julilili42/papers huggingface dataset:
Structural Basis for Regulation of the Opposing (p)ppGpp Synthetase and Hydrolase within the Stringent Response Orchestrator Rel
2020-09-01

The stringent response enables metabolic adaptation of bacteria under stress conditions and is governed by RelA/SpoT Homolog (RSH)-type enzymes. Long RSH-type enzymes encompass an N-terminal domain (NTD) harboring the second messenger nucleotide (p)ppGpp hydrolase and synthetase activity and a stress-perceiving and regulatory C-terminal domain (CTD). CTD-mediated binding of Rel to stalled ribosomes boosts (p)ppGpp synthesis. However, how the opposing activities of the NTD are controlled in the absence of stress was poorly understood. Here, we demonstrate on the RSH-type protein Rel that the critical regulative elements reside within the TGS (ThrRS, GTPase, and SpoT) subdomain of the CTD, which associates to and represses the synthetase to concomitantly allow for activation of the hydrolase. Furthermore, we show that Rel forms homodimers, which appear to control the interaction with deacylated-tRNA, but not the enzymatic activity of Rel. Collectively, our study provides a detailed molecular view into the mechanism of stringent response repression in the absence of stress.
SFPQ Depletion Is Synthetically Lethal with BRAFV600E in Colorectal Cancer Cells
2020-09-01

Oncoproteins such as the BRAF<sup>V600E</sup> kinase endow cancer cells with malignant properties, but they also create unique vulnerabilities. Targeting of BRAF<sup>V600E</sup>-driven cytoplasmic signaling networks has proved ineffective, as patients regularly relapse with reactivation of the targeted pathways. We identify the nuclear protein SFPQ to be synthetically lethal with BRAF<sup>V600E</sup> in a loss-of-function shRNA screen. SFPQ depletion decreases proliferation and specifically induces S-phase arrest and apoptosis in BRAF<sup>V600E</sup>-driven colorectal and melanoma cells. Mechanistically, SFPQ loss in BRAF-mutant cancer cells triggers the Chk1-dependent replication checkpoint, results in decreased numbers and reduced activities of replication factories, and increases collision between replication and transcription. We find that BRAF<sup>V600E</sup>-mutant cancer cells and organoids are sensitive to combinations of Chk1 inhibitors and chemically induced replication stress, pointing toward future therapeutic approaches exploiting nuclear vulnerabilities induced by BRAF<sup>V600E</sup>.
Makemake + Sedna: A Continuum Radiation Transport and Photoionization Framework for Astrophysical Newtonian Fluid Dynamics
2020-09-01

Abstract Astrophysical fluid flow studies often encompass a wide range of physical processes to account for the complexity of the system under consideration. In addition to gravity, a proper treatment of thermodynamic processes via continuum radiation transport and/or photoionization is becoming the state of the art. We present a major update of our continuum radiation transport module, Makemake, and a newly developed module for photoionization, Sedna, coupled to the magnetohydrodynamics code PLUTO. These extensions are currently not publicly available; access can be granted on a case-by-case basis. We explain the theoretical background of the equations solved, elaborate on the numerical layout, and present a comprehensive test suite for radiation–ionization hydrodynamics. The grid-based radiation and ionization modules support static one-dimensional, two-dimensional, and three-dimensional grids in Cartesian, cylindrical, and spherical coordinates. Each module splits the radiation field into two components, one originating directly from a point source—solved using a ray-tracing scheme—and a diffuse component—solved with a three-dimensional flux-limited diffusion (FLD) solver. The FLD solver for the continuum radiation transport makes use of either the equilibrium one-temperature approach or the linearization two-temperature approach. The FLD solver for the photoionization module enables accounting for the temporal evolution of the radiation field from direct recombination of free electrons into hydrogen’s ground state as an alternative to on-the-spot approximation. A brief overview of completed and ongoing scientific studies is given to explicitly illustrate the multipurpose nature of the numerical framework presented.
RCPNet: Deep-Learning based Relative Camera Pose Estimation for UAVs
2020-09-01

