julilili42/papers huggingface dataset:
The Role of Rewards in Motivation--Beyond dichotomies
2023-11-28

A vast amount of research has examined how extrinsic rewards influence motivation in learning. Whereas some studies have indicated that rewards are beneficial for increasing students’ motivation, others have argued that rewards undermine motivation, especially so-called intrinsic motivation. In this review, building on the reward-learning framework of knowledge acquisition, we argue that the two perspectives do not actually contradict each other and that researchers should look beyond the simple dichotomy of whether rewards are good or bad for motivation. The reward-learning framework of knowledge acquisition conceptualizes rewards as either extrinsic incentives (i.e., extrinsic rewards) or internal positive feelings that arise from the learning process or from knowledge acquisition itself (i.e., intrinsic rewards). Importantly, the framework suggests the possibility of motivation transformations in that extrinsic rewards can serve as an “entry point” for engagement, thus helping students start up the positive feedback loop of internally rewarding learning processes. However, once such a positive feedback loop has been established, extrinsic incentives could interrupt the process, potentially undermining long-term engagement. We enrich our discussion with references to gamification and educational videogames and end with a call for personalized reward provision systems that consider the roles that different types of rewards play in different tasks and for different students in different moments of the knowledge acquisition process.
Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase dependent mechanism
2023-11-28

Abstract The Parkinson’s Disease (PD)-linked protein Leucine Rich Repeat Kinase 2 (LRRK2) consists of seven domains, including a kinase and a Roc G domain. Despite the availability of several high-resolution structures, the dynamic regulation of its unique intramolecular domain stack is nevertheless still not well understood. By in-depth biochemical analysis, assessing the Michaelis-Menten kinetics of the Roc G domain, we have confirmed that LRRK2 has similar to other Roco protein family members a KM value of LRRK2 that lays within the range of the physiological GTP concentrations within the cell. Furthermore, the R1441G PD variant located within a mutational hotspot in the Roc domain showed an increased catalytic efficiency. The most common PD variant G2019S, located in the kinase domain showed an increased KM and reduced catalytic efficiency, suggesting a negative feedback mechanism from the kinase domain to the G-domain. Auto-phosphorylation of the G1+2 residue (T1343) in the Roc P-loop motif is critical for this phosphoregulation of both the KM as well as the kcat values of the Roc-catalyzed GTP hydrolysis, most likely by changing the monomer-dimer equilibrium. Together our data reveal a novel intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase dependent mechanism. Interestingly, PD mutants differently change the kinetics of the GTPase cycle, which might in part explain the difference in penetrance of these mutations in PD patients.
Reactivation strength during cued recall is modulated by graph distance within cognitive maps
2023-11-28

Declarative memory retrieval is thought to involve reinstatement of the neuronal activity patterns elicited and encoded during a prior learning episode. Recently, it has been suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained over a brief 8-minute consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic (MEG) recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not with retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and limited to low performers. The results provide further evidence for the existence of different performance-dependent retrieval mechanisms suggesting graded clustered reactivation as a plausible mechanism to search within abstract cognitive maps.
Dietary reconstructions of Magdalenian canids from SW-Germany do not indicate that the area was a centre of early European wolf domestication
2023-11-28

In their paper ‘A refined proposal for the origin of dogs: the case study of Gnirshöhle, a Magdalenian cave site’ , Baumann and colleagues [1] claim that their data ‘support the hypothesis that the Hegau Jura was a potential center of early European wolf domestication’ , and that ‘such a scenario becomes plausible considering a close proximity of canids and humans thereby introducing a controlled, or at least a restrictive diet’ . The study focusses on fossil remains of ‘large canids’ from the Gnirshöhle cave site in SW Germany. Morphometric data on only one specimen, GN-999, as well as collagen δ 15 N and δ 13 C isotopic data and mitochondrial DNA analyses on the Gnirshöhle specimens and a comparative sample were used to conclude that the Gnirshöhle specimens shed light on the ‘origin of dogs’ as purported by the title of the paper. Here we argue that the paper is fundamentally flawed and excluded available relevant data.
The halfway similarity avoidance rule replicated using phonetic data from European language varieties
2023-11-28

