Miracle-dz/UniFAR-FTUs huggingface dataset:
microRNA-138 modulates cardiac patterning during embryonic development

Organ patterning during embryonic development requires precise temporal and spatial regulation of protein activity. microRNAs (miRNAs), small noncoding RNAs that typically inhibit protein expression, are broadly important for proper development, but their individual functions during organogenesis are largely unknown. We report that miR-138 is expressed in specific domains in the zebrafish heart and is required to establish appropriate chamber-specific gene expression patterns. Disruption of miR-138 function led to ventricular expansion of gene expression normally restricted to the atrio-ventricular valve region and, ultimately, to disrupted ventricular cardiomyocyte morphology and cardiac function. Temporal-specific knockdown of miR-138 by antagomiRs showed miR-138 function was required during a discrete developmental window, 24–34 h post-fertilization (hpf). miR-138 functioned partially by repressing the retinoic acid synthesis enzyme, aldehyde dehydrogenase-1a2, in the ventricle. This activity was complemented by miR-138-mediated ventricular repression of the gene encoding versican (cspg2), which was positively regulated by retinoic-acid signaling. Our findings demonstrate that miR-138 helps establish discrete domains of gene expression during cardiac morphogenesis by targeting multiple members of a common pathway, and also establish the use of antagomiRs in fish for temporal knockdown of miRNA function.
Linezolid Compared with Eperezolid, Vancomycin, and Gentamicin in an In Vitro Model of Antimicrobial Lock Therapy for Staphylococcus epidermidis Central Venous Catheter-Related Biofilm Infections

ABSTRACT Central venous catheter (CVC)-related infection (CVC-RI) is a common complication of CVC use. The most common etiological agents of CVC-RI are gram-positive organisms, in particular, staphylococci. An in vitro model for the formation of biofilms by Staphylococcus epidermidis ATCC 35984 on polyurethane coupons in a modified Robbins device was established. Biofilm formation was confirmed by electron microscopy and was quantified by determination of viable counts. Mueller-Hinton broth was replaced with sterile physiological saline (control) or a solution of vancomycin (10 mg/ml), gentamicin (10 mg/ml), linezolid (2 mg/ml), or eperezolid (4 mg/ml). Viable counts were performed with the coupons after exposure to antimicrobials for periods of 24, 72, 168, and 240 h. The mean viable count per coupon following establishment of the biofilm was 4.6 × 108 CFU/coupon, and that after 14 days of exposure to physiological saline was 2.5 × 107 CFU/coupon. On exposure to vancomycin (10 mg/ml), the mean counts were 2.5 × 107 CFU/coupon at 24 h, 4.3 × 106 CFU/coupon at 72 h, 1.4 × 105 CFU/coupon at 168 h, and undetectable at 240 h. With gentamicin (10 mg/ml) the mean counts were 2.7 × 107 CFU/coupon at 24 h, 3.7 × 106 CFU/coupon at 72 h, 8.4 × 106 CFU/coupon at 168 h, and 6.5 × 106 CFU/coupon at 240 h. With linezolid at 2 mg/ml the mean counts were 7.1 × 105 CFU/coupon at 24 h and not detectable at 72, 168, and 240 h. With eperezolid (4 mg/ml) no viable cells were recovered after 168 h. These data suggest that linezolid (2 mg/ml) and eperezolid (4 mg/ml) achieve eradication of S. epidermidis biofilms more rapidly than vancomycin (10 mg/ml) and gentamicin (10 mg/ml).
On Inexact LPV Control Design of Continuous–Time Polytopic Systems

Robust dynamic output design most often relies on nonconvex problems. This is precisely the case with linear parameter-varying (LPV) control when the measured varying parameters do not exactly fit the real ones. This paper provides a solution in the convex programming framework with the use of linear matrix inequality (LMI) solvers in the case of polytopic parameter dependence. A bounded uncertainty set is defined from the difference between the measured and the true parameters from which LMI stabilization and performance conditions are obtained after bounding. As a desired property, the proposed conditions reduce to the classical LPV ones whenever the true parameters are available for control synthesis.
Under Which Conditions Do Early Adolescents Need Maternal Support?

