bluuebunny/crossref_metadata_2025_split huggingface dataset:
Law Reporting in England 1550–1650
Authors: Baker John 
Published: November 2017

AbstractEnglish law reports between 1550 and 1650 seem far more accessible today than the “year books” that preceded them. This is not because they were produced differently, for a different readership or by a different kind of reporter, but because the legal system itself had changed. We also encounter in the Tudor period the first reports written by eminent lawyers, two of whom (Plowden and Coke) saw a selection of them through the press in their lifetimes. Recent editorial work on the better reports has revealed something of the way they were compiled, and also of what was omitted when contemporary notes were turned into printed volumes.Coke's reports are the most famous, traditionally cited simply as The Reports. Work has just begun on an edition of the underlying notebooks (first discovered just forty years ago), which will probably require at least six volumes. Coke's reporting style was controversial, and his alleged subjectivity was seized upon by Francis Bacon as one of the grounds for bringing him down in 1616. However, Bacon's scheme of 1617 to engage professional reporters, paid by the crown, seems to have collapsed after a few years. Law reporting was thus to remain a matter of private initiative until the end of the eighteenth century, and many of the best reports – even those written by judges – have still not been published. Anyone seeking to trace the evolution of a legal doctrine or practice before about 1700 must regard manuscript reports as an essential recourse.
What is the importance of islands to environmental conservation?
Authors: KUEFFER CHRISTOPH , KINNEY KEALOHANUIOPUNA 
Published: November 2017

SUMMARYThis article discusses four features of islands that make them places of special importance to environmental conservation. First, investment in island conservation is both urgent and cost-effective. Islands are threatened hotspots of diversity that concentrate unique cultural, biological and geophysical values, and they form the basis of the livelihoods of millions of islanders. Second, islands are paradigmatic places of human–environment relationships. Island livelihoods have a long tradition of existing within spatial, ecological and ultimately social boundaries and are still often highly dependent on local resources and social cohesion. Island cultures and their rich biocultural knowledge can be an important basis for revitalizing and innovating sustainable human–nature relationships. Third, islands form a global web that interlinks biogeographic regions and cultural spaces. They are nodes in a global cultural network: as multicultural island societies, through diaspora islander communities on continents and through numerous political and trade relationships among islands and between islands and countries on continents. Fourth, islands can serve as real-world laboratories that enable scientific innovation, integration of local and generalized knowledge and social learning and empowerment of local actors. We conclude that island systems can serve as globally distributed hubs of innovation, if the voices of islanders are better recognized.
Class matters: the sociolinguistics ofgooseandgoatin Manchester English
Authors: Baranowski Maciej 
Published: November 2017

AbstractThis paper reports on patterns of sociolinguistic variation and change in Manchester'sgooseandgoatvowels on the basis of the acoustic analysis of 122 speakers, stratified by age, gender, socioeconomic status, and ethnicity.Goosefronting is an internal change showing little social differentiation, except before /l/ as inschoolandpool, where, in contrast to most other dialects of English,gooseshows advanced fronting inversely correlated with socioeconomic status.Goatfronting, on the other hand, is a change brought from outside the dialect by the highest status groups, displaying a pattern of monotonic social stratification, a female lead, and a strong effect of ethnicity. The role of attitudes toward the community in the realization of the vowels is compared with the effect of social class construed in terms of distances between social groups. Social class turns out to be a better predictor, suggesting that the role of attitudes and identity may be overestimated in research eschewing a systematic exploration of social class at the same time.
The effects of PI3K-mediated signalling on glioblastoma cell behaviour
Authors: Langhans Julia , Schneele Lukas , Trenkler Nancy , von Bandemer Hélène , Nonnenmacher Lisa , Karpel-Massler Georg , Siegelin Markus D. , Zhou Shaoxia , Halatsch Marc-Eric , Debatin Klaus-Michael , Westhoff Mike-Andrew 
Published: November 2017