Abstract Previous work using lexical data from around the world has suggested that distances between language varieties are distributed such that varieties are typically either rather similar, qualifying as dialects of the same language, or rather dissimilar, qualifying as different languages, with a scarcity of varieties that are around halfway similar. Using a potentially biased sample, Wichmann (2019) observed that there is a bimodal distribution of distances with two roughly normal distributions separated by a valley. Here we test whether a similar distribution is found when using another source of data and an unbiased sample drawn from the cells of a geographical grid (of central Europe). The data consists of 18 lexemes from 274 doculects. Using Bayesian beta regression and leave-one-out cross-validation, we show that the data follows a bimodal distribution which is robust to sampling, and also to at least some aspects of the data (coarse- vs. fine-grained phonetic transcriptions).
ChemProp2 Dataset: Investigating potential biotransformations with a panel of 23 Drugs on Synthetic Community (Com20) to elucidate Drug-Microbiome-Host Dynamics
2023-11-28

&lt;p&gt;Tested 23 drugs against Synthetic community (Com20) at two different timepoints (t=0, t= 2 hrs) to look for potential biotransformations&lt;br&gt;&lt;br&gt;List of drugs tested:&lt;br&gt;Acarbose, Clemizole, Amlodipine, Clindamycin, Amoxicillin, Clomifen, Aprepitant, Clotrimazole, Avermectin B1, Diacerein, Azithromycin, Dicumarol, Control, Dienestrol, Benzbromarone, Dienogest, Ceterizin, Doxycycline hyclate, Chlorpromazine, Duloxetin, Chlorprothixene, Erythromycin, Cilnidipine, Ethinylestradiol&lt;br&gt;&lt;br&gt;Samples were measured (in March 18/19, 2023) using an UHPLC-Q Exactive HF Orbitrap mass spectrometer, equipped with a C18 column, following the LC-MS/MS method.&lt;/p&gt;
ChemProp2 Dataset: Investigating potential biotransformations with a panel of 45 Drugs on Synthetic Community (Com20) to elucidate Drug-Microbiome-Host Dynamics
2023-11-28

This dataset contains the examination of each of the 45 drugs on the synthetic community Com20, conducted at two distinct timepoints: initially (time 0) and after a 2-hour interval.List of drugs: Ethopropazine, Methotrexate, Felodipine, Miconazole, Floxuridine, Nalidixic acid, Fluconazole, Niclosamide, Ketoconazole, Omeprazole, Lacidipine, Pentamidine isothionate, DMSO, Promethazine, Lansoprazole, Protriptyline, Loratadine, Sertindole, Loxapine, Simvastatin, L-Thyroxine, Streptozotocin, Metformin, Tamoxifen, Tazobactam, Doxorubicin, Telmisartan, Ofloxacin, Terfenadine, Oxolinic acid, Thioguanosine, Tobramycin, Tiratricol, Vancomycin, Water, Rivaroxoban, Metronidazole, Tolfenamic acid, Clarithromycin, Tribenoside, Norfloxacin, Zafirlukast, Montelukast, Sertraline, Fluoxetine, Clomipramin, Novobiocin
Structure of Staphylococcus aureus ClpP Bound to the Covalent Active‐Site Inhibitor Cystargolide A
2023-11-29

Abstract The caseinolytic protease is a highly conserved serine protease, crucial to prokaryotic and eukaryotic protein homeostasis, and a promising antibacterial and anticancer drug target. Herein, we describe the potent cystargolides as the first natural β‐lactone inhibitors of the proteolytic core ClpP. Based on the discovery of two clpP genes next to the cystargolide biosynthetic gene cluster in Kitasatospora cystarginea , we explored ClpP as a potential cystargolide target. We show the inhibition of Staphylococcus aureus ClpP by cystargolide A and B by different biochemical methods in vitro. Synthesis of semisynthetic derivatives and probes with improved cell penetration allowed us to confirm ClpP as a specific target in S. aureus cells and to demonstrate the anti‐virulence activity of this natural product class. Crystal structures show cystargolide A covalently bound to all 14 active sites of ClpP from S. aureus , Aquifex aeolicus , and Photorhabdus laumondii , and reveal the molecular mechanism of ClpP inhibition by β‐lactones, the predominant class of ClpP inhibitors.
Immunocompetent PDMS‐Free Organ‐on‐Chip Model of Cervical Cancer Integrating Patient‐Specific Cervical Fibroblasts and Neutrophils
2023-11-29

