bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative Events in Liver Transplantation Using Donation After Circulatory Death Donors
Authors: Chadha Ryan M. , Croome Kristopher P. , Aniskevich Stephen , Pai Sher‐Lu , Nguyen Justin , Burns Justin , Perry Dana , Taner C. Burcin
Published: September 2019

Liver grafts from donation after circulatory death (DCD) are a source of organs to decrease wait‐list mortality. While there have been lower rates of graft loss, there are concerns of an increased incidence of intraoperative events in recipients of DCD grafts. We aim to look at the incidence of intraoperative events between recipients of livers from DCD and donation after brain death (DBD) donors. We collected data for 235 DCD liver recipients between 2006 and 2017. We performed a 1:1 propensity match between these patients and patients with DBD donors. Variables included recipient age, liver disease etiology, biological Model for End‐Stage Liver Disease (MELD) score, allocation MELD score, diagnosis of hepatocellular carcinoma, and year of transplantation. DCD and DBD groups had no significant differences in incidence of postreperfusion syndrome (P = 0.75), arrhythmia requiring cardiopulmonary resuscitation (P = 0.66), and treatments for hyperkalemia (P = 0.84). In the DCD group, there was a significant increase in amount of total intraoperative and postreperfusion blood products (with exception of postreperfusion packed red blood cells) utilized (P < 0.05 for all products), significant differences in postreperfusion thromboelastography parameters, as well as inotropes and vasopressors used (P < 0.05 for all infusions). There was no difference in patient (P = 0.49) and graft survival (P = 0.10) at 1, 3, and 5 years. In conclusion, DCD grafts compared with a cohort of DBD grafts have a similar low incidence of major intraoperative events, but increased incidence of transient vasopressor/inotropic usage and increased blood transfusion requirements. This does not result in differences in longterm outcomes. While centers should continue to look at DCD liver donors, they should be cognizant regarding intraoperative care to prevent adverse outcomes.
Models of Intrauterine growth restriction and fetal programming in rabbits
Authors: Lopez‐Tello Jorge , Arias‐Alvarez Maria , Gonzalez‐Bulnes Antonio , Sferuzzi‐Perri Amanda N.
Published: September 2019

Intrauterine growth restriction (IUGR) affects approximately 10% of human pregnancies globally and has immediate and life‐long consequences for offspring health. However, the mechanisms underlying the pathogenesis of IUGR and its association with later health and disease outcomes are poorly understood. To address these knowledge gaps, the use of experimental animals is critically important. Since the 50's different environmental, pharmacological, and surgical manipulations have been performed in the rabbit to improve our knowledge of the control of fetal growth, fetal responses to IUGR, and mechanisms by which offspring may be programmed by an adverse gestational environment. The purpose of this review is therefore to summarize the utility of the rabbit as a model for IUGR research. It first summarizes the knowledge of prenatal and postnatal development in the rabbit and how these events relate to developmental milestones in humans. It then describes the methods used to induce IUGR in rabbits and the knowledge gained about the mechanisms determining prenatal and postnatal outcomes of the offspring. Finally, it discusses the application of state of the art approaches in the rabbit, including high‐resolution ultrasound, magnetic resonance imaging, and gene targeting, to gain a deeper integrative understanding of the physiological and molecular events governing the development of IUGR. Overall, we hope to engage and inspire investigators to employ the rabbit as a model organism when studying pregnancy physiology so that we may advance our understanding of mechanisms underlying IUGR and its consequences in humans and other mammalian species.
Steady‐state imaging with inhomogeneous magnetization transfer contrast using multiband radiofrequency pulses
Authors: Malik Shaihan J. , Teixeira Rui P. A. G. , West Daniel J. , Wood Tobias C. , Hajnal Joseph V.
Published: September 2019

Purpose

Inhomogeneous magnetization transfer (ihMT) is an emerging form of MRI contrast that may offer high specificity for myelinated tissue. Existing ihMT and pulsed MT sequences often use separate radiofrequency pulses for saturation and signal excitation. This study investigates the use of nonselective multiband radiofrequency pulses for simultaneous off‐resonance saturation and on‐resonance excitation specifically for generation of ihMT contrast within rapid steady‐state pulse sequences.

