Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs

When it is difficult to develop selective ligands within a family of related G‐protein‐coupled receptors (GPCRs), chemically engineered receptors activated solely by synthetic ligands (RASSLs) are useful alternatives for probing receptor function. In the present work, we explored whether a RASSL of the free fatty acid receptor 2 (FFA2) could be developed on the basis of pharmacological variation between species orthologs. For this, bovine FFA2 was characterized, revealing distinct ligand selectivity compared with human FFA2. Homology modeling and mutational analysis demonstrated a single mutation in human FFA2 of C4.57G resulted in a human FFA2 receptor with ligand selectivity similar to the bovine receptor. This was exploited to generate human FFA2‐RASSL by the addition of a second mutation at a known orthosteric ligand interaction site, H6.55Q. The resulting FFA2‐RASSL displayed a >100‐fold loss of activity to endogenous ligands, while responding to the distinct ligand sorbic acid with pEC50 values for inhibition of cAMP, 5.83 ± 0.11; Ca2+ mobilization, 4.63 ± 0.05; ERK phosphorylation, 5.61 ± 0.06; and dynamic mass redistribution, 5.35 ± 0.06. This FFA2‐RASSL will be useful in future studies on this receptor and demonstrates that exploitation of pharmacological variation between species orthologs is a powerful method to generate novel chemically engineered GPCRs. —Hudson, B. D. , Christiansen, E. , Tikhonova, I. G. , Grundmann, M. , Kostenis, E. , Adams, D. R. , Ulven, T. , Milligan, G. Chemically engineering ligand selectivity at the free fatty acid receptor 2 based on pharmacological variation between species orthologs. FASEB J. 26, 4951–4965 (2012). www.fasebj. org
Anchor Shot Detection in TRECVID-2005 Broadcast News Videos

In this paper, we discuss a new method for detecting anchor shots in broadcast news video. Our approach makes use of face information that includes the position, the size and the number of faces detected in the image frame. To alleviate the adverse effects caused by occasional face detection errors, we propose two new ideas based on multiple queries and zero face padding. Our experiments over TRECVID 2005 data confirm the robustness of our approach – 97.6% precision at 85.7% recall and improves the baseline up to the maximum of about 15% in recall with the almost same precision.
Bioaerosol Challenges to Antimicrobial Surface Treatments: Enhanced Efficacy Against MS2 Coli Phage of Air Filter Media Coated With Polystyrene-4-Methyltrimethylammonium Triiodide

Abstract : Two samples each of two commercial (COTS) soft respiratory protection (SRP) masks and seven SRP masks augmented with a quaternary ammonium derivative of polystyrene as the triiodide salt were sealed to an adapter and challenged for 6 hours with an aerosol containing ~10(8) plaque-forming units (PFUs) of MS2 coli phage. Compared to a positive control (open path), average % reduction in PFUs for the first and second COTS and the iodinated SRP masks was 98.18%, 99.55% and 99.9945%, respectively. The two-log enhancement in removal efficiency is attributed to the available iodine's killing ~99% of penetrating coli phage particles. In a swatch test, 47-cm2 discs of the iodinated medium cut from a mask achieved 99.9999% average % reduction in PFUs.
Potential Role of Uric Acid as a Risk Factor for Cardiovascular Disease

Cardiovascular epidemic and uric acid The cardiovascular epidemic is a worldwide phenomenon that accounts for almost 50% of all deaths in industrialized nations, and coronary artery disease (CAD) is one of the most serious forms of cardiovascular disease (CVD). Despite the rapid progress made in modern medicine with regard to controlling the known risk factors for CAD, this worldwide epidemic still heads the list of national health concerns, which raises the possibility of the presence of unknown or underestimated risk factors. Therefore, we need to identify novel risk factors for CVD, including a potential therapeutic target. While there is no doubt that multiple factors play different roles in the development of CVD, recent studies have revealed the potential role of hyperuricemia as a novel risk factor. Uric acid is the final product of purine metabolism in humans, and its level is determined by dietary intake, rate of cell turn-over in the body, and renal excretion. Interestingly, primates are the only species with high uric acid levels, as there has been a uricase mutation to degrade uric acid into allantoin during hominoid evolution in contrast to most mammals in which serum uric acid levels range between 0.5 to 1.5 mg/dL [1]. Interestingly, uric acid levels have been increasing in human populations over the last 100 years and, thus, correlate with the CVD epidemic [2]. Most importantly, there is astrong evidence from clinical studies and experimental animal models that uric acid is associated with hypertension and other CVDs. Elevated uric acid is observed in 89% of new onset essential hypertension in adolescents and in 25 to 50% of untreated hypertension in adults [3]. These effects are independent of renal function or body weight. However, despite solid experimental data supporting the causative role of uric acid in CVD, most authorities have viewed hyperuricemia as a secondary and not causal effect, because hyperuricemia is associated with other CVD risk factors such as male gender, obesity, hypertension, renal dysfunction, and diuretic use.
Adapting Deep Network Features to Capture Psychological Representations