Maternal support is known as a protective factor during infancy, childhood, and adolescence. However, less is known about the conditions leading to support-seeking behaviors toward mothers in early adolescence. In comparison with younger children, it is assumed that the specific nature of these conditions changes with continuing cognitive maturation. To shed light on the normative development of attachment-related behaviors beyond infancy and, more specifically, on the activating conditions for support seeking, 98 early adolescents were instructed to write about a distressing situation during which they needed their mother’s support. Seven distressing conditions could be derived from the current data. Two not previously described age-relevant conditions, academic failure and social conflict, were identified. Notably, 62% of the reported conditions referred to situations Bowlby (1969/1982) originally proposed, empirically confirming the importance of these conditions in early adolescence.
Macroevolutionary Dynamics and Historical Biogeography of Primate Diversification Inferred from a Species Supermatrix

Phylogenetic relationships, divergence times, and patterns of biogeographic descent among primate species are both complex and contentious. Here, we generate a robust molecular phylogeny for 70 primate genera and 367 primate species based on a concatenation of 69 nuclear gene segments and ten mitochondrial gene sequences, most of which were extracted from GenBank. Relaxed clock analyses of divergence times with 14 fossil-calibrated nodes suggest that living Primates last shared a common ancestor 71–63 Ma, and that divergences within both Strepsirrhini and Haplorhini are entirely post-Cretaceous. These results are consistent with the hypothesis that the Cretaceous-Paleogene mass extinction of non-avian dinosaurs played an important role in the diversification of placental mammals. Previous queries into primate historical biogeography have suggested Africa, Asia, Europe, or North America as the ancestral area of crown primates, but were based on methods that were coopted from phylogeny reconstruction. By contrast, we analyzed our molecular phylogeny with two methods that were developed explicitly for ancestral area reconstruction, and find support for the hypothesis that the most recent common ancestor of living Primates resided in Asia. Analyses of primate macroevolutionary dynamics provide support for a diversification rate increase in the late Miocene, possibly in response to elevated global mean temperatures, and are consistent with the fossil record. By contrast, diversification analyses failed to detect evidence for rate-shift changes near the Eocene-Oligocene boundary even though the fossil record provides clear evidence for a major turnover event (“Grande Coupure”) at this time. Our results highlight the power and limitations of inferring diversification dynamics from molecular phylogenies, as well as the sensitivity of diversification analyses to different species concepts.
Enriching reverse engineering with semantic clustering

Understanding a software system by just analyzing the structure of the system reveals only half of the picture, since the structure tells us only how the code is working but not what the code is about. What the code is about can be found in the semantics of the source code: names of identifiers, comments etc. In this paper, we analyze how these terms are spread over the source artifacts using latent semantic indexing, an information retrieval technique. We use the assumption that parts of the system that use similar terms are related. We cluster artifacts that use similar terms, and we reveal the most relevant terms for the computed clusters. Our approach works at the level of the source code which makes it language independent. Nevertheless, we correlated the semantics with structural information and we applied it at different levels of abstraction (e.g. classes, methods). We applied our approach on three large case studies and we report the results we obtained.
A systematic method to obtain ultimate bounds for perturbed systems

In this paper, we develop a systematic method to obtain ultimate bounds for both continuous- and discrete-time perturbed systems. The method is based on a componentwise analysis of the system in modal coordinates and thus exploits the system geometry as well as the perturbation structure without requiring calculation of a Lyapunov function for the system. The method is introduced for linear systems having constant componentwise perturbation bounds and is then extended to the case of state-dependent perturbation bounds. This extension enables the method to be applied to non-linear systems by treating the perturbed non-linear system as a linear system with a perturbation bounded by a non-linear function of the state. Examples are provided where the proposed systematic method yields bounds that are tighter or at least not worse than those obtained via standard Lyapunov analysis. We also show how our method can be combined with Lyapunov analysis to improve on the bounds provided by either approach.
Source time scale and optimal buffer/bandwidth tradeoff for heterogeneous regulated traffic in a network node