In this paper, we propose a deep neural-network based regression approach, combined with a 3D structure based computer vision method, to solve the relative camera pose estimation problem for autonomous navigation of UAVs. Different from existing learning-based methods that train and test camera pose estimation in the same scene, our method succeeds in estimating relative camera poses across various urban scenes via a single trained model. We also built a Tuebingen Buildings database of RGB images collected by a drone in eight urban scenes. Over 10,000 images with corresponding 6DoF poses as well as 300,000 image pairs with their relative translational and rotational information are included in the dataset. We evaluate the accuracy of our method in the same scene and across scenes, using the Cambridge Landmarks dataset and the Tuebingen Buildings dataset. We compare the performance with existing learning-based pose regression methods PoseNet and RPNet on these two benchmark datasets.
Two-variable logics with some betweenness relations: Expressiveness, satisfiability and membership
2020-09-01

We study two extensions of FO2[<], first-order logic interpreted in finite words, in which formulas are restricted to use only two variables. We adjoin to this language two-variable atomic formulas that say, "the letter appears between positions and " and "the factor appears between positions and ". These are, in a sense, the simplest properties that are not expressible using only two variables. We present several logics, both first-order and temporal, that have the same expressive power, and find matching lower and upper bounds for the complexity of satisfiability for each of these formulations. We give effective conditions, in terms of the syntactic monoid of a regular language, for a property to be expressible in these logics. This algebraic analysis allows us to prove, among other things, that our new logics have strictly less expressive power than full first-order logic FO[<]. Our proofs required the development of novel techniques concerning factorizations of words.
Ectopic fat accumulation in human astrocytes impairs insulin action
2020-09-01

Astrocytes provide neurons with structural support and energy in form of lactate, modulate synaptic transmission, are insulin sensitive and act as gatekeeper for water, ions, glutamate and second messengers. Furthermore, astrocytes are important for glucose sensing, possess neuroendocrine functions and also play an important role in cerebral lipid metabolism. To answer the question, if there is a connection between lipid metabolism and insulin action in human astrocytes, we investigated if storage of ectopic lipids in human astrocytes has an impact on insulin signalling in those cells. Human astrocytes were cultured in the presence of a lipid emulsion, consisting of fatty acids and triglycerides, to induce ectopic lipid storage. After several days, cells were stimulated with insulin and gene expression profiling was performed. In addition, phosphorylation of Akt as well as glycogen synthesis and cell proliferation was assessed. Ectopic lipid storage was detected in human astrocytes after lipid exposure and lipid storage was persistent even when the fat emulsion was removed from the cell culture medium. Chronic exposure to lipids induced profound changes in the gene expression profile, whereby some genes showed a reversible gene expression profile upon removal of fat, and some did not. This included FOXO-dependent expression patterns. Furthermore, insulin-induced phosphorylation of Akt was diminished and also insulin-induced glycogen synthesis and proliferation was impaired in lipid-laden astrocytes. Chronic lipid exposure induces lipid storage in human astrocytes accompanied by insulin resistance. Analyses of the gene expression pattern indicated the potential of a partially reversible gene expression profile. Targeting astrocytic insulin resistance by reducing ectopic lipid load might represent a promising treatment target for insulin resistance of the brain in obesity, diabetes and neurodegeneration.
Frontal, Parietal, and Temporal Brain Areas Are Differentially Activated When Disambiguating Potential Objects of Joint Attention
2020-09-01

Abstract Humans establish joint attention with others by following the other’s gaze. Previous work has suggested that a cortical patch (gaze-following patch, GFP) close to the posterior superior temporal sulcus (pSTS) may serve as a link between the extraction of the other’s gaze direction and the resulting shifts of attention, mediated by human lateral intraparietal area (hLIP). However, it is not clear how the brain copes with situations in which information on gaze direction alone is insufficient to identify the target object because more than one may lie along the gaze vector. In this fMRI study, we tested human subjects on a paradigm that allowed the identification of a target object based on the integration of the other’s gaze direction and information provided by an auditory cue on the relevant object category. Whereas the GFP activity turned out to be fully determined by the use of gaze direction, activity in hLIP reflected the total information needed to pinpoint the target. Moreover, in an exploratory analysis, we found that a region in the inferior frontal junction (IFJ) was sensitive to the total information on the target. An examination of the BOLD time courses in the three identified areas suggests functionally complementary roles. Although the GFP seems to primarily process directional information stemming from the other’s gaze, the IFJ may help to analyze the scene when gaze direction and auditory information are not sufficient to pinpoint the target. Finally, hLIP integrates both streams of information to shift attention to distinct spatial locations.
The Backward Crosstalk Effect Does Not Depend on the Degree of a Preceding Response Conflict
2020-09-01

