bluuebunny/crossref_metadata_2025 huggingface dataset:
PP177 Health Preference Research In Europe: A Review Of Its Use
Authors: Marsh Kevin , Mühlbacher Axel , van Til Janine , Juhnke Christin , Choi Yookyung Christy , Duenas Alejandra , Greiner Wolfgang , Haas Kara , Hawken Natalia , Hiligsmann Mickael , Hockley Kimberley , Ivlev Ilya , Liu Frank , Molsen-David Elizabeth , Oehrlein Elisabeth , Ostermann Jan , Poder Thomas
Published: December 2019

Introduction

Health Technology Assessment (HTA) and regulatory decisions involve value judgements. As patient groups, industry, and regulatory agencies conduct more preference studies to quantify these judgements, a better understanding of the methods and practices is needed. Currently, there is no systematic mapping of the use of preference data in Europe. This study aimed to identify (i) the use of quantitative preference data by all relevant HTA bodies and regulatory authorities of the European Union (EU) member states, and (ii) key standards and guidelines.

Methods

This study used a mixed method approach based on a systematic literature review, survey and subsequent interviews with decision makers and experts.

Results

A total of 62 survey responses were received. Many respondents reported that their agencies were responsible for supporting more than one type of decision, with 69.0 percent supporting approval decisions, 64.3 percent supporting reimbursement decisions, 61.9 percent supporting pricing decisions, and 64.2 percent supporting guideline development. Respondents reported that their agencies supported these decisions in multiple ways: 78.6 percent by assessing health technologies; 54.8 percent by appraising health technologies; 45.2 percent by compiling an HTA report; 7.1 percent by conducting primary research; 9.5 percent by conducting secondary research. More than 40 percent (42.9 percent) of agencies had the final say on one of the decisions of interest – approval, reimbursement, or pricing. Of the 31 countries studied, 71 percent (n = 22) used quantitative preference data in their reimbursement and pricing decisions. Of those, 86 percent (n = 19) used general population preferences to inform the estimation of quality-adjusted life years (QALY) as part of cost utility analysis.

Conclusions

Much of this use of preference data can be understood within the standard framework of economic analysis adopted by many HTA agencies; either in in the form of: standard ways to estimate QALYs; ways to broaden the impacts of technologies captured in the QALY; or ways to weigh health gain with other decision-making criteria, such as disease severity or innovativeness.
VP47 Secondary Prevention For CV Disease: Population And Outcomes Using RWD
Authors: Sciattella Paolo , Mennini Francesco
Published: December 2019

Introduction

The study goal was to estimate prevalence of population in secondary prevention for Atherosclerotic Cardiovascular Disease (ASCVD) stratified by the pharmacological treatment and related outcomes using Health Information Systems (HIS).

Methods

From HIS of Marche and Umbria Regions (1.8 millions of inhabitants) which collect information related to hospitalizations, drugs prescriptions, outpatient visits and results of laboratory tests, we identified all patients aged ≤ 80 years with one or more hospitalization with DRG related to Acute Coronary Syndrome, Peripheral Artery Disease, Ischemic Stroke and Transient Ischemic Attack and discharge date between 2011 and 2014 (study period). Pharmacological treatment for each subject was defined selecting all prescriptions of Statins, Ezetimibe and Simvastatin/Ezetimibe, retrieved between the date of the last prescription in the study period and the previous 90 days. We stratified patient in no-treated, treated with low/medium intensity statins (LMS), high-dose statins (HDS) and other Lipid-Lowering Therapies (LLTs). Furthermore, for Umbria region, we selected the last blood levels test of LDL-cholesterol occurred in period 2011-2016. Starting from test date, we defined the pharmacological treatment in the previous 90 days. Subject were stratified based on LDL-C levels in target (<70) and not at-target (≥70) patients.

Results

Population in secondary prevention for ASCVD in period 2011-2014 in Marche and Umbria was estimated in 23,043 (prevalence: 4.3 x 1,000 inhabitants), corresponding to more than 800,000 subjects in Italian population. Within treated patients: 51.3% received LMS, 38.1% HDS and 10.6% other LLTs. No-treated patients were 27.8%. LDL-C target was achieved by 34.9% of patients treated with LMS and by 46.1% of patients treated with other LLTs.

Conclusions

The study, based on Italian administrative databases, allowed to estimate the very high risk population in secondary prevention for ASCVD. It highlighted a relevant proportion of no-treated patients, and an high proportion of patients that did not achieve recommended LDL-C target.
The Gender Gap Is a Race Gap: Women Voters in US Presidential Elections
Authors: Junn Jane , Masuoka Natalie
Published: December 2019

Scholarship on women voters in the United States has focused on the gender gap, showing that, since the 1980s, women are more likely to vote for Democratic Party candidates than men. The persistence of the gender gap has nurtured the conclusion that women are Democrats. This article presents evidence upending that conventional wisdom. It analyzes data from the American National Election Study to demonstrate that white women are the only group of female voters who support Republican Party candidates for president. They have done so by a majority in all but 2 of the last 18 elections. The relevance of race for partisan choice among women voters is estimated with data collected in 2008, 2012, and 2016, and the significance of being white is identified after accounting for political party identification and other predictors.
Constraints from luminosity-displacement correlation of high-mass X-ray binaries
Authors: Zuo Zhao-yu
Published: December 2019