AbstractThe PI3K/Akt/mTOR signalling network is activated in almost 90% of all glioblastoma, the most common primary brain tumour, which is almost invariably lethal within 15 months of diagnosis. Despite intensive research, modulation of this signalling cascade has so far yielded little therapeutic benefit, suggesting that the role of the PI3K network as a pro-survival factor in glioblastoma and therefore a potential target in combination therapy should be re-evaluated. Therefore, we used two distinct pharmacological inhibitors that block signalling at different points of the cascade, namely, GDC-0941 (Pictilisib), a direct inhibitor of the near apical PI3K, and Rapamycin which blocks the side arm of the network that is regulated by mTOR complex 1. While both substances, at concentrations where they inhibit their primary target, have similar effects on proliferation and sensitisation for temozolomide-induced apoptosis, GDC-0941 appears to have a stronger effect on cellular motility than Rapamycin. In vivo GDC-0941 effectively retards growth of orthotopic transplanted human tumours in murine brains and significantly prolongs mouse survival. However, when looking at genetically identical cell populations that are in alternative states of differentiation, i.e. stem cell-like cells and their differentiated progeny, a more complex picture regarding the PI3K/Akt/mTOR pathway emerges. The pathway is differently regulated in the alternative cell populations and, while it contributes to the increased chemo-resistance of stem cell-like cells compared to differentiated cells, it only contributes to the motility of the latter. Our findings are the first to suggest that within a glioblastoma tumour the PI3K network can have distinct, cell-specific functions. These have to be carefully considered when incorporating inhibition of PI3K-mediated signals into complex combination therapies.
Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches
Authors: Mariot Virginie , Joubert Romain , Hourdé Christophe , Féasson Léonard , Hanna Michael , Muntoni Francesco , Maisonobe Thierry , Servais Laurent , Bogni Caroline , Le Panse Rozen , Benvensite Olivier , Stojkovic Tanya , Machado Pedro M. , Voit Thomas , Buj-Bello Ana , Dumonceaux Julie 
Published: November 2017

AbstractMuscular dystrophies are characterized by weakness and wasting of skeletal muscle tissues. Several drugs targeting the myostatin pathway have been used in clinical trials to increase muscle mass and function but most showed limited efficacy. Here we show that the expression of components of the myostatin signaling pathway is downregulated in muscle wasting or atrophying diseases, with a decrease of myostatin and activin receptor, and an increase of the myostatin antagonist, follistatin. We also provide in vivo evidence in the congenital myotubular myopathy mouse model (knock-out for the myotubularin coding geneMtm1) that a down-regulated myostatin pathway can be reactivated by correcting the underlying gene defect. Our data may explain the poor clinical efficacy of anti-myostatin approaches in several of the clinical studies and the apparent contradictory results in mice regarding the efficacy of anti-myostatin approaches and may inform patient selection and stratification for future trials.
Optical charge state control of spin defects in 4H-SiC
Authors: Wolfowicz Gary , Anderson Christopher P. , Yeats Andrew L. , Whiteley Samuel J. , Niklas Jens , Poluektov Oleg G. , Heremans F. Joseph , Awschalom David D. 
Published: November 2017

AbstractDefects in silicon carbide (SiC) have emerged as a favorable platform for optically active spin-based quantum technologies. Spin qubits exist in specific charge states of these defects, where the ability to control these states can provide enhanced spin-dependent readout and long-term charge stability. We investigate this charge state control for two major spin qubits in 4H-SiC, the divacancy and silicon vacancy, obtaining bidirectional optical charge conversion between the bright and dark states of these defects. We measure increased photoluminescence from divacancy ensembles by up to three orders of magnitude using near-ultraviolet excitation, depending on the substrate, and without degrading the electron spin coherence time. This charge conversion remains stable for hours at cryogenic temperatures, allowing spatial and persistent patterning of the charge state populations. We develop a comprehensive model of the defects and optical processes involved, offering a strong basis to improve material design and to develop quantum applications in SiC.
Super-radiance reveals infinite-range dipole interactions through a nanofiber
Authors: Solano P. , Barberis-Blostein P. , Fatemi F. K. , Orozco L. A. , Rolston S. L. 
Published: November 2017