Theory and Methods

A matrix‐based signal modeling approach was developed and applied for both balanced steady state free precession and spoiled gradient echo sequences, accounting specifically for multiband pulses. Phantom experiments were performed using a combination of balanced steady state free precession and spoiled gradient echo sequences, and compared with model fits. A human brain imaging exam was performed using balanced steady state free precession sequences to demonstrate the achieved contrast.

Results

A simple signal model derived assuming instantaneous radiofrequency pulses was shown to agree well with full integration of the governing equations and provided fits to phantom data for materials with strong ihMT contrast (PL161 root mean square error = 0.9%, and hair conditioner root mean square error = 2.4%). In vivo ihMT ratio images showed the expected white matter contrast that has been seen by other ihMT investigations, and the observed ihMT ratios corresponded well with predictions.

Conclusions

ihMT contrast can be generated by integrating multiband radiofrequency pulses directly into both spoiled gradient echo and balanced steady state free precession sequences, and the presented signal modeling approach can be used to understand the acquired signals.
North American extreme precipitation events and related large-scale meteorological patterns: a review of statistical methods, dynamics, modeling, and trends
Authors: Barlow Mathew , Gutowski William J. , Gyakum John R. , Katz Richard W. , Lim Young-Kwon , Schumacher Russ S. , Wehner Michael F. , Agel Laurie , Bosilovich Michael , Collow Allison , Gershunov Alexander , Grotjahn Richard , Leung Ruby , Milrad Shawn , Min Seung-Ki
Published: September 2019

This paper surveys the current state of knowledge regarding large-scale meteorological patterns (LSMPs) associated with short-duration (less than 1 week) extreme precipitation events over North America. In contrast to teleconnections, which are typically defined based on the characteristic spatial variations of a meteorological field or on the remote circulation response to a known forcing, LSMPs are defined relative to the occurrence of a specific phenomenon—here, extreme precipitation—and with an emphasis on the synoptic scales that have a primary influence in individual events, have medium-range weather predictability, and are well-resolved in both weather and climate models. For the LSMP relationship with extreme precipitation, we consider the previous literature with respect to definitions and data, dynamical mechanisms, model representation, and climate change trends. There is considerable uncertainty in identifying extremes based on existing observational precipitation data and some limitations in analyzing the associated LSMPs in reanalysis data. Many different definitions of “extreme” are in use, making it difficult to directly compare different studies. Dynamically, several types of meteorological systems—extratropical cyclones, tropical cyclones, mesoscale convective systems, and mesohighs—and several mechanisms—fronts, atmospheric rivers, and orographic ascent—have been shown to be important aspects of extreme precipitation LSMPs. The extreme precipitation is often realized through mesoscale processes organized, enhanced, or triggered by the LSMP. Understanding of model representation, trends, and projections for LSMPs is at an early stage, although some promising analysis techniques have been identified and the LSMP perspective is useful for evaluating the model dynamics associated with extremes.
In-Hospital Mortality in Patients with Idiopathic Pulmonary Fibrosis: A US Cohort Study
Authors: Durheim Michael T. , Judy Jennifer , Bender Shaun , Baumer Dorothy , Lucas Joseph , Robinson Scott B. , Mohamedaly Omar , Shah Bimal R. , Leonard Thomas , Conoscenti Craig S. , Palmer Scott M.
Published: September 2019

Purpose

In patients with idiopathic pulmonary fibrosis (IPF), hospitalizations are associated with high mortality. We sought to determine in-hospital mortality rates and factors associated with in-hospital mortality in patients with IPF.

Methods

Patients with IPF were identified from the Premier Healthcare Database, a representative administrative dataset that includes > 20% of hospital discharges in the US, using an algorithm based on diagnostic codes and billing data. We used logistic regression to analyze associations between patient-, hospital-, and treatment-related characteristics and a composite primary outcome of death during the index visit, lung transplant during the index visit and > 1 day after admission, or death during a readmission within 90 days.

