bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of flight delays in aviation system using different classification algorithms and feature selection methods
Authors: Anderson A. B. A. , Kumar A. J. Sanjeev , Christopher A. B. Arockia
Published: August 2019

Data mining is a process of finding correlations and collecting and analysing a huge amount of data in a database to discover patterns or relationships. Flight delay creates significant problems in the present aviation system. Data mining techniques are desired for analysing the performance in which micro-level causes propagate to make system-level patterns of delay. Analysing flight delays is very difficult – both when looking from a historical view as well as when estimating delays with forecast demand. This paper proposes using Decision Tree (DT), Support Vector Machine (SVM), Naive Bayesian (NB), K-nearest neighbour (KNN) and Artificial Neural Network (ANN) to study and analyse delays among aircrafts. The performance of different data mining methods is found in the different regions of the updated datasets on these classifiers. Finally, the result shows a significant variation in the performance of different data mining methods and feature selection for this problem. This paper aims to deal with how data mining techniques can be used to understand difficult aircraft system delays in aviation. Our aim is to develop a classification model for studying and reducing delay using different data mining methods and, in this manner, to show that DT has a greater classification accuracy. The different feature selectors are used in this study in order to reduce the number of initial attributes. Our results clearly demonstrate the value of DT for analysing and visualising how system-level effects happen from subsystem-level causes.
Interest Groups and the (Non-)Enforcement Powers of EU Agencies: The Case of Energy Regulation
Authors: MAGGETTI Martino
Published: August 2019

Some EU agencies have been recently entrusted with enforcement powers, which imply a crucial extension of their regulatory reach. However, other comparable agencies did not receive such powers. This paper explores the case of energy regulation as an instance of these “negative” cases, and suggests that the lack of enforcement powers may have been partially determined by business interest groups. To illustrate this argument, this article firstly relies on official documentation to show that key interest groups were consistently opposed to the option of granting enforcement powers to the EU agency in charge (ACER). Secondly, it is suggested that these interest groups, which have been largely incorporated in regulatory networks during the prehistory of the agency, had access to, and exerted influence in, the governance of EU energy policy, and could plausibly have been able to concretise their preferences. A systematic examination of the representation of interest groups in the European network of energy regulators (CEER/ERGEG) during the period 2004–2011 is undertaken to corroborate this point. The conclusion draws attention to the fact that, although interest groups are less visible than other actors and their presence is less formalised, they could be very influential on decision-making processes within European networks and agencies.
A nonclonal outbreak of vancomycin-sensitive Enterococcus faecalis bacteremia in a neonatal intensive care unit
Authors: Kotsanas Despina , Tan Kenneth , Scott Carmel , Baade Britta , Cheng Michaela Hui Ling , Tan Zien Vanessa , Taylor Jacqueline E. , Kwong Jason C. , Seemann Torsten , Coombs Geoffrey W. , Howden Benjamin P. , Stuart Rhonda L.
Published: August 2019

Objective:

To describe an outbreak of bacteremia caused by vancomycin-sensitive Enterococcus faecalis (VSEfe).

Design:

An investigation by retrospective case control and molecular typing by whole-genome sequencing (WGS).

Setting:

A tertiary-care neonatal unit in Melbourne, Australia.

Methods:

Risk factors for 30 consecutive neonates with VSEfe bacteremia from June 2011 to December 2014 were analyzed using a case control study. Controls were neonates matched for gestational age, birth weight, and year of birth. Isolates were typed using WGS, and multilocus sequence typing (MLST) was determined.

Results:

Bacteremia for case patients occurred at a median time after delivery of 23.5 days (interquartile range, 14.9–35.8). Previous described risk factors for nosocomial bacteremia did not contribute to excess risk for VSEfe. WGS typing results designated 43% ST179 as well as 14 other sequence types, indicating a polyclonal outbreak. A multimodal intervention that included education, insertion checklists, guidelines on maintenance and access of central lines, adjustments to the late onset sepsis antibiotic treatment, and the introduction of diaper bags for disposal of soiled diapers after being handled inside the bed, led to termination of the outbreak.

Conclusions:

Typing using WGS identified this outbreak as predominately nonclonal and therefore not due to cross transmission. A multimodal approach was then sought to reduce the incidence of VSEfe bacteremia.
Engaging Hearts and Minds: How and Why Legal Organizations Use Public Education
Authors: Trowbridge David L.
Published: August 2019

While scholars recognize that cause lawyers use public education as a reform tactic, they rarely place this tactic at the center of their analysis, leaving a gap in our understanding of how cause lawyers use extrajudicial tactics to navigate the limits of litigation. In this article, I examine the role of public education in the work of cause lawyers, through a study of lawyers from eight legal organizations representing the rights of LGBTQ people. Through interviews, archival work, and analysis of publications, I find that lawyers and organizations use education for four functions: (1) to prime a pathway to successful litigation; (2) to control for backlash; (3) to leverage pressure during litigation or policy negotiation; and (4) to generate community and public awareness. This article shows that public education is not simply an ancillary tool to these groups—it is vital to their missions and their everyday work.
A paradigm for longitudinal complex network analysis over patient cohorts in neuroscience
Authors: Shappell Heather , Tripodis Yorghos , Killiany Ronald J. , Kolaczyk Eric D.
Published: August 2019