Abstract Despite preventive measures and available treatments, cervical cancer still ranks as the fourth most prevalent cancer among women worldwide and remains the leading cause of cancer death in women in many developing countries. To gain further insights into pathogenesis and to develop novel (immuno)therapies, more sophisticated human models recreating patient heterogeneities and including aspects of the tumor microenvironment are urgently required. A novel polydimethylsiloxane‐free microfluidic platform, designed specifically for the generation and ccultivation of cervical cancerous tissue, is introduced. The microscale open‐top tissue chambers of the cervical cancer‐on‐chip (CCoC) enable facile generation and long‐term cultivation of SiHa spheroids in co‐culture with donor‐derived cervical fibroblasts. The resulting 3D tissue emulates physiological architecture and allows dissection of distinct effects of the stromal tissue on cancer viability and growth. Treatment with cisplatin at clinically‐relevant routes of administration and dosing highlights the platform's applicability for drug testing. Moreover, the model is amenable for integration and recruitment of donor‐derived neutrophils from the microvasculature‐like channel into the tissue, all while retaining their ability to produce neutrophil extracellular traps. In the future, the immunocompetent CCoC featuring donor‐specific primary cells and tumor spheroids has the potential to contribute to the development of new (immuno)therapeutic options.
Investigating the effect of hippocampal sclerosis on parietal memory network
2023-11-29

Abstract Objective We aimed to investigate differences in episodic memory networks between patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis and healthy controls, especially with regards to the parietal memory network (PMN), as well as their relation to neuropsychological memory performance after mesial temporal resection. Methods 28 healthy subjects as well as 21 patients with TLE (12 left, 9 right) were investigated using a spatial memory fMRI paradigm, which has been shown to activate the PMN. Regions of interest (ROI) were defined based on the results of the second‐level analyses and activations within the predefined ROIs were compared across groups and correlated with postoperative verbal and nonverbal memory scores. Results Healthy subjects showed activations within regions belonging to the dorsal visual stream and the PMN as well as the bilateral parahippocampal place area, the bilateral frontal eye field, and the bilateral middle frontal gyrus. Comparison between groups revealed that TLE patients activated significantly less in the left middle occipital gyrus and the right precuneus. The activation pattern in left TLE patients showed further reductions, mainly in areas belonging to the dorsal visual stream and the PMN within the left hemisphere. Activations within the left superior parietal lobulus, bilateral inferior parietal lobulus, bilateral middle temporal gyrus, left precuneus, left frontal eye field, and left middle frontal gyrus correlated significantly with postoperative verbal memory scores, and activations within the left superior parietal lobulus, left inferior parietal lobulus, left middle temporal gyrus, and left precuneus correlated significantly with higher performance in postoperative nonverbal memory scores. Significance The PMN is involved in episodic memory encoding. Higher activations in areas belonging to the PMN and the dorsal visual stream, especially within the left hemisphere, before amygdalohippocampectomy may result in higher postoperative memory scores. Plain language summary This study aims to investigate the effects of epilepsy due to hippocampal sclerosis, i.e. scarring in the temporal lobe, on memory networks in the brain. We discovered that especially patients with left‐sided hippocampal sclerosis show reduced brain activations in visual areas and memory networks within the left hemisphere of the brain during orientation in space. Importantly, higher activations within these areas may result in better memory after epilepsy surgery.
1,3-Diphenylureido hydroxamate as a promising scaffold for generation of potent antimalarial histone deacetylase inhibitors
2023-11-29