Results

The cohort comprised 6665 patients with IPF hospitalized between October 2011 and October 2014. A total of 963 (14.4%) met the primary outcome. Factors significantly associated with a higher risk of the primary outcome included mechanical ventilation [odds ratio 4.65 (95% CI 3.73, 5.80)], admission to the intensive care unit [1.83 (1.52, 2.21)], treatment with opioids (3.06 [2.57, 3.65]), and a diagnosis of pneumonia [1.44 (1.21, 1.71)]. Factors significantly associated with a lower risk included concurrent chronic obstructive pulmonary disease [0.65 (0.55, 0.77)] and female sex [0.67 (0.57, 0.79)].

Conclusions

Patients with IPF, particularly those receiving mechanical ventilation or intensive care, are at substantial risk of death or lung transplant during hospitalization or death during a readmission within 90 days.
Principles of Risk-Based Rock Engineering Design
Authors: Spross Johan , Stille Håkan , Johansson Fredrik , Palmstrøm Arild
Published: September 2019

In comparison with other types of construction, the development of rock engineering design codes has been slow. Codes must, however, be developed with relevant discipline-specific characteristics in mind. This paper, therefore, presents a generic design framework for rock engineering. The framework is based on the presumption that rock engineering design must be viewed as decision-making under uncertainty, which makes the design process subject to general risk management principles, as risk is defined as “effect of uncertainties on objectives” (ISO 31000). Thus, rock engineering design codes ultimately need to facilitate design processes that target the risk, to enable design of structures that not only are sufficiently safe and durable and cost-effectively constructed, but also imply safe and healthy work conditions during construction and an acceptably low environmental impact. The presented framework satisfies this fundamental requirement and the authors find codification of its principles to be rather straightforward, as long as the level of detail in the code is governed by a strict application of ISO’s general risk management principles. Further details on methods and practical recommendations can instead be supplemented in separate handbooks and application guidelines.
The Influence of Climate Change on the Restoration Trajectory of a Nutrient-Rich Deep Lake
Authors: Radbourne Alan D. , Ryves David B. , Madgwick Genevieve , Anderson N. John
Published: September 2019

Nutrient reduction in impacted lowland freshwater systems is ecologically and culturally important. Gaining a greater insight into how lakes respond to lowering nutrient loads and how climate-driven physical limnology affects present and future cycling of available nutrients is important for ecosystem resource management. This study examines the nutrient decline in a hypereutrophic freshwater lake (Rostherne Mere, Cheshire, UK) 25 years after sewage effluent diversion, a uniquely long-term analysis of a recovering nutrient-rich deep lake. Using nutrient, phytoplankton, climate and catchment hydrological monitoring, the contemporary lake system is compared to previous studies from 1990 to 2002. Nutrient change since point source load diversion showed annual average and maximum phosphorus (P) concentrations decreased significantly for the first 10 years (1992: ~ 600 µg P L−1; 2002: ~ 200 µg P L−1), but have since stabilised due to a substantial legacy sediment P internal load. Dissolved inorganic nitrogen (DIN) concentrations have not substantially changed since diversion, resulting in the alteration of the DIN/SRP ratio from a system characterised by N limitation (N:P ~ 5), to one predominantly P limited (N:P > 20). Nutrient changes over this time are shown to drive ecological change, especially in the cyanobacterial and algal communities. Furthermore, very high-resolution monitoring of lake inflow and outflow (every 5 min during 2016) shows that water residence time at this lake is significantly shorter than previously estimated (~ 0.8 years compared to previous estimates of ~ 1.6–2.4 years). Together with long-term data demonstrating that the stratification period at Rostherne Mere has increased by 40 days over the last ~ 50 years (due to later autumnal mixing), we show that a rapid rate of epilimnetic flushing together with a long stratification period substantially reduces the available epilimnetic P during the summer cyanobacterial bloom. This is of growing importance for many such lakes, given widespread climate-driven lengthening of stratification and a national trend of decreasing summer rainfall (decreasing seasonal flushing) but more intense summer storm events (resulting in short-term flushing events).
Markovian lifts of positive semidefinite affine Volterra-type processes
Authors: Cuchiero Christa , Teichmann Josef
Published: September 2019

