Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing the application of the 3Rs: a survey among animal welfare officers in The Netherlands

Implementation of the 3Rs (Replacement, Refinement and Reduction) in animal studies is a legal requirement in many countries. In The Netherlands, animal welfare officers (AWOs) are appointed to monitor the welfare of laboratory animals. As part of this task, AWOs give advice to researchers and can therefore have an influential role in implementing 3R methods in research. A national survey was conducted to gain more insight into how Dutch AWOs obtain and apply 3R information in their daily work. Nearly half of the AWO population filled out the questionnaire (15/32; a response rate of 46.9%). Two-thirds of the respondents pointed out that finding 3R information is not an easy task and more than half of the respondents believed that information on possibilities to implement the 3Rs is regularly being missed. The respondents indicated that most 3R information is obtained directly from colleagues and other AWOs. Special online 3R databases are rarely used. All the responding AWOs feel that they contribute to Refinement (15/15), nearly one-third of the respondents feel they contribute to Reduction (4/15), and one AWO feels he/she contributes to Replacement (1/15). According to the respondents, better exchange of knowledge can contribute to more successful implementation of the 3Rs. How this knowledge exchange can best be established and facilitated needs further exploration. To this end, the authors make suggestions for a 3R-integrated evidence-based approach.
A quorum sensing-mediated switch contributes to natural transformation of Vibrio cholerae

There is a fundamental gap in our understanding of how horizontal gene transfer contributes to the enormous range of genetic variations that are observed among bacteria. The objective of our study was to better understand how the acquisition of genetic material by natural transformation is regulated within a population of Vibrio cholerae cells. V. cholerae is an aquatic bacterium and a facultative human pathogen. It acquires natural competence for transformation in response to changing environmental signals, such as the presence of chitinous surfaces, the absence of monomeric sugars and quorum sensing-linked autoinducers. The latter play a distinctive role in V. cholerae as they fine-tune a switch from the degradation of extracellular DNA toward the uptake of intact DNA strands in competence-induced cells. The link between quorum sensing and natural competence for transformation will be discussed. Furthermore, we speculate on the overrepresentation of transformation-negative strains of V. cholerae in patient-derived culture collections, which might be the result of a biased sampling strategy as virulence and natural transformation are contrarily regulated by the quorum sensing network.
IL-33 reduces the development of atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the vasculature commonly leading to myocardial infarction and stroke. We show that IL-33, which is a novel IL-1–like cytokine that signals via ST2, can reduce atherosclerosis development in ApoE−/− mice on a high-fat diet. IL-33 and ST2 are present in the normal and atherosclerotic vasculature of mice and humans. Although control PBS-treated mice developed severe and inflamed atherosclerotic plaques in the aortic sinus, lesion development was profoundly reduced in IL-33–treated animals. IL-33 also markedly increased levels of IL-4, -5, and -13, but decreased levels of IFNγ in serum and lymph node cells. IL-33 treatment also elevated levels of total serum IgA, IgE, and IgG1, but decreased IgG2a, which is consistent with a Th1-to-Th2 switch. IL-33–treated mice also produced significantly elevated antioxidized low-density lipoprotein (ox-LDL) antibodies. Conversely, mice treated with soluble ST2, a decoy receptor that neutralizes IL-33, developed significantly larger atherosclerotic plaques in the aortic sinus of the ApoE−/− mice compared with control IgG-treated mice. Furthermore, coadministration of an anti–IL-5 mAb with IL-33 prevented the reduction in plaque size and reduced the amount of ox-LDL antibodies induced by IL-33. In conclusion, IL-33 may play a protective role in the development of atherosclerosis via the induction of IL-5 and ox-LDL antibodies.
Efficient large-scale power grid analysis based on preconditioned Krylov-subspace iterative methods

