Miracle-dz/UniFAR-FTUs huggingface dataset:
The Helminth-Derived Immunomodulator AvCystatin Reduces Virus Enhanced Inflammation by Induction of Regulatory IL-10+ T Cells

Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis. AvCystatin ablated eosinophil influx, reducing both weight loss and neutrophil recruitment without impairing anti-viral immune responses. AvCystatin also protected mice from excessive inflammation following primary RSV infection, significantly reducing neutrophil influx and cytokine production in the airways. Interestingly, we found that AvCystatin induced an influx of CD4+ FoxP3+ interleukin-10-producing T cells in the airway and lungs, correlating with immunoprotection, and the corresponding cells could also be induced by adoptive transfer of AvCystatin-primed F4/80+ macrophages. Thus, AvCystatin ameliorates enhanced RSV pathology without increasing susceptibility to, or persistence of, viral infection and warrants further investigation as a possible therapy for virus-induced airway disease.
Individual Differences in Irony Use Depend on Context

We investigated individual differences in irony use depending on context. In Study 1, we manipulated contextual factors, including the speaker’s emotion and the listener’s emotion, and assessed the likelihood of irony use. In Study 2, we manipulated the relationship between the speaker and the listener and assessed the rate of irony use with free description. Correlations between participants’ responses to various measures of personality traits and differences in irony use between conditions and mean irony use across conditions were examined. Regulation of interpersonal relationships and preference for supportive humor predicted the differences in irony use between conditions, whereas expressive suppression, self-control, and preference for playful humor predicted irony use regardless of condition. These results confirmed our hypothesis that the speaker’s social abilities about management of interpersonal relationship and tendency toward emotion regulation were associated with individual differences in irony use depending on context and in general, respectively.
THE DEVELOPMENT EFFECTS OF HIGH-SPEED RAIL STATIONS AND IMPLICATIONS FOR CALIFORNIA

High-speed rail is the most visible form of new technology accompanying and enhancing the transformation to an information-based economy, and is likely to have the greatest spatial development effects of any of these technologies. This report studies the development effects of high-speed rail stations on behalf of the California Department of Transportation (Caltrans), which is currently considering the use of high-speed rail in California. Since high-speed rail is a relatively new technology and is in use in only a few countries, the development effects of high-speed rail stations are somewhat difficult to discern and categorize. Nonetheless, a review of the literature on its development effects in Japan, France, and Germany, and observation of stations in the latter two countries, reveals significant development effects at the regional, urban, and station levels. These include changes to the following: population and employment growth rates; ridership; business behavior; real estate values and activity; business and employment location; and residential location. A review of related rail systems, heavy and commuter rail, reveals similar effects and opportunities for value capture. The development effects of high-speed rail stations are most clearly associated with a strong regional economy and good links with other transportation modes, especially rail links to the local city center and public sector support of development. The presence of these factors can help provide the formation of significant development activity around stations catering to the information-exchange sector, such as offices and hotels, the stimulation of retail activities in the area, and increases in overall land value of approximately 20 percent. At the regional and urban levels, concentrations of information-exchange sector employment and centers of higher education are associated with above-average employment and population growth rates, as well as access to high-speed rail. In California, high-speed rail would reinforce existing population and employment patterns and future growth trends. In order to fully exploit station development opportunities and ensure ridership, the agency responsible for developing a high-speed rail system in California must take an active role in station area development and coordinate its activities with local transportation agencies.
Materials Design Rules for Multivalent Ion Mobility in Intercalation Structures

The diffusion of ions in solid materials plays an important role in many aspects of materials science such as the geological evolution of minerals, materials synthesis, and in device performance across several technologies. For example, the realization of multivalent (MV) batteries, which offer a realistic route to superseding the electrochemical performance of Li-ion batteries, hinges on the discovery of host materials that possess adequate mobility of the MV intercalant to support reasonable charge and discharge times. This has proven especially challenging, motivating the current investigation of ion mobility (Li+, Mg2+, Zn2+, Ca2+, and Al3+) in spinel Mn2O4, olivine FePO4, layered NiO2, and orthorhombic δ-V2O5. In this study, we not only quantitatively assess these structures as candidate cathode materials, but also isolate the chemical and structural descriptors that govern MV diffusion. Our finding that matching the intercalant site preference to the diffusion path topology of the host structure con.
Searching for stem cells in the adult pancreas: A futile effort?