We consider stochastic partial differential equations appearing as Markovian lifts of matrix-valued (affine) Volterra-type processes from the point of view of the generalized Feller property (see, e.g., Dörsek and Teichmann in A semigroup point of view on splitting schemes for stochastic (partial) differential equations, 2010. arXiv:1011.2651). We introduce in particular Volterra Wishart processes with fractional kernels and values in the cone of positive semidefinite matrices. They are constructed from matrix products of infinite dimensional Ornstein–Uhlenbeck processes whose state space is the set of matrix-valued measures. Parallel to that we also consider positive definite Volterra pure jump processes, giving rise to multivariate Hawkes-type processes. We apply these affine covariance processes for multivariate (rough) volatility modeling and introduce a (rough) multivariate Volterra Heston-type model.
Revealing Evolutionarily Optimal Strategies in Self-Reproducing Systems via a New Computational Approach
Authors: Sandhu Simran Kaur , Morozov Andrew , Kuzenkov Oleg
Published: September 2019

Modelling the evolution of complex life history traits and behavioural patterns observed in the natural world is a challenging task. Here, we develop a novel computational method to obtain evolutionarily optimal life history traits/behavioural patterns in population models with a strong inheritance. The new method is based on the reconstruction of evolutionary fitness using underlying equations for population dynamics and it can be applied to self-reproducing systems (including complicated age-structured models), where fitness does not depend on initial conditions, however, it can be extended to some frequency-dependent cases. The technique provides us with a tool to efficiently explore both scalar-valued and function-valued traits with any required accuracy. Moreover, the method can be implemented even in the case where we ignore the underlying model equations and only have population dynamics time series. As a meaningful ecological case study, we explore optimal strategies of diel vertical migration (DVM) of herbivorous zooplankton in the vertical water column which is a widespread phenomenon in both oceans and lakes, generally considered to be the largest synchronised movement of biomass on Earth. We reveal optimal trajectories of daily vertical motion of zooplankton grazers in the water column depending on the presence of food and predators. Unlike previous studies, we explore both scenarios of DVM with static and dynamic predators. We find that the optimal pattern of DVM drastically changes in the presence of dynamic predation. Namely, with an increase in the amount of food available for zooplankton grazers, the amplitude of DVM progressively increases, whereas for static predators DVM would abruptly cease.
Protective and defensive roles of non-glandular trichomes against multiple stresses: structure–function coordination
Authors: Karabourniotis George , Liakopoulos Georgios , Nikolopoulos Dimosthenis , Bresta Panagiota
Published: September 2019

As superficial structures, non-glandular trichomes, protect plant organs against multiple biotic and abiotic stresses. The protective and defensive roles of these epidermal appendages are crucial to developing organs and can be attributed to the excellent combination of suitable structural traits and chemical reinforcement in the form of phenolic compounds, primarily flavonoids. Both the formation of trichomes and the accumulation of phenolics are interrelated at the molecular level. During the early stages of development, non-glandular trichomes show strong morphological similarities to glandular ones such as the balloon-like apical cells with numerous phenolics. At later developmental stages, and during secondary wall thickening, phenolics are transferred to the cell walls of the trichomes. Due to the diffuse deposition of phenolics in the cell walls, trichomes provide protection against UV-B radiation by behaving as optical filters, screening out wavelengths that could damage sensitive tissues. Protection from strong visible radiation is also afforded by increased surface light reflectance. Moreover, the mixtures of trichome phenolics represent a superficial chemical barrier that provides protection against biotic stress factors such as herbivores and pathogens. Although the cells of some trichomes die at maturity, they can modulate their quantitative and qualitative characteristics during development, depending on the prevailing conditions of the external biotic or abiotic environment. In fact, the structure and chemical constituents of trichomes may change due to the particular light regime, herbivore damage, wounding, water stress, salinity and the presence of heavy metals. Hence, trichomes represent dynamic protective structures that may greatly affect the outcome of many plant–environment interactions.
Do women benefit more than men from off-pump coronary artery bypass grafting?
Authors: ter Woorst J. F. , Hoff A. H. T. , Haanschoten M. C. , Houterman S. , van Straten A. H. M. , Soliman-Hamad M. A.
Published: September 2019

Objectives

Outcomes after coronary artery bypass grafting (CABG) are worse in women than in men. This study aims to investigate whether off-pump coronary artery bypass (OPCAB) surgery improves the outcomes in women by comparing different outcome measures in both genders.

