bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Telos Reconciliation Dossier (IG XII.4.132): Democracy, Demagogues and Stasis in an Early Hellenistic Polis
Authors: Simonton Matthew 
Published: September 2019

AbstractThis article examines the remarkable inscribed monument IG XII.4.132, a dossier of documents dealing with political strife and reconciliation in the small island polis of Telos, as an important new piece of evidence for democracy in the early Hellenistic period. Placing the monument in its historical, geographical and political context, I argue that the background to the strife was most likely the activity of ‘demagogues’ in the courts of democratic Telos. Furthermore, we should view the terms of the reconciliation against the backdrop of issues of community service, publicity and memorialization, all contested political topics in the late Classical and early Hellenistic periods. The dossier shows that the kinds of ‘high politics’ and stasis that affected major poleis could be found also in the small cities of the Greek world, with important local variations. The document sits at a historical crossroads in terms both of judicial practices (including the use of foreign judges) and of constitutional forms (democracy and oligarchy).
The Ostensible Author of PS.-Aeschines Letter 10 Reconsidered
Authors: Guo Zilong 
Published: September 2019

AbstractThis article examines the alleged author, or first-person narrator, of the tenth pseudonymous letter in the Corpus Aeschineum. It argues that the forger, in a short epistolary novel that describes the seduction of a certain Callirhoe in Troy, uses puns (αἰσχύνειν, ἀναισχυντία, etc.) on the name of the fourth-century BC orator Aeschines. It notes that αἰσχρός-words recur in ancient works and, as a rhetorical device, are attested in Demosthenes. The forger’s aims are, first, to serialize the ‘Aeschinean’ letters as a whole by relating them to the same author and, second, to create an ‘aischrologic’ counterpart of the Callirhoe, which is attributed to Chariton (Χαρίτων/‘The Graceful’). Thus there is less likelihood of suggesting other figures such as the eponymous Aeschines Socraticus.
Enhancing Magic Sets with an Application to Ontological Reasoning
Authors: ALVIANO MARIO , LEONE NICOLA , VELTRI PIERFRANCESCO , ZANGARI JESSICA 
Published: September 2019

AbstractMagic sets are a Datalog to Datalog rewriting technique to optimize query answering. The rewritten program focuses on a portion of the stable model(s) of the input program which is sufficient to answer the given query. However, the rewriting may introduce new recursive definitions, which can involve even negation and aggregations, and may slow down program evaluation. This paper enhances the magic set technique by preventing the creation of (new) recursive definitions in the rewritten program. It turns out that the new version of magic sets is closed for Datalog programs with stratified negation and aggregations, which is very convenient to obtain efficient computation of the stable model of the rewritten program. Moreover, the rewritten program is further optimized by the elimination of subsumed rules and by the efficient handling of the cases where binding propagation is lost. The research was stimulated by a challenge on the exploitation of Datalog/dlv for efficient reasoning on large ontologies. All proposed techniques have been hence implemented in the dlv system, and tested for ontological reasoning, confirming their effectiveness.
Paracoherent Answer Set Semantics meets Argumentation Frameworks
Authors: AMENDOLA GIOVANNI , RICCA FRANCESCO 
Published: September 2019

AbstractIn the last years, abstract argumentation has met with great success in AI, since it has served to capture several non-monotonic logics for AI. Relations between argumentation framework (AF) semantics and logic programming ones are investigating more and more. In particular, great attention has been given to the well-known stable extensions of an AF, that are closely related to the answer sets of a logic program. However, if a framework admits a small incoherent part, no stable extension can be provided. To overcome this shortcoming, two semantics generalizing stable extensions have been studied, namely semi-stable and stage. In this paper, we show that another perspective is possible on incoherent AFs, called paracoherent extensions, as they have a counterpart in paracoherent answer set semantics. We compare this perspective with semi-stable and stage semantics, by showing that computational costs remain unchanged, and moreover an interesting symmetric behaviour is maintained.
Applying Constraint Logic Programming to SQL Semantic Analysis
Authors: SÁENZ-PÉREZ FERNANDO 
Published: September 2019