The study of complex brain networks, where structural or functional connections are evaluated to create an interconnected representation of the brain, has grown tremendously over the past decade. Many of the statistical network science tools for analyzing brain networks have been developed for cross-sectional studies and for the analysis of static networks. However, with both an increase in longitudinal study designs and an increased interest in the neurological network changes that occur during the progression of a disease, sophisticated methods for longitudinal brain network analysis are needed. We propose a paradigm for longitudinal brain network analysis over patient cohorts, with the key challenge being the adaptation of Stochastic Actor-Oriented Models to the neuroscience setting. Stochastic Actor-Oriented Models are designed to capture network dynamics representing a variety of influences on network change in a continuous-time Markov chain framework. Network dynamics are characterized through both endogenous (i.e. network related) and exogenous effects, where the latter include mechanisms conjectured in the literature. We outline an application to the resting-state functional magnetic resonance imaging setting with data from the Alzheimer’s Disease Neuroimaging Initiative study. We draw illustrative conclusions at the subject level and make a comparison between elderly controls and individuals with Alzheimer’s disease.
White Jews: An Intersectional Approach
Authors: Schraub David
Published: August 2019

“Intersectionality,” a concept coined and developed by legal scholar Kimberlé Crenshaw, examines how our various identities change in meaning and valence when placed in dynamic relation with one another. Instead of exploring identity traits like “race,” “gender,” “religion,” and so on in isolation, an intersectional approach asks what these various characteristics “do” to one another in combination. I suggest that an intersectional approach—asking “what does Whiteness do to Jewishness?”—can help illuminate elements of the Jewish experience that would otherwise remain obscure. The core claim is that Whiteness and Jewishness in combination function in ways that are not necessarily grasped if one atomizes the identities and holds them apart. What Whiteness “does” to Jewishness is act as an accelerant for certain forms of antisemitic marginalization even as it ratifies a racialized hierarchy within the Jewish community. Absent an intersectional vantage, many political projects and controversies surrounding Jewish equality will be systematically misunderstood.
Miocene and Plio-Pleistocene foraminiferal assemblages from Seymour Island, Antarctica
Authors: Badaró Victor C.S. , Petri Setembrino
Published: August 2019

Here we describe new microfossil assemblages for the Miocene Hobbs Glacier Formation and the first possibly indigenous assemblages for the Plio-Pleistocene Weddell Sea Formation on Seymour Island, West Antarctica. The assemblages are composed mainly of foraminifers, but radiolarians, calcitarchs and poriferan sclerites are also present. For the Hobbs Glacier Formation, we report the foraminifersBolivinasp.,Oolina globosaandRosalinacf.globularis; and for the Weddell Sea Formation, we reportFavulina hexagona,Globigerinita uvula,Globocassidulinacf.subglobosaandPsammosphaera fusca. The low abundance and diversity of microfossils, allied with the complex taphonomical processes that prevailed in Antarctic glacial–marine palaeoenvironments, make it impossible to define whether the assemblages are composed of a mixture of indigenous and re-elaborated specimens or exclusively of re-elaborated remains. Nevertheless, the indigenous nature of some specimens is suggested by their inherent fragility, excellent preservation and/or taxonomic association with indigenous assemblages from correlated strata. The taxonomic compositions are not directly comparable with other Antarctic assemblages, although most of the species were previously reported from pre-Quaternary or modern deposits of both West and East Antarctica. This lack of correspondence is probably due to preservation biases, but any further significance is hidden by the complex taphonomy of the deposits.
On the matrix Monge–Kantorovich problem
Authors: CHEN YONGXIN , GANGBO WILFRID , GEORGIOU TRYPHON T. , TANNENBAUM ALLEN
Published: August 2019

The classical Monge–Kantorovich (MK) problem as originally posed is concerned with how best to move a pile of soil or rubble to an excavation or fill with the least amount of work relative to some cost function. When the cost is given by the square of the Euclidean distance, one can define a metric on densities called the Wasserstein distance. In this note, we formulate a natural matrix counterpart of the MK problem for positive-definite density matrices. We prove a number of results about this metric including showing that it can be formulated as a convex optimisation problem, strong duality, an analogue of the Poincaré–Wirtinger inequality and a Lax–Hopf–Oleinik–type result.
Left ventricular non-compaction in a child with bicuspid aortic valve and aortic coarctation
Authors: Karatza Ageliki , Mylonas Konstantinos S. , Tzifa Aphrodite
Published: August 2019

We present the case of a 3-year-old boy with bicuspid aortic valve, aortic coarctation, and left ventricular non-compaction. The diagnosis was made post-natally with ultrasonography and was verified by cardiac MRI. Aortic coarctation was initially repaired surgically. At age 3 months, recoarctation and heart failure developed. Balloon angioplasty was performed with immediate improvement. At age 3 years, the patient remains asymptomatic and normotensive.
Examining Gender Differences in Neurocognitive Functioning Across Adulthood
Authors: Siedlecki Karen L. , Falzarano Francesca , Salthouse Timothy A.
Published: August 2019

Objective:

Previous research has shown that women have an advantage on verbal episodic memory and processing speed tasks, while men show an advantage on spatial ability measures. Previous work has also found differences in cognition across age. The current study examines gender differences in neurocognitive functioning across adulthood, whether age moderates this effect, and whether these differences remain consistent with practice across multiple testing sessions.