We study the problem of resource allocation and control for a network node with regulated traffic. Both guaranteed lossless service and statistical service with small loss probability are considered. We investigate the relationship between source characteristics and the buffer/bandwidth tradeoff under both services. Our contributions are the following. For guaranteed lossless service, we find that the optimal resource allocation scheme suggests that sources sharing a network node with finite bandwidth and buffer space divide into groups according to time scales defined by their leaky-bucket parameters. This time-scale separation determines the manner by which the buffer and bandwidth resources at the network node are shared among the sources. For statistical service with a small loss probability, we present a new approach for estimating the loss probability in a shared buffer multiplexer using the "extremal" on-off, periodic sources. Under this approach, the optimal resource allocation for statistical service is achieved by maximizing both the benefits of buffering sharing and bandwidth sharing. The optimal buffer/bandwidth tradeoff is again determined by a time-scale separation.
Intelligent Systems to Support Deliberative Democracy in Environmental Regulation

Among normative models for democracy, the Deliberative model suggests that public policy decisions should be made only following rational, public deliberation of alternative courses of action. We argue that such a model is particularly appropriate for the assessment of environmental and health risks of new substances and technologies, and for the development of appropriate regulatory responses. To give operational effect to these ideas, we propose a dialectical argumentation formalism for an intelligent system within which deliberative debates about risk and regulation can be conducted. Our formalism draws on various philosophies of argumentation, scientific and moral discourse, and communicative action, due to Toulmin, Pera, Alexy and Habermas.
Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study

Objective To examine clinical effectiveness and safety of apixaban 2.5 mg, dabigatran 110 mg, and rivaroxaban 15 mg compared with warfarin among patients with atrial fibrillation who had not previously taken an oral anticoagulant. Design Propensity weighted (inverse probability of treatment weighted) nationwide cohort study. Setting Individual linked data from three nationwide registries in Denmark. Participants Patients with non-valvular atrial fibrillation filling a first prescription for an oral anticoagulant from August 2011 to February 2016. Patients who filled a prescription for a standard dose non-vitamin K antagonist oral anticoagulant (novel oral anticoagulants, NOACs) were excluded. To control for baseline differences in the population, a propensity score for receipt of either of the four treatment alternatives was calculated to apply an inverse probability treatment weight. Intervention Initiated anticoagulant treatment (dabigatran 110 mg, rivaroxaban 15 mg, apixaban 2.5 mg, and warfarin). Main outcome measures Patients were followed in the registries from onset of treatment for the primary effectiveness outcome of ischaemic stroke/systemic embolism and for the principal safety outcome of any bleeding events. Results Among 55 644 patients with atrial fibrillation who met inclusion criteria, the cohort was distributed according to treatment: apixaban n=4400; dabigatran n=8875; rivaroxaban n=3476; warfarin n=38 893. The overall mean age was 73.9 (SD 12.7), ranging from a mean of 71.0 (warfarin) to 83.9 (apixaban). During one year of follow-up, apixaban was associated with higher (weighted) event rate of ischaemic stroke/systemic embolism (4.8%), while dabigatran, rivaroxaban, and warfarin had event rates of 3.3%, 3.5%, and 3.7%, respectively. In the comparison between a non-vitamin K antagonist oral anticoagulant and warfarin in the inverse probability of treatment weighted analyses and investigation of the effectiveness outcome, the hazard ratios were 1.19 (95% confidence interval 0.95 to 1.49) for apixaban, 0.89 (0.77 to 1.03) for dabigatran, and 0.89 (0.69 to 1.16) for rivaroxaban. For the principal safety outcome versus warfarin, the hazard ratios were 0.96 (0.73 to 1.27) for apixaban, 0.80 (0.70 to 0.92) for dabigatran, and 1.06 (0.87 to 1.29) for rivaroxaban. Conclusion In this propensity weighted nationwide study of reduced dose non-vitamin K antagonist oral anticoagulant regimens, apixaban 2.5 mg twice a day was associated with a trend towards higher rates of ischaemic stroke/systemic embolism compared with warfarin, while rivaroxaban 15 mg once a day and dabigatran 110 mg twice a day showed a trend towards lower thromboembolic rates. The results were not significantly different. Rates of bleeding (the principal safety outcome) were significantly lower for dabigatran, but not significantly different for apixaban and rivaroxaban compared with warfarin.
Behavioral and mechanical determinants of collective subsurface nest excavation