AbstractThis paper proposes the use of Constraint Logic Programming (CLP) to model SQL queries in a data-independent abstract layer by focusing on some semantic properties for signalling possible errors in such queries. First, we define a translation from SQL to Datalog, and from Datalog to CLP, so that solving this CLP program will give information about inconsistency, tautology, and possible simplifications. We use different constraint domains which are mapped to SQL types, and propose them to cooperate for improving accuracy. Our approach leverages a deductive system that includes SQL and Datalog, and we present an implementation in this system which is currently being tested in classroom, showing its advantages and differences with respect to other approaches, as well as some performance data.
On Uniform Equivalence of Epistemic Logic Programs
Authors: FABER WOLFGANG , MORAK MICHAEL , WOLTRAN STEFAN 
Published: September 2019

AbstractEpistemic Logic Programs (ELPs) extend Answer Set Programming (ASP) with epistemic negation and have received renewed interest in recent years. This led to the development of new research and efficient solving systems for ELPs. In practice, ELPs are often written in a modular way, where each module interacts with other modules by accepting sets of facts as input, and passing on sets of facts as output. An interesting question then presents itself: under which conditions can such a module be replaced by another one without changing the outcome, for any set of input facts? This problem is known as uniform equivalence, and has been studied extensively for ASP. For ELPs, however, such an investigation is, as of yet, missing. In this paper, we therefore propose a characterization of uniform equivalence that can be directly applied to the language of state-of-the-art ELP solvers. We also investigate the computational complexity of deciding uniform equivalence for two ELPs, and show that it is on the third level of the polynomial hierarchy.
Symbolic Analysis of Maude Theories with Narval
Authors: ALPUENTE MARÍA , ESCOBAR SANTIAGO , SAPIÑA JULIA , BALLIS DEMIS 
Published: September 2019

AbstractConcurrent functional languages that are endowed with symbolic reasoning capabilities such as Maude offer a high-level, elegant, and efficient approach to programming and analyzing complex, highly nondeterministic software systems. Maude’s symbolic capabilities are based on equational unification and narrowing in rewrite theories, and provide Maude with advanced logic programming capabilities such as unification modulo user-definable equational theories and symbolic reachability analysis in rewrite theories. Intricate computing problems may be effectively and naturally solved in Maude thanks to the synergy of these recently developed symbolic capabilities and classical Maude features, such as: (i) rich type structures with sorts (types), subsorts, and overloading; (ii) equational rewriting modulo various combinations of axioms such as associativity, commutativity, and identity; and (iii) classical reachability analysis in rewrite theories. However, the combination of all of these features may hinder the understanding of Maude symbolic computations for non-experienced developers. The purpose of this article is to describe how programming and analysis of Maude rewrite theories can be made easier by providing a sophisticated graphical tool called Narval that supports the fine-grained inspection of Maude symbolic computations.
Relating Two Dialects of Answer Set Programming
Authors: HARRISON AMELIA , LIFSCHITZ VLADIMIR 
Published: September 2019

AbstractThe input language of the answer set solver clingo is based on the definition of a stable model proposed by Paolo Ferraris. The semantics of the ASP-Core language, developed by the ASP Standardization Working Group, uses the approach to stable models due to Wolfgang Faber, Nicola Leone, and Gerald Pfeifer. The two languages are based on different versions of the stable model semantics, and the ASP-Core document requires, “for the sake of an uncontroversial semantics,” that programs avoid the use of recursion through aggregates. In this paper we prove that the absence of recursion through aggregates does indeed guarantee the equivalence between the two versions of the stable model semantics, and show how that requirement can be relaxed without violating the equivalence property.
Revisiting the relationships between human well-being and ecosystems in dynamic social-ecological systems: Implications for stewardship and development
Authors: Masterson Vanessa A. , Vetter Susanne , Chaigneau Tomas , Daw Tim M. , Selomane Odirilwe , Hamann Maike , Wong Grace Y. , Mellegård Viveca , Cocks Michelle , Tengö Maria 
Published: September 2019