Deep neural networks have become increasingly successful at solving classic perception problems such as object recognition, semantic segmentation, and scene understanding, often reaching or surpassing human-level accuracy. This success is due in part to the ability of DNNs to learn useful representations of high-dimensional inputs, a problem that humans must also solve. We examine the relationship between the representations learned by these networks and human psychological representations recovered from similarity judgments. We find that deep features learned in service of object classification account for a significant amount of the variance in human similarity judgments for a set of animal images. However, these features do not capture some qualitative distinctions that are a key part of human representations. To remedy this, we develop a method for adapting deep features to align with human similarity judgments, resulting in image representations that can potentially be used to extend the scope of psychological experiments.
Relations between recurrent trauma exposure and recent life stress and salivary cortisol among children

Abstract The present study evaluated the independent and cumulative effects of recent life stress, previous trauma, and recent trauma exposure on salivary cortisol levels among school-aged children. Sixty-eight children (mean age = 10.7 years) reported their exposure to life stressors and traumatic events in the 12 months preceding the study. Children and their caregivers reported frequency of exposure to trauma earlier in life. Exposure to life stress within the past 12 months was related to higher afternoon cortisol levels. Exposure to high levels of recent trauma in combination with frequent exposure to trauma earlier in life was related to both lower morning cortisol levels and higher afternoon cortisol levels. Results suggest that frequency, duration, and severity of exposure to stress and trauma played key roles in the prediction of basal cortisol levels in a community sample of urban youth.
Preparation and properties of biocomposites composed of bio‐based epoxy resin, tannic acid, and microfibrillated cellulose

As new bio-based epoxy resin systems, glycerol polyglycidyl ether (GPE) and sorbitol polyglycidyl ether (SPE) were cured with tannic acid (TA) at various conditions. When the curing conditions were optimized for the improvement of thermal and mechanical properties, the most balanced properties were obtained for the GPE/TA and SPE/TA cured at 160 °C for 2–3 h at the epoxy/hydroxyl ratio of 1/1. The cured SPE/TA had a higher glass transition temperature (Tg) and tensile strength than the cured GPE/TA. Next, biocomposites of GPE/TA and SPE/TA with microfibrillated cellulose (MFC) were prepared by mixing aqueous solution of the epoxy/curing reagent with MFC, and subsequent drying and curing at the optimized condition. For both the GPE/TA/MFC and SPE/TA/MFC biocomposites, Tg and the storage modulus at rubbery plateau region increased with increasing MFC content over the studied range of 3–15 wt %. The tensile strength at 25 °C for GPE/TA/MFC biocomposite with MFC content 10 wt % was 76% higher than that of control GPE/TA, while the tensile modulus was little improved. On the other hand, the tensile strength and modulus of SPE/TA/MFC biocomposite with MFC content 10 wt % were 30 and 55% higher than those of control SPE/TA, respectively. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 425–433, 2010
Quality Estimation: an experimental study using unsupervised similarity measures

We present the approach we took for our participation to the WMT12 Quality Estimation Shared Task: our main goal is to achieve reasonably good results without appeal to supervised learning. We have used various similarity measures and also an external resource (Google N-grams). Details of results clarify the interest of such an approach.
Evaluating the implicit feedback models for adaptive video retrieval

Interactive video retrieval systems are becoming popular. On the one hand, these systems try to reduce the effect of the semantic gap, an issue currently being addressed by the multimedia retrieval community. On the other hand, such systems enhance the quality of information seeking for the user by supporting query formulation and reformulation. Interactive systems are very popular in the textual retrieval domain. However, they are relatively unexplored in the case of multimedia retrieval. The main problem in the development of interactive retrieval systems is the evaluation cost.The traditional evaluation methodology, as used in the information retrieval domain, is not applicable. An alternative is to use a user-centred evaluation methodology. However, such schemes are expensive in terms of effort, cost and are not scalable. This problem gets exacerbated by the use of implicit indicators, which are useful and increasingly used in predicting user intentions. In this paper, we explore the effectiveness of a number of interfaces and feedback mechanisms and compare their relative performance using a simulated evaluation methodology. The results show the relatively better performance of a search interface with the combination of explicit and implicit features.
Bringing Process to Post Production

