the important question of why evolution has elected to maintain NLRP3 function. We propose that the primary physiological functions of NLRP3 in health are to engage pathways to clear noxious substances (e.g. protein aggregates and crystals), and to regulate metabolism. We discuss the newly identified functions for NLRP3 in metabolic homeostasis, and how NLRP3 beneficial functions in homeostasis may become detrimental during the onset of inflammatory and metabolic diseases. A common feature of most NLRP3-driven diseases is that they are associated with ageing or metabolic excess, and indeed, Nlrp3 deficiency promotes ‘healthspan’ in ageing mice. This suggests that beneficial functions of NLRP3 in youth may become increasingly countered by NLRP3-dependent pathology as an individual ages, and we propose a general model by which ageing or nutrient excess may provide a tipping point to switch NLRP3 function from beneficial to pathological. The physiological role of NLRP3 in healthy individuals remains incompletely understood and future research will need to address this if NLRP3 is to become a successful therapeutic target for the clinical management of inflammatory diseases.
Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy
Authors: Findlay John M. , Castro-Giner Francesc , Makino Seiko , Rayner Emily , Kartsonaki Christiana , Cross William , Kovac Michal , Ulahannan Danny , Palles Claire , Gillies Richard S. , MacGregor Thomas P. , Church David , Maynard Nicholas D. , Buffa Francesca , Cazier Jean-Baptiste , Graham Trevor A. , Wang Lai-Mun , Sharma Ricky A. , Middleton Mark , Tomlinson Ian 
Published: April 2016

AbstractHow chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful.
Cdk1 activity acts as a quantitative platform for coordinating cell cycle progression with periodic transcription
Authors: Banyai Gabor , Baïdi Feriel , Coudreuse Damien , Szilagyi Zsolt 
Published: April 2016

AbstractCell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires the periodic expression of particular gene clusters in different cell cycle phases. However, the interplay between the networks that generate these transcriptional oscillations and the core cell cycle machinery remains largely unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate that periodic expression is governed by quantitative changes in Cdk1 activity, with different clusters directly responding to specific activity levels. We further establish that cell cycle events neither participate in nor interfere with the Cdk1-driven transcriptional program, provided that cells are exposed to the appropriate Cdk1 activities. These findings contrast with current models that propose self-sustained and Cdk1-independent transcriptional oscillations. Our work therefore supports a model in which Cdk1 activity serves as a quantitative platform for coordinating cell cycle transitions with the expression of critical genes to bring about proper cell cycle progression.
Frequency and bandwidth conversion of single photons in a room-temperature diamond quantum memory
Authors: Fisher Kent A. G. , England Duncan G. , MacLean Jean-Philippe W. , Bustard Philip J. , Resch Kevin J. , Sussman Benjamin J. 
Published: April 2016

AbstractThe spectral manipulation of photons is essential for linking components in a quantum network. Large frequency shifts are needed for conversion between optical and telecommunication frequencies, while smaller shifts are useful for frequency-multiplexing quantum systems, in the same way that wavelength division multiplexing is used in classical communications. Here we demonstrate frequency and bandwidth conversion of single photons in a room-temperature diamond quantum memory. Heralded 723.5 nm photons, with 4.1 nm bandwidth, are stored as optical phonons in the diamond via a Raman transition. Upon retrieval from the diamond memory, the spectral shape of the photons is determined by a tunable read pulse through the reverse Raman transition. We report central frequency tunability over 4.2 times the input bandwidth, and bandwidth modulation between 0.5 and 1.9 times the input bandwidth. Our results demonstrate the potential for diamond, and Raman memories in general, as an integrated platform for photon storage and spectral conversion.
Prevention of gastrointestinal lead poisoning using recombinant Lactococcus lactis expressing human metallothionein-I fusion protein
Authors: Xiao Xue , Zhang Changbin , Liu Dajun , Bai Weibin , Zhang Qihao , Xiang Qi , Huang Yadong , Su Zhijian 
Published: April 2016