We have modeled the luminosity-displacement correlation of high-mass X-ray binaries (HMXBs) with an evolutionary population synthesis (EPS) code. Detailed properties including offsets of simulated HMXBs are presented under both common envelope prescriptions usually adopted (i.e., the αCE formalism and the γ algorithm), and several theoretical models describing the natal kicks. We suggest that the distinct observational properties may be used as potential evidence to discriminate between models.
Wind inhibition in HMXBs: the effect of clumping and implications for X-ray luminosity
Authors: Krtička Jiří , Kubát Jiří , Krtičková Iva
Published: December 2019

Winds of hot stars are driven by the radiative force due to absorption of light in the lines of heavier elements. Consequently, the mass-loss rate and the wind velocity depend on the ionization state of the wind. As a result of this, there is a feedback between the ionizing X-ray source and the stellar wind in HMXBs powered by wind accretion. We study the influence of the small-scale wind structure (clumping) on this feedback using our NLTE hydrodynamical wind models. We find that clumping weakens the effect of X-ray irradiation. Moreover, we show that the observed X-ray luminosities of HMXBs can not be explained by wind accretion scenario without introducing the X-ray feedback. Taking into account the feedback, the observed and estimated X-ray luminosities nicely agree. We identify two cases of X-ray feedback with low and high X-ray luminosities that can explain the dichotomy between SFXTs and sgXBs.
How pulses in short gamma-ray bursts constrain HMXRB evolution
Authors: Hakkila Jon , Preece Robert D.
Published: December 2019

We demonstrate how pulse structures in Short gamma-ray bursts (SGRBs), coupled with observations of GRB/GW 170817A, constrain the geometries of dying HMXRB systems composed of merging neutron stars.
Emission-line diagnostics of core-collapse supernova host HII regions including interacting binary population
Authors: Xiao Lin , Eldridge J. J. , Galbany L. , Stanway E.
Published: December 2019

Considering as many as 70% of massive stars interact with a binary companion (Sana et al.2012, 2014), we created a new model of the optical nebular emission of HII regions by combining the results of the Binary Population and Spectral Synthesis (BPASS, Eldridge, Stanway et al.2017) code with the photoionization code (CLOUDY). This is discussed more in detail in Xiao et al.2018a. Then we use this model to explore a variety of emission-line diagnostics of CCSN host HII regions from the PMAS/PPAK Integral-field Supernova hosts COmpilation (PISCO, Galbany et al.2018). We determine the age, metallicity and gas parameters for H II regions associated with CCSNe, contrasting the above variables to distribution type II and type Ibc SNe. We find their nebular emission and CCSN progenitor types are largely determined by past and ongoing binary interactions, for example mass loss, mass gain and stellar mergers. However we note these two types SNe have little preference in their host environment metallicity measured by oxygen abundance or in progenitor initial mass, except that at lower metallicities supernovae are more likely to be of type II. The BPASS and nebular emission models are available from bpass.auckland.ac.nz and warwick.ac.uk/bpass.
Multicolour photometry of SS 433
Authors: Koçak D. , İçli T. , Yakut K.
Published: December 2019

We presented long-term optical observations of the high mass X-ray binary system SS 433 (V1343 Aql) with a black hole component. New observations have been obtained by using the 0.6m telescope at the TÜBİTAK National Observatory (TUG) in B, V, R and I filters. We aim to investigate the long-term photometric behavior of the system.
Gamma-ray bursts: A brief survey of the diversity
Authors: Mészáros Attila , Řípa Jakub
Published: December 2019

The separation of the gamma-ray bursts (GRBs) into short/hard and long/soft subclasses, respectively, is well supported both theoretically and observationally. The long ones are coupled to supernovae type Ib/Ic - the short ones are connected to the merging of two neutron stars, where one or even both neutron stars can be substituted by black holes. These short GRBs - as merging binaries - can also serve as the sources of gravitation waves, and are observable as the recently detected macronovae. Since 1998 there are several statistical studies suggesting the existence of more than two subgroups. There can be a subgroup having an intermediate durations; there can be a subgroup with ultra-long durations; the long/soft subgroup itself can be divided into two subclasses with respect to the luminosity of GRBs. The authors with other collaborators provided several statistical studies in this topic. This field of the GRB-diversity is briefly surveyed in this contribution.
Clarifying the population of HMXBs in the Small Magellanic Cloud
Authors: Maravelias Grigoris , Zezas Andreas , Antoniou Vallia , Hatzidimitriou Despina , Haberl Frank
Published: December 2019

Almost all confirmed optical counterparts of HMXBs in the SMC are OB stars with equatorial decretion disks (OBe). These sources emit strongly in Balmer lines and standout when imaged through narrow-band Hα imaging. The lack of secure counterparts for a significant fraction of the HMXBs motivated us to search for more. Using the catalogs for OB/OBe stars (Maravelias et al.2017) and for HMXBs (Haberl & Sturm 2016) we detect 70 optical counterparts (out of 104 covered by our survey). We provide the first identification of the optical counterpart to the source XTEJ0050-731. We verify that 17 previously uncertain optical counterparts are indeed the proper matches. Regarding 52 confirmed HMXBs (known optical counterparts with Hα emission), we detect 39 as OBe and another 13 as OB stars. This allows a direct estimation of the fraction of active OBe stars in HMXBs that show Hα emission at a given epoch to be at least ∼75% of their total HMXB population.
A Global Probabilistic Prediction of Cold Seeps and Associated SEAfloor FLuid Expulsion Anomalies (SEAFLEAs)
Authors: Phrampus Benjamin J. , Lee Taylor R. , Wood Warren T.
Published: December 2019