AbstractAtoms interact with each other through the electromagnetic field, creating collective states that can radiate faster or slower than a single atom, i.e., super- and sub-radiance. When the field is confined to one dimension it enables infinite-range atom–atom interactions. Here we present the first report of infinite-range interactions between macroscopically separated atomic dipoles mediated by an optical waveguide. We use cold 87Rb atoms in the vicinity of a single-mode optical nanofiber (ONF) that coherently exchange evanescently coupled photons through the ONF mode. In particular, we observe super-radiance of a few atoms separated by hundreds of resonant wavelengths. The same platform allows us to measure sub-radiance, a rarely observed effect, presenting a unique tool for quantum optics. This result constitutes a proof of principle for collective behavior of macroscopically delocalized atomic states, a crucial element for new proposals in quantum information and many-body physics.
A strategy for effective latent HIV reactivation using subtherapeutic drug doses
Authors: Cotterell James , Neely G. Gregory 
Published: November 2017

AbstractCell state switches underlie a plethora of biological phenomena and disease treatment strategies. Hence the ability to efficiently switch states in a chosen direction is of central importance in a number of scenarios. Increasing the concentration of an effector that results in a given switch is often limited by side effects. Approaches are thus increasingly sought to bypass these constraints, increasing the frequency of state switching without increasing the frequency of the side effect. Here, we employ dynamical systems theory to uncover a simple strategy as to how to maximize the probability of reactivating latent Human immunodeficiency virus (HIV) whilst maintaining minimal side effects. We demonstrate that continuous supply of an effector is significantly more likely to result in a switch with minimal side effects than the same effector supplied in temporally discrete doses. Importantly this continual dosage is likely to occur far below the Minimum effective dose at a concentration that has classically been thought subtherapeutic. We therefore suggest that in many interventional settings there exists potential to reduce drug dose much further than has previously been thought possible yet still maintaining efficacy.
Low-dose levels of bisphenol A inhibit telomerase via ER/GPR30-ERK signalling, impair DNA integrity and reduce cell proliferation in primary PBMC
Authors: Herz Corinna , Tran Hoai Thi Thu , Schlotz Nina , Michels Karin , Lamy Evelyn 
Published: November 2017

AbstractControversy exists about the human health risk of environmental exposure to bisphenol A (BPA). Telomerase activity is emerging both as biomarker and contributing factor for age-related diseases. The effects of BPA exposure at 1–1000 nM on telomerase, DNA integrity and cell proliferation were investigated in PBMC from human donors. Telomerase activity was determined by TRAP-ELISA assay and mRNA expression by qRT-PCR. Mechanistic studies were carried out on the ER/GPR30-ERK pathway using specific inhibitors/antagonists, the comet assay to quantify DNA damage and flow cytometry for cell proliferation. 24 h BPA exposure inhibited telomerase in a non-monotonic pattern with a peak inhibition of 32% at 1 nM (p ≤ 0.01). A significant telomerase inhibition was evident at 1 h after exposure with a minimum at 6 h. Elevated levels of DNA damage frequency and decrease in cell proliferation were evident upon long-term exposure. The results further demonstrate that BPA triggered rapidly an ER/GPR30-ERK transduction pathway that leads to decreased telomerase activity in human PBMC. This is the first study to demonstrate adverse impact of BPA at levels of current human exposure on telomerase in normal cells, mediated by ER/GPR30-ERK. The results suggest a potentially harmful influence of BPA on immune cells and should be addressed in future studies.
Adsorbed Conformations of PCE Superplasticizers in Cement Pore Solution Unraveled by Molecular Dynamics Simulations
Authors: Hirata Tsuyoshi , Ye Jun , Branicio Paulo , Zheng Jianwei , Lange Alex , Plank Johann , Sullivan Michael 
Published: November 2017