Method:

Data from the Virginia Cognitive Aging Project were used, which included participants between the ages of 18 and 99 years (N = 5125). Participants completed measures assessing five cognitive domains: episodic memory, processing speed, reasoning, spatial visualization, and vocabulary.

Results:

Results showed that gender was significantly related to memory, speed, and spatial visualization, but not to vocabulary or reasoning. Results of invariance analyses across men and women provided evidence of configural and metric invariance, along with partial scalar invariance. Additionally, there was little evidence that age or practice influenced the gender effect on neurocognition.

Conclusions:

Consistent with the previous research, these results suggest that there is a female advantage in episodic memory and processing speed, and a male advantage in spatial visualization. Gender was shown to influence cognition similarly across adulthood. Furthermore, the influence of gender remained the same across three sessions, which is consistent with the previous work that has shown that training does not differentially impact performance on spatial ability measures for females compared to males.
Inducing Factors and Impacts of the October 2017 California Wildfires
Authors: Li Andy X. , Wang Yuan , Yung Yuk L.
Published: August 2019

The California wildfires of October 2017 were one of the largest wildfires in the state's history. Using surface temperature, surface pressure, cloud liquid and ice water contents, precipitation data, and wind data, we explore possible reasons for the wildfires. It is found that the mean surface temperature in California has increased, while mean cloud water contents and mean precipitation in California has decreased over the past 39 years. Higher temperatures, higher surface pressures, lower cloud water contents, lower precipitation, enhanced surface Santa Ana winds, and enhanced sinking air have set up favorable meteorological conditions for stronger wildfires in California, such as the October 2017 wildfires. Furthermore, the CO2 data from the Orbiting Carbon Observatory 2 satellite have, for the first time, made it possible for us to quantitatively characterize the impact of wildfires on atmospheric CO2 in California, which revealed that atmospheric CO2 increased by 2 ppm after the October 2017 California wildfires. Analyses in this study can help us better understand the causes and impacts of wildfires.
Insights Into the Major Processes Driving the Global Distribution of Copper in the Ocean From a Global Model
Authors: Richon Camille , Tagliabue Alessandro
Published: August 2019

Copper (Cu) is an unusual micronutrient as it can limit primary production but can also become toxic for growth and cellular functioning under high concentrations. Cu also displays an atypical linear profile, which will modulate its availability to marine microbes across the ocean. Multiple chemical forms of Cu coexist in seawater as dissolved species and understanding the main processes shaping the Cu biogeochemical cycling is hampered by key knowledge gaps. For instance, the drivers of its specific linear profile in seawater are unknown, and the bioavailable form of Cu for marine phytoplankton is debated. Here we developed a global 3‐D biogeochemical model of oceanic Cu within the NEMO/PISCES global model, which represents the global distribution of dissolved copper well. Using our model, we find that reversible scavenging of Cu by organic particles drives the dissolved Cu vertical profile and its distribution in the deep ocean. The low modeled inorganic copper (Cu') in the surface ocean means that Cu' cannot maintain phytoplankton cellular copper requirements within observed ranges. The global budget of oceanic Cu from our model suggests that its residence time may be shorter than previously estimated and provides a global perspective on Cu cycling and the main drivers of Cu biogeochemistry in different regions. Cu scavenging within particle microenvironments and uptake by denitrifying bacteria could be a significant component of Cu cycling in oxygen minimum zones.
SKS Splitting Beneath Mount St. Helens: Constraints on Subslab Mantle Entrainment
Authors: Eakin C. M. , Wirth E. A. , Wallace A. , Ulberg C. W. , Creager K. C. , Abers G. A.
Published: August 2019

