Miracle-dz/UniFAR-FTUs huggingface dataset:
Defined Flanking Spacers and Enhanced Proteolysis Is Essential for Eradication of Established Tumors by an Epitope String DNA Vaccine1

Loss of immunogenic epitopes by tumors has urged the development of vaccines against multiple epitopes. Recombinant DNA technologies have opened the possibility to develop multiepitope vaccines in a relatively rapid and efficient way. We have constructed four naked DNA-based multiepitope vaccines, containing CTL, Th cell, and B cell epitopes of the human papillomavirus type 16. Here we show that gene gun-mediated vaccination with an epitope-based DNA vaccine protects 100% of the vaccinated mice against a lethal tumor challenge. The addition of spacers between the epitopes was crucial for the epitope-induced tumor protection, as the same DNA construct without spacers was significantly less effective and only protected 50% of the mice. When tested for therapeutic potential, only the epitope construct with defined spacers significantly reduced the size of established tumors, but failed to induce tumor regression. Only after targeting the vaccine-encoded protein to the protein degradation pathway by linking it to ubiquitin, the vaccine-induced T cell-mediated eradication of 100% of 7-day established tumors in mice. The finding that defined flanking sequences around epitopes and protein targeting dramatically increased the efficacy of epitope string DNA vaccines against established tumors will be of importance for the further development of multiepitope DNA vaccines toward clinical application.
Recruitment of intra- and extracardiac cells into the myocardial lineage during mouse development.

The tubular heart differentiates from the bilateral cardiac fields in the splanchnic mesoderm. The expression of smooth muscle proteins has been shown to accompany the early phases of cardiac muscle formation. In this study we show that during elongation of the arterial pole of the mouse linear heart tube, alpha-smooth muscle actin (alpha-Sma) expression extends in the area that has been shown to become recruited into the myocardial lineage, but does not yet express myocardial markers. These data suggest that alpha-Sma identifies mesodermal cells that during subsequent development will be recruited into the myocardial lineage. Myocardium formation is not only observed at the arterial pole, but also at the venous pole and in the intracardiac mesenchyme. This results in the formation of the caval and pulmonary myocardium, the smooth-walled atrial myocardium, the myocardial atrioventricular septum, and the myocardial outlet septum. To determine whether recruitment into the myocardial lineage also takes place in these regions, the spatiotemporal pattern of expression of alpha-Sma and of the myocardial markers sarcoplasmatic reticulum calcium ATPase (Serca2a), alpha-myosin heavy chain (Mhc), and beta-Mhc were examined. We show that prior to the expression of myocardial markers, alpha-Sma is expressed in these regions, which suggests that these mesodermal cells become recruited into the cardiac lineage after formation of the linear heart tube.
Pain Catastrophizing Scale for Francophone Adolescents: a preliminary validation.

BACKGROUND In adults, it is well known that high levels of pain catastrophizing are related to increased pain and disability as well as to heightened anxiety and depression. However, due to the lack of a measure of pain catastrophizing adapted for francophone adolescents, little is known about the role of catastrophizing in this population. OBJECTIVES To adapt the French version of the Pain Catastrophizing Scale (PCS) and to examine the psychometric properties and factorial structure of the PCS for Francophone Adolescents (PCS-Ado). METHODS The French version of the PCS was modified by a group of experts. The format of the questions was modified to be appropriate for adolescents aged between 12 and 18 years. To assess the psychometric properties of the PCS-Ado, 345 adolescents completed the PCS-Ado and questionnaires measuring depression, anxiety and intensity of pain. Twelve to 16 weeks later, participants completed the questionnaires again to examine the test-retest reliability of the PCS-Ado. RESULTS Results revealed a three-factor solution similar to the original PCS. In addition, results revealed that PCS-Ado had good internal consistency (PCS-Ado total: 0.85; rumination: 0.72; magnification: 0.66; helplessness: 0.74), and high test-retest reliability (r=0.73). Finally, significant correlations among catastrophizing, depression, anxiety and pain intensity support the construct validity of the PCS-Ado. CONCLUSIONS The results suggest that the PCS-Ado is valid and reliable with francophone adolescents. Further research is required to assess the validity of the PCS-Ado in clinical settings.
Inhibition of the Neutral Magnesium-dependent Sphingomyelinase by Glutathione*