AbstractThe conformations of polycarboxylate ether (PCE) type superplasticizer polymers adsorbed on the surface of MgO in cement pore solution are simulated by molecular dynamics (MD). Three types of PCEs commonly applied to concrete are simulated, namely a methacrylate type PCE (PCEM-P), an allyl ether type PCE (PCEA-P), and an isoprenyl ether type PCE (PCEI-P) with ethylene oxide (EO) unit numbers (P) of 25, 34 and 25, respectively. It is observed that the adsorbed layer thickness is inversely proportional to the experimentally measured adsorbed amount at the initial paste flow of 26 ± 0.5 cm. Simulation results indicate that the adsorbed layer thickness is sensitive to the initial polymer orientations against the model MgO surface. I.e., polymer molecules initially placed parallel/perpendicularly against the MgO surface gradually forms a train shaped or a loop and tail adsorption profile, respectively. As a result, the loop and tail shaped conformation gives a higher layer thickness.
Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage
Authors: Ginjala Vasudeva , Rodriguez-Colon Lizahira , Ganguly Bratati , Gangidi Prawallika , Gallina Paul , Al-Hraishawi Husam , Kulkarni Atul , Tang Jeremy , Gheeya Jinesh , Simhadri Srilatha , Yao Ming , Xia Bing , Ganesan Shridar 
Published: November 2017

AbstractUpon induction of DNA breaks, ATM activation leads to a cascade of local chromatin modifications that promote efficient recruitment of DNA repair proteins. Errors in this DNA repair pathway lead to genomic instability and cancer predisposition. Here, we show that the protein lysine methyltransferase G9a (also known as EHMT2) and GLP1 (also known as EHMT1) are critical components of the DNA repair pathway. G9a and GLP1 rapidly localizes to DNA breaks, with GLP1 localization being dependent on G9a. ATM phosphorylation of G9a on serine 569 is required for its recruitment to DNA breaks. G9a catalytic activity is required for the early recruitment of DNA repair factors including 53BP and BRCA1 to DNA breaks. Inhibition of G9a catalytic activity disrupts DNA repair pathways and increases sensitivity to ionizing radiation. Thus, G9a is a potential therapeutic target in the DNA repair pathway.
Comprehensive high-throughput image analysis for therapeutic efficacy of architecturally complex heterotypic organoids
Authors: Bulin Anne-Laure , Broekgaarden Mans , Hasan Tayyaba 
Published: November 2017

AbstractBioengineered three-dimensional (3D) tumor models that incorporate heterotypic cellular communication are gaining interest as they can recapitulate key features regarding the intrinsic heterogeneity of cancer tissues. However, the architectural complexity and heterogeneous contents associated with these models pose a challenge for toxicological assays to accurately report treatment outcomes. To address this issue, we describe a comprehensive image analysis procedure for structurally complex organotypic cultures (CALYPSO) applied to fluorescence-based assays to extract multiparametric readouts of treatment effects for heterotypic tumor cultures that enables advanced analyses. The capacity of this approach is exemplified on various 3D models including adherent/suspension, mono-/heterocellular cultures and several disease types. The subsequent analysis revealed specific morphological effects of oxaliplatin chemotherapy, radiotherapy, and photodynamic therapy. The procedure can be readily implemented in most laboratories to facilitate high-throughput toxicological screening of pharmaceutical agents and treatment regimens on organotypic cultures of human disease to expedite drug and therapy development.
Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
Authors: Wang Yanyan , Lin Cai , Cao Yun , Duan Zhongliang , Guan Zhixun , Xu Jing , Zhu Xing-Quan , Xia Chaoming 
Published: November 2017

AbstractThe pathology of schistosome egg-induced liver granuloma, fibrosis and eventually liver scarring is complicated. CD4+ helper T (Th) cells play critical roles in both host humoral immunity and cellular immunity against parasitic infection and immunopathology in schistosomiasis. Follicular helper T (Tfh) cells are another specialized subset of Th cells and involved in infectious diseases. However, the immune regulatory mechanism of Tfh cells in severe liver pathology of schistosomiasis is still poorly understood. In this study, using a S. japonicum-infected mouse model, we studied the dynamics and effects of Tfh cells in vivo and demonstrated that Tfh phenotype molecules ICOS, PD-1 and functional factor IL-21 were positively correlated with disease development by flow cytometry. Meanwhile, our results also showed that Tfh cells enriched in splenic germinal center (GC) and promoted B cells producing IgM with the progress of hepatic immunopathology by B-T co-culture experiments. More importantly, our data indicated that IL-21 contributed to the formation and development of hepatic egg granuloma and subsequent fibrosis by driving GC responses and activating HSCs by immunohistochemical detection and blocking assay in vitro. Our findings contribute to the better understanding of the immunopathogenesis of schistosomiasis and have implications for therapeutic intervention of hepatic fibrotic diseases.
Regulation of ethylene-responsive SlWRKYs involved in color change during tomato fruit ripening
Authors: Wang Ling , Zhang Xue-lian , Wang Lu , Tian Yanan , Jia Ning , Chen Shuzhen , Shi Ning-bo , Huang Xuemei , Zhou Chu , Yu Yaowen , Zhang Zhao-qi , Pang Xue-qun 
Published: November 2017