Abstract. A common observation in dual tasking is a performance decrement in one or both tasks compared with single tasking. Besides, more specific interference occurs depending on certain characteristics of the two tasks. In particular, even Task 1 performance is often improved when responses in both tasks are compatible (e.g., both require left responses) compared to when they are incompatible: the compatibility-based backward crosstalk effect (BCE). Similar to what is observed for conflict tasks, the BCE is sequentially modulated: It is larger following compatible than following incompatible trials. Previous work has attributed this observation to adaptation effects triggered by response conflict arising during incompatible trials. In two experiments, we assessed sequential modulations following trials with different degrees of such a response conflict. In contrast to our expectations, a clear and sizeable sequential modulation was observed even under conditions where no BCE, and thus no empirical sign of an objective response conflict, was present in the previous trial. Therefore, our results show sequential modulations even without prior response conflict, which is not the (sole) trigger of sequential modulations accordingly. We discuss these results with regard to other potential triggers such as the subjective experience of conflict or difficulty, episodic retrieval, and repetitions of response combinations.
Sequencing for an interdisciplinary molecular tumor board in patients with advanced breast cancer: experiences from a case series
2020-09-01

Using a high throughput-panel sequencing approach to identify actionable mutations in patients with metastatic breast cancer, we identified potential target-related treatment options in a large proportion of our patients, some of which would not have been considered without this data. Prospective clinical trials with compounds targeting the identified actionable mutations are needed to determine which treatments can indeed improve survival or quality of life by limiting exposure to ineffective drugs in advanced breast cancer.
Slowly rotating topological neutron stars: universal relations and epicyclic frequencies
2020-09-01

Abstract In the modern era of abundant X-ray detections and the increasing momentum of gravitational waves astronomy, tests of general relativity in strong field regime become increasingly feasible and their importance for probing gravity cannot be understated. To this end, we study the characteristics of slowly rotating topological neutron stars in the tensor-multi-scalar theories of gravity following the static study of this new type of compact objects by two of the authors. We explore the moment of inertia and verify that universal relations known from general relativity hold for this new class of compact objects. Furthermore, we study the properties of their innermost stable circular orbits and the epicyclic frequencies due to the latter’s hinted link to observational quantities such as quasi-periodic X-ray spectrum features.
Depth relationships and measures of tissue thickness in dorsal midbrain
2020-09-01

Abstract Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest‐neighbor Euclidean distance from one reference surface, while the second used a level‐set approach that combines signed distances from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for delineating depth for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level‐set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth‐mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi.
CFD Prediction of Tip Vortex Aging in the Wake of a Multi-MW Wind Turbine
2020-09-01

Abstract In the present study, prediction from high-fidelity Computational Fluid Dynamics (CFD) simulations of the tip vortex aging in the near-wake of a multi-MW wind turbine is evaluated and compared to in-situ measurements as well as results of a semi-empirical model. Optimized tip vortex refinement is also introduced to investigate the influence of the grid topology on the vortex evolution. The grid refinement affects only the vortex core size and a reduction of the core radius by a factor of 3.4 was achieved with the chosen parameters. On the refined setup, vortex core sizes and strength are comparable with in-situ Unmanned Aircraft System (UAS) based measurements at 0.5 rotor radius downstream of the wind turbine. A comparison of the aging function with a semi-empirical vortex helix model shows a good agreement with the refined CFD results, but the core size predicted by the model is smaller than in simulations and experiments.
Between Boundary-Work and Cosmopolitan Aspirations
2020-09-01