Sphingomyelin hydrolysis through the activation of sphingomyelinases has become a potentially important signaling pathway with the product ceramide implicated in the regulation of cell growth, differentiation, apoptosis, and inflammatory responses. However, little is known about the regulation of sphingomyelinases. In this study, we show that the magnesium-dependent, neutral pH-optimum and membrane-associated sphingomyelinase (N-SMase) is inhibited, in a dose-dependent manner, by glutathione (GSH) at physiological concentrations with a greater than 95% inhibition observed at 5 mm GSH. The inhibitory effect of GSH was reproduced by γ-glutamyl-cysteine, but not the cysteinyl-glycine fragment of GSH. The S-modified GSH analogs were as effective as GSH in inhibiting the N-SMase. On the other hand, neither dithiothreitol nor β-mercaptoethanol had any effect on the N-SMase, suggesting that the sulfhydryl in GSH is not required for inhibition of N-SMase. GSH had no effect on the acid pH-optimum SMase, whereas dithiothreitol inhibited the acid SMase. These results suggest that in cells the N-SMase is inactive in the presence of physiological concentrations of GSH (1–20 mm). Finally, treatment of cultured Molt-4 cells with the GSH synthesis inhibitor,l-buthionine-(SR)-sulfoximine, resulted in a time-dependent depletion of GSH, accompanied by an increased hydrolysis of sphingomyelin and production of ceramide. Since GSH depletion is observed in a variety of cells in the process of cellular injury and apoptosis, these studies suggest that depletion of GSH may be an important mechanism in activation of N-SMase. This mechanism may therefore bring together the fields of oxidative stress and signaling through products of sphingomyelin hydrolysis.
Structure and function in the herpes simplex virus 1 RNA-binding protein U(s)11: mapping of the domain required for ribosomal and nucleolar association and RNA binding in vitro

The herpes simplex virus 1 US11 protein is an RNA-binding regulatory protein that specifically and stably associates with 60S ribosomal subunits and nucleoli and is incorporated into virions. We report that US11/ beta-galactosidase fusion protein expressed in bacteria bound to rRNA from the 60S subunit and not the 40S subunit. This binding reflects the specificity of ribosomal subunit association. Analyses of deletion mutants of the US11 gene showed that specific RNA binding activity, nucleolar localization, and association with 60S ribosomal subunits were found to map to the amino acid sequences of the carboxyl terminus of US11 protein, suggesting that these activities all reflect specific binding of US11 to large subunit rRNA. The carboxyl-terminal half of the protein consists of a regular tripeptide repeat of the sequence RXP and constitutes a completely novel RNA-binding domain. All of the mutant US11 proteins could be incorporated into virus particles, suggesting that the signal for virion incorporation either is at the amino-terminal four amino acids or is redundant in the protein.
Normalising Slovene data: historical texts vs. user-generated content

The paper presents two manually annotated Slovene language text normalisation datasets, one of historical texts and the other of tweets, and proposes several variants of character-based statistical machine translation to normalise the spelling of their words. The systems differ in whether they perform token-level or segment-level normalisation and whether they make use of additional language resources. The systems are evaluated automatically against the gold standard as well as manually, against a newly developed typology of errors intended to analyse in detail the effect of different types of data and different levels of data standardness. The evaluations show that segment-level normalisation can be useful given a high enough level of to-ken ambiguity, that the same system can be used regardless of the data type, and that background resources will always prove useful.
DESIGN AND DEVELOPMENT OF AN UAV WITH HYBRID FLIGHT CAPABILITIES

3 Introduction 3 1 State of the art 7 1.1 Convertible aircraft . 7 1.1.1 Tilt-rotor . 8 1.1.2 Tilt-wing . 9 1.1.3 Dual-system UAV . 11 1.2 Tail-sitters . 12 1.2. 1 Mono Thrust Transitioning (MTT) . 12 1.2. 2 Collective Thrust Transitioning (CTT) . 14 1.2. 3 Differential Thrust Transitioning (DTT) UAVs . 14 1.3 Flight transition methods . 16 2 Problem formulation 19
Complete Genome Sequence of a Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Variant with a New Insertion in Glycoprotein 5, Isolated from a Stillborn Fetus