A newly compiled, open‐source database of focused fluid flow sites (e.g., cold seeps) and associated SEAfloor FLuid Expulsion Anomalies (SEAFLEAs) reveals a variable distribution of anomalies across global continental margins. The SEAFLEA distribution is heavily biased toward North American continental margins, with most observations between 100‐ and 200‐m water depth globally, and with an equal distribution between active and passive margins. Using a machine learning classification methodology based on outlier detection algorithms, we predict the probability of encountering a SEAFLEA globally. Results show the highest probability in regions with multiple SEAFLEA observations and parametrically similar regions concentrated on continental margins. In general, geologic, biologic, and chemical predictors are the best predictors of SEAFLEAs. We validate our results using a random and geospatial validation technique that reveals our methods are robust to random variations in observations, but that certain margins, such as the Svalbard Margin, represent parametrically distinct locals. These distinct regions have control over the global distribution of predicted anomalies due to their unique features. Our final prediction on a global 5 × 5 arc minute grid reveals that the average probability of encountering a SEAFLEA is 33.1 ± 17.7% on active margins and 31.2 ± 18.9% on passive margins, showing equal likelihood of encountering fluid expulsion between passive and active margins. Therefore, the lateral compaction on active margins does not increase the likelihood of fluid expulsion relative to the predominantly vertical compaction on passive margins. These results however say nothing of the fluid flux rates or density of expulsion features.
A New Framework to Incorporate High‐Latitude Input for Mesoscale Electrodynamics
Authors: Ozturk D. S. , Meng X. , Verkhoglyadova O. P. , Varney R. H. , Reimer A. S. , Semeter J. L.
Published: December 2019

Global circulation models (GCMs) for the ionosphere‐thermosphere system traditionally use empirical models to specify upper boundary conditions to represent solar wind and magnetospheric drivers. However, the magnetosphere, ionosphere, and thermosphere systems are coupled on different spatial and temporal scales. During increased levels of geomagnetic activity, these empirical models can't resolve dynamic electric field variability (
500 km,
15 min) because of their statistical nature and/or low spatial and temporal resolutions. This results in an underestimation of energy input to the ionosphere, causing disagreements between model results and observations. This paper introduces a new framework to incorporate dynamic electric fields into GCMs: High‐latitude Input for Mesoscale Electrodynamics (HIME). As a demonstration HIME uses the Poker Flat Incoherent Scatter Radar (PFISR) electric field estimates during an experiment on 2 March 2017. The electric potentials were calculated using the PFISR estimates and merged with a global empirical model of electric potential. A set of high‐latitude electric potential drivers were used to drive the University of Michigan Global Ionosphere Thermosphere Model (GITM) to understand the effects of driving at different scales. Data versus model comparisons for ion temperature, electron temperature, and electron density are provided along the PFISR beams. The ion convection velocities and neutral winds at the PFISR location are compared with the PFISR and Scanning Doppler Imager data. The effects of different multiscale drivers are investigated. The results showed that energy deposited by HIME‐driven simulations was locally larger by approximately an order of magnitude compared to the empirical model‐driven results.
Generic parameters of first-order kinetics accurately describe soil organic matter decay in bare fallow soils over a wide edaphic and climatic range
Authors: Menichetti Lorenzo , Ågren Göran I. , Barré Pierre , Moyano Fernando , Kätterer Thomas
Published: December 2019

The conventional soil organic matter (SOM) decay paradigm considers the intrinsic quality of SOM as the dominant decay limitation with the result that it is modelled using simple first-order decay kinetics. This view and modelling approach is often criticized for being too simplistic and unreliable for predictive purposes. It is still under debate if first-order models can correctly capture the variability in temporal SOM decay observed between different agroecosystems and climates. To address this question, we calibrated a first-order model (Q) on six long-term bare fallow field experiments across Europe. Following conventional SOM decay theory, we assumed that parameters directly describing SOC decay (rate of SOM quality change and decomposer metabolism) are thermodynamically constrained and therefore valid for all sites. Initial litter input quality and edaphic interactions (both local by definition) and microbial efficiency (possibly affected by nutrient stoichiometry) were instead considered site-specific. Initial litter input quality explained most observed kinetics variability, and the model predicted a convergence toward a common kinetics over time. Site-specific variables played no detectable role. The decay of decades-old SOM seemed mostly influenced by OM chemistry and was well described by first order kinetics and a single set of general kinetics parameters.
Autonomous lab-on-a-chip generic architecture for disposables with integrated actuation
Authors: Suska Anke , Filippini Daniel
Published: December 2019