Observations of seismic anisotropy can provide direct constraints on the character of mantle flow in subduction zones, critical for our broader understanding of subduction dynamics. Here we present over 750 new SKS splitting measurements in the vicinity of Mount St. Helens in the Cascadia subduction zone using a combination of stations from the iMUSH broadband array and Cascades Volcano Observatory network. This provides the highest density of splitting measurements yet available in Cascadia, acting as a focused “telescope” for seismic anisotropy in the subduction zone. We retrieve spatially consistent splitting parameters (mean fast direction Φ: 74°, mean delay time ∂t: 1.0 s) with the azimuthal occurrence of nulls in agreement with the fast direction of splitting. When averaged across the array, a 90° periodicity in splitting parameters as a function of back azimuth is revealed, which has not been recovered previously with single‐station observations. The periodicity is characterized by a sawtooth pattern in Φ with a clearly defined 45° trend. We present new equations that reproduce this behavior based upon known systematic errors when calculating shear wave splitting from data with realistic seismic noise. The corrected results suggest a single layer of anisotropy with an ENE‐WSW fast axis parallel to the motion of the subducting Juan de Fuca plate; in agreement with predictions for entrained subslab mantle flow. The splitting pattern is consistent with that seen throughout Cascadia, suggesting that entrainment of the underlying asthenosphere with the subducting slab is coherent and widespread.
Visibility and Line‐of‐Sight Extinction Estimates in Gale Crater During the 2018/MY34 Global Dust Storm
Authors: Smith Christina L. , Moores John E. , Lemmon Mark , Guzewich Scott D. , Moore Casey A. , Ellison Douglas , Khayat Alain S. J.
Published: August 2019

Northern line‐of‐sight extinction within Gale Crater during the 2018 global dust storm was monitored daily using Mars Science Laboratory's Navcam. Additional observations with Mastcam (north) and Navcam (all directions) were obtained at a lower cadence. Using feature identification and georeferencing, extinction was estimated in all possible directions. Peak extinction of >1.1 km−1 was measured between sols 2086 and 2090, an order of magnitude higher than previous maxima. Northern and western directions show an initial decrease, followed by a secondary peak in extinction, not seen in column opacity measurements. Due to foreground topography, eastern direction results are provided only as limits, and southern results were indeterminable. Mastcam red and green filter results agree well, but blue filter results show higher extinctions, likely due to low signal‐to‐noise. Morning results are systematically higher than afternoon results, potentially indicative of atmospheric mixing.
The Effects of Vertically Propagating Tides on the Mean Dynamical Structure of the Lower Thermosphere
Authors: Jones McArthur , Forbes Jeffrey M. , Sassi Fabrizio
Published: August 2019

Numerical experiments performed with the National Center for Atmospheric Research thermosphere‐ionosphere‐electrodynamics general circulation model forced with an observationally based diurnal and semidiurnal tidal spectrum are utilized to investigate the physical processes by which the dissipation of vertically propagating tides act to alter the zonally and diurnally averaged (“zonal‐mean”) dynamical state of the thermosphere. Below 150 km the largest contributors to the zonal‐mean zonal wind distribution are the pressure gradient, Coriolis, and the tidally driven momentum flux divergence terms, the latter being about half the former two. Ion drag plays a smaller role in the lower thermosphere but becomes increasingly important at higher altitudes (i.e., above ∼150 km). We also find that the tidally driven heat flux divergence term contributes to the generation of zonal‐mean zonal winds through its coupling into the pressure gradient term. Tidally induced zonally and diurnally averaged zonal wind changes achieve values of up to 30 m/s in the lower thermosphere, of which about a third can be traced to the heat flux divergence. Tidal amplitudes used to force the thermosphere‐ionosphere‐electrodynamics general circulation model lower boundary represent conservative estimates, since they are based on forcing by a multiyear 60‐day mean tidal climatology, which significantly underestimates their amplitudes at any given time. Eliassen‐Palm Fluxes further support the conclusion that the heat flux divergence has a statistically significant direct impact on the zonal‐mean zonal wind balance in the lower thermosphere.
Alteration of Particle Drift Resonance Dynamics Near Poloidal Mode Field Line Resonance Structures
Authors: Degeling A. W. , Rankin R. , Wang Y. , Shi Q. Q. , Zong Q.‐G.
Published: August 2019

We examine the effect on drift‐resonant particle dynamics of a strongly peaked internally driven poloidal mode field line resonance (FLR; with specified frequency ω in the Pc5 range and azimuthal mode number m≫1). Using an analytic magneto‐hydrodynamic model in a dipole field to describe the ultra low frequency wave mode, we use the bounce‐averaged formalism of Northrop (1963) to obtain equations of motion for charged particles in the wave frame and find an analytic solution for the case of a temporally constant ultra low frequency wave amplitude profile. Focusing on equatorially mirroring electrons in this study, we demonstrate that, for sufficiently peaked radial profiles, multiple drift resonances appear that are associated with the FLR peak. These are in addition to the well‐known zeroth‐order drift resonance location, occurring when the unperturbed drift speed
satisfies the resonance condition (
). The additional resonances arise because the strongly peaked FLR wave field components provide sufficiently strong perturbations to the azimuthal drift speed to cause multiple zero crossings in the resonance condition. These additional resonances have trapping periods much lower than that of the zeroth‐order resonance and considerably complicate the electron dynamics. Further properties of these resonances and their measurable effect on electron dynamics are discussed. For example, their effect on observations of energetic electron flux on board satellites in the vicinity of an FLR is calculated and shown to significantly distort the typical signature associated with drift resonance (modulations in electron flux at the wave frequency with a 180° phase change across the resonant energy).
The Semiannual and 4.4‐Year Modulations of Extreme High Tides
Authors: Ray R. D. , Merrifield M. A.
Published: August 2019