In this paper, we propose preconditioned Krylov-subspace iterative methods to perform efficient DC and transient simulations for large-scale linear circuits with an emphasis on power delivery circuits. We also prove that a circuit with inductors can be simplified from MNA to NA format, and the matrix becomes an s.p.d. matrix. This property makes it suitable for the conjugate gradient with incomplete Cholesky decomposition as the preconditioner, which is faster than other direct and iterative methods. Extensive experimental results on large-scale industrial power grid circuits show that our method is over 200 times faster for DC analysis and around 10 times faster for transient simulation compared to SPICE3. Furthermore, our algorithm reduces over 75% of memory usage than SPICE3 while the accuracy is not compromised.
The 2013 speaker recognition evaluation in mobile environment

This paper evaluates the performance of the twelve primary systems submitted to the evaluation on speaker verification in the context of a mobile environment using the MOBIO database. The mobile environment provides a challenging and realistic test-bed for current state-of-the-art speaker verification techniques. Results in terms of equal error rate (EER), half total error rate (HTER) and detection error trade-off (DET) confirm that the best performing systems are based on total variability modeling, and are the fusion of several sub-systems. Nevertheless, the good old UBM-GMM based systems are still competitive. The results also show that the use of additional data for training as well as gender-dependent features can be helpful.
Estimator-based reactive synthesis under incomplete information

Lack of complete run-time information about the environment behavior significantly increases the computational complexity and limits the applicability of practical reactive synthesis methods, e.g., synthesis from generalized reactivity( 1) specifications. We tackle this difficulty by splitting incomplete-information controller synthesis into estimator construction and complete-information synthesis steps. The estimator, which executes in parallel to the controller, establishes approximations of the unobserved variables that are salient for the synthesis step. It essentially provides an abstraction from the belief space of the controller, whose exponential growth often plagues incomplete-information synthesis, by keeping track of only the properties of relevance for the specification engineer and the scenario under consideration. We formalize an estimator notion for controller synthesis, and present a framework in which such estimators work in concert with controllers reacting partly to the estimator outputs to realize given temporal logic specifications. In order to limit the size and structure of the estimators, we focus on positional estimators in computation. Moreover, we demonstrate how such estimators are well-suited to be used in the context of generalized reactivity(1) synthesis. We illustrate the use of the estimator-based synthesis method on a running example motivated by intelligent transportation systems.
Picomonas judraskeda Gen. Et Sp. Nov.: The First Identified Member of the Picozoa Phylum Nov., a Widespread Group of Picoeukaryotes, Formerly Known as ‘Picobiliphytes’

In 2007, a novel, putatively photosynthetic picoeukaryotic lineage, the ‘picobiliphytes’, with no known close eukaryotic relatives, was reported from 18S environmental clone library sequences and fluorescence in situ hybridization. Although single cell genomics later showed these organisms to be heterotrophic rather than photosynthetic, until now this apparently widespread group of pico-(or nano-)eukaryotes has remained uncultured and the organisms could not be formally recognized. Here, we describe Picomonas judraskeda gen. et sp. nov., from marine coastal surface waters, which has a ‘picobiliphyte’ 18S rDNA signature. Using vital mitochondrial staining and cell sorting by flow cytometry, a single cell-derived culture was established. The cells are biflagellate, 2.5–3.8×2–2.5 µm in size, lack plastids and display a novel stereotypic cycle of cell motility (described as the “jump, drag, and skedaddle”-cycle). They consist of two hemispherical parts separated by a deep cleft, an anterior part that contains all major cell organelles including the flagellar apparatus, and a posterior part housing vacuoles/vesicles and the feeding apparatus, both parts separated by a large vacuolar cisterna. From serial section analyses of cells, fixed at putative stages of the feeding cycle, it is concluded that cells are not bacterivorous, but feed on small marine colloids of less than 150 nm diameter by fluid-phase, bulk flow endocytosis. Based on the novel features of cell motility, ultrastructure and feeding, and their isolated phylogenetic position, we establish a new phylum, Picozoa, for Picomonas judraskeda, representing an apparently widespread and ecologically important group of heterotrophic picoeukaryotes, formerly known as ‘picobiliphytes’.
The Importance of Predation Risk and Missed Opportunity Costs for Context-Dependent Foraging Patterns