Non-technical summaryWe argue that the ways in which we as humans derive well-being from nature – for example by harvesting firewood, selling fish or enjoying natural beauty – feed back into how we behave towards the environment. This feedback is mediated by institutions (rules, regulations) and by individual capacities to act. Understanding these relationships can guide better interventions for sustainably improving well-being and alleviating poverty. However, more attention needs to be paid to how experience-related benefits from nature influence attitudes and actions towards the environment, and how these relationships can be reflected in more environmentally sustainable development projects.
Selective eradication of human non-small cell lung cancer cells using aptamer-decorated nanoparticles harboring a cytotoxic drug cargo
Authors: Engelberg Shira , Netzer Einat , Assaraf Yehuda G. , Livney Yoav D. 
Published: September 2019

AbstractTargeted cancer therapy is currently the leading modality to enhance treatment selectivity and efficacy, as well as to minimize untoward toxicity to healthy tissues. Herein, we devised and studied nanoparticles (NPs) composed of the biocompatible block-copolymer PEG-PCL entrapping the hydrophobic chemotherapeutic drug paclitaxel (PTX), which are targeted to human non-small cell lung cancer (NSCLC) cells. To achieve selective NSCLC targeting, these NPs were decorated with single-stranded oligonucleotide-based S15 aptamers (S15-APTs), which we have recently shown to serve as efficient tumor cell targeting ligands. Prepared without using surfactants, these 15 nm PEG-PCL/PTX NPs entered NSCLC cells via clathrin-mediated endocytosis. These NPs demonstrated efficient encapsulation of PTX, high selectivity to- and potent eradication of human A549 NSCLC cells, with a remarkable half maximal inhibitory concentration (IC50) of 0.03 μM PTX. In contrast, very high IC50 values of 1.7, 4.2, 43, 87, and 980 µM PTX were obtained towards normal human bronchial epithelial BEAS2B, cervical carcinoma HeLa, colon adenocarcinoma CaCo-2, neonatal foreskin fibroblast FSE, and human embryonic kidney HEK-293 cells, respectively. These results demonstrate 2–5 orders of magnitude difference in the selective cytotoxicity towards NSCLCs, reflecting a potentially outstanding therapeutic window. Moreover, the dual utility of aptamer-decorated NPs for both drug stabilization and selective tumor targeting was studied by increasing APT concentrations during NP “decoration”. The optimal aptamer density on the surface of NPs for selective targeting, for high fluorescence diagnostic signal and for maintaining small particle size to enable endocytosis, was achieved by using 30 nM APTs during NP decoration. Collectively, our findings suggest that these APT-decorated NPs hold great preclinical promise in selective targeting and eradication of human NSCLC cells without harming normal tissues.
High impact of miRNA-4521 on FOXM1 expression in medulloblastoma
Authors: Senfter Daniel , Samadaei Mahzeiar , Mader Robert M. , Gojo Johannes , Peyrl Andreas , Krupitza Georg , Kool Marcel , Sill Martin , Haberler Christine , Ricken Gerda , Czech Thomas , Slavc Irene , Madlener Sibylle 
Published: September 2019

AbstractMedulloblastoma, an embryonal tumor of the cerebellum/fourth ventricle, is one of the most frequent malignant brain tumors in children. Although genetic variants are increasingly used in treatment stratification, survival of high-risk patients, characterized by leptomeningeal dissemination, TP53 mutation or MYC amplification, is still poor. FOXM1, a proliferation-specific oncogenic transcription factor, is deregulated in various solid tumors, including medulloblastoma, and triggers cellular proliferation, migration and genomic instability. In tissue samples obtained from medulloblastoma patients, the significant upregulation of FOXM1 was associated with a loss of its putative regulating microRNA, miR-4521. To understand the underlying mechanism, we investigated the effect of miR-4521 on the expression of the transcription factor FOXM1 in medulloblastoma cell lines. Transfection of this microRNA reduced proliferation and invasion of several medulloblastoma cell lines and induced programmed cell death through activation of caspase 3/7. Further, downstream targets of FOXM1 such as PLK1 and cyclin B1 were significantly reduced thus affecting the cell cycle progression in medulloblastoma cell lines. In conclusion, a restoration of miRNA-4521 may selectively suppress the pathophysiological effect of aberrant FOXM1 expression and serve as a targeted approach for medulloblastoma therapy.
TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP
Authors: Knop Janin , Spilgies Lisanne M. , Rufli Stefanie , Reinhart Ramona , Vasilikos Lazaros , Yabal Monica , Owsley Erika , Jost Philipp J. , Marsh Rebecca A. , Wajant Harald , Robinson Mark D. , Kaufmann Thomas , Wong W. Wei-Lynn 
Published: September 2019