ABSTRACT Collective construction of topologically complex structures is one of the triumphs of social behavior. For example, many ant species construct underground nests composed of networks of tunnels and chambers. Excavation by these ‘superorganisms’ depends on the biomechanics of substrate manipulation, the interaction of individuals, and media stability and cohesiveness. To discover principles of robust social excavation, we used X-ray computed tomography to monitor the growth in three dimensions of nests built by groups of fire ants (Solenopsis invicta) in laboratory substrates composed of silica particles, manipulating two substrate properties: particle size and gravimetric moisture content. Ants were capable of nest construction in all substrates tested other than completely dry or fully saturated; for a given particle size, nest volume was relatively insensitive to moisture content. Tunnels were deepest at intermediate moisture content and the maximum tunnel depth correlated with measured yield force on small rod-shaped intruders (a proxy for cohesive strength). This implies that increased cohesive strength allowed creation of tunnels that were resistant to perturbation but did not decrease individual excavation ability. Ants used two distinct behaviors to create pellets composed of wetted particles, depending on substrate composition. However, despite the ability to create larger stable pellets in more cohesive substrates, pellet sizes were similar across all conditions. We posit that this pellet size balances the individual's load-carrying ability with the need to carry this pellet through confined crowded tunnels. We conclude that effective excavation of similarly shaped nests can occur in a diversity of substrates through sophisticated digging behaviors by individuals which accommodate both differing substrate properties and the need to work within the collective. Highlighted Article: The work described in the paper is the first and the most complete study of the principles underlying nest excavation behaviors of ants in vivo in 3D settings.
Long-term outcome of social skills intervention based on interactive LEGO© play

LEGO© building materials have been adapted as a therapeutic modality for increasing motivation to participate in social skills intervention, and providing a medium through which children with social and communication handicaps can effectively interact. A 3 year retrospective study of long-term outcome for autistic spectrum children participating in LEGO© therapy (N = 60) compared Vineland Adaptive Behavior Scale socialization domain (VABS–SD) and Gilliam Autism Rating Scale social interaction subscale (GARS–SI) scores preand post-treatment with a matched comparison sample (N = 57) who received comparable non-LEGO© therapy. Although both groups made significant gains on the two outcome measures, LEGO© participants improved significantly more than the comparison subjects. Diagnosis and pre-treatment full-scale IQ scores did not predict outcome scores; however, Vineland adaptive behavior composite, Vineland communication domain, and verbal IQ all predicted outcome on the VABS–SD, especially for the LEGO© therapy group. Results are discussed in terms of implications for methods of social skills intervention for autistic spectrum disorders.
C1q induction and global complement pathway activation do not contribute to ALS toxicity in mutant SOD1 mice