Correct assessment of risks and costs of foraging is vital for the fitness of foragers. Foragers should avoid predation risk and balance missed opportunities. In risk-heterogeneous landscapes animals prefer safer locations over riskier, constituting a landscape of fear. Risk-uniform landscapes do not offer this choice, all locations are equally risky. Here we investigate the effects of predation risk in patches, travelling risk between patches, and missed social opportunities on foraging decisions in risk-uniform and risk-heterogeous landscapes. We investigated patch leaving decisions of 20 common voles (M. arvalis) in three experimental landscapes: safe risk-uniform, risky risk-uniform and risk-heterogeneous. We varied both the predation risk level and the predation risk distribution between two patches experimentally and in steps, assuming that our manipulation consequently yield different distributions and levels of risk while foraging, risk while travelling, and costs of missed, social opportunities (MSOCs). We measured mean GUDs (giving-up density of food left in the patch) for both patches as a measure of foraging gain, and delta GUD, the differences among patches, as a measure of the spatial distribution of foraging effort over a period of six hours. Distribution of foraging effort was most even in the safe risk-uniform landscapes and least even in the risk-heterogeneous landscape, with risky risk-uniform landscapes in between. Foraging gain was higher in the safe than in the two riskier landscapes (both uniform and heterogeneous). Results supported predictions for the effects of risk in foraging patches and while travelling between patches, however predictions for the effects of missed social opportunities were not met in this short term experiment. Thus, both travelling and foraging risk contribute to distinct patterns observable high risk, risk-uniform landscapes.
Molecular deletion of 9p sequences in non‐small cell lung cancer and malignant mesothelioma

Previously we have reported non‐random cytogenetic abnormalities involving the short arm of chromosome 9 (9p) in the majority of primary non‐small cell lung cancer (NSCLC) patient samples, which indicated loss of DNA sequences. In another lung tumor, pleural malignant mesothelioma (MM), cytogenetic changes also include apparent deletions of 9p. To define the location and extent of deletions of 9p in NSCLC and MM, Southern blot analyses on six NSCLC and five MM cell lines using molecular probes to 9p loci (IFNA, IFNBI, D9S3, and D9S19) were performed, and DNA dosage was determined by densitometry. Our data demonstrated reduced dosage of 9p sequences in three of six NSCLC and four of five MM lines. A homozygous deletion of D9S3 was found in one NSCLC and one MM cell line. The region of common loss overlapped the D9S3 locus and was flanked by the IFNBI and D9S19 loci. IFNBI has previously been localized to 9p22, and the D9S3 and D9S19 loci have been mapped in this study by in situ hybridization to 9p21 and 9p13, respectively. We hypothesize the existence of one or more tumor suppressor genes on 9p with a role in the development or progression of NSCLC and MM. © 1993 Wiley‐Liss, Inc.
ROCK1 as a potential therapeutic target in osteosarcoma

Osteosarcoma is the most common primary malignancy of bone. Patients with localized disease are routinely treated with surgery and chemotherapy. Unfortunately, many of these patients eventually relapse even after high‐dose pre‐ and postoperative chemotherapy. Upon recurrence of the tumor locally or distantly, they have limited treatment options that are usually unsuccessful. Our prior studies screening lentiviral shRNA libraries, searching for kinases involved in osteosarcoma cell growth and proliferation have identified the Rho‐associated coiled‐coil containing protein kinase 1 (ROCK1) as a possible hit. We show in this study that ROCK1 is highly expressed in various tumor cell lines and tumor tissues from osteosarcoma patients. ROCK1 knockdown by synthetic siRNA decreases cell proliferation, viability and induces apoptosis in osteosarcoma cell lines KHOS and U‐2OS. Finally, we established the relationship between expression levels of ROCK1 and clinical prognosis in osteosarcoma patients by using immunohistochemistry. There were significant differences in overall survival between cohorts of patients with ROCK1 levels categorized as high‐staining, moderate‐staining, and low‐staining. High levels of ROCK1 were associated with poor outcomes in clinical osteosarcoma. These findings suggest that knockdown of ROCK1 inhibits proliferation and induces apoptosis in osteosarcoma cell lines. ROCK1 may be a promising therapeutic target for the treatment of osteosarcoma patients. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1259–1266, 2011
Genome-Wide Heterogeneity of Nucleotide Substitution Model Fit