AbstractLow-level lead poisoning is an insidious disease that affects millions of children worldwide, leading to biochemical and neurological dysfunctions. Blocking lead uptake via the gastrointestinal tract is an important prevention strategy. With this in mind, we constructed the recombinant Lactococcus lactis strain pGSMT/MG1363, which constitutively expressed the fusion protein glutathione S-transferase (GST)–small molecule ubiquitin-like modifier protein (SUMO)–metallothionein-I (GST-SUMO-MT). The thermodynamic data indicated that the average number of lead bound to a GST-SUMO-MT molecule was 3.655 and this binding reaction was a spontaneous, exothermic and entropy-increasing process. The total lead-binding capacity of pGSMT/MG1363 was 4.11 ± 0.15 mg/g dry mass. Oral administration of pGSMT/MG1363 (1 × 1010 Colony-Forming Units) to pubertal male rats that were also treated with 5 mg/kg of lead acetate daily significantly inhibited the increase of blood lead levels, the impairment of hepatic function and the decrease of testosterone concentration in the serum, which were all impaired in rats treated by lead acetate alone. Moreover, the administration of pGSMT/MG1363 for 6 weeks did not affect the serum concentration of calcium, magnesium, potassium or sodium ions. This study provides a convenient and economical biomaterial for preventing lead poisoning via the digestive tract.
N-acetylaspartate catabolism determines cytosolic acetyl-CoA levels and histone acetylation in brown adipocytes
Authors: Prokesch A. , Pelzmann H. J. , Pessentheiner A. R. , Huber K. , Madreiter-Sokolowski C. T. , Drougard A. , Schittmayer M. , Kolb D. , Magnes C. , Trausinger G. , Graier W. F. , Birner-Gruenberger R. , Pospisilik J. A. , Bogner-Strauss J. G. 
Published: April 2016

AbstractHistone acetylation depends on the abundance of nucleo-cytoplasmic acetyl-CoA. Here, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. N-acetylaspartate (NAA) is a highly abundant brain metabolite catabolized by aspartoacylase yielding aspartate and acetate. The latter can be further used for acetyl-CoA production. Prior to this work, the presence of NAA has not been described in adipocytes. Here, we show that accumulation of NAA decreases the brown adipocyte phenotype. We increased intracellular NAA concentrations in brown adipocytes via media supplementation or knock-down of aspartoacylase and measured reduced lipolysis, thermogenic gene expression and oxygen consumption. Combinations of approaches to increase intracellular NAA levels showed additive effects on lipolysis and gene repression, nearly abolishing the expression of Ucp1, Cidea, Prdm16 and Ppara. Transcriptome analyses of aspartoacylase knock-down cells indicate deficiencies in acetyl-CoA and lipid metabolism. Concordantly, cytoplasmic acetyl-CoA levels and global histone H3 acetylation were decreased. Further, activating histone marks (H3K27ac and H3K9ac) in promoters/enhancers of brown marker genes showed reduced acetylation status. Taken together, we present a novel route for cytoplasmic acetyl-CoA production in brown adipocytes. Thereby, we mechanistically connect the NAA pathway to the epigenomic regulation of gene expression, modulating the phenotype of brown adipocytes.
Molecular Interactions between Tarantula Toxins and Low-Voltage-Activated Calcium Channels
Authors: Salari Autoosa , Vega Benjamin S. , Milescu Lorin S. , Milescu Mirela 
Published: April 2016

AbstractFew gating-modifier toxins have been reported to target low-voltage-activated (LVA) calcium channels and the structural basis of toxin sensitivity remains incompletely understood. Studies of voltage-gated potassium (Kv) channels have identified the S3b–S4 “paddle motif,” which moves at the protein-lipid interface to drive channel opening, as the target for these amphipathic neurotoxins. Voltage-gated calcium (Cav) channels contain four homologous voltage sensor domains, suggesting multiple toxin binding sites. We show here that the S3–S4 segments within Cav3.1 can be transplanted into Kv2.1 to examine their individual contributions to voltage sensing and pharmacology. With these results, we now have a more complete picture of the conserved nature of the paddle motif in all three major voltage-gated ion channel types (Kv, Nav and Cav). When screened with tarantula toxins, the four paddle sequences display distinct toxin binding properties, demonstrating that gating-modifier toxins can bind to Cav channels in a domain specific fashion. Domain III was the most commonly and strongly targeted and mutagenesis revealed an acidic residue that is important for toxin binding. We also measured the lipid partitioning strength of all toxins tested and observed a positive correlation with their inhibition of Cav3.1, suggesting a key role for membrane partitioning.
Discovery and characterisation of a novel toxin from Dendroaspis angusticeps, named Tx7335, that activates the potassium channel KcsA
Authors: Rivera-Torres Iván O. , Jin Tony B. , Cadene Martine , Chait Brian T. , Poget Sébastien F. 
Published: April 2016