This article presents a historical genealogy of EASA and European anthropology. Performing a heuristic exercise of ethnographic epoché , it critically examines European anthropologists’ writings on European anthropology and EASA as they appear in different statements and accounts, especially in the Association’s newsletters and reports of its conferences, understanding these documents as praxeologically embedded in anthropologists’ everyday production of knowledge. Drawing on the sociology of critique and the concept of boundarywork, it argues that EASA created its own ‘space of critique’, funnelling previous discussions on European anthropology, and becoming a platform for its production and its contestation as a site for the production of ‘hierarchies of knowledge’. Those contestations reflect an original and longstanding tension between EASA’s inclusive cosmopolitan aspiration and the exclusionary practice of boundary-work.
Preference for directive versus participative leadership: the role of regulatory mode and context quality definition
2020-09-01

Prior work showed that leadership preferences depend not only on followers’ characteristics, but also on contextual features. We investigated how regulatory mode (assessment – a concern with “getting things right” vs. locomotion – a concern with “getting things done” in goal pursuit) and the definition of quality criteria (i.e., whether or not there are predefined standards to evaluate task or work performance) jointly influence followers’ preferences for directive and participative leadership. We measured (Study 1, N = 503) and experimentally induced (Study 2, N = 497) followers’ regulatory mode before presenting them with task instructions that either clearly defined quality criteria or left them undefined. In both studies, participants were led to believe that they would work on a task with a supervising leader and indicated their preferred leader style for the task. Contrary to predictions, results do not suggest that the definition of quality criteria moderates the influence of followers’ regulatory mode on their leadership preferences. Independent of quality criteria conditions, both chronic assessment and locomotion predicted preferences for directive leadership; additionally, chronic locomotion strongly predicted preferences for participative leadership. However, induced regulatory mode did not influence leadership preferences. Further work is needed to better understand the role of context on self-regulatory dynamics and leadership style preferences.
Evaluating secondary school students’ interest and conceptual understanding of circuits
2020-09-01

Electric circuits are an important element of physics classes in Austria, Germany, and most countries around the world.However, many students leave secondary school without having an adequate conceptual understanding of simple circuits.Voltage in particular has proven to be a difficult concept as students think of it as a property or component of the electric current.Furthermore, research has shown that girls tend to have a lower interest in physics than boys and that context-based physics instruction is a promising approach to increase girls' interest.However, it is unclear whether decades of research on students' conceptual difficulties e.g. with voltage as well as research into ways to promote girls' interest have had a significant impact on physics classrooms.For this reason, the conceptual understanding of electric circuits as well as the interest in physics of N = 1207 traditionally taught students in Germany and Austria was assessed using a valid and reliable multiple-choice test.The empirical evaluation of the data shows that female students are still not as interested in physics as their male peers, despite achieving the same total learning gain in the multiple-choice test.An analysis of two items of the test instrument focusing on potential differences furthermore suggests that traditional instruction still fails to provide students with an adequate conceptual understanding of voltage as an independent physical quantity that refers to a difference in electric potential between two points in a circuit.These results highlight the need to develop research-based curricula on electric circuits that take into account the findings on students' interests and alternative conceptions.
Measuring students' interest in physics
2020-09-01

Interest is not only regarded a prerequisite for learning motivation but also an educational objective. There is however a major concern regarding the decline during students school career which has been observed frequently [1]. Therefore, in general education and particularly in physics education great importance is attached to fostering students interest and a lot of research has been conducted in this regard. To measure students interest, a number of well-established research scales are available for German-speaking countries, which are primarily based on two constructs of interest. One common construct by Hoffmann, Häußler and Lehrke differentiates between the interest that students show in physical contents and their interest in physics as a school subject [2, 3]. In addition, another construct by Krapp widely used in educational psychology distinguishes between the emotional- and value-related significance of an activity or its content [4]. So far, these two constructs have largely been used unrelated. For the study presented in this paper, they have been connected resulting in four different combinations of emotional and value-related significance attributed to physical contents and physics lessons. These constitute four possible scales which have been integrated in a questionnaire and evaluated in a sample of N = 1529 high school students. An exploratory as well as a confirmatory factor analysis has been performed to test the assumed theoretical structure of the underlying constructs. Our data suggests that a revision of the combined scales is necessary as two of the four coincide: all items including emotional valences load on one factor only, while items with value-related valences are distinguishable between interest in physical contents (factor two) and interest in physics lessons (factor three). In this paper we present our study supporting this newly developed measurement model and according research scales for high school students interest in physics.