At a genomic scale, the patterns that have shaped molecular evolution are believed to be largely heterogeneous. Consequently, comparative analyses should use appropriate probabilistic substitution models that capture the main features under which different genomic regions have evolved. While efforts have concentrated in the development and understanding of model selection techniques, no descriptions of overall relative substitution model fit at the genome level have been reported. Here, we provide a characterization of best-fit substitution models across three genomic data sets including coding regions from mammals, vertebrates, and Drosophila (24,000 alignments). According to the Akaike Information Criterion (AIC), 82 of 88 models considered were selected as best-fit models at least in one occasion, although with very different frequencies. Most parameter estimates also varied broadly among genes. Patterns found for vertebrates and Drosophila were quite similar and often more complex than those found in mammals. Phylogenetic trees derived from models in the 95% confidence interval set showed much less variance and were significantly closer to the tree estimated under the best-fit model than trees derived from models outside this interval. Although alternative criteria selected simpler models than the AIC, they suggested similar patterns. All together our results show that at a genomic scale, different gene alignments for the same set of taxa are best explained by a large variety of different substitution models and that model choice has implications on different parameter estimates including the inferred phylogenetic trees. After taking into account the differences related to sample size, our results suggest a noticeable diversity in the underlying evolutionary process. All together, we conclude that the use of model selection techniques is important to obtain consistent phylogenetic estimates from real data at a genomic scale.
Changes in Dimensionality and Fractal Scaling Suggest Soft-Assembled Dynamics in Human EEG

Humans are high-dimensional, complex systems consisting of many components that must coordinate in order to perform even the simplest of activities. Many behavioral studies, especially in the movement sciences, have advanced the notion of soft-assembly to describe how systems with many components coordinate to perform specific functions while also exhibiting the potential to re-structure and then perform other functions as task demands change. Consistent with this notion, within cognitive neuroscience it is increasingly accepted that the brain flexibly coordinates the networks needed to cope with changing task demands. However, evaluation of various indices of soft-assembly has so far been absent from neurophysiological research. To begin addressing this gap, we investigated task-related changes in two distinct indices of soft-assembly using the established phenomenon of EEG repetition suppression. In a repetition priming task, we assessed evidence for changes in the correlation dimension and fractal scaling exponents during stimulus-locked event-related potentials, as a function of stimulus onset and familiarity, and relative to spontaneous non-task-related activity. Consistent with predictions derived from soft-assembly, results indicated decreases in dimensionality and increases in fractal scaling exponents from resting to pre-stimulus states and following stimulus onset. However, contrary to predictions, familiarity tended to increase dimensionality estimates. Overall, the findings support the view from soft-assembly that neural dynamics should become increasingly ordered as external task demands increase, and support the broader application of soft-assembly logic in understanding human behavior and electrophysiology.
Laser Capture Microdissection

Laser capture microdissection (LCM) under direct microscopic visualization permits rapid one-step procurement of selected human cell populations from a section of complex, heterogeneous tissue. In this technique, a transparent thermoplastic film (ethylene vinyl acetate polymer) is applied to the surface of the tissue section on a standard glass histopathology slide; a carbon dioxide laser pulse then specifically activates the film above the cells of interest. Strong focal adhesion allows selective procurement of the targeted cells. Multiple examples of LCM transfer and tissue analysis, including polymerase chain reaction amplification of DNA and RNA, and enzyme recovery from transferred tissue are demonstrated.
Ca2+-Induced Deprotonation of Peptide Hormones Inside Secretory Vesicles in Preparation for Release