Methods

Patients who underwent isolated CABG, either on-pump (ONCAB) or OPCAB, between January 1998 and June 2017 were included. Primary endpoints were 30-day and 120-day mortality. Logistic regression models were constructed to evaluate the effect of the CABG technique on important outcomes such as mortality and the need for blood transfusion.

Results

The data of 17,052 patients were analysed, 3,684 of whom were women (414 OPCAB) and 13,368 men (1,483 OPCAB). The mean number of grafts was lower in the OPCAB group of both genders (p < 0.001). Postoperatively, both men and women undergoing OPCAB surgery received fewer red blood cell transfusions (p < 0.001) and had higher postoperative haemoglobin levels (p < 0.001) than those undergoing ONCAB. Early mortality occurred less frequently after OPCAB surgery in both genders, although the difference was not significant. However, 120-day mortality was significantly lower after OPCAB surgery in women, even after correction for preoperative risk factors [odds ratio (OR) = 0.356, 95% confidence interval (CI) 0.144–0.882, p = 0.026]. The difference in 120-day mortality was not significant in men (OR = 0.787, 95% CI 0.498–1.246, p = 0.307).

Conclusions

Women undergoing CABG benefit more from OPCAB surgery than from ONCAB surgery in terms of 120-day mortality. This difference was not found in men in our patient population.
Can IMF program design resurrect investor sentiment? An empirical investigation
Authors: Vadlamannati Krishna Chaitanya
Published: September 2019

Does international investor sentiment improve when a crises-ridden country participates in an International Monetary Fund (IMF) program? I argue that merely participating in an IMF program may not revive the sentiments of investors. Rather, investor sentiment would improve when governments enhance the credibility of their commitment to reforms by accepting severe conditions imposed by the IMF, which incur ex ante and ex post political costs. Using panel data on 166 countries during the 1992–2013 period (twenty-two years), I find that countries participating in IMF programs, with conditions attached, specifically prior actions and performance criteria conditions, after controlling for endogeneity concerns using exogeneous instruments, are associated with an increase in long-term investor sentiment. These results are robust to using alternative data, variables and estimation methods. My findings are in stark contrast to those who argue that IMF conditional programs are akin to swallowing a bitter pill. In fact, my results demonstrate that the so-called bitter pill may act as a palliative.
Positive contagion and the macrostructures of generalized balance
Authors: Friedkin Noah E. , Proskurnikov Anton V. , Bullo Francesco
Published: September 2019

Balance theory has advanced with interdisciplinary contributions from social science, physical science, engineering, and mathematics. The common focus of attention is social networks in which every individual has either a positive or negative, cognitive or emotional, appraisal of every other individual. The current frontier of work on balance theory is a hunt for a dynamical model that predicts the temporal evolution of any such appraisal network to a particular structure in the complete set of balanced networks allowed by the theory. Finding such a model has proved to be a difficult problem. In this article, we contribute a parsimonious solution of the problem that explicates the conditions under which a network will evolve either to a set of mutually antagonistic cliques or to an asymmetric structure that allows agreement, cooperation, and compromise among cliques.
KING ARTHUR’S ROUND TABLE REVISITED: A REVIEW OF TWO RIVAL INTERPRETATIONS OF A HENGE MONUMENT NEAR PENRITH, IN CUMBRIA
Authors: Leach Stephen
Published: September 2019