Regenerative medicine has been attracting great attention, not only from scientists, but also from the general public. In fact, the Nobel Prize in Physiology or Medicine 2012 was awarded for the discovery that mature cells can be reprogrammed to become pluripotent. With the help of his colleagues, Shinya Yamanaka, one of the 2012 Nobel Prize winners, showed that differentiated adult cells can revert to immature embryonic stem (ES) cell‐like cells, which are called induced‐pluripotent stem (iPS) cells, by the introduction of defined factors1. In principle, iPS cells can differentiate into any type of cells, including pancreatic β‐cells, if appropriate culture protocols are applied. Therefore, shouldn't efforts be made to identify tissue stem cells in the adult pancreas?
Evaluation of demographic history and neutral parameterization on the performance of FST outlier tests

FST outlier tests are a potentially powerful way to detect genetic loci under spatially divergent selection. Unfortunately, the extent to which these tests are robust to nonequilibrium demographic histories has been understudied. We developed a landscape genetics simulator to test the effects of isolation by distance (IBD) and range expansion on FST outlier methods. We evaluated the two most commonly used methods for the identification of FST outliers (FDIST2 and BayeScan, which assume samples are evolutionarily independent) and two recent methods (FLK and Bayenv2, which estimate and account for evolutionary nonindependence). Parameterization with a set of neutral loci (‘neutral parameterization’) always improved the performance of FLK and Bayenv2, while neutral parameterization caused FDIST2 to actually perform worse in the cases of IBD or range expansion. BayeScan was improved when the prior odds on neutrality was increased, regardless of the true odds in the data. On their best performance, however, the widely used methods had high false‐positive rates for IBD and range expansion and were outperformed by methods that accounted for evolutionary nonindependence. In addition, default settings in FDIST2 and BayeScan resulted in many false positives suggesting balancing selection. However, all methods did very well if a large set of neutral loci is available to create empirical P‐values. We conclude that in species that exhibit IBD or have undergone range expansion, many of the published FST outliers based on FDIST2 and BayeScan are probably false positives, but FLK and Bayenv2 show great promise for accurately identifying loci under spatially divergent selection.
Learning Step Size Controllers for Robust Neural Network Training

This paper investigates algorithms to automatically adapt the learning rate of neural networks (NNs). Starting with stochastic gradient descent, a large variety of learning methods has been proposed for the NN setting. However, these methods are usually sensitive to the initial learning rate which has to be chosen by the experimenter. We investigate several features and show how an adaptive controller can adjust the learning rate without prior knowledge of the learning problem at hand.
The multistage model of cancer development: some implications

The multistage model, introduced by Armitage and Doll, was very successful at describing many features of cancer development. Doll and Peto noted a significant departure below the prediction of the model and suggested that this could be due to undercounting of cases at older ages, or to the ‘biology of extreme old age. ’ Moolgavkar pointed out that it could also be due to the approximation used. The recent observation that cancer incidence falls rapidly above age 80 has stimulated new modelling investigations, such as the Pompei-Wilson beta model (which does reproduce the rapid fall). In the present paper, we argue that Moolgavkar’s criticisms, while mathematically correct, do not affect the conclusions, particularly the constancy of the number of stages across different cancer registries (Cook, Doll and Fellingham. 1969: A mathematical model for the age distribution of cancer in man. International Journal of Cancer 4, 93-112). We discuss several exact solutions, compare them with the most recent data, and prove rigorously that the standard Armitage-Doll multistage model can never reproduce the sharp turnaround in cancer incidence at old age seen in the data. We discuss in detail multistage processes which have a property observed in many laboratory studies, namely that some stages progress much faster than the others. We verify mathematically the intuition that sufficiently fast stages do not appreciably affect the incidence rate of cancer, and discuss implications of this fact for cancer treatment strategies. We also show that the simplest possible modification of the Armitage-Doll model to incorporate cellular senescence just leads to the Pompei-Wilson beta model.
A Theory of Conditionals Based on Hierarchies of Situations

We present an approach to the semantics of subjunctive conditionals based on the situation semantics notion of a constraint, in which the connection between antecedent A and consequent B of a conditional ‘if A were the case, B would be’ is an informational relation between types of situations. We also argue that the information contained in a hierarchy of planning schemas as commonly used in Artificial Intelligence enables an agent to represent the semantic objects involved in evaluating conditionals and thus to understand a subclass of subjunctive conditionals. A logic of situations based on modelling situations as sets of possible worlds is given; then a logic of conditionals based on hierarchies of situations is presented. The bridge between the logic and the planning representation is an explicit construction showing how a hierarchy of situations suitable for evaluating conditionals can be generated from a collection of planning schemas. We conclude with a discussion of the theory, including the paradoxes of conditional implication, the difference between truth conditions and assertibility conditions for subjunctive conditionals, the relationship between subjunctive and indicative conditionals, conditionals and explanation, competing conditionals and the conditional excluded middle, and ‘might’ conditionals.
ACOUSTIC CUES FOR 3-D SHAPE INFORMATION