ABSTRACT Here, we report the complete genome sequence of strain GD-2011, a highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) that was isolated from a stillborn fetus. The GD-2011 strain is characterized by a discontinuous 30–amino acid deletion in the nonstructural protein 2. In addition, GD-2011 had a 1–amino acid insertion in glycoprotein 5, which does not exist in any other HP-PRRSV strains.
Characterization of cis-acting elements affecting strength and phloem specificity of the coconut foliar decay virus promoter

IP: 54.70. 40.11 On: Wed, 15 May 2019 22:29:32 Journal of General Virology (1998), 79, 1495–1499. Printed in Great Britain . SHORT COMMUNICATION
Angiotensin II Inhibits Human Trophoblast Invasion through AT1 Receptor Activation*

Trophoblast implantation depends, in part, on the controlled production of plasmin from plasminogen, a process regulated by plasminogen activators and plasminogen activator inhibitors. We have determined that angiotensin II (Ang II) stimulates plasminogen activator inhibitor-1 (PAI-1) synthesis and secretion in human trophoblasts in a time- and concentration-dependent manner. Our results indicate that Ang II activates PAI-1gene expression through the AT1 receptor and involves the calcium-dependent activation of calcineurin and the nuclear translocation of NFAT. Increased PAI-1 synthesis and secretion is associated with reduced trophoblast invasion as judged by an in vitro invasion assay. These studies are the first to link the renin-angiotensin system with the fibrinolytic system to regulate trophoblast invasion.
Circumferential pulmonary vein isolation as index procedure for persistent atrial fibrillation: a comparison between radiofrequency catheter ablation and second-generation cryoballoon ablation.

AIMS To assess the 1 year efficacy of pulmonary vein isolation (PVI) as index procedure for persistent atrial fibrillation (PersAF) comparing conventional radiofrequency irrigated-tip catheter ablation (RFCA) using contact-force technology and ablation using the second-generation cryoballoon (CB-AdvA). METHODS AND RESULTS One hundred consecutive patients (74 male, 74%; mean age 62.4 ± 9.6 years) with drug-refractory PersAF undergoing PVI using RFCA and CB-AdvA were enrolled. Follow-up was based on outpatient clinic visits including Holter-electrocardiograms. Recurrence of atrial tachyarrhythmias (ATas) was defined as a symptomatic or documented episode >30 s. Among 100 patients, 50 underwent RFCA whereas 50 CB-AdvA. Mean procedure and fluoroscopy times were 90.5 ± 41.7 vs. 140.2 ± 46.9 min and 14.5 ± 6.6 vs. 19.8 ± 6.8 min in the CB-Adv and in the RFCA group, respectively (P < 0.01). At 1 year follow-up, after a 3 months blanking period (BP), freedom from ATas off-drugs after a single procedure was 60% (28/50 patients) in the CB-Adv and 56% (27/50 patients) in the RFCA group (P = 0.71). Multivariate analysis demonstrated that PersAF duration (P = 0.01) and relapses during BP (P = 0.02) were independent predictors of ATa recurrences following the index procedure. CONCLUSION Freedom from ATas following PersAF ablation with RFCA and CB-Adv is comparable at 1 year follow-up after a single procedure. Ablation with the CB-Adv is associated with shorter procedure time and radiation exposure as compared with RFCA. Atrial tachyarrhythmias occurrence during BP and longer time of PersAF seem to be significant predictors of arrhythmia recurrences after the index procedure.
LIKELIHOOD-FREE IMPORTANCE WEIGHTING