In most places extreme high tides undergo a clear seasonal variation. It is well known that semidiurnal tides tend to peak during equinox seasons, and diurnals during solstice seasons. This is a consequence of the solar and lunar declinations, which when large maximize diurnal tides at the expense of semidiurnals. The semiannual range modulation of tidal extremes for a pure semidiurnal tide is determined mainly by the amplitude of the K2 constituent; a pure diurnal is determined mainly by P1. Mixed tidal regimes tend to experience maxima very roughly around the times of solstice, but not always, with the semiannual modulation generally a complicated function of constituent amplitudes and phases. These modulations are here mapped worldwide by analyzing tidal extremes predicted with a global tide model. The known 4.4‐year modulation in extreme tides is a consequence of declinational and perigean effects coming in and out of phase. The phase of the 4.4‐year modulation is controlled by the phase of the semiannual modulation, irrespective of whether the tide is diurnal, semidiurnal, or mixed.
Investigating the association between body fat and depression via Mendelian randomization
Authors: Speed Maria S. , Jefsen Oskar H. , Børglum Anders D. , Speed Doug , Østergaard Søren D.
Published: August 2019

Obesity and depression are major public health concerns that are both associated with substantial morbidity and mortality. There is a considerable body of literature linking obesity to the development of depression. Recent studies using Mendelian randomization indicate that this relationship is causal. Most studies of the obesity–depression association have used body mass index as a measure of obesity. Body mass index is defined as weight (measured in kilograms) divided by the square of height (meters) and therefore does not distinguish between the contributions of fat and nonfat to body weight. To better understand the obesity–depression association, we conduct a Mendelian randomization study of the relationship between fat mass, nonfat mass, height, and depression, using genome-wide association study results from the UK Biobank (n = 332,000) and the Psychiatric Genomics Consortium (n = 480,000). Our findings suggest that both fat mass and height (short stature) are causal risk factors for depression, while nonfat mass is not. These results represent important new knowledge on the role of anthropometric measures in the etiology of depression. They also suggest that reducing fat mass will decrease the risk of depression, which lends further support to public health measures aimed at reducing the obesity epidemic.
An autophagy-inducing and TLR-2 activating BCG vaccine induces a robust protection against tuberculosis in mice
Authors: Khan Arshad , Bakhru Pearl , Saikolappan Sankaralingam , Das Kishore , Soudani Emily , Singh Christopher R. , Estrella Jaymie L. , Zhang Dekai , Pasare Chandrashekhar , Ma Yue , Sun Jianjun , Wang Jin , Hunter Robert L. , Tony Eissa N. , Dhandayuthapani Subramanian , Jagannath Chinnaswamy
Published: August 2019

Mycobacterium bovisBCG is widely used as a vaccine against tuberculosis due toM. tuberculosis(Mtb), which kills millions of people each year. BCG variably protects children, but not adults against tuberculosis. BCG evades phagosome maturation, autophagy, and reduces MHC-II expression of antigen-presenting cells (APCs) affecting T-cell activation. To bypass these defects, an autophagy-inducing, TLR-2 activating C5 peptide from Mtb-derived CFP-10 protein was overexpressed in BCG in combination with Ag85B. Recombinant BCG85C5induced a robust MHC-II-dependent antigen presentation to CD4 T cells in vitro, and elicited stronger TH1 cytokines (IL-12, IL-1β, and TNFα) from APCs of C57Bl/6 mice increasing phosphorylation of p38MAPK and ERK. BCG85C5also enhanced MHC-II surface expression of MΦs by inhibiting MARCH1 ubiquitin ligase that degrades MHC-II. BCG85C5infected APCs from MyD88 or TLR-2 knockout mice showed decreased antigen presentation. Furthermore, BCG85C5induced LC3-dependent autophagy in macrophages increasing antigen presentation. Consistent with in vitro effects, BCG85C5markedly expanded both effector and central memory T cells in C57Bl/6 mice protecting them against both primary aerosol infection with Mtb and reinfection, but was less effective among TLR-2 knockout mice. Thus, BCG85C5induces stronger and longer lasting immunity, and is better than BCG against tuberculosis of mice.
Musical playschool activities are linked to faster auditory development during preschool-age: a longitudinal ERP study
Authors: Putkinen Vesa , Tervaniemi Mari , Huotilainen Minna
Published: August 2019

The influence of musical experience on brain development has been mostly studied in school-aged children with formal musical training while little is known about the possible effects of less formal musical activities typical for preschool-aged children (e.g., before the age of seven). In the current study, we investigated whether the amount of musical group activities is reflected in the maturation of neural sound discrimination from toddler to preschool-age. Specifically, we recorded event-related potentials longitudinally (84 recordings from 33 children) in a mismatch negativity (MMN) paradigm to different musically relevant sound changes at ages 2–3, 4–5 and 6–7 years from children who attended a musical playschool throughout the follow-up period and children with shorter attendance to the same playschool. In the first group, we found a gradual positive to negative shift in the polarities of the mismatch responses while the latter group showed little evidence of age-related changes in neural sound discrimination. The current study indicates that the maturation of sound encoding indexed by the MMN may be more protracted than once thought and provides first longitudinal evidence that even quite informal musical group activities facilitate the development of neural sound discrimination during early childhood.
High-resolution dynamic inversion imaging with motion-aberrations-free using optical flow learning networks
Authors: Li Jin , Liu Zilong
Published: August 2019