The acidic environment inside secretory vesicles ensures that neuropeptides and peptide hormones are packaged in a concentrated condensed form. Although this is optimal for storage, decondensation limits release. Thus, it would be advantageous to alter the physical state of peptides in preparation for exocytosis. Here, we report that depolarization of the plasma membrane rapidly increases enhanced green fluorescent protein (EGFP)-tagged hormone fluorescence inside secretory vesicles. This effect requires Ca2+ influx and persists when exocytosis is inhibited byN-ethylmaleimide. Peptide deprotonation appears to produce this response, because it is not seen when the vesicle pH gradient is collapsed or when a pH-insensitive GFP variant is used. These data demonstrate that Ca2+ evokes alkalinization of the inside of secretory vesicles before exocytosis. Thus, Ca2+ influx into the cytoplasm alters the physical state of intravesicular contents in preparation for release.
Robust Evaluation of Topic Models

◮ Despite recent advances in learning and inference algorithms, evaluating the predictive performance of topic models is still painfully slow and unreliable. ◮ We propose a new strategy for computing relative log-likelihood (or perplexity) scores of topic models, based on annealed importance sampling. ◮ The proposed method has smaller Monte Carlo error than previous approaches, leading to marked improvements in both accuracy and computation time.
ELM-resolved divertor erosion in the JET ITER-Like Wall

Tungsten erosion in H-mode plasmas is quantified in the outer divertor of the JET ITER-Like Wall environment with optical emission spectroscopy on the 400.9 nm atomic neutral tungsten line. A novel cross-calibration procedure is developed to link slow, high spectral resolution spectroscopy and fast photomultiplier tube measurements in order to obtain ELM-resolved photon fluxes. Inter-ELM W erosion is exclusively impurity sputtering by beryllium because of the high sputter threshold for deuterons. Low beryllium concentrations resulted in low inter-ELM sputter yields of around 10−4 with respect to the total flux. Intra-ELM W sources, which dominate the total W tungsten source, vary independently from the inter-ELM source. The amount of W erosion could only be partly explained by beryllium sputtering, indicating that during ELMs sputtering by fuel species is important. The total W outer divertor source is found to linearly increase with the power crossing the separatrix, whilst excessive divertor fueling can break this trend. The influence of the W source rate on the tungsten content of the core plasma is investigated using soft x-ray emission to determine the tungsten content. At low source rates the content is determined by the source, but at higher source rates, other phenomena determine the total tungsten content. Indications of impurity flushing by ELMs is seen at ELM frequencies above approximately 40 Hz. The inner/outer divertor asymmetry of the W source during ELMs is investigated, and the outer divertor W source is larger by a factor of 1.8±0.7 ? >.
Clinical Outcome of Catheter Ablation in Patients With Nonparoxysmal Atrial Fibrillation: Results of 3-Year Follow-Up

Background—Catheter ablation of atrial fibrillation (AF) became an effective therapy for patients with drug-refractory AF, and the indications have broadened to include nonparoxysmal AF patients. However, data about the long-term effectiveness of ablation in patients with nonparoxysmal AF are lacking. The aim of the present study was to investigate the long-term outcomes of catheter ablation in patients with nonparoxysmal AF. Methods and Results—A total of 88 nonparoxysmal AF patients who received a stepwise catheter ablation (isolation of the pulmonary veins plus substrate modification) from 2006 to 2008 were enrolled. Freedom of recurrence was defined as the absence of atrial arrhythmias without using any antiarrhythmic agents after the catheter ablation. There were 63 patients (71.6%) with recurrences (47 patients with AF and 16 patients with atrial flutter/atrial tachycardia) after the initial procedure during a median follow-up period of 36.8 months. A CHADS2 score of ≥3 and the left atrial (LA) diameter were significant predictors of recurrences in the multivariable analysis. Of the patients with CHADS2 scores of ≥3 and an LA dimension ≥44 mm, all had recurrences within 1 year after the initial procedure. The overall recurrence-free rate could increase to 47.7% after the second procedure and 51.1% after the third procedure. Conclusions—The long-term recurrence-free rate of ablation in nonparoxysmal AF was only 28.4% after a single procedure, and multiple procedures were necessary to raise the recurrence-free rate. The CHADS2 score and LA dimension may help us to identify patients who will have recurrences after catheter ablations of nonparoxysmal AF.