A learned generative model often gives biased statistics relative to the underlying data distribution. A standard technique to correct this bias is by importance weighting samples from the model by the likelihood ratio under the model and true distributions. When the likelihood ratio is unknown, it can be estimated by training a probabilistic classifier to distinguish samples from the two distributions. In this paper, we employ this likelihood-free importance weighting framework to correct for the bias in using state-of-the-art deep generative models.We find that this technique consistently improves standard goodness-of-fit metrics for evaluating the sample quality of state-of-the-art generative models, suggesting reduced bias. Finally, we demonstrate its utility on representative applications in a) data augmentation for classification using generative adversarial networks, and b) model-based policy evaluation using off-policy data.
Rating the Raters: Evaluating how ESG Rating Agencies Integrate Sustainability Principles

Environmental, social, and governance (ESG) rating agencies, acting as relevant financial market actors, should take a stand on working towards achieving a more sustainable development. In this context, the objective of this paper is, on the one hand, to understand how criteria used by ESG rating agencies in their assessment processes have evolved over the last ten years and, on the other hand, to analyze whether ESG rating agencies are contributing to fostering sustainable development by the inclusion of sustainability principles into their assessment processes and practices according to the ESG criteria. This research is based on a comparative descriptive analysis of the public information provided by the most representative ESG rating and information provider agencies in the financial market in two periods: 2008 and 2018. The findings show that ESG rating agencies have integrated new criteria into their assessment models to measure corporate performance more accurately and robustly in order to respond to new global challenges. However, a deep analysis of the criteria also shows that ESG rating agencies do not fully integrate sustainability principles into the corporate sustainability assessment process.
Wiring optimization explanation in neuroscience:  What is special about it?

This paper examines the explanatory distinctness of wiring optimization models in neuroscience. Wiring optimization models aim to represent the organizational features of neural and brain systems as optimal (or near-optimal) solutions to wiring optimization problems. My claim is that that wiring optimization models provide design explanations. In particular, they support ideal interventions on the decision variables of the relevant design problem and assess the impact of such interventions on the viability of the target system.
Digital control for efficiency improvements in interleaved boost PFC rectifiers

This paper presents a simple passive power sharing approach to paralleling power-factor correction (PFC) modules. A digital controller senses only the total inductor current, and drives the modules with matched phase-shifted control signals. Advantages of the approach include simplified current sensing and control, support for arbitrarily large number of paralleled modules, and minimization of conduction losses at heavy loads. Increased current stresses resulting from unequal power sharing are evaluated in terms of parameter mismatches. To maintain high efficiency over very wide range of loads, the digital controller further includes adaptive near-zero-voltage switching and adaptive frequency operation in discontinuous conduction mode (DCM), as well as phase shedding at light loads. Experimental results are shown for a 600 W two-phase boost PFC, rectifier.
InSAR as an operational tool for mining sector

InSAR (interferometric synthetic aperture radar) uses satellite radar imagery to precisely measure ground deformation. TRE developed advanced techniques, PSInSAR and subsequently SqueeSAR, as standard monitoring tools in a number of applications: natural hazards, geothermal, oil and gas, mining, urban and infrastructures monitoring. Thanks to its capability in detecting millimeter level displacements over long periods and large areas, SqueeSAR analysis can be considered complementary to conventional geological and geomorphological studies in landslide detection and monitoring, supporting also the effectiveness of landslide inventories at regional scale. In this presentation, we would like to present some results obtained in several sectors; as a matter of fact these data has been widely used by civil protection and planning authorities, but also by oil and gas, and mining companies. In order to give consistency to these statements, after a brief introduction on the capabilities of the technology, a set of examples will be presented taking into account lots of different displacement phenomena. Landslide monitoring has been the first application for these kind of measurements, while in recent years oil and gas people strongly exploited there measurements in order to maximise the efficiency of their models by means of a cost effective, easily repeatable set of surface displacements. Some of these project are being presented, showing how it is possible to infer subsurface events from a set of very precise surface data. Some examples over mining areas are presented. In the case of open pit, greater attention would be put on the immediate surroundings of the pit and on the nearby facilities (tailing ponds and waste piles); on the other hand, surface effects of underground mining − mainly in terms of subsidence − are being measured with millimeter accuracy.
P rats develop physical dependence on alcohol via voluntary drinking: changes in seizure thresholds, anxiety, and patterns of alcohol drinking.