Dynamic optical imaging (e.g. time delay integration imaging) is troubled by the motion blur fundamentally arising from mismatching between photo-induced charge transfer and optical image movements. Motion aberrations from the forward dynamic imaging link impede the acquiring of high-quality images. Here, we propose a high-resolution dynamic inversion imaging method based on optical flow neural learning networks. Optical flow is reconstructed via a multilayer neural learning network. The optical flow is able to construct the motion spread function that enables computational reconstruction of captured images with a single digital filter. This works construct the complete dynamic imaging link, involving the backward and forward imaging link, and demonstrates the capability of the back-ward imaging by reducing motion aberrations.
Malaria-anemia comorbidity prevalence as a measure of malaria-related deaths in sub-Saharan Africa
Authors: Papaioannou Isidoros , Utzinger Jürg , Vounatsou Penelope
Published: August 2019

Different methods and data sources have been utilized to determine the relationship between malaria and mortality in endemic countries. Most of these efforts have focused on deaths directly attributed to malaria, while they overlooked causes of mortality that might be indirectly related to the disease, for instance anemia. We estimated the association of malaria parasitaemia, anemia, and malaria-anemia comorbidity with all-cause under-five mortality and evaluated the potential of malaria-anemia comorbidity prevalence to quantify malaria-related deaths in sub-Saharan Africa. We analysed data from Demographic and Health Surveys (DHS) and employed Bayesian geostatistical models. Mortality hazard obtained from malaria-anemia comorbidity prevalence was up to 3·5 times higher compared to the hazard related to Plasmodium parasitaemia only. Malaria parasite prevalence alone could not always capture a statistically important association with under-five mortality. Geographical variation of the malaria-anemia comorbidity effect was observed in most, but not all, countries. We concluded that the malaria burden in sub-Saharan Africa is considerably underestimated when anemia in not taken into account and that the malaria-anemia comorbidity prevalence provides a useful measure of the malaria-related deaths.
The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways
Authors: Buckley Melanie L. , Williams Jessica O. , Chan Yee-Hung , Laubertová Lucia , Gallagher Hayley , Moss Joe W. E. , Ramji Dipak P.
Published: August 2019

Atherosclerosis, a chronic inflammatory disorder of the walls of arteries, causes more deaths worldwide than any other disease. Cytokines, which are present at high levels in atherosclerotic plaques, play important roles in regulating the initiation and the progression of the disease. Previous studies using animal and cell culture model systems revealed protective, anti-atherogenic effects of the cytokine interleukin-33 (IL-33). The action of this cytokine involves both the induction and suppression of expression of many genes. Unfortunately, the signaling pathways that are responsible for the inhibition of gene expression by this cytokine are poorly understood. Further studies are required given the important roles of genes whose expression is inhibited by IL-33 in key cellular processes associated with atherosclerosis such as monocyte recruitment, foam cell formation and lipoprotein metabolism. We have investigated here the roles of various known IL-33 activated signaling pathways in such inhibitory actions using RNA interference-mediated knockdown assays and monocyte chemotactic protein-1 and intercellular adhesion molecule-1 as model genes. Key roles were identified for extracellular signal-regulated kinase-1/2, p38α kinase, c-Jun N-terminal kinase-1/2, phosphoinositide 3-kinase-γ, and p50 and p65 nuclear factor-κB in such inhibitory action of IL-33. These studies provide new insights on the signaling pathways through which IL-33 inhibits the macrophage expression of key atherosclerosis-associated genes.
A simple, reproducible and cost-effective procedure to analyse gut phageome: from phage isolation to bioinformatic approach
Authors: d’Humières Camille , Touchon Marie , Dion Sara , Cury Jean , Ghozlane Amine , Garcia-Garcera Marc , Bouchier Christiane , Ma Laurence , Denamur Erick , P.C.Rocha Eduardo
Published: August 2019