Significance Activation of the immune system within the nervous system is widely found in neurodegenerative diseases, including ALS. In mice that develop fatal paralytic disease from ALS-causing superoxide dismutase (SOD1) mutants, motor neurons activate expression of C1q, the initiating component of the classic complement system. As C1q and complement play a central role in developmental synapse elimination, disease-linked activation has suggested that it drives motor neuron denervation. Instead, suppressing C1q induction by gene deletion is shown to enhance loss, not retention, of synapses, whereas elimination of global complement activation by C1q or C3 gene deletions leave onset and progression of paralytic disease unaffected. Thus, C1q induction and complement activation are not significant contributors to SOD1 mutant-mediated ALS disease mechanism in mice. Accumulating evidence from mice expressing ALS-causing mutations in superoxide dismutase (SOD1) has implicated pathological immune responses in motor neuron degeneration. This includes microglial activation, lymphocyte infiltration, and the induction of C1q, the initiating component of the classic complement system that is the protein-based arm of the innate immune response, in motor neurons of multiple ALS mouse models expressing dismutase active or inactive SOD1 mutants. Robust induction early in disease course is now identified for multiple complement components (including C1q, C4, and C3) in spinal cords of SOD1 mutant-expressing mice, consistent with initial intraneuronal C1q induction, followed by global activation of the complement pathway. We now test if this activation is a mechanistic contributor to disease. Deletion of the C1q gene in mice expressing an ALS-causing mutant in SOD1 to eliminate C1q induction, and complement cascade activation that follows from it, is demonstrated to produce changes in microglial morphology accompanied by enhanced loss, not retention, of synaptic densities during disease. C1q-dependent synaptic loss is shown to be especially prominent for cholinergic C-bouton nerve terminal input onto motor neurons in affected C1q-deleted SOD1 mutant mice. Nevertheless, overall onset and progression of disease are unaffected in C1q- and C3-deleted ALS mice, thus establishing that C1q induction and classic or alternative complement pathway activation do not contribute significantly to SOD1 mutant-mediated ALS pathogenesis in mice.
Interpreting Anaphoric Shell Nouns using Antecedents of Cataphoric Shell Nouns as Training Data

Interpreting anaphoric shell nouns (ASNs) such as this issue and this fact is essential to understanding virtually any substantial natural language text. One obstacle in developing methods for automatically interpreting ASNs is the lack of annotated data. We tackle this challenge by exploiting cataphoric shell nouns (CSNs) whose construction makes them particularly easy to interpret (e.g., the fact that X). We propose an approach that uses automatically extracted antecedents of CSNs as training data to interpret ASNs. We achieve precisions in the range of 0.35 (baseline = 0.21) to 0.72 (baseline = 0.44), depending upon the shell noun.
Environmental Factors Affect Acidobacterial Communities below the Subgroup Level in Grassland and Forest Soils

ABSTRACT In soil, Acidobacteria constitute on average 20% of all bacteria, are highly diverse, and are physiologically active in situ. However, their individual functions and interactions with higher taxa in soil are still unknown. Here, potential effects of land use, soil properties, plant diversity, and soil nanofauna on acidobacterial community composition were studied by cultivation-independent methods in grassland and forest soils from three different regions in Germany. The analysis of 16S rRNA gene clone libraries representing all studied soils revealed that grassland soils were dominated by subgroup Gp6 and forest soils by subgroup Gp1 Acidobacteria. The analysis of a large number of sites (n = 57) by 16S rRNA gene fingerprinting methods (terminal restriction fragment length polymorphism [T-RFLP] and denaturing gradient gel electrophoresis [DGGE]) showed that Acidobacteria diversities differed between grassland and forest soils but also among the three different regions. Edaphic properties, such as pH, organic carbon, total nitrogen, C/N ratio, phosphorus, nitrate, ammonium, soil moisture, soil temperature, and soil respiration, had an impact on community composition as assessed by fingerprinting. However, interrelations with environmental parameters among subgroup terminal restriction fragments (T-RFs) differed significantly, e.g., different Gp1 T-RFs correlated positively or negatively with nitrogen content. Novel significant correlations of Acidobacteria subpopulations (i.e., individual populations within subgroups) with soil nanofauna and vascular plant diversity were revealed only by analysis of clone sequences. Thus, for detecting novel interrelations of environmental parameters with Acidobacteria, individual populations within subgroups have to be considered.