Recent developments in the field of business process management have made it possible to effectively deal with large collections of process models that exhibit many similarities but also context-dependent differences. In this paper these developments are exploited in the domain of screen business. In particular, different processes in audio editing are described in an integrated artifact, called reference process model, capturing their context-dependent variation points. This model can then be configured by domain experts, who are asked to select the process variants that best suit the needs of a specific audio editing project, via the use of a questionnaire. It is argued that configurable reference process models provide a structured basis for communicating the state-of-the-art in this rapidly evolving field.
Insecticide Activity of Essential Oils of Mentha longifolia, Pulicaria gnaphalodes and Achillea wilhelmsii Against Two Stored Product Pests, the Flour Beetle, Tribolium castaneum, and the Cowpea Weevil, Callosobruchus maculatus

Abstract Essential oils extracted from the foliage of Mentha longifolia (L.) (Lamiales: Lamiaceae) and Pulicaria gnaphalodes Ventenat (Asterales: Asteraceae), and flowers of Achillea wilhelmsii C. Koch (Asterales: Asteraceae) were tested in the laboratory for volatile toxicity against two storedproduct insects, the flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae) and the cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae). The chemical composition of the isolated oils was examined by gas chromatography-mass spectrometry. InM longifolia, the major compounds were piperitenon (43.9%), tripal (14.3%), oxathiane (9.3%), piperiton oxide (5.9%), and d-limonene (4.3%). In P. gnaphalodes, the major compounds were chrysanthenyl acetate (22.38%), 2L -4L-dihydroxy eicosane (18.5%), verbenol (16.59%), dehydroaromadendrene (12.54%), β-pinen (6.43%), and 1,8 cineol (5.6%). In A. wilhelmsii, the major compounds were 1,8 cineole (13.03%), caranol (8.26%), alpha pinene (6%), farnesyl acetate (6%), and p-cymene (6%). C maculatus was more susceptible to the tested plant products than T castaneum. The oils of the three plants displayed the same insecticidal activity against C. maculatus based on LC50 values (between 1.54µl/L air in P. gnaphalodes, and 2.65 µl/L air in A. wilhelmsii). While the oils of A. wilhelmsii and M. longifolia showed the same strong insecticidal activity against T. castaneum (LC50 = 10.02 and 13.05 µl/L air, respectively), the oil of P. gnaphalodes revealed poor activity against the insect (LC50 = 297.9 µl/L air). These results suggested that essential oils from the tested plants could be used as potential control agents for stored-product insects.
A Topic Modeling Approach and Its Integration into the Random Walk Framework for Academic Search

In this paper, we propose a unified topic modeling approach and its integration into the random walk framework for academic search. Specifically, we present a topic model for simultaneously modeling papers, authors, and publication venues. We combine the proposed topic model into the random walk framework. Experimental results show that our proposed approach for academic search significantly outperforms the baseline methods of using BM25 and language model, and those of using the existing topic models (including pLSI, LDA, and the AT model).
Minimum Wages and Union Bargaining in a Dual Labour Market

The paper analyses the links between a binding minimum wage and union bargaining. A dual labour market model is developed where the first sector outcome is characterised by bargaining between unions and firms, while in the second sector firms have to pay a statutory minimum wage. It is shown that a minimum wage increase has negative employment effects only if the bargaining outcome is described by the Nash solution. However, this result does not hold if the Kalai-Smorodinsky solution is applied to model union bargaining. A higher minimum wage can then lead to more employment in the unionised sector and to a lower unemployment rate.
Getting “Just Deserts” or Seeing the “Silver Lining”: The Relation between Judgments of Immanent and Ultimate Justice

People can perceive misfortunes as caused by previous bad deeds (immanent justice reasoning) or resulting in ultimate compensation (ultimate justice reasoning). Across two studies, we investigated the relation between these types of justice reasoning and identified the processes (perceptions of deservingness) that underlie them for both others (Study 1) and the self (Study 2). Study 1 demonstrated that observers engaged in more ultimate (vs. immanent) justice reasoning for a “good” victim and greater immanent (vs. ultimate) justice reasoning for a “bad” victim. In Study 2, participants' construals of their bad breaks varied as a function of their self-worth, with greater ultimate (immanent) justice reasoning for participants with higher (lower) self-esteem. Across both studies, perceived deservingness of bad breaks or perceived deservingness of ultimate compensation mediated immanent and ultimate justice reasoning respectively.
Inhibitory Control, Impulsiveness, and Attention Deficit Hyperactivity Disorder

ABSTRAGT. This article describes a new measure for studying inhibitory control, the stop signal paradigm, and the race model of inhibitory control of action (Logan & Cowan, 1984) on which it is based. This measure and model permit distinction and measurement of various processes which determine whether or not an action can be inhibited. Three studies are described that find a deficit in attention deficit hyperactivity disorder (ADHD) in inhibitory control of an ongoing action and in the processes involved in the reengagement of an alternative action following inhibition of an ongoing action. No evidence of deficient attentional capacity was found in ADHD that could account for these deficits. These deficits were most pronounced in children who had ADHD according to reports of both parent and teacher (pervasive ADHD) compared to those whose ADHD was reported by either parent or teacher but not both. No deficit was evident in children with conduct disorder (CD) or in those with a combined presentation of ADHD and CD despite the fact that these groups were characterized by clinical impulsiveness. The article discusses the implications of these findings for models of the relationship of cognitive deficit and behavior. The concept of impulsiveness is central to explanations of various problems of childhood including academic difficulties In particular, impulsiveness has been important in defining and explaining the two most common psychiatric conditions of childhood, attention deficit hyperactivity disorder
Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury

Interleukin-1 receptor antagonist (IL1ra) has demonstrated efficacy in a wide range of animal models of neuronal injury. We have previously published a randomised controlled study of IL1ra in human severe TBI, with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines. In this study, we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain. We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury, particularly in samples from the first 48 h following injury. The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space. Chemokines related to recruitment of macrophages from the plasma compartment (MCP-1) and biasing towards a M1 microglial phenotype (GM-CSF, IL1) are increased in patient samples in the rhIL1ra-treated patients. In control patients, cytokines and chemokines biased to a M2 microglia phenotype (IL4, IL10, MDC) are relatively increased. This pattern of response suggests that a simple classification of IL1ra as an ‘anti-inflammatory’ cytokine may not be appropriate and highlights the importance of the microglial response to injury.
Angiotensin II Stimulates Spinally Projecting Paraventricular Neurons through Presynaptic Disinhibition

Paraventricular nucleus (PVN) neurons that project to the spinal cord are important in the control of sympathetic outflow. Angiotensin II (Ang II) can stimulate PVN neurons, but its cellular mechanisms are not clear. In this study, we determined the effect of Ang II on the excitatory and inhibitory synaptic inputs to spinally projecting PVN neurons. Whole-cell patch-clamp recordings were performed on PVN neurons labeled by a retrograde fluorescence tracer injected into the thoracic spinal cord of rats. Immunocytochemistry labeling revealed that the immunoreactivity of angiotensin type 1 (AT1) receptors was colocalized with a presynaptic marker, synaptophysin, in the PVN. Application of 0.1–5 μm Ang II significantly decreased the amplitude of evoked GABAergic IPSCs in a concentration-dependent manner. Also, Ang II decreased the frequency of miniature IPSCs from 2.56 ± 0.45 to 1.05 ± 0.20 Hz (p < 0.05; n = 12), without affecting the amplitude and the decay time constant. The effect of Ang II on miniature IPSCs was blocked by losartan but not PD123319. However, Ang II had no effect on the evoked glutamatergic EPSCs and did not alter the frequency and amplitude of miniature EPSCs at concentrations that attenuated IPSCs. Furthermore, Ang II increased the firing rate of PVN neurons from 3.75 ± 0.36 to 7.89 ± 0.85 Hz (p < 0.05; n = 9), and such an effect was abolished by losartan. In addition, Ang II failed to excite PVN neurons in the presence of bicuculline. Thus, this study provides substantial new evidence that Ang II excites spinally projecting PVN neurons by attenuation of GABAergic synaptic inputs through activation of presynaptic AT1 receptors.
Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality. The most widely used marker of disease severity and progression is FEV1. However, FEV1 correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD. Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD. Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker. Methods Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV1, cardiovascular disease, exacerbation and mortality. Results There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality. Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity. The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear. Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations. Conclusions Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality.
Differences of Reasons for Alert Overrides on Contraindicated Co-prescriptions by Admitting Department

Objectives To reveal differences in drug-drug interaction (DDI) alerts and the reasons for alert overrides between admitting departments. Methods A retrospective observational study was performed using longitudinal Electronic Health Record (EHR) data and information from an alert and logging system. Adult patients hospitalized in the emergency department (ED) and general ward (GW) during a 46-month period were included. For qualitative analyses, we manually reviewed all reasons for alert overrides, which were recorded as free text in the EHRs. Results Among 14,780,519 prescriptions, 51,864 had alerts for DDIs (0.35%; 1.32% in the ED and 0.23% in the GW). The alert override rate was higher in the ED (94.0%) than in the GW (57.0%) (p < 0.001). In an analysis of the study population, including ED and GW patients, 'clinically irrelevant alert' (52.0%) was the most common reason for override, followed by 'benefit assessed to be greater than the risk' (31.1%) and 'others' (17.3%). The frequency of alert overrides was highest for anti-inflammatory and anti-rheumatic drugs (89%). In a sub-analysis of the population, 'clinically irrelevant alert' was the most common reason for alert overrides in the ED (69.3%), and 'benefit assessed to be greater than the risk' was the most common reason in the GW (61.4%). Conclusions We confirmed that the DDI alerts and the reasons for alert overrides differed by admitting department. Different strategies may be efficient for each admitting department.