The microbiota of the human gut is a complex and rich community where bacteria and their viruses, the bacteriophages, are dominant. There are few studies on the phage community and no clear standard for isolating them, sequencing and analysing their genomes. Since this makes comparisons between studies difficult, we aimed at defining an easy, low-cost, and reproducible methodology. We analysed five different techniques to isolate phages from human adult faeces and developed an approach to analyse their genomes in order to quantify contamination and classify phage contigs in terms of taxonomy and lifestyle. We chose the polyethylene glycol concentration method to isolate phages because of its simplicity, low cost, reproducibility, and of the high number and diversity of phage sequences that we obtained. We also tested the reproducibility of this method with multiple displacement amplification (MDA) and showed that MDA severely decreases the phage genetic diversity of the samples and the reproducibility of the method. Lastly, we studied the influence of sequencing depth on the analysis of phage diversity and observed the beginning of a plateau for phage contigs at 20,000,000 reads. This work contributes to the development of methods for the isolation of phages in faeces and for their comparative analysis.
Integrated genomic epidemiology and phenotypic profiling of Clostridium difficile across intra-hospital and community populations in Colombia
Authors: Muñoz Marina , Restrepo-Montoya Daniel , Kumar Nitin , Iraola Gregorio , Camargo Milena , Díaz-Arévalo Diana , Roa-Molina Nelly S. , Tellez Mayra A. , Herrera Giovanny , Ríos-Chaparro Dora I. , Birchenall Claudia , Pinilla Darío , Pardo-Oviedo Juan M. , Rodríguez-Leguizamón Giovanni , Josa Diego F. , Lawley Trevor D. , Patarroyo Manuel A. , Ramírez Juan David
Published: August 2019

Clostridium difficile, the causal agent of antibiotic-associated diarrhea, has a complex epidemiology poorly studied in Latin America. We performed a robust genomic and phenotypic profiling of 53 C. difficile clinical isolates established from diarrheal samples from either intrahospital (IH) or community (CO) populations in central Colombia. In vitro tests were conducted to evaluate the cytopathic effect, the minimum inhibitory concentration of ten antimicrobial agents, the sporulation efficiency and the colony forming ability. Eleven different sequence types (STs) were found, the majority present individually in each sample, however in three samples two different STs were isolated. Interestingly, CO patients were infected with STs associated with hypervirulent strains (ST-1 in Clade-2). Three coexistence events (two STs simultaneously detected in the same sample) were observed always involving ST-8 from Clade-1. A total of 2,502 genes were present in 99% of the isolates with 95% of identity or more, it represents a core genome of 28.6% of the 8,735 total genes identified in the set of genomes. A high cytopathic effect was observed for the isolates positive for the two main toxins but negative for binary toxin (TcdA+/TcdB+/CDT− toxin production type), found only in Clade-1. Molecular markers conferring resistance to fluoroquinolones (cdeA and gyrA) and to sulfonamides (folP) were the most frequent in the analyzed genomes. In addition, 15 other markers were found mostly in Clade-2 isolates. These results highlight the regional differences that C. difficile isolates display, being in this case the CO isolates the ones having a greater number of accessory genes and virulence-associated factors.
Fluidic Self-Assembly on Electroplated Multilayer Solder Bumps with Tailored Transformation Imprinted Melting Points
Authors: Kaltwasser Mahsa , Schmidt Udo , Lösing Lars , Biswas Shantonu , Stauden Thomas , Bund Andreas , Jacobs Heiko O.
Published: August 2019

This communication presents fluidic self-assembly of Si-chip on a sequentially electroplated multilayer solder bump with tailored transformation imprinted melting points. The multilayer solder bump is a lead free ternary solder system, which provides a route to transform the melting point of interconnects for applications in solder directed fluidic self-assembly. The outermost metal layers form a low melting point Bi33.7In66.3 solder shell (72 °C). This solder shell enables fluidic self-assembly and self-alignment of freely in water suspended Si-dies at relatively low temperature (75 °C) leading to well-ordered chip arrays. The reduction of the free surface energy of the shell-water interface provides the driving force for the self-assembly. The lowermost metal layer is a high melting point solder and acts as a core. After the self-assembly is complete, a short reflow causes the transformation of the core and the shell yielding a stable high melting point solder with adjustable melting points. The chosen ternary solder system enables the realization of interconnects with melting points in the range of 112 °C to 206 °C.
Characterization of subcutaneous and omental adipose tissue in patients with obesity and with different degrees of glucose impairment
Authors: Belligoli Anna , Compagnin Chiara , Sanna Marta , Favaretto Francesca , Fabris Roberto , Busetto Luca , Foletto Mirto , Dal Prà Chiara , Serra Roberto , Prevedello Luca , Da Re Chiara , Bardini Romeo , Mescoli Claudia , Rugge Massimo , Fioretto Paola , Conci Scilla , Bettini Silvia , Milan Gabriella , Vettor Roberto
Published: August 2019

Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients.
Optimized CRISPR/Cas9-mediated in vivo genome engineering applicable to monitoring dynamics of endogenous proteins in the mouse neural tissues
Authors: Matsuda Takahiko , Oinuma Izumi
Published: August 2019