The integration of actuators within disposable lab-on-a-chip devices is a demanding goal that requires reliable mechanisms, systematic fabrication procedures and marginal costs compatible with single-use devices. In this work an affordable 3D printed prototype that offers a compact and modular configuration to integrate actuation in autonomous lab-on-a-chip devices is demonstrated. The proposed concept can handle multiple step preparation protocols, such as the enzyme-linked immunosorbent assay (ELISA) configuration, by integrating reagents, volume metering capabilities with performance comparable to pipettes (e.g. 2.68% error for 5 μL volume), arbitrary dilution ratio support, effective mixing and active control of the sample injection. The chosen architecture is a manifold served by multiple injectors ending in unidirectional valves, which exchange a null dead volume when idle, thus isolating reagents until they are used. Functionalization is modularly provided by a plug-in element, which together with the selection of reagents can easily repurpose the platform to diverse targets, and this work demonstrates the systematic fabrication of 6 injectors/device at a development cost of USD$ 0.55/device. The concept was tested with a commercial ELISA kit for tumor necrosis factor (TNF), a marker for infectious, inflammatory and autoimmune disorders, and its performance satisfactorily compared with the classical microplate implementation.
A sulfur-containing volatile emitted by potato-associated bacteria confers protection against late blight through direct anti-oomycete activity
Authors: Chinchilla Delphine , Bruisson Sébastien , Meyer Silvan , Zühlke Daniela , Hirschfeld Claudia , Joller Charlotte , L’Haridon Floriane , Mène-Saffrané Laurent , Riedel Katharina , Weisskopf Laure
Published: December 2019

Plant diseases are a major cause for yield losses and new strategies to control them without harming the environment are urgently needed. Plant-associated bacteria contribute to their host’s health in diverse ways, among which the emission of disease-inhibiting volatile organic compounds (VOCs). We have previously reported that VOCs emitted by potato-associated bacteria caused strong in vitro growth inhibition of the late blight causing agent Phytophthora infestans. This work focuses on sulfur-containing VOCs (sVOCs) and demonstrates the high in planta protective potential of S-methyl methane thiosulfonate (MMTS), which fully prevented late blight disease in potato leaves and plantlets without phytotoxic effects, in contrast to other sVOCs. Short exposure times were sufficient to protect plants against infection. We further showed that MMTS’s protective activity was not mediated by the plant immune system but lied in its anti-oomycete activity. Using quantitative proteomics, we determined that different sVOCs caused specific proteome changes in P. infestans, indicating perturbations in sulfur metabolism, protein translation and redox balance. This work brings new perspectives for plant protection against the devastating Irish Famine pathogen, while opening new research avenues on the role of sVOCs in the interaction between plants and their microbiome.
A Novel Method for Calculation of Molecular Energies and Charge Distributions by Thermodynamic Formalization
Authors: Kim TongIl , Ri ChungIl , Yun HakSung , An RyongNam , Han GwangBok , Chae SungIl , Kim GyongNam , Jong GwangChol , Jon Yung
Published: December 2019

The paper describes a new approach to the thermodynamic formalization for calculation of molecular energy and charge distribution in ground state by means of the variational equation of DFT. In order to thermodynamically formalize the molecular calculation, the pseudo chemical potential (PCP) is conceptualized, where a molecule is broken into multi-phase(atom) one-component(electron) systems and the energy of system is represented as PCP. Calculation of the molecular energy and atomic charge by PCP is put forward, thereafter the approach is proved to be valid and its efficiency (accuracy and calculation speed) is verified.
High beta rhythm amplitude in olfactory learning signs a well-consolidated and non-flexible behavioral state
Authors: Fourcaud-Trocmé Nicolas , Lefèvre Laura , Garcia Samuel , Messaoudi Belkacem , Buonviso Nathalie
Published: December 2019

Beta rhythm (15–30 Hz) is a major candidate underlying long-range communication in the brain. In olfactory tasks, beta activity is strongly modulated by learning but its condition of expression and the network(s) responsible for its generation are unclear. Here we analyzed the emergence of beta activity in local field potentials recorded from olfactory, sensorimotor and limbic structures of rats performing an olfactory task. Rats performed successively simple discrimination, rule transfer, memory recall tests and contingency reversal. Beta rhythm amplitude progressively increased over learning in most recorded areas. Beta amplitude reduced to baseline when new odors were introduced, but remained high during memory recall. Intra-session analysis showed that even expert rats required several trials to reach a good performance level, with beta rhythm amplitude increasing in parallel. Notably, at the beginning of the reversal task, beta amplitude remained high while performance was low and, in all tested animals, beta amplitude decreased before rats were able to learn the new contingencies. Connectivity analysis showed that beta activity was highly coherent between all structures where it was expressed. Overall, our results suggest that beta rhythm is expressed in a highly coherent network when context learning - including both odors and reward - is consolidated and signals behavioral inflexibility.
A theoretical, dynamical evaluation method of the steric hindrance in nitroxide radicals using transition states of model reactions
Authors: Yamazaki Yudai , Naganuma Jun , Gotoh Hiroaki
Published: December 2019