AbstractDue to their central role in essential physiological processes, potassium channels are common targets for animal toxins. These toxins in turn are of great value as tools for studying channel function and as lead compounds for drug development. Here, we used a direct toxin pull-down assay with immobilised KcsA potassium channel to isolate a novel KcsA-binding toxin (called Tx7335) from eastern green mamba snake (Dendroaspis angusticeps) venom. Sequencing of the toxin by Edman degradation and mass spectrometry revealed a 63 amino acid residue peptide with 4 disulphide bonds that belongs to the three-finger toxin family, but with a unique modification of its disulphide-bridge scaffold. The toxin induces a dose-dependent increase in both open probabilities and mean open times on KcsA in artificial bilayers. Thus, it unexpectedly behaves as a channel activator rather than an inhibitor. A charybdotoxin-sensitive mutant of KcsA exhibits similar susceptibility to Tx7335 as wild-type, indicating that the binding site for Tx7335 is distinct from that of canonical pore-blocker toxins. Based on the extracellular location of the toxin binding site (far away from the intracellular pH gate), we propose that Tx7335 increases potassium flow through KcsA by allosterically reducing inactivation of the channel.
Realization of Minimum and Maximum Gate Function in Ta2O5-based Memristive Devices
Authors: Breuer Thomas , Nielen Lutz , Roesgen Bernd , Waser Rainer , Rana Vikas , Linn Eike 
Published: April 2016

AbstractRedox-based resistive switching devices (ReRAM) are considered key enablers for future non-volatile memory and logic applications. Functionally enhanced ReRAM devices could enable new hardware concepts, e.g. logic-in-memory or neuromorphic applications. In this work, we demonstrate the implementation of ReRAM-based fuzzy logic gates using Ta2O5 devices to enable analogous Minimum and Maximum operations. The realized gates consist of two anti-serially connected ReRAM cells offering two inputs and one output. The cells offer an endurance up to 106 cycles. By means of exemplary input signals, each gate functionality is verified and signal constraints are highlighted. This realization could improve the efficiency of analogous processing tasks such as sorting networks in the future.
Synergy of TLR3 and 7 ligands significantly enhances function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway
Authors: Hu Yue , Cong Xiaoyan , Chen Lei , Qi Jing , Wu Xiangju , Zhou Mingming , Yoo Dongwan , Li Feng , Sun Wenbo , Wu Jiaqiang , Zhao Xiaomin , Chen Zhi , Yu Jiang , Du Yijun , Wang Jinbao 
Published: April 2016

AbstractPRRS is one of the most important diseases in swine industry. Current PRRS inactivated vaccine provides only a limited protection and cannot induce sufficient cell-mediated immune responses. In this study, we first found that the mRNA and protein levels of Th1-type cytokines (IFN-γ, IL-12) and Th2-type cytokines (IL-6, IL-10) were significantly increased through TRIF/MyD88-NF-κB signaling pathway when porcine peripheral blood monocyte-derived dendritic cells (MoDCs) were treated with poly (I: C) of TLR3 ligand and imiquimod of TLR7 ligand, along with inactivated PRRSV antigen. Meanwhile, the ability of catching PRRSV antigen was also significantly enhanced. In mice experiment, it was found that the PRRSV-specific T lymphocyte proliferation, the percentages of CD4+, CD8+ T lymphocytes and PRRSV-specific CD3+ T cells producing IFN-γ and IL-4, the levels of Th1- and Th2-type cytokines and the titers of neutralization antibody were significantly enhanced in poly (I: C), imiquimod along with inactivated PRRSV group. Taken together, results of our experiments described for the first time that synergy of TLR3 and 7 ligands could significantly enhance the function of DCs to present inactivated PRRSV antigen through TRIF/MyD88-NF-κB signaling pathway and be used as adjuvant candidate for the development of novel PRRS inactivated vaccine.
Predator-prey dynamics stabilised by nonlinearity explain oscillations in dust-forming plasmas
Authors: Ross A. E. , McKenzie D. R. 
Published: April 2016

AbstractDust-forming plasmas are ionised gases that generate particles from a precursor. In nature, dust-forming plasmas are found in flames, the interstellar medium and comet tails. In the laboratory, they are valuable in generating nanoparticles for medicine and electronics. Dust-forming plasmas exhibit a bizarre, even puzzling behaviour in which they oscillate with timescales of seconds to minutes. Here we show how the problem of understanding these oscillations may be cast as a predator-prey problem, with electrons as prey and particles as predators. The addition of a nonlinear loss term to the classic Lotka-Volterra equations used for describing the predator-prey problem in ecology not only stabilises the oscillations in the solutions for the populations of electrons and particles in the plasma but also explains the behaviour in more detail. The model explains the relative phase difference of the two populations, the way in which the frequency of the oscillations varies with the concentration of the precursor gas and the oscillations of the light emission, determined by the populations of both species. Our results demonstrate the value of adopting an approach to a complex physical science problem that has been found successful in ecology, where complexity is always present.