AbstractThe pediatric immune deficiency X-linked proliferative disease-2 (XLP-2) is a unique disease, with patients presenting with either hemophagocytic lymphohistiocytosis (HLH) or intestinal bowel disease (IBD). Interestingly, XLP-2 patients display high levels of IL-18 in the serum even while in stable condition, presumably through spontaneous inflammasome activation. Recent data suggests that LPS stimulation can trigger inflammasome activation through a TNFR2/TNF/TNFR1 mediated loop inxiap−/−macrophages. Yet, the direct role TNFR2-specific activation plays in the absence of XIAP is unknown. We found TNFR2-specific activation leads to cell death inxiap−/−myeloid cells, particularly in the absence of the RING domain. RIPK1 kinase activity downstream of TNFR2 resulted in a TNF/TNFR1 cell death, independent of necroptosis. TNFR2-specific activation leads to a similar inflammatory NF-kB driven transcriptional profile as TNFR1 activation with the exception of upregulation of NLRP3 and caspase-11. Activation and upregulation of the canonical inflammasome upon loss of XIAP was mediated by RIPK1 kinase activity and ROS production. While both the inhibition of RIPK1 kinase activity and ROS production reduced cell death, as well as release of IL-1β, the release of IL-18 was not reduced to basal levels. This study supports targeting TNFR2 specifically to reduce IL-18 release in XLP-2 patients and to reduce priming of the inflammasome components.
Rapid accelerations of Antarctic Peninsula outlet glaciers driven by surface melt
Authors: Tuckett Peter A. , Ely Jeremy C. , Sole Andrew J. , Livingstone Stephen J. , Davison Benjamin J. , Melchior van Wessem J. , Howard Joshua 
Published: September 2019

AbstractAtmospheric warming is increasing surface melting across the Antarctic Peninsula, with unknown impacts upon glacier dynamics at the ice-bed interface. Using high-resolution satellite-derived ice velocity data, optical satellite imagery and regional climate modelling, we show that drainage of surface meltwater to the bed of outlet glaciers on the Antarctic Peninsula occurs and triggers rapid ice flow accelerations (up to 100% greater than the annual mean). This provides a mechanism for this sector of the Antarctic Ice Sheet to respond rapidly to atmospheric warming. We infer that delivery of water to the bed transiently increases basal water pressure, enhancing basal motion, but efficient evacuation subsequently reduces water pressure causing ice deceleration. Currently, melt events are sporadic, so efficient subglacial drainage cannot be maintained, resulting in multiple short-lived (<6 day) ice flow perturbations. Future increases in meltwater could induce a shift to a glacier dynamic regime characterised by seasonal-scale hydrologically-driven ice flow variations.
Genome-wide recombination map construction from single individuals using linked-read sequencing
Authors: Dréau Andreea , Venu Vrinda , Avdievich Elena , Gaspar Ludmila , Jones Felicity C. 
Published: September 2019