Steric hindrance is known to affect the stability, reactivity, and radical trapping ability of stable nitroxide radicals. Therefore, a quantitative evaluation and prediction model of steric hindrance is needed to select and design the optimum nitroxide radicals for specific applications. In this study, a dynamic parameter of steric hindrance (DPSH) is proposed and its characteristics are investigated. Unlike using only the equilibrium structure to evaluate the steric hindrance, DPSH is a dynamic value calculated from the theoretical activation enthalpies for two model reactions of radical addition to olefins. Using DPSH, the steric hindrance was evaluated for a total of 43 alkyl radicals, nitroxide radicals, and radicals derived from phenols, and the results were compared with those of other methods. The DPSH values for radicals can vary when the energy barrier for structural change varies, even if the equilibrium structures of the radicals have the same steric shielding. Finally, for radicals other than nitroxide radicals, the DPSH values were consistent with the predictions from their structures, which suggests that the DPSH has a wide range of applications. We expect DPSH to be used and developed in the analysis of steric factors in various reactions.
Transition Probabilities of Noise-induced Transitions of the Atlantic Ocean Circulation
Authors: Castellana Daniele , Baars Sven , Wubs Fred W. , Dijkstra Henk A.
Published: December 2019

The Atlantic Meridional Overturning Circulation (AMOC) is considered to be a tipping element of the climate system. As it cannot be excluded that the AMOC is in a multiple regime, transitions can occur due to atmospheric noise between the present-day state and a weaker AMOC state. For the first time, we here determine estimates of the transition probability of noise-induced transitions of the AMOC, within a certain time period, using a methodology from large deviation theory. We find that there are two types of transitions, with a partial or full collapse of the AMOC, having different transition probabilities. For the present-day state, we estimate the transition probability of the partial collapse over the next 100 years to be about 15%, with a high sensitivity of this probability to the surface freshwater noise amplitude.
Conflictual influence of humidity during shelter selection of the American cockroach (Periplaneta americana)
Authors: Calvo Martín Mariano , Nicolis Stamatios C. , Planas-Sitjà Isaac , Deneubourg Jean-Louis
Published: December 2019

In collective decision-making, when confronted with different options, groups usually show a more marked preference for one of the options than do isolated individuals. This results from the amplification of individual preferences by social interactions within the group. We show, in an unusual counter-example, that when facing a binary choice between shelters with different relative humidities, isolated cockroaches of the species Periplaneta americana select the wettest shelter, while groups select the driest one. This inversion of selection results from a conflictual influence of humidity on the probabilities of entering and leaving each shelter. It is shown that the individual probability of entering the wettest shelter is higher than the group probability and is increased by previous entries and exits. The probability of leaving each shelter decreases in the population due to social interactions, but this decrease is less pronounced in the wettest shelter, suggesting weaker social interactions. A theoretical model is developed and highlights the existence of tipping points dependent on population size, beyond which an inversion of selection of a resting place is observed.
Bevacizumab improves survival in metastatic colorectal cancer patients with primary tumor resection: A meta-analysis
Authors: Cao Dedong , Zheng Yongfa , Xu Huilin , Ge Wei , Xu Ximing
Published: December 2019

It is not well determined whether primary tumor resection is associated with better outcomes in metastatic colorectal cancer (mCRC) patients treated with bevacizumab. In this meta-analysis, we aimed to assess the prognostic role of primary tumor resection in mCRC treated with bevacizumab. Electronic databases including the Cochrane library, Embase, and Pubmed were searched until April 2018. Clinical studies assessing the influence of primary tumor resection on the efficacy of bevacizumab in patients with mCRC were identified. The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). Seven studies including 2760 mCRC patients were finally included. The results of the meta-analysis were in favor of bevacizumab to patients with resected primary tumor in terms of OS (HR = 0.50, 95%CI: 0.39–0.64; p < 0.01), and PFS (HR = 0.65, 95%CI: 0.51–0.81; p < 0.01). Administration of bevacizumab in mCRC patients with resected primary tumor had a better OS (HR = 0.65, 95%CI: 0.56–0.74; p < 0.01), when compared to chemotherapy(CT). Adding bevacizumab to mCRC patients without resection of primary tumor also had a better OS (HR = 0.78, 95%CI: 0.65–0.94; p < 0.01) and PFS (HR = 0.71, 95%CI: 0.57–0.88; p < 0.01) compared to chemotherapy alone. In conclusion, mCRC patients with resected primary tumor have better survival than those without surgery of primary tumor when treated with bevacizumab. Primary tumor resection status should be taken into consideration when using bevacizumab in mCRC.
Precursory worldwide signatures of earthquake occurrences on Swarm satellite data
Authors: De Santis A. , Marchetti D. , Pavón-Carrasco F. J. , Cianchini G. , Perrone L. , Abbattista C. , Alfonsi L. , Amoruso L. , Campuzano S. A. , Carbone M. , Cesaroni C. , De Franceschi G. , De Santis Anna , Di Giovambattista R. , Ippolito A. , Piscini A. , Sabbagh D. , Soldani M. , Santoro F. , Spogli L. , Haagmans R.
Published: December 2019