AbstractWRKY transcription factors (TFs) play important roles in stress responses in planta. However, the function of WRKY TFs in the regulation of fruit ripening is unclear. Here, 23 tomato SlWRKYs that are similar to ethylene-responsive WRKY genes from other plant species, or show up-regulation during fruit ripening in previous genome-wide study, were selected, and their function in fruit ripening was investigated. Twelve SlWRKYs were found to be responsive to ethylene (SlER-WRKYs), showing expression patterns similar to those of genes related to fruit ripening. Eight SlER-WRKYs—SlWRKY16, 17, 22, 25, 31, 33, 53, and 54, detected in the nuclei—interacted with and activated the promoters of 4 genes related to color change: Pheophytin Pheophorbide Hydrolase (SlPPH), Pheophorbide a Oxygenase (SlPAO), Phytoene Synthase 1 (SlPSY1) and Phytoene Desaturase (SlPDS). Yeast two-hybrid and bimolecular fluorescence complement (BiFC) assays in Arabidopsis protoplasts indicated that protein interactions occurred between SlWRKY17 and SlRIN, SlERF2b or SlERF7; SlWRKY33 and SlERF7; SlWRKY54 and SlERF2b; and SlWRKY16 and SlWRKY17. Suppression of SlWRKY 16, 17, 53 or 54 by virus-induced gene silencing (VIGS) retarded the red coloration of the fruit. Our study provides comprehensive molecular evidence that WRKY TFs function in fruit ripening, particularly in color change, and are linked to the intricate regulatory network of other ripening regulators.
Light and Capillary Waves Propagation in Water Fibers
Authors: Douvidzon Mark L. , Maayani Shai , Martin Leopoldo L. , Carmon Tal 
Published: November 2017

AbstractThe confinement of light and sound, while they are traveling in fibers, enables a variety of light-matter interactions. Therefore, it is natural to ask if fibers can also host capillary waves. Capillary waves are similar to those we see when throwing a stone into a puddle. Such capillary waves are prohibited in microfluidic devices where the liquid is bounded by solid walls. In contrast, we have fabricated fibers, which are made entirely from water and are suspended in air. The water fiber can therefore move, e.g. in a resonant mode that reassembles the motion of a guitar string. In our experiment, light guided through the water fiber allows optical interrogation of is capillary oscillations. Co-confining two important oscillations in nature: capillary and electromagnetic, might allow a new type of devices called Micro-Electro-Capillary-Systems [MECS]. The softness of MECS is a million times higher when compared to what the current solid-based technology permits, which accordingly improves MECS response to minute forces such as small changes in acceleration. Additionally, MECS might allow new ways to optically interrogate viscosity and surface tension, as well as their changes caused by introducing an analyte into the system.
Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid protein of the Zika virus
Authors: Slomnicki Lukasz P. , Chung Dong-Hoon , Parker Austin , Hermann Taylor , Boyd Nolan L. , Hetman Michal 
Published: November 2017

AbstractWe report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus. The anti-nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C prevented nucleolar localization, ribosomal stress and apoptosis. Consistent with a casual relationship between ZIKV-C-induced ribosomal stress and apoptosis, ZIKV-C-overexpressing neurons were protected by loss-of-function manipulations targeting the ribosomal stress effector Tp53 or knockdown of the ribosomal stress mediator RPL11. Finally, capsid protein of Dengue virus, but not West Nile virus, induced ribosomal stress and apoptosis. Thus, anti-nucleolar and pro-apoptotic effects of protein C are flavivirus-species specific. In the case of ZIKV, capsid protein-mediated ribosomal stress may contribute to neuronal death, neurodevelopmental disruption and microcephaly.