julilili42/papers huggingface dataset:
Effect-Based Trigger Values for Mixtures of Chemicals in Surface Water Detected with In Vitro Bioassays
2020-11-30

Abstract Effect-based trigger (EBT) values for in vitro bioassays are important for surface water quality monitoring because they define the threshold between acceptable and poor water quality. They have been derived for highly specific bioassays, such as hormone-receptor activation in reporter gene bioassays, by reading across from existing chemical guideline values. This read-across method is not easily applicable to bioassays indicative of adaptive stress responses, which are triggered by many different chemicals, and activation of nuclear receptors for xenobiotic metabolism, to which many chemicals bind with rather low specificity. We propose an alternative approach to define the EBT from the distribution of specificity ratios of all active chemicals. The specificity ratio is the ratio between the predicted baseline toxicity of a chemical in a given bioassay and its measured specific endpoint. Unlike many previous read-across methods to derive EBTs, the proposed method accounts for mixture effects and includes all chemicals, not only high-potency chemicals. The EBTs were derived from a cytotoxicity EBT that was defined as equivalent to 1% of cytotoxicity in a native surface water sample. The cytotoxicity EBT was scaled by the median of the log-normal distribution of specificity ratios to derive the EBT for effects specific for each bioassay. We illustrate the new approach using the example of the AREc32 assay, indicative of the oxidative stress response, and 2 nuclear receptor assays targeting the peroxisome proliferator–activated receptor gamma and the arylhydrocarbon receptor. The EBTs were less conservative than previously proposed but were able to differentiate untreated and insufficiently treated wastewater from wastewater treatment plant effluent with secondary or tertiary treatment and surface water. Environ Toxicol Chem 2021;40:487–499. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Abstract New effect-based triggers were derived for bioassays that are responsive to many different chemicals with relatively low potency accounting for their mixture effects. AhR = arylhydrocarbon receptor; BEQ = bioanalytical equivalent concentration; EBT = effect-based trigger; PPARγ = peroxisome proliferator–activated receptor gamma; SR = specificity ratio; WWTP = wastewater-treatment plant.
Functions of Landscape in Games—A Theoretical Approach with Case Examples
2020-11-30

The significance of play in the construction of landscape involving the feedback relationships between social conventions and the individual and between the individual and physical space, contrastingly, has so far received only little scientific attention. Games, however, take on great significance in the process of socialization in order to introduce the socializing person into the interpretations, valuations, and practices of the social world, which applies correspondingly to landscape. Play is an essential element of comprehending the concept “landscape”. Accordingly, this present essay deals with conceptual considerations of the function of games in relation to the social and individual construction of landscape. The theoretical framing of landscape will be carried out within the theory of the three landscapes, following Karl Popper’s three worlds. This theoretical framing also involves fundamental considerations on the connection between games and landscapes, which will be illustrated in more detail by means of two case examples, i.e., model railroads and pinball landscapes. It is shown that the playful engagement with landscape takes place in two dimensions: On the one hand, role expectations, norms, and values associated with landscape are conveyed, thus providing guidance for individual construction and individual experience of landscape. On the other hand, landscape contingencies can be tested. They address norms of interpretation and evaluation of landscape that are considered as bound together. Moreover, innovations can be tested, which may have been established in the social understanding of landscape.
TAT-RasGAP317-326kills cells by targeting inner-leaflet–enriched phospholipids
2020-11-30

Significance TAT-RasGAP 317–326 can lyse cancer cells in a manner distinct from known programmed cell death pathways through its ability to target specific plasma membrane lipids. The killing properties of this peptide may therefore be difficult for cancer cells to alleviate through resistance-building alterations within known regulated cell death pathways. TAT-RasGAP 317–326 and compounds with similar anticancer activities can potentially complement existing anticancer therapies based on the use of genotoxins or radiation that induce apoptosis.
Transport and Noise Properties of sub-100-nm Planar Nb Josephson Junctions with Metallic Hf-Ti Barriers for nano-SQUID Applications
2020-11-30

We analyze electric transport and noise properties at 4.2 K of self-shunted superconductor-normal metal-superconductor (SNS) sandwich-type Josephson junctions, comprising Nb as the superconductor and Hf-Ti as the normal conducting material, with lateral dimensions down to approximately 80 nm. The junctions are fabricated with an optimized multilayer Nb technology based on nanopatterning by electron-beam lithography and chemical-mechanical polishing. The dependence of transport properties on the junction geometry (lateral size and barrier thickness dHf−Ti) is studied, yielding a characteristic voltage Vc up to approximately 100 μ⁢V for the smallest dHf−Ti =17 nm. The observed small hysteresis in the current-voltage curves of devices with high Vc and large size can be attributed to self-heating of the junctions and fitted with an extended version of the resistively shunted junction model. Measurements of voltage noise of single junctions are consistent with the model including self-heating effects. The potential of our technology for further miniaturization of nanoscale superconducting quantum interference devices and for the improvement of their performance is discussed.
The role of structured reporting and structured operation planning in functional endoscopic sinus surgery
2020-11-30