BACKGROUND It has been proposed that the alcohol-preferring P rat meets many of the criteria for an animal model of alcoholism. However, the development of alcohol dependence has not been explored in rats that self-administer ethanol for less than 15-20 weeks. The present study investigated the development of physical dependence upon alcohol after 2-6 weeks of voluntary alcohol intake. Changes in bicuculline-induced seizure thresholds, microstructure of alcohol drinking, and anxiety-related behavior were used as indices of alcohol dependence. In addition, we evaluated the microstructure of alcohol drinking associated with the development of physical dependence upon alcohol. METHODS Alcohol (10% ethanol solution) was measured in graduated drinking tubes with both alcohol and water available continuously. Microstructure of alcohol intake was monitored by a computerized drinkometer. Physical dependence upon alcohol was determined by measuring bicuculline-induced seizure thresholds after alcohol withdrawal. Anxiety-related behavior of P rats after alcohol withdrawal was determined by the social interaction and elevated plus maze tests. RESULTS Initial alcohol intake in the alcohol-preferring P rat was relatively modest (3.9 +/- 0.4 g/kg/day). Four days of forced alcohol exposure (initiation) followed by 6 weeks of voluntary drinking resulted in an increase of alcohol intake to 5.5 +/- 0.2 g/kg/day. Ethanol self-administration for 6 weeks, but not for 2 or 4 weeks, produced a significant reduction (30%; p < 0.05) in bicuculline-induced seizure thresholds during alcohol withdrawal. Alterations in the microstructure of alcohol intake (i.e., 90% increase in the size of alcohol drinking bouts compared to the baseline [p < 0.001] with no change in bout frequency) were associated with the development of alcohol dependence. Termination of alcohol intake after 6 weeks of voluntary alcohol consumption resulted in increased anxiety according to both the social interaction and elevated plus maze tests. CONCLUSIONS The results of this study indicate that 6 weeks of voluntary alcohol intake are sufficient for the development of physical dependence upon alcohol in the alcohol-preferring P rats as measured by susceptibility to bicuculline-induced seizures. This time is much shorter than the 15-20 weeks reported earlier. Development of physical dependence to alcohol was associated with an increase in daily alcohol intake (40% over the baseline), an increase in alcohol intake during each drinking bout (90% over the baseline), and elevated anxiety during alcohol withdrawal.
D UAL SPACE LEARNING WITH VARIATIONAL AUTOEN-CODERS

This paper proposes a dual variational autoencoder (DualVAE), a framework for generating images corresponding to multiclass labels. Recent research on conditional generative models, such as the Conditional VAE, exhibit image transfer by changing labels. However, when the dimension of multiclass labels is large, these models cannot change images corresponding to labels, because learning multiple distributions of the corresponding class is necessary to transfer an image. This leads to the lack of training data. Therefore, instead of conditioning with labels, we condition with latent vectors that include label information. DualVAE divides one distribution of the latent space by linear decision boundaries using labels. Consequently, DualVAE can easily transfer an image by moving a latent vector toward a decision boundary and is robust to the missing values of multiclass labels. To evaluate our proposed method, we introduce a conditional inception score (CIS) for measuring how much an image changes to the target class. We evaluate the images transferred by DualVAE using the CIS in CelebA datasets and demonstrate state-of-the-art performance in a multiclass setting.
Loughborough University Institutional Repository The development process of intrinsic gamification in a learning difficulty context

The paper explores the development process of intrinsic gamification in a learning difficulty context through an in-depth case study. We found out that simplicity is the most vital mechanic and the freedom in the software benefits users physically, mentally and socially. As a result, the software meets user’s competence, autonomy and connection needs and thus intrinsically motivates them to use it more.
Esophageal Temperature Monitoring During Radiofrequency Ablation of Atrial Fibrillation

Introduction: Ablative strategies for atrial fibrillation have centered on the left atrium, in particular the pulmonary veins. An emphasis on ablating outside the ostia of the pulmonary veins appears to have reduced the risk of pulmonary vein stenosis. Unfortunately, ablation in the posterior left atrium has been reported to result in fatal atrio‐esophageal fistula.