The study of the preparation phase of large earthquakes is essential to understand the physical processes involved, and potentially useful also to develop a future reliable short-term warning system. Here we analyse electron density and magnetic field data measured by Swarm three-satellite constellation for 4.7 years, to look for possible in-situ ionospheric precursors of large earthquakes to study the interactions between the lithosphere and the above atmosphere and ionosphere, in what is called the Lithosphere-Atmosphere-Ionosphere Coupling (LAIC). We define these anomalies statistically in the whole space-time interval of interest and use a Worldwide Statistical Correlation (WSC) analysis through a superposed epoch approach to study the possible relation with the earthquakes. We find some clear concentrations of electron density and magnetic anomalies from more than two months to some days before the earthquake occurrences. Such anomaly clustering is, in general, statistically significant with respect to homogeneous random simulations, supporting a LAIC during the preparation phase of earthquakes. By investigating different earthquake magnitude ranges, not only do we confirm the well-known Rikitake empirical law between ionospheric anomaly precursor time and earthquake magnitude, but we also give more reliability to the seismic source origin for many of the identified anomalies.
Localized spatial distributions of disease phases yield long-term persistence of infection
Authors: Moitra Promit , Sinha Sudeshna
Published: December 2019

We explore the emergence of persistent infection in two patches where the phases of disease progression of the individuals is given by the well known SIRS cycle modelling non-fatal communicable diseases. We find that a population structured into two patches with significantly different initial states, yields persistent infection, though interestingly, the infection does not persist in a homogeneous population having the same average initial composition as the average of the initial states of the two patches. This holds true for inter-patch links ranging from a single connection to connections across the entire inter-patch boundary. So a population with spatially uniform distribution of disease phases leads to disease extinction, while a population spatially separated into distinct patches aids the long-term persistence of disease. After transience, even very dissimilar patches settle down to the same average infected sub-population size. However the patterns of disease spreading in the patches remain discernibly dissimilar, with the evolution of the total number of infecteds in the two patches displaying distinct periodic wave forms, having markedly different amplitudes, though identical frequencies. We quantify the persistent infection through the size of the asymptotic infected set. We find that the number of inter-patch links does not affect the persistence in any significant manner. The most important feature determining persistence of infection is the disparity in the initial states of the patches, and it is clearly evident that persistence increases with increasing difference in the constitution of the patches. So we conclude that populations with very non-uniform distributions, where the individuals in different phases of disease are strongly compartmentalized spatially, lead to sustained persistence of disease in the entire population.
Serum circular RNAs act as blood-based biomarkers for hypertrophic obstructive cardiomyopathy
Authors: Sonnenschein Kristina , Wilczek Adriana Luisa , de Gonzalo-Calvo David , Pfanne Angelika , Derda Anselm Arthur , Zwadlo Carolin , Bavendiek Udo , Bauersachs Johann , Fiedler Jan , Thum Thomas
Published: December 2019

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and is associated with a high risk of sudden cardiac death. HCM is characterized by pronounced hypertrophy of cardiomyocytes, fiber disarray and development of fibrosis and can be divided into a non-obstructive (HNCM) and obstructive form (HOCM) therefore requiring personalized therapeutic therapies. In the present study, we investigated the expression patterns of several circulating circular RNAs (circRNAs) as potential biomarkers in patients with HCM. We included 64 patients with HCM and 53 healthy controls to the study and quantitatively measured the expression of a set of circRNAs already known to be associated with cardiac diseases (circDNAJC6) and/or being highly abundant in blood (circTMEM56 and circMBOAT2). Abundancy of circRNAs was then correlated to relevant clinical parameters. Serum expression levels of circRNAs DNAJC6, TMEM56 and MBOAT2 were downregulated in patients with HCM. The inverse association between circRNA levels and HCM remained unchanged even after adjusting for confounding factors. All circRNAs, evaluated separately or in combination, showed a robust discrimination capacity when comparing control subjects with HCM, HNCM or HOCM patients (AUC from 0.722 to 0.949). Two circRNAs, circTMEM56 and circDNAJC6, significantly negatively correlated with echocardiographic parameters for HOCM. Collectively, circulating circRNAs DNAJC6, TMEM56 and MBOAT2 can distinguish between healthy and HCM patients. In addition, circTMEM56 and circDNAJC6 could serve as indicators of disease severity in patients with HOCM. Thus, circRNAs emerge as novel biomarkers for HCM facilitating the clinical decision making in a personalized manner.
Optimized nitrogen management enhances lodging resistance of rice and its morpho-anatomical, mechanical, and molecular mechanisms
Authors: Pan Junfeng , Zhao Junliang , Liu Yanzhuo , Huang Nongrong , Tian Ka , Shah Farooq , Liang Kaiming , Zhong Xuhua , Liu Bin
Published: December 2019

Increasing evidence shows that improved nitrogen management can enhance lodging resistance and lower internodes play a key role in the lodging resistance of rice. However, little is known about the cellular and molecular mechanisms underlying the enhanced lodging resistance under improved nitrogen management. In the present study, two rice varieties, with contrasting lodging resistance, were grown under optimized N management (OPT) and farmers’ fertilizer practices. Under OPT, the lower internodes of both cultivars were shorter but the upper internodes were longer, while both culm diameter and wall thickness of lower internodes were dramatically increased. Microscopic examination showed that the culm wall of lower internodes under OPT contained more sclerenchyma cells beneath epidermis and vascular bundle sheath. The genome-wide gene expression profiling revealed that transcription of genes encoding cell wall loosening factors was down-regulated while transcription of genes participating in lignin and starch synthesis was up-regulated under OPT, resulting in inhibition of longitudinal growth, promotion in transverse growth of lower internodes and enhancement of lodging resistance. This is the first comprehensive report on the morpho-anatomical, mechanical, and molecular mechanisms of lodging resistance of rice under optimized N management.
Serotonin transporter deficiency alters socioemotional ultrasonic communication in rats
Authors: Golebiowska Joanna , Hołuj Małgorzata , Potasiewicz Agnieszka , Piotrowska Diana , Kuziak Agata , Popik Piotr , Homberg Judith R. , Nikiforuk Agnieszka
Published: December 2019