Computed tomography (CT) scans represent the gold standard in the planning of functional endoscopic sinus surgeries (FESS). Yet, radiologists and otolaryngologists have different perspectives on these scans. In general, residents often struggle with aspects involved in both reporting and operation planning. The aim of this study was to compare the completeness of structured reports (SR) of preoperative CT images and structured operation planning (SOP) to conventional reports (CR) and conventional operation planning (COP) to potentially improve future treatment decisions on an individual level. In total, 30 preoperative CT scans obtained for surgical planning of patients scheduled for FESS were evaluated using SR and CR by radiology residents. Subsequently, otolaryngology residents performed a COP using free texts and a SOP using a specific template. All radiology reports and operation plannings were evaluated by two experienced FESS surgeons regarding their completeness for surgical planning. User satisfaction of otolaryngology residents was assessed by using visual analogue scales. Overall radiology report completeness was significantly higher using SRs regarding surgically important structures compared to CRs (84.4 vs. 22.0%, p&lt;0.001). SOPs produced significantly higher completeness ratings (97% vs. 39.4%, p&lt;0.001) regarding pathologies and anatomical variances. Moreover, time efficiency was not significantly impaired by implementation of SR (148 s vs. 160 s, p = 0.61) and user satisfaction was significantly higher for SOP (VAS 8.1 vs. 4.1, p&lt;0.001). Implementation of SR and SOP results in a significantly increased completeness of radiology reports and operation planning for FESS. Consequently, the combination of both facilitates surgical planning and may decrease potential risks during FESS.
Bilingual and Multilingual Mental Lexicon: A Modeling Study With Linear Discriminative Learning
2020-11-30

Abstract This study addresses whether there is anything special about learning a third language, as compared to learning a second language, that results solely from the order of acquisition. We use a computational model based on the mathematical framework of Linear Discriminative Learning to explore this question for the acquisition of a small trilingual vocabulary, with English as L1, German or Mandarin as L2, and Mandarin or Dutch as L3. Our simulations reveal that when qualitative differences emerge between the learning of a first, second, and third language, these differences emerge from distributional properties of the particular languages involved rather than the order of acquisition per se, or any difference in learning mechanism. One such property is the number of homophones in each language, since within‐language homophones give rise to errors in production. Our simulations also show the importance of suprasegmental information in determining the kinds of production errors made.
Computational Model Informs Effective Control Interventions against Y. enterocolitica Co-Infection
2020-11-30

The complex interplay between pathogens, host factors, and the integrity and composition of the endogenous microbiome determine the course and outcome of gastrointestinal infections. The model organism Yersinia entercolitica (Ye) is one of the five top frequent causes of bacterial gastroenteritis based on the Epidemiological Bulletin of the Robert Koch Institute (RKI), 10 September 2020. A fundamental challenge in predicting the course of an infection is to understand whether co-infection with two Yersinia strains, differing only in their capacity to resist killing by the host immune system, may decrease the overall virulence by competitive exclusion or increase it by acting cooperatively. Herein, we study the primary interactions among Ye, the host immune system and the microbiota, and their influence on Yersinia population dynamics. The employed model considers commensal bacterial in two host compartments (the intestinal mucosa the and lumen), the co-existence of wt and mut Yersinia strains, and the host immune responses. We determine four possible equilibria: disease-free, wt-free, mut-free, and co-existence of wt and mut in equilibrium. We also calculate the reproduction number for each strain as a threshold parameter to determine if the population may be eradicated or persist within the host. We conclude that the infection should disappear if the reproduction numbers for each strain fall below one, and the commensal bacteria growth rate exceeds the pathogen’s growth rate. These findings will help inform medical control strategies. The supplement includes the MATLAB source script, Maple workbook, and figures.
Preserved Inhibitory Control Deficits of Overweight Participants in a Gamified Stop-Signal Task: Experimental Study of Validity (Preprint)
2020-11-30

<sec> <title>BACKGROUND</title> Gamification in mental health could increase training adherence, motivation, and transfer effects, but the external validity of gamified tasks is unclear. This study documents that gamified task variants can show preserved associations between markers of behavioral deficits and health-related variables. We draw on the inhibitory control deficit in overweight populations to investigate effects of gamification on performance measures in a web-based experimental task. </sec> <sec> <title>OBJECTIVE</title> This study tested whether associations between inhibitory control and overweight were preserved in a gamified stop-signal task (SST). </sec> <sec> <title>METHODS</title> Two versions of an adaptive SST were developed and tested in an online experiment. Participants (n=111) were randomized to 1 of the 2 task variants and completed a series of questionnaires along with either the gamified SST or a conventional SST. To maximize its possible effects on participants’ inhibitory control, the gamified SST included multiple game elements in addition to the task itself and the stimuli. Both variants drew on the identical core mechanics, but the gamified variant included an additional narrative, graphical theme, scoring system with visual and emotional feedback, and the presence of a companion character. In both tasks, food and neutral low-poly stimuli were classified based on their color tone (go trials), but responses were withheld in 25% of the trials (stop trials). Mean go reaction times and stop-signal reaction times (SSRT) were analyzed as measures of performance and inhibitory control. </sec> <sec> <title>RESULTS</title> Participants in the gamified SST had longer reaction times (803 [SD 179] ms vs 607 [SD 90] ms) and worse inhibitory control (SSRT 383 [SD 109] ms vs 297 [SD 45] ms). The association of BMI with inhibitory control was relatively small (&lt;i&gt;r&lt;/i&gt;=.155, 95% CI .013-.290). Overweight participants had longer reaction times (752 [SD 217] ms vs 672 [SD 137] ms) and SSRTs (363 [SD 116] ms vs 326 [SD 77] ms). Gamification did not interact with the effect of overweight on mean performance or inhibitory control. There were no effects of gamification on mood and user experience, despite a negative effect on perceived efficiency. </sec> <sec> <title>CONCLUSIONS</title> The detrimental effects of heightened BMI on inhibitory control were preserved in a gamified version of the SST. Overall, the effects of overweight were smaller than in previously published web-based and laboratory studies. Gamification elements can impact behavioral performance, but gamified tasks can still assess inhibitory control deficits. Although our results are promising, according validations may differ for other types of behavior, gamification, and health variables. </sec>
Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB–IVA: oncologic results of a prospective randomized international multicenter (Uterus-11) intergroup study
2020-12-01

Our study did not show a difference in disease-free survival between surgical and clinical staging in patients with locally advanced cervical cancer. There was a significant benefit in disease-free survival for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging. The high risk of distant metastases in both arms emphasizes the need for further evaluation.
Recent insights into the regulatory networks of NLRP3 inflammasome activation
2020-12-01

ABSTRACT The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is a fascinating cellular machinery endowed with the capacity for rapid proteolytic processing of the pro-inflammatory cytokine IL-1β and the cell death effector gasdermin D (GSDMD). Although its activity is essential to fight infection and support tissue homeostasis, the inflammasome complex, which consists of the danger sensor NLRP3, the adaptor apoptosis-associated speck-like protein containing a CARD (ASC; also known as PYCARD), caspase-1 and probably other regulatory proteins, also bears considerable potential for detrimental inflammation, as observed in human conditions such as gout, heart attack, stroke and Alzheimer's disease. Thus, multi-layered regulatory networks are required to ensure the fine balance between rapid responsiveness versus erroneous activation (sufficient and temporally restricted versus excessive and chronic activity) of the inflammasome. These involve multiple activation, secretion and cell death pathways, as well as modulation of the subcellular localization of NLRP3, and its structure and activity, owing to post-translational modification by other cellular proteins. Here, we discuss the exciting progress that has recently been made in deciphering the regulation of the NLRP3 inflammasome. Additionally, we highlight open questions and describe areas of research that warrant further exploration to obtain a more comprehensive molecular and cellular understanding of the NLRP3 inflammasome.
SARS-CoV-2 reinfection and implications for vaccine development
2020-12-01

Coronavirus disease 2019 (COVID-19) pandemic continues to constitute a public health emergency of international concern. Multiple vaccine candidates for COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have entered clinical trials. However, some evidence suggests that patients who have recovered from COVID-19 can be reinfected. For example, in China, two discharged COVID-19 patients who had recovered and fulfilled the discharge criteria for COVID-19 were retested positive to a reverse transcription polymerase chain reaction (RT-PCR) assay for the virus. This finding is critical and could hamper COVID-19 vaccine development. This review offers literature-based evidence of reinfection with SARS-CoV-2, provides explanation for the possibility of SARS-CoV-2 reinfection both from the agent and host points of view, and discusses its implication for COVID-19 vaccine development.
Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy
2020-12-01

Background Inhibitors of immune checkpoint programmed cell death protein 1 (PD-1) receptor on T cells have shown remarkable clinical outcomes in metastatic melanoma. However, most patients are resistant to therapy. Production of extracellular adenosine, via CD73-mediated catabolism of AMP, contributes to suppress T-cell-mediated responses against cancer. In this study, we analyzed the expression and activity of soluble CD73 in sera of patients with melanoma undergoing anti-PD-1± cytotoxic T-lymphocyte-associated antigen 4 therapy. Methods Soluble CD73 expression and activity were retrospectively analyzed in serum of a total of 546 patients with melanoma from different centers before starting treatment (baseline) with anti-PD-1 agents, nivolumab or pembrolizumab, and compared with those of 96 healthy subjects. The CD73 activity was correlated with therapy response and survival of patients. Results Patients with melanoma show significantly higher CD73 activity and expression than those observed in healthy donors (p&lt;0.0001). Elevated pretreatment levels of CD73 activity were associated with non-response to therapy with nivolumab or pembrolizumab. During treatment, levels of soluble CD73 activity remain unchanged from baseline and still stratify clinical responders from non-responders. High levels of serum CD73 enzymatic activity associate with reduced overall survival (OS; HR=1.36, 95% CI 1.03 to 1.78; p=0.03) as well as progression-free survival (PFS; HR=1.42, 95% CI 1.13 to 1.79, p=0.003). Further, the multivariate Cox regression analysis indicates that serum CD73 activity is an independent prognostic factor besides serum lactate dehydrogenase levels and the presence of brain metastases for both OS (p=0.009) and PFS (p=0.001). Conclusion Our data indicate the relevance of serum CD73 in patients with advanced melanoma receiving anti-PD-1 therapy and support further investigation on targeting CD73 in combination with anti-PD-1 antibodies.
Driver Drowsiness Classification Based on Eye Blink and Head Movement Features Using the k-NN Algorithm
2020-12-01

Modern advanced driver-assistance systems analyze the driving performance to gather information about the driver's state. Such systems are able, for example, to detect signs of drowsiness by evaluating the steering or lane keeping behavior and to alert the driver when the drowsiness state reaches a critical level. However, these kinds of systems have no access to direct cues about the driver's state. Hence, the aim of this work is to extend the driver drowsiness detection in vehicles using signals of a driver monitoring camera. For this purpose, 35 features related to the driver's eye blinking behavior and head movements are extracted in driving simulator experiments. Based on that large dataset, we developed and evaluated a feature selection method based on the k-Nearest Neighbor algorithm for the driver's state classification. A concluding analysis of the best performing feature sets yields valuable insights about the influence of drowsiness on the driver's blink behavior and head movements. These findings will help in the future development of robust and reliable driver drowsiness monitoring systems to prevent fatigue-induced accidents.
Resilience unwanted: Between control and cooperation in disaster response
2020-12-01

This article conceptualizes resilience as an emergent and contingent practice that shapes societal relationships in unexpected ways. It focuses on the case of the 2013 floods in Dresden, a city that witnessed three major floods within 11 years. Emergent volunteer activities on the ground and on social media played a significant role during the flood emergency response efforts. Drawing on Philippe Bourbeau’s definition of resilience as a process of patterned adjustment, the article regards these emergent structures as incidents of resilience. In the case of Dresden, not only was resilience not explicitly requested by the state, but it was in several incidents actively not wanted. While most of the volunteering activities arising from social media platforms intended to support the disaster management authorities, the case shows how subversive forms of resilience were mobilized to resist official plans. They finally urged authorities to adapt to a new social and technological reality in order to render unaffiliated volunteering governable. Resilience thus emerges as an adaptive process that shapes and is shaped by societal relations. The article thus seeks to add another facet to the debate on resilience by demonstrating how resilience helps us to make sense of complex and interdependent adaptation processes.
Drawing Distinctions: What is Post-Critical Pedagogy?
2020-12-01

Post-critical pedagogy is an attempt to step outside the endless repetition of critical research in education. ‘Posting’ critique and thereby posing the question of alternatives works against a stagnating tendency for current educational debates to appear unsatisfactory, paralysing, and tedious. This essay describes the limits of critical pedagogy and possibilities of a ‘post-critical pedagogy’. It is structured according to the term’s three elements of ‘critique’, ‘post’, and ‘pedagogy’. For each of these elements, the essay describes two ways of understanding; not to play them off against each other, but to show how manifold post-critical pedagogy can and should be. The essay concludes with a proposal of three analytical dimensions for further work on a post-critical pedagogy.