Three-dimensional resonators, such as cavities or rooms, affect the perceived timbral character of any sound source there enclosed. It is well understood how the resonator size, or the material of the enclosure, are conveyed to the listener by means of specific features of acoustic signals. On the other hand, the perception of the shape of a resonator is a much subtler issue that we investigate in this paper, taking the sphere and the cube as reference cases. The perceptual study is motivated by the availability of a compact resonator model whose parameters can be tuned to represent different shapes.
Correlation between the activity of single auditory cortical neurons and sound-localization behavior in the macaque monkey.

Lesion studies have indicated that the auditory cortex is crucial for the perception of acoustic space, yet it remains unclear how these neurons participate in this perception. To investigate this, we studied the responses of single neurons in the primary auditory cortex (AI) and the caudomedial field (CM) of two monkeys while they performed a sound-localization task. Regression analysis indicated that the responses of approximately 80% of neurons in both cortical areas were significantly correlated with the azimuth or elevation of the stimulus, or both, which we term "spatially sensitive. " The proportion of spatially sensitive neurons was greater for stimulus azimuth compared with stimulus elevation, and elevation sensitivity was primarily restricted to neurons that were tested using stimuli that the monkeys also could localize in elevation. Most neurons responded best to contralateral speaker locations, but we also encountered neurons that responded best to ipsilateral locations and neurons that had their greatest responses restricted to a circumscribed region within the central 60 degrees of frontal space. Comparing the spatially sensitive neurons with those that were not spatially sensitive indicated that these two populations could not be distinguished based on either the firing rate, the rate/level functions, or on their topographic location within AI. Direct comparisons between the responses of individual neurons and the behaviorally measured sound-localization ability indicated that proportionally more neurons in CM had spatial sensitivity that was consistent with the behavioral performance compared with AI neurons. Pooling the responses across neurons strengthened the relationship between the neuronal and psychophysical data and indicated that the responses pooled across relatively few CM neurons contain enough information to account for sound-localization ability. These data support the hypothesis that auditory space is processed in a serial manner from AI to CM in the primate cerebral cortex.
Special education administrators and workload determination for teachers of students with visual impairments : a Delphi study

Itinerant teachers of students with visual impairments (TSVIs) support access to the curriculum for students with visual impairments by promoting the use of adaptive tools, materials, and strategies to mitigate the impact of visual impairment on learning and development. Traditionally, the number of students served by the TSVI is referred to as a “caseload” and is used as an indicator of the breadth of the TSVI’s professional responsibilities. This study uses “workload” as a more inclusive term that encompasses the full scope of the itinerant TSVIs’ professional practice, including direct, consultative, and indirect service to students with visual impairments and their educational teams. Given the low incidence of visual impairment among children and youth, many special education administrators responsible for staffing TSVI positions do not have an awareness of the specialized educational programming needs of these learners that factor into TSVI workload. Resources targeted to special education administrators that consider a broad scope of educational programming, personnel, and policy factors are required to support data-driven workload determinations for itinerant TSVIs. The purpose of the study was to develop a set of factors that experts rate as important considerations in the process of TSVI workload determination. This study was conducted using the Delphi approach, an iterative process through which consensus is built among a panel of knowledgeable experts on a topic of specialized interest. Panelists rated the importance of 45 initial educational programming, personnel, and policy-level factors with 22 panelist-nominated factors added in the second survey round. Four survey rounds were required to arrive at a set of 45 confirmed factors. Each factor included in the final set of confirmed factors had a rating at a high level of importance, strong consensus among panelists, and stability across survey rounds. After adjusting for the total number of initial and nominated factors in each thematic cluster, educational programming factors accounted for the greatest proportion of confirmed factors, followed by personnel-level factors and policy-level factors. The results of the study are intended to provide special education administrators with a set of evidence-based factors to inform the process of workload determination for itinerant TSVIs.
An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker

Abstract Chronic widespread musculoskeletal pain (CWP) is common, having a population prevalence of 10%. This study aimed to define the biological basis of the CWP/body mass association by using a systems biology approach. Adult female twins (n = 2444) from the TwinsUK registry who had extensive clinical, anthropometric, and “omic” data were included. Nontargeted metabolomics screening including 324 metabolites was carried out for CWP and body composition using dual-energy X-ray absorptiometry. The biological basis of these associations was explored through a genome-wide association study and replicated in an independent population sample (Cooperative Health Research in the Region of Augsburg [KORA] study, n = 2483). A causal role for the genetic variants identified was sought in CWP using a Mendelian randomisation study design. Fat mass/height2 was the body composition variable most strongly associated with CWP (TwinsUK: P = 2.4 × 10−15 and KORA: P = 1.59 × 10−10). Of 324 metabolites examined, epiandrosterone sulfate (EAS) was highly associated with both CWP (P = 1.05 × 10−09 in TwinsUK and P = 3.70 × 10−06 in KORA) and fat mass/height2. Genome-wide association study of EAS identified imputed single nucleotide polymorphism rs1581492 at 7q22.1 to be strikingly associated with EAS levels (P ⩽ 2.49 × 10−78), and this result was replicated in KORA (P = 2.12 × 10−9). Mendelian randomization by rs1581492 genotype showed that EAS is unlikely to be causally related to CWP. Using an agnostic omics approach to focus on the association of CWP with body mass index, we have confirmed a steroid hormone association and identified a genetic variant upstream of the CYP genes, which likely controls this response. This study suggests that steroid hormone abnormalities result from pain rather than causing it, and EAS may provide a biomarker that identifies subgroups at risk of CWP.
Pixel-wise Segmentation of Street with Neural Networks

Pixel-wise street segmentation of photographs taken from a drivers perspective is important for self-driving cars and can also support other object recognition tasks. A framework called SST was developed to examine the accuracy and execution time of different neural networks. The best neural network achieved an $F_1$-score of 89.5% with a simple feedforward neural network which trained to solve a regression task.
The vulnerability of calretinin-containing hippocampal interneurons to temporal lobe epilepsy

This review focuses on the vulnerability of a special interneuron type—the calretinin (CR)-containing interneurons—in temporal lobe epilepsy (TLE). CR is a calcium-binding protein expressed mainly by GABAergic interneurons in the hippocampus. Despite their morphological heterogeneity, CR-containing interneurons form a distinct subpopulation of inhibitory cells, innervating other interneurons in rodents and to some extent principal cells in the human. Their dendrites are strongly connected by zona adherentiae and presumably by gap junctions both in rats and humans. CR-containing interneurons are suggested to play a key role in the hippocampal inhibitory network, since they can effectively synchronize dendritic inhibitory interneurons. The sensitivity of CR-expressing interneurons to epilepsy was discussed in several reports, both in animal models and in humans. In the sclerotic hippocampus the density of CR-immunopositive cells is decreased significantly. In the non-sclerotic hippocampus, the CR-containing interneurons are preserved, but their dendritic tree is varicose, segmented, and zona-adherentia-type contacts can be less frequently observed among dendrites. Therefore, the dendritic inhibition of pyramidal cells may be less effective in TLE. This can be partially explained by the impairment of the CR-containing interneuron ensemble in the epileptic hippocampus, which may result in an asynchronous and thus less effective dendritic inhibition of the principal cells. This phenomenon, together with the sprouting of excitatory pathway axons and enhanced innervation of principal cells, may be involved in seizure generation. Preventing the loss of CR-positive cells and preserving the integrity of CR-positive dendrite gap junctions may have antiepileptic effects, maintaining proper inhibitory function and helping to protect principal cells in epilepsy.
Küchenhoff , Lederer , Lesaffre : Asymptotic Variance Estimation for the Misclassification SIMEX

Most epidemiological studies suffer from misclassification in the response and/or the covariates. Since ignoring misclassification induces bias on the parameter estimates, correction for such errors is important. For measurement error, the continuous analog to misclassification, a general approach for bias correction is the SIMEX (simulation extrapolation) originally suggested by Cook and Stefanski (1994). This approach has been recently extended to regression models with a possibly misclassified categorical response and/or the covariates by Küchenhoff et al. (2005), and is called the MC-SIMEX approach. To assess the importance of a regressor not only its (corrected) estimate is needed, but also its standard error. For the original SIMEX approach. Carroll et al. (1996) developed a method for estimating the asymptotic variance. Here we derive the asymptotic variance estimators for the MC-SIMEX approach, extending the methodology of Carroll et al. (1996). We also include the case where the misclassification probabilities are estimated by a validation study. An extensive simulation study shows the good performance of our approach. The approach is illustrated using an example in caries research including a logistic regression model, where the response and a binary covariate are possibly misclassified.