To analyze the expression, localization, and functional dynamics of target proteins in situ, especially in living cells, it is important to develop a convenient, versatile, and efficient method to precisely introduce exogenous genes into the genome, which is applicable for labeling and engineering of the endogenous proteins of interest. By combining the CRISPR/Cas9 genome editing technology with an electroporation technique, we succeeded in creating knock-in alleles, from which GFP (RFP)-tagged endogenous proteins are produced, in neurons and glial cells in vivo in the developing mouse retina and brain. Correct gene targeting was confirmed by single-cell genotyping and Western blot analysis. Several gene loci were successfully targeted with high efficiency. Moreover, we succeeded in engineering the mouse genome to express foreign genes from the endogenous gene loci using a self-cleaving 2A peptide. Our method could be used to monitor the physiological changes in localization of endogenous proteins and expression levels of both mRNA and protein at a single cell resolution. This work discloses a powerful and widely applicable approach for visualization and manipulation of endogenous proteins in neural tissues.
Transcriptome profiling of microRNAs associated with latent autoimmune diabetes in adults (LADA)
Authors: Yu Ke , Huang Zhou , Zhou Jing , Lang Jianan , Wang Yan , Yin Xingqi , Zhou Yuan , Zhao Dong
Published: August 2019

LADA (latent autoimmune diabetes in adults), a special subtype of type 1 diabetes, turns out to exhibit phenotypes mimicking the type 2 diabetes, which results in serious misdiagnosis issues. In order to better distinguish LADA from other diabetes subtypes, specific diagnostic and prognostic biomarkers of LADA are required. Circulating microRNAs (miRNAs) are recently shown to be promising biomarkers for disease diagnosis and subtyping. In this study, serum samples from LADA patients and type 2 diabetes patients were collected during the first diagnosis of diabetes and the miRNA transcriptomes of these patients and healthy individuals were profiled. Comparative analysis shows that the differentially expressed miRNAs between groups and their predicted target genes are enriched for several functions including immune regulation. Besides, a few miRNAs showing distinct expression pattern in LADA patients could discriminate LADA from type 2 diabetes, as validated by further qRT-PCR assay. In all, our study implies potential miRNA biomarkers which would be investigated in further clinical researches.
Identifying potential novel drugs against Helicobacter pylori by targeting the essential response regulator HsrA
Authors: González Andrés , Salillas Sandra , Velázquez-Campoy Adrián , Espinosa Angarica Vladimir , Fillat María F. , Sancho Javier , Lanas Ángel
Published: August 2019

The increasing antibiotic resistance evolved by Helicobacter pylori has alarmingly reduced the eradication rates of first-line therapies. To overcome the current circulating resistome, we selected a novel potential therapeutic target in order to identify new candidate drugs for treating H. pylori infection. We screened 1120 FDA-approved drugs for molecules that bind to the essential response regulator HsrA and potentially inhibit its biological function. Seven natural flavonoids were identified as HsrA binders. All of these compounds noticeably inhibited the in vitro DNA binding activity of HsrA, but only four of them, apigenin, chrysin, kaempferol and hesperetin, exhibited high bactericidal activities against H. pylori. Chrysin showed the most potent bactericidal activity and the most synergistic effect in combination with clarithromycin or metronidazole. Flavonoid binding to HsrA occurs preferably at its C-terminal effector domain, interacting with amino acid residues specifically involved in forming the helix-turn-helix DNA binding motif. Our results validate the use of HsrA as a novel and effective therapeutic target in H. pylori infection and provide molecular evidence of a novel antibacterial mechanism of some natural flavonoids against H. pylori. The results further support the valuable potential of natural flavonoids as candidate drugs for novel antibacterial strategies.
Low immunogenic endothelial cells endothelialize the Left Ventricular Assist Device
Authors: Figueiredo Constanca , Eicke Dorothee , Yuzefovych Yuliia , Avsar Murat , Hanke Jasmin Sarah , Pflaum Michael , Schmitto Jan-Dieter , Blasczyk Rainer , Haverich Axel , Wiegmann Bettina
Published: August 2019

Low haemocompatibility of left ventricular assist devices (LVAD) surfaces necessitates anticoagulative therapy. Endothelial cell (EC) seeding can support haemocompatibility, however, the availability of autologous ECs is limited. In contrast, allogeneic ECs are readily available in sufficient quantity, but HLA disparities induce harmful immune responses causing EC loss. In this study, we investigated the feasibility of using allogeneic low immunogenic ECs to endothelialize LVAD sintered inflow cannulas (SIC). To reduce the immunogenicity of ECs, we applied an inducible lentiviral vector to deliver short-hairpins RNA to silence HLA class I expression. HLA class I expression on ECs was conditionally silenced by up to 70%. Sufficient and comparable endothelialization rates were achieved with HLA-expressing or HLA-silenced ECs. Cell proliferation was not impaired by cell-to-Sintered Inflow Cannulas (SIC) contact or by silencing HLA expression. The levels of endothelial phenotypic and thrombogenic markers or cytokine secretion profiles remained unaffected. HLA-silenced ECs-coated SIC exhibited reduced thrombogenicity. In contrast to native ECs, HLA-silenced ECs showed lower cell lysis rates when exposed to allogeneic T cells or specific anti-HLA antibodies. Allogeneic HLA-silenced ECs could potentially become a valuable source for LVAD endothelialization to reduce immunogenicity and correspondingly the need for anticoagulative therapy which can entail severe side effects.