It has been widely established that serotonin plays important role in the regulation of emotional and social behaviour. Rodents with a genetic deletion of the serotonin reuptake transporter (SERT) are used as a model to study lifelong consequences of increased extracellular 5‐HT levels due to its impaired reuptake. SERT knock-out (SERT-KO) mice and rats consistently showed anxiety-like symptoms and social deficits. Nevertheless, the impact of SERT deletion on socioemotional ultrasonic communication has not been addressed. Here we investigated the impact of lifelong serotonin abundance on ultrasonic vocalisation accompanying social interactions and open field exploration in rats. SERT-KO rats displayed reduced overall duration of social contacts, but increased time spent on following the conspecific. The altered pattern of social behaviour in SERT-KO rats was accompanied by the structural changes in ultrasonic vocalisations, as they differed from their controls in distribution of call categories. Moreover, SERT deletion resulted in anxiety-like behaviours assessed in the open field test. Their anxious phenotype resulted in a lower tendency to emit appetitive 50-kHz calls during novelty exploration. The present study demonstrates that genetic deletion of SERT not only leads to the deficits in social interaction and increased anxiety but also affects ultrasonic communication.
Health-promoting phytochemicals and antioxidant capacity in different organs from six varieties of Chinese kale
Authors: Chang Jiaqi , Wang Mengyu , Jian Yue , Zhang Fen , Zhu Jun , Wang Qiaomei , Sun Bo
Published: December 2019

Chinese kale (Brassica oleracea var. alboglabra) has high nutritional value. This study investigated the contents of glucosinolates, antioxidants (chlorophylls, carotenoids, vitamin C, and total phenolics), and antioxidant capacity in five organs from six varieties of Chinese kale. The highest concentrations of individual and total glucosinolates were in the roots and inflorescences, respectively. The highest levels of antioxidants and antioxidant capacity were in inflorescences and leaves. Plant organs played a predominant role in glucosinolate and antioxidant accumulation. Glucoiberin, glucoraphanin, and glucobrassicin, the main anticarcinogenic glucosinolates, could be enhanced simultaneously because of their high positive correlations. The relationship between glucosinolates and antioxidant capacity indicated that glucobrassicin might contribute to the total antioxidant capacity. These results provide useful information related to consumption, breeding of functional varieties, and use of the non-edible organs of Chinese kale.
Characterization of Holstein and Normande whole milk miRNomes highlights breed specificities
Authors: Le Guillou S. , Leduc A. , Laubier J. , Barbey S. , Rossignol M.-N. , Lefebvre R. , Marthey S. , Laloë D. , Le Provost F.
Published: December 2019

The concept of milk as a healthy food has opened the way for studies on milk components, from nutrients to microRNAs, molecules with broad regulatory properties present in large quantities in milk. Characterization of these components has been performed in several species, such as humans and bovine, depending on the stages of lactation. Here, we have studied the variation in milk microRNA composition according to genetic background. Using high throughput sequencing, we have characterized and compared the milk miRNomes of Holstein and Normande cattle, dairy breeds with distinct milk production features, in order to highlight microRNAs that are essential for regulation of the lactation process. In Holstein and Normande milk, 2,038 and 2,030 microRNAs were identified, respectively, with 1,771 common microRNAs, of which 1,049 were annotated and 722 were predicted. The comparison of the milk miRNomes of two breeds allowed to highlight 182 microRNAs displaying significant differences in the abundance. They are involved in the regulation of lipid metabolism and mammary morphogenesis and development, which affects lactation. Our results provide new insights into the regulation of molecular mechanisms involved in milk production.
IL-33/ST2 axis promotes glioblastoma cell invasion by accumulating tenascin-C
Authors: Zhang Jian-fei , Tao Tao , Wang Kang , Zhang Guo-xiang , Yan Yujin , Lin Hui-ran , Li Yong , Guan Min-wu , Yu Jian-jun , Wang Xin-dong
Published: December 2019

Tenascin-C (TNC), a very large multimeric glycoprotein, is overexpressed in human glioblastomas, leading to a highly motile and invasive phenotype of glioma cells. However, the regulation of TNC expression in glioma has remained unclear until now. Our data suggest that interleukin-33 (IL-33) may promote the accumulation of TNC protein by autocrine or paracrine modes of action in glioma. In the present study, the expression levels of TNC, IL-33, and ST2 were measured in glioma tissue specimens, and the impact of altered IL-33 expression on TNC was investigated in vitro and in vivo. In contrast with control treatment, IL-33 treatment increased TNC expression, and knockdown of IL-33 attenuated TNC expression in glioma cells. Furthermore, IL-33 induced the activation of nuclear factor κB (NF-κB) and increased the expression of TNC in U251 cells. In addition, blockage of the IL-33-ST2-NFκB pathway resulted in downregulation of TNC production. IL-33 promoted glioma cell invasion by stimulating the secretion of TNC. Similarly, knockdown of TNC inhibited the invasiveness of glioma cells. These findings provide a novel perspective on the role of the IL-33/NF-κB/TNC signalling pathway in supporting cancer progression. Thus, targeting the IL-33/NF-κB/TNC signalling pathway may be a useful therapeutic approach in glioma.
Tuning PFKFB3 Bisphosphatase Activity Through Allosteric Interference
Authors: Macut Helena , Hu Xiao , Tarantino Delia , Gilardoni Ettore , Clerici Francesca , Regazzoni Luca , Contini Alessandro , Pellegrino Sara , Luisa Gelmi Maria
Published: December 2019