In 1937 R G Collingwood carried out an excavation at King Arthur’s Round Table, a henge monument near Penrith. He wished to test the hypothesis that this may once have contained a circle of upright stones or wooden posts. His interim report, published in 1938, suggested that, on the evidence of excavation, this indeed might well have been the case. Unfortunately, illness prevented Collingwood returning to the site in 1938. In 1939 a second season of excavation was conducted under the direction of Gerhard Bersu. Bersu dismissed all of Collingwood’s interpretations. He argued that there were no post-holes, and that the artificial surface seen by Collingwood was in fact entirely natural. And there the matter has rested – with most later commentators, such as Richmond, Hodder and Bradley, favouring Bersu’s interpretation of the site and only a small minority, including Grace Simpson (the daughter of F G Simpson who worked with Collingwood on Hadrian’s Wall), favouring Collingwood’s. The present review of the two rival interpretations is occasioned by the discovery of a previously unpublished letter in which Collingwood gives his response to Bersu’s interpretations. The author argues that in fact the balance of probability greatly favours Collingwood’s interpretation rather than Bersu’s.
Does Trading Anonymously Enhance Liquidity?
Authors: Dennis Patrick J. , Sandås Patrik
Published: September 2019

Is liquidity better when a trade counterparty’s brokerage firm is unknown (anonymous) or known (transparent)? We examine a quasinatural experiment where some firms switched from transparent to anonymous trading and then, 1 year later, switched back. Our results for inside spread, price impact, and limit order book depth suggest that liquidity improves when anonymous post-trade reporting is introduced and liquidity worsens when anonymous post-trade reporting is reversed.
The Telos Reconciliation Dossier (IG XII.4.132): Democracy, Demagogues and Stasis in an Early Hellenistic Polis
Authors: Simonton Matthew
Published: September 2019

This 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

This 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.
Crystal structure of atropine sulfate monohydrate, (C17H24NO3)2(SO4)·(H2O)
Authors: Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: September 2019

The crystal structure of atropine sulfate monohydrate has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Atropine sulfate monohydrate crystallizes in space group P21/n (#14) with a = 19.2948(5), b = 6.9749(2), c = 26.9036(5) Å, β = 94.215(2)°, V = 3610.86(9) Å3, and Z = 4. Each of the two independent protonated nitrogen atoms participates in a strong hydrogen bond to the sulfate anion. Each of the two independent hydroxyl groups acts as a donor in a hydrogen bond to the sulfate anion, but only one of the water molecule hydrogen atoms acts as a hydrogen bond donor to the sulfate anion. The hydrogen bonds are all discrete but link the cations, anion, and water molecule along [101]. Although atropine and hyoscyamine (atropine is racemic hyoscyamine) crystal structures share some features, such as hydrogen bonding and phenyl–phenyl packing, the powder patterns show that the structures are very different. The powder pattern for atropine sulfate monohydrate has been submitted to ICDD for inclusion in the Powder Diffraction File™.
Crystal structure of bisoprolol fumarate Form I, (C18H32NO4) (C4H2O4)0.5
Authors: Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: September 2019

The crystal structure of bisoprolol fumarate Form I has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional techniques. Bisoprolol fumarate Form I crystallizes in space group P-1 (#2) with a = 8.165 70(5) Å, b = 8.516 39(12) Å, c = 16.751 79(18) Å, α = 89.142(1)°, β = 78.155(1)°, γ = 81.763(1)°, V = 1128.265(10) Å3, and Z = 2. The neutral side chain of the bisoprolol cation is probably disordered. The cation and anion are linked by N–H⋯O and O–H⋯O hydrogen bonds. The cations are also linked by N–H⋯O hydrogen bonds. The result is alternating layers of hydrophilic and hydrophobic layers parallel to the ab-plane. The density of the structure is relatively low at 1.130 g cm−3, but there are no obvious voids in the structure. The powder pattern is included in the Powder Diffraction File™ as entry 00-066-1625.
Enhancing Magic Sets with an Application to Ontological Reasoning
Authors: ALVIANO MARIO , LEONE NICOLA , VELTRI PIERFRANCESCO , ZANGARI JESSICA
Published: September 2019

Magic 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

In 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

This 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

Epistemic 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

Concurrent 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

The 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 summary

We 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

Targeted 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

Medulloblastoma, 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

The 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

Atmospheric 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

Meiotic 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

The 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.