AbstractMeiotic recombination rates vary across the genome, often involving localized crossover hotspots and coldspots. Studying the molecular basis and mechanisms underlying this variation has been challenging due to the high cost and effort required to construct individualized genome-wide maps of recombination crossovers. Here we introduce a new method, called ReMIX, to detect crossovers from gamete DNA of a single individual using Illumina sequencing of 10X Genomics linked-read libraries. ReMIX reconstructs haplotypes and identifies the valuable rare molecules spanning crossover breakpoints, allowing quantification of the genomic location and intensity of meiotic recombination. Using a single mouse and stickleback fish, we demonstrate how ReMIX faithfully recovers recombination hotspots and landscapes that have previously been built using hundreds of offspring. ReMIX provides a high-resolution, high-throughput, and low-cost approach to quantify recombination variation across the genome, providing an exciting opportunity to study recombination among multiple individuals in diverse organisms.
Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch
Authors: Suddala Krishna C. , Price Ian R. , Dandpat Shiba S. , Janeček Michal , Kührová Petra , Šponer Jiří , Banáš Pavel , Ke Ailong , Walter Nils G. 
Published: September 2019

AbstractThe widespread Mn2+-sensing yybP-ykoY riboswitch controls the expression of bacterial Mn2+ homeostasis genes. Here, we first determine the crystal structure of the ligand-bound yybP-ykoY riboswitch aptamer from Xanthomonas oryzae at 2.96 Å resolution, revealing two conformations with docked four-way junction (4WJ) and incompletely coordinated metal ions. In >100 µs of MD simulations, we observe that loss of divalents from the core triggers local structural perturbations in the adjacent docking interface, laying the foundation for signal transduction to the regulatory switch helix. Using single-molecule FRET, we unveil a previously unobserved extended 4WJ conformation that samples transient docked states in the presence of Mg2+. Only upon adding sub-millimolar Mn2+, however, can the 4WJ dock stably, a feature lost upon mutation of an adenosine contacting Mn2+ in the core. These observations illuminate how subtly differing ligand preferences of competing metal ions become amplified by the coupling of local with global RNA dynamics.
Plasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross
Authors: Sá Juliana M. , Kaslow Sarah R. , Moraes Barros Roberto R. , Brazeau Nicholas F. , Parobek Christian M. , Tao Dingyin , Salzman Rebecca E. , Gibson Tyler J. , Velmurugan Soundarapandian , Krause Michael A. , Melendez-Muniz Viviana , Kite Whitney A. , Han Paul K. , Eastman Richard T. , Kim Adam , Kessler Evan G. , Abebe Yonas , James Eric R. , Chakravarty Sumana , Orr-Gonzalez Sachy , Lambert Lynn E. , Engels Theresa , Thomas Marvin L. , Fasinu Pius S. , Serre David , Gwadz Robert W. , Walker Larry , DeConti Derrick K. , Mu Jianbing , Bailey Jeffrey A. , Sim B. Kim Lee , Hoffman Stephen L. , Fay Michael P. , Dinglasan Rhoel R. , Juliano Jonathan J. , Wellems Thomas E. 
Published: September 2019

AbstractMainstay treatment forPlasmodium vivaxmalaria has long relied on chloroquine (CQ) against blood-stage parasites plus primaquine against dormant liver-stage forms (hypnozoites), however drug resistance confronts this regimen and threatens malaria control programs. Understanding the basis ofP. vivaxchloroquine resistance (CQR) will inform drug discovery and malaria control. Here we investigate the genetics ofP. vivaxCQR by a cross of parasites differing in drug response. Gametocytogenesis, mosquito infection, and progeny production are performed with mixed parasite populations in nonhuman primates, as methods forP. vivaxcloning and in vitro cultivation remain unavailable. Linkage mapping of progeny surviving >15 mg/kg CQ identifies a 76 kb region in chromosome 1 includingpvcrt, an ortholog of thePlasmodium falciparumCQR transporter gene. Transcriptional analysis supports upregulatedpvcrtexpression as a mechanism of CQR.
Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage
Authors: Sambeat Audrey , Ratajczak Joanna , Joffraud Magali , Sanchez-Garcia José L. , Giner Maria P. , Valsesia Armand , Giroud-Gerbetant Judith , Valera-Alberni Miriam , Cercillieux Angelique , Boutant Marie , Kulkarni Sameer S. , Moco Sofia , Canto Carles 
Published: September 2019

AbstractSupplementation with the NAD+ precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD+ synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD+ levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders.