julilili42/papers huggingface dataset:
Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2)
2021-10-13

The ribosomal protein S6 kinase beta 2 (S6K2) is thought to play an important role in malignant cell proliferation, but is understudied compared to its closely related homolog S6 kinase beta 1 (S6K1). To better understand the biological function of S6K2, chemical probes are needed, but the high similarity between S6K2 and S6K1 makes it challenging to selectively address S6K2 with small molecules. We were able to design the first potent and highly isoform-specific S6K2 inhibitor from a known S6K1-selective inhibitor, which was merged with a covalent inhibitor engaging a cysteine located in the hinge region in the fibroblast growth factor receptor kinase (FGFR) 4 via a nucleophilic aromatic substitution (SNAr) reaction. The title compound shows a high selectivity over kinases with an equivalently positioned cysteine, as well as in a larger kinase panel. A good stability towards glutathione and Nα-acetyl lysine indicates a non-promiscuous reactivity pattern. Thus, the title compound represents an important step towards a high-quality chemical probe to study S6K2-specific signaling.
Basement membrane proteins improve human islet survival in hypoxia: Implications for islet inflammation
2021-10-13

Enzymatic digestion of the pancreas during islet isolation is associated with disintegration of the islet basement membrane (IBM) that can cause reduction of functional and morphological islet integrity. Attempts to re-establish IBM by coating the surface of culture vessels with various IBM proteins (IBMP) have resulted in loss of islet phenotype and function. This study investigated the capability of Collagen-IV, Laminin-521 and Nidogen-1, utilised as single or combined media supplements, to protect human islets cultured in hypoxia. When individually supplemented to media, all IBMP significantly improved islet survival and in-vitro function, finally resulting in as much as a two-fold increase of islet overall survival. In contrast, combining IBMP enhanced the production of chemokines and reactive oxygen species diminishing all positive effects of individually added IBMP. This impact was concentration-dependent and concerned nearly all parameters of islet integrity. Predictive extrapolation of these findings to data from 116 processed human pancreases suggests that more than 90% of suboptimal pancreases could be rescued for clinical islet transplantation increasing the number of transplantable preparations from actual 25 to 40 when adding Nidogen-1 to pretransplant culture. This study suggests that media supplementation with essential IBMP protects human islets from hypoxia. Amongst those, certain IBMP may be incompatible when combined or applied at higher concentrations. STATEMENT OF SIGNIFICANCE: Pancreatic islet transplantation is a minimally-invasive treatment that can reverse type 1 diabetes in certain patients. It involves infusing of insulin-producing cell-clusters (islets) from donor pancreases. Unfortunately, islet extraction is associated with damage of the islet basement membrane (IBM) causing reduced islet function and cell death. Attempts to re-establish the IBM by coating the surface of culture vessels with IBM proteins (IBMP) have been unsuccessful. Instead, we dissolved the most relevant IBM components Collagen-IV, Laminin-521 and Nidogen-1 in media routinely used for clinical islet culture and transplantation. We found human islet survival and function was substantially improved by IBMP, particularly Nidogen-1, when exposed to a hypoxic environment as found in vivo. We also investigated IBMP combinations. Our present findings have important clinical implications.
Weakly supervised segmentation of tumor lesions in PET-CT hybrid imaging
2021-10-13

<b>Purpose</b>: We introduce and evaluate deep learning methods for weakly supervised segmentation of tumor lesions in whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) based solely on binary global labels ("tumor" versus "no tumor"). <b>Approach</b>: We propose a three-step approach based on (i) a deep learning framework for image classification, (ii) subsequent generation of class activation maps (CAMs) using different CAM methods (CAM, GradCAM, GradCAM++, ScoreCAM), and (iii) final tumor segmentation based on the aforementioned CAMs. A VGG-based classification neural network was trained to distinguish between PET image slices with and without FDG-avid tumor lesions. Subsequently, the CAMs of this network were used to identify the tumor regions within images. This proposed framework was applied to FDG-PET/CT data of 453 oncological patients with available manually generated ground-truth segmentations. Quantitative segmentation performance was assessed for the different CAM approaches and compared with the manual ground truth segmentation and with supervised segmentation methods. In addition, further biomarkers (MTV and TLG) were extracted from the segmentation masks. <b>Results</b>: A weakly supervised segmentation of tumor lesions was feasible with satisfactory performance [best median Dice score 0.47, interquartile range (IQR) 0.35] compared with a fully supervised U-Net model (median Dice score 0.72, IQR 0.36) and a simple threshold based segmentation (Dice score 0.29, IQR 0.28). CAM, GradCAM++, and ScoreCAM yielded similar results. However, GradCAM led to inferior results (median Dice score: 0.12, IQR 0.21) and was likely to ignore multiple instances within a given slice. CAM, GradCAM++, and ScoreCAM yielded accurate estimates of metabolic tumor volume (MTV) and tumor lesion glycolysis. Again, worse results were observed for GradCAM. <b>Conclusions</b>: This work demonstrated the feasibility of weakly supervised segmentation of tumor lesions and accurate estimation of derived metrics such as MTV and tumor lesion glycolysis.
Codiversification of gut microbiota with humans
2021-10-13

Abstract Some gut microbes have cospeciated with hominids, but whether they further codiversified with human populations is unclear. Here, we identify predominant gut microbial species sharing a parallel evolutionary history with human populations. Patterns of strain transfer between populations are generally consistent with an African origin, and suggest long-term vertical transmission over thousands of generations. We show the same strains also faithfully transmit between mothers and their children. Consistent with the development of intimate symbiosis, species with strongest patterns of codiversification have the smallest genomes. This study reveals long-term fidelity of gut microbiota with human populations through transmission among individuals living in close proximity. Dominance of specific strains in different populations is based in part on vertical transmission and they may provide population-specific health benefits. One-sentence summary Identification of gut microbes that codiversified with human populations.
Unknown cardiac mass in a patient with follicular thyroid carcinoma
2021-10-13

A 73-year-old asymptomatic man with a history of follicular thyroid carcinoma who underwent a thyroidectomy with lymphadenectomy in 2012, combined with radioiodine therapy and multiple stereotactic radiations presented for follow-up. A computed tomography scan showed a previously unknown mass in the right ventricle that compromised the right ventricular outflow tract (RVOT) (Panel A, red arrow). Cardiovascular magnetic resonance imaging confirmed the finding. A mass (∼2.9 cm × 2.5 cm × 2.1 cm) adjacent to the right ventricular septum immediately before the right ventricular outflow tract was seen, being compatible with a metastasis of the known follicular thyroid carcinoma. It was rated as non-invasive, and since there was a topographical proximity to the right coronary artery, an operation was recommended to prevent its compression (Panel B, red arrow). The cardiac mass could be clearly demonstrated in the intraoperative TOE examination (Panels C and D) and its surgical removal turned out to be without difficulty. Panel E displays the intraoperative findings of the cardiac mass after the tumour has been peeled from the right ventricular myocardium. The suspected diagnosis of metastasis of a follicular thyroid carcinoma was then confirmed by the histological examination (Panel F).
The “situative nature” of competence and value beliefs and the predictive power of autonomy support: A multilevel investigation of repeated observations.
2021-10-14

In their situated expectancy-value theory, Eccles and Wigfield (2020) assume students' competence and value beliefs to be situation-specific and thereby to be "situative" in nature.Even though motivation research has gradually been developing an understanding of this situative nature, for instance, by disentangling time-consistent and fluctuating proportions of competence and value beliefs at the analytical level of the individual, most studies still have not disentangled them at the class level.The present study sought to close this gap by applying a multilevel modeling approach based on data from 1,617 ninth-grade students in 78 classrooms across five consecutive math lessons.Our findings revealed significant proportions of trait variance and state residual variance in students' competence beliefs, value beliefs, and their perceptions of autonomy-supportive teaching behaviors at the individual and class levels.Larger amounts of variance could be attributed to the individual level compared with the class level and to fluctuating compared with time-consistent proportions (across levels).Furthermore, students' perceptions of autonomy-supportive teaching behaviors predicted their situation-specific competence and value beliefs, whereby time-consistent differences, both between students and between classes, explained more variance than fluctuations within students and within classes.Thus, our findings supported the situative nature of competence and value beliefs but also revealed that, by and large, time-consistent differences in the perceptions of autonomysupportive teaching behaviors between students and classes had more predictive power for students' competence and value beliefs than intraindividual and intra-class fluctuations over time.
Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis
2021-10-14

Comprehensive simultaneous hybrid CMR/FDG-PET imaging is useful for the detection of CS and provides additional value for identifying active disease. Our results may have implications for enhanced diagnosis as well as improved identification of patients with aCS in whom anti-inflammatory therapy may be most beneficial.
Respiratory Viruses Dynamics and Interactions: Ten Years of Surveillance in Central Europe
2021-10-14

Abstract Background: Lower respiratory tract infections are among the main causes of death. Although there are many respiratory viruses, diagnostic efforts are focused mainly on influenza. The Respiratory Viruses Network (RespVir) collects infection data, primarily from German university hospitals, for a high diversity of infections by respiratory pathogens. In this study, we computationally analysed a subset of the RespVir database, covering 217,150 samples tested for 17 different viral pathogens in the time span from 2010 to 2019. Methods: We calculated the prevalence of 17 respiratory viruses, analysed their seasonality patterns using information-theoretic measures and agglomerative clustering, and analysed their propensity for dual infection using a new metric dubbed average coinfection exclusion score (ACES). Results: After initial data pre-processing, we retained 206,814 samples, corresponding to 1,408,657 performed tests. We found that Influenza viruses were reported for less than half of all infections and that they exhibited the highest degree of seasonality Coinfections of viruses are frequent, the most prevalent coinfection was rhinovirus/bocavirus and most of the virus pairs had a positive ACES indicating a tendency to exclude each other regarding infection. Conclusions: The analysis of respiratory viruses dynamics in monoinfection and coinfection contributes to the prevention, diagnostic, treatment, and development of new therapeutics. Data obtained from multiplex testing is fundamental for this analysis and should be prioritized over single pathogen testing.
Temporal response modelling uncovers electrophysiological correlates of trial-by-trial error-driven learning
2021-10-14

Humans learn from statistical regularities in the environment. There has been increasing interest in recent decades regarding the mechanisms underlying such learning. We used Error-Driven Learning (EDL) to simulate participants’ trial-by-trial learning during exposure to a bimodal distribution of non-native lexical tones. This gave us estimates of the degree of expectation of upcoming stimuli over the course of the experiment. The expectation estimates were combined with Temporal Response Function fitting to generate a prediction of the trial-by-trial ERP waveform. The expectation estimates of certain EDL simulations were significantly more informative about the ERP signal than discrete stimulus conditions or overall stimulus probability. These results show that trial-by-trial changes in neural activity can be captured by EDL estimates of expectation. Hence, we tentatively conclude that learning of statistical regularities, as reflected in neural activity, involves continual updating of expectations depending on error-driven learning from cues in the environment.
Seeing the churches like the state: taxes and wealth redistribution in late antique Italy
2021-10-14

Two key economic questions tend to be asked about the transformation of the Roman world. First, how did Roman fiscal structures continue, disintegrate and transform? Second, how did emerging churches play a role in the redistribution of wealth through new administrative structures to create a new social system, what Ian Wood has called a ‘temple society’? These two processes – one focussing on the continuity or discontinuity of the Roman economic structures and the other on churches within that system – are usually examined separately or assumed to follow, what we call here, a ‘Gallic model’. In this article, we first demonstrate that Wood’s ‘temple society’ is far more complex in its emergence in Italy than in Gaul. Second, we argue that the churches of Italy remained embedded within late Roman fiscal structures, even as they transformed during late antiquity. Fiscal arrangements, examined through the churches of Rome and Ravenna, established churches as ever more central economic actors to the state fiscal system by 600 and shaped their long‐term wealth redistribution process.
Determination and Monitoring of Quality Parameters: A Detailed Study of Optical Elements of a Lens-Based Raman Spectrometer
2021-10-14

A lens-based Raman spectrometer is characterized by studying the optical elements in the optical path and we study the measure of aberration–diffraction effects. This is achieved by measuring the spectral resolution (SR) thus encompassing almost all optical elements of a spectrometer that are mostly responsible for such effects. An equation for SR is used to determine the quality factor Q which measures aberration/diffraction effects occurring in a spectrometer. We show how the quality factor changes with different spectrometer parameters such as grating groove density, the wavelength of excitation, pinhole width, charge-coupled device (CCD) pixel density, etc. This work provides an insight into the quality of a spectrometer and helps to monitor the performance of the spectrometer over a certain period. Commercially available spectrometers or home-built spectrometers are prone to misalignment in optical elements and can benefit from this work that allows maintaining the overall quality of the setup. Performing such experiments over a period helps to minimize the aberration/diffraction effects occurring as a result of time and maintaining the quality of measurements.
The Carolingian local ecclesia as a ‘temple society’?
2021-10-14

This article assesses the question to what extent the model of a ‘temple society’ can be fruitfully employed as a tool of analysis for the Carolingian ecclesia , by which we mean not only the rich, well‐endowed churches, but also the small, local ones. An investigation of the many different forms of ecclesiastical land‐holding, and of the various functions a church and its ministers did (and did not) fulfil for early medieval Christians, shows the shape of the Carolingian ‘ ecclesia ‐society’ as it took shape in the course of the ninth century .
Bragg condition for scattering into a guided optical mode
2021-10-14

We theoretically investigate light scattering from an array of atoms into the guided modes of a waveguide. We show that the scattering of a plane wave laser field into the waveguide modes is dramatically enhanced for angles that deviate from the geometric Bragg angle. We derive a modified Bragg condition, and show that it arises from the dispersive interactions between the guided light and the atoms. Moreover, we identify various parameter regimes in which the scattering rate features a qualitatively different dependence on the atom number, such as linear, quadratic, oscillatory or constant behavior. We show that our findings are robust against voids in the atomic array, facilitating their experimental observation and potential applications. Our work sheds new light on collective light scattering and the interplay between geometry and interaction effects, with implications reaching beyond the optical domain.
Vector-like quarks decaying into singly and doubly charged bosons at LHC
2021-10-14

A bstract We investigate the production of vector-like quarks with charge 5 / 3 at the LHC and their subsequent decays into new singly or doubly charged bosons plus a heavy quark (top or bottom). In particular, we explore final states with same-sign di-leptons (electron or muon pairs), with the leptons coming from the decay of the new bosons and, in the case of production of singly charged bosons, from top quarks as well. These processes are predicted by classes of models based on extensions of the gauge group of the Standard Model, such as the 331 Model, where the electroweak symmetry is described by SU(3) L × U(1) X , X being a new abelian charge. For this purpose, a CMS search for vector-like partners with charge 5/3 decaying into Wt is recast to obtain model-independent bounds and projected reaches at future luminosity stages of the LHC. The results are then interpreted as mass bounds for the new particles predicted in the 331 Model and as a constraint on the scale of its spontaneous symmetry breaking. The complete set of model-independent results are provided as recast efficiencies, to allow for reinterpretation in different scenarios.
The Influence of Neuroticism on the Muscle Response in the Trapezius and Frontalis Muscles to Anticipatory Stress
2021-10-14

Abstract. Objective quantification of mental stress in the workplace would be beneficial for designing work tasks to avoid the negative consequences of mental stress. Methods such as surface electromyography have proven to be sensitive to mental demands. However, there is little knowledge about the muscle response and moderating factors during anticipatory stress paradigms. This study examined whether the personality dimension neuroticism moderates the muscle response to the expectation of an unpredictable electrical shock. Forty-seven subjects underwent three expectation phases, in which they could expect a pleasant audio signal (NoShock) or an electric shock in two conditions (anticipation of the first: Shock1, and second electric shock: Shock2) at an unpredictable moment. The frontalis muscle activity and the upper and upper/middle parts of the trapezius muscle were recorded using surface electromyography. Neuroticism was surveyed using the Big Five Inventory to assign the subjects to a group with lower or higher neuroticism. Shock1 only induced higher trapezius muscle activity in the higher neuroticism group, which vanished during Shock2, while the frontalis muscle showed no significant effects. The results suggest that neuroticism should be considered a moderating factor in assessing anticipatory stress using surface electromyography at the trapezius muscle.
Computer Vision and Pattern Recognition 2020
2021-10-15

This special issue covers a wide range of topics from the area of Computer Vision, Pattern Recognition, and Machine Learning.This breadth of scope is reflected by the papers included in this special issue, which touch topics including geometric Computer Vision, medical image processing, physical scene understanding, and interpretability of deep neural networks.This special issue consists of extended versions of the best papers originally presented at the 42nd German Conference on Pattern Recognition (DAGM GCPR 2020), held virtually between September 28th and October 1st, 2020.This special issue consists of 4 papers that are briefly discussed as follows:The first article, by Annika Hagemann, Moritz Knorr, Holger Janssen, and Christoph Stiller on "Inferring bias and uncertainty in camera calibration" introduces an evaluation scheme to capture the fundamental error sources in camera calibration: systematic errors (biases) and uncertainty (variance).The proposed bias detection method is able to detect systematic errors and can thus be used to reveal inaccuracies in the calibration setup.It can thus be used for camera model selection.A novel resampling-based uncertainty estimator enables uncertainty estimation under non-ideal conditions and thereby extends the classical covariance estimator.In "Assignment Flow For Order-Constrained OCT Segmentation", Dmitrij Sitenko, Bastian Boll, and Christoph Schnörr propose a novel, purely data driven geometric approach to order-constrained 3D Optical Coherence Tomography retinal cell layer segmentation which takes as input data in any metric space and provides basic operations that can be effectively computed in parallel.Compared to established
“... Inconceivable, Unrealistic and Inhumane”. Internet Communication on the Flood Disaster in West Germany of July 2021 between Conspiracy Theories and Moralization—A Neopragmatic Explorative Study
2021-10-15

The aim of this article is an explorative study of the debate on the flood in the western part of Germany in July 2021, based on the comments found below the coverage of a German public television channel (ZDF) published on YouTube. Based on the neopragmatic framing of the analysis by connecting morality and mass media according to Luhmann, as well as Dahrendorf’s conflict theory, four patterns of interpretation were identified which illustrate a high moralization of the conflict: conclusions drawn from the storm (e.g., of a political nature, references to COVID-19, etc.), far-reaching, predominantly negative interpretations that place the storm and its consequences in the context of other negatively interpreted aspects, as well as rational and empathetic interpretations regarding expressions of sympathy and offers of help, and, ultimately, interpretations that range from climate change and planning failures to various conspiracy-theoretical claims of responsibility for the flooding. All in all, a transformation from conflicts of interest and facts to conflicts of identity and values is taking place, revealing two utopias: the utopia in which man and nature are in harmonic unity, as well as the utopia of the satisfaction of individual (material) needs in a stable material-spatial and legal framework. Science has an instrumental application in both utopias.