The human inducible phospho-fructokinase bisphosphatase isoform 3, PFKFB3, is a crucial regulatory node in the cellular metabolism. The enzyme is an important modulator regulating the intracellular fructose-2,6-bisphosphate level. PFKFB3 is a bifunctional enzyme with an exceptionally high kinase to phosphatase ratio around 740:1. Its kinase activity can be directly inhibited by small molecules acting directly on the kinase active site. On the other hand, here we propose an innovative and indirect strategy for the modulation of PFKFB3 activity, achieved through allosteric bisphosphatase activation. A library of small peptides targeting an allosteric site was discovered and synthesized. The binding affinity was evaluated by microscale thermophoresis (MST). Furthermore, a LC-MS/MS analytical method for assessing the bisphosphatase activity of PFKFB3 was developed. The new method was applied for measuring the activation on bisphosphatase activity with the PFKFB3-binding peptides. The molecular mechanical connection between the newly discovered allosteric site to the bisphosphatase activity was also investigated using both experimental and computational methods.
Switching of multi-state magnetic structures via domain wall propagation triggered by spin-orbit torques
Authors: Das Shubhankar , Zaig Ariel , Nhalil Hariharan , Avraham Liran , Schultz Moty , Klein Lior
Published: December 2019

Spin-orbit torques emerge as a promising method for manipulating magnetic configurations of spintronic devices. Here, we show that these torques can induce a magnetization reversal via domain wall propagation which may open new ways in developing novel spintronic devices and in particular in realizing high-density multi-level magnetic memory. Our devices are bi-layer heterostructures of Ni0.8Fe0.2 on top of β-Ta patterned in the form of two or three crossing ellipses which exhibit in the crossing area shape-induced biaxial and triaxial magnetic anisotropy, respectively. We demonstrate field-free switching between discrete remanent magnetic states of the structures by spin-orbit torques induced by flowing electrical current through one of the ellipses. We note switchings induced by the coupling between the ellipses where current flowing in one ellipse triggers a reversal in a neighboring ellipse which propagates from the center outwards. Numerical tools successfully simulate the observed coupling-induced switching using experimentally extracted parameters.
Bivariate analysis of barley scald resistance with relative maturity reveals a new major QTL on chromosome 3H
Authors: Zhang Xuechen , Ovenden Ben , Orchard Beverley A. , Zhou Meixue , Park Robert F. , Singh Davinder , Milgate Andrew
Published: December 2019

The disease scald of barley is caused by the pathogen Rhynchosporium commune and can cause up to 30–40% yield loss in susceptible cultivars. In this study, the Australian barley cultivar ‘Yerong’ was demonstrated to have resistance that differed from Turk (Rrs1 (Rh3 type)) based on seedling tests with 11 R. commune isolates. A doubled haploid population with 177 lines derived from a cross between ‘Yerong’ and the susceptible Australian cultivar ‘Franklin’ was used to identify quantitative trait loci (QTL) for scald resistance. A QTL on chromosome 3H was identified with large effect, consistent with a major gene conferring scald resistance at the seedling stage. Under field conditions, a bivariate analysis was used to model scald percentage of infected leaf area and relative maturity, the residuals from the regression were used as our phenotype for QTL analysis. This analysis identified one major QTL on chromosome 3H, which mapped to the same position as the QTL at seedling stage. The identified QTL on 3H is proposed to be different from the Rrs1 on the basis of seedling resistance against different R. commune isolates and physical map position. This study increases the current understanding of scald resistance and identifies genetic material possessing QTLs useful for the marker-assisted selection of scald resistance in barley breeding programs.
Quantum process capability
Authors: Kuo Chung-Cheng , Chen Shih-Hsuan , Lee Wei-Ting , Chen Hung-Ming , Lu He , Li Che-Ming
Published: December 2019

Physical processes in the quantum regime possess non-classical properties of quantum mechanics. However, methods for quantitatively identifying such processes are still lacking. Accordingly, in this study, we develop a framework for characterizing and quantifying the ability of processes to cause quantum-mechanical effects on physical systems. We start by introducing a new concept, referred to as quantum process capability, to evaluate the effects of an experimental process upon a prescribed quantum specification. Various methods are then introduced for measuring such a capability. It is shown that the methods are adapted to quantum process tomography for implementation of process capability measure and applicable to all physical processes that can be described using the general theory of quantum operations. The utility of the proposed framework is demonstrated through several examples, including processes of entanglement, coherence, and superposition. The formalism proposed in this study provides a generic approach for the identification of dynamical processes in quantum mechanics and facilitates the general classification of quantum-information processing.