Abstract We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a–d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro , mechanistic studies demonstrated target activity for Pf HDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c , 7c , and 8c , identified as the most active in phenotypic assays and Pf HDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of Pf HDAC1, with an IC 50 value of 0.74 μM in the phenotypic screening on Pf 3D7 and 0.8 μM against multidrug-resistant Pf Dd2 parasites. Despite its potent inhibition of Pf HDAC1, 8c remains the least active on human HDAC1, displaying remarkable selectivity. In silico studies suggest that the phenyl linker has an ideal length in the series for permitting effective interactions of the hydroxamate with Pf HDAC1 and that this compound series could bind as well as in Hs HDAC1. Taken together, these results highlight the potential of diphenylurea hydroxamates as a privileged scaffold for the generation of potent antimalarial HDAC inhibitors with improved selectivity over human HDACs.
A Step Towards Absolute Versions of Metamathematical Results
2023-11-29

Abstract There is a well-known gap between metamathematical theorems and their philosophical interpretations. Take Tarski’s Theorem. According to its prevalent interpretation, the collection of all arithmetical truths is not arithmetically definable. However, the underlying metamathematical theorem merely establishes the arithmetical undefinability of a set of specific Gödel codes of certain artefactual entities, such as infix strings, which are true in the standard model. That is, as opposed to its philosophical reading, the metamathematical theorem is formulated (and proved) relative to a specific choice of the Gödel numbering and the notation system. A similar observation applies to Gödel’s and Church’s theorems, which are commonly taken to impose severe limitations on what can be proved and computed using the resources of certain formalisms. The philosophical force of these limitative results heavily relies on the belief that these theorems do not depend on contingencies regarding the underlying formalisation choices. The main aim of this paper is to provide metamathematical facts which support this belief. While employing a fixed notation system, I showed in previous work ( Review of Symbolic Logic , 2021, 14(1):51–84) how to abstract away from the choice of the Gödel numbering. In the present paper, I extend this work by establishing versions of Tarski’s, Gödel’s and Church’s theorems which are invariant regarding both the notation system and the numbering. This paper thus provides a further step towards absolute versions of metamathematical results which do not rely on contingent formalisation choices.
Patient-Related Factors Associated with Adverse Outcomes Following Weaning from Veno-Arterial Extracorporeal Membrane Oxygenation
2023-11-29

Background: Veno-arterial extracorporeal membrane oxygenation (vaECMO) removal reflects a critical moment and factors of adverse outcomes are incompletely understood. Thus, we studied various patient-related factors during vaECMO removal to determine their association with outcomes. Methods: A total of 58 patients from a university hospital were included retrospectively. Demographic, clinical, and echocardiographic parameters were recorded while under vaECMO support, as well as the need for inotropic and vasoactive-inotropic scores (VIS). Successful weaning was defined as 28-day survival without reinitiation of vaECMO. Results: Patient age differed significantly between patients with a successful and a failed vaECMO weaning (54 ± 14 vs. 62 ± 12 years, p = 0.029). In univariable logistic regression, age (OR 0.952 (0.909–0.997), p = 0.038), the necessities for inotropic agents at the time of echocardiography (OR 0.333 (0.113–0.981), p = 0.046), and vaECMO removal (OR 0.266 (0.081–0.877), p = 0.030) as well as the dobutamine dose during removal (OR 0.649 (0.473–0.890), p = 0.007), were significantly associated with a successful weaning from vaECMO. Age (HR 1.048 (1.006–1.091), p = 0.024) and the VIS (HR 1.030 (1.004–1.056), p = 0.025) at the time of vaECMO removal were independently associated with survival in bivariable Cox regression. In Kaplan–Meier analysis, a VIS of &gt;5.1 at vaECMO removal was associated with impaired survival (log-rank p = 0.025). Conclusions: In this cohort, age and the extent of vasoactive-inotropic agents were associated with adverse outcomes following vaECMO, whereas echocardiographic biventricular function during vaECMO support was not.
Brazil’s pragmatic equidistance: hedging and the Second World War
2023-11-29

Can hedging be applied to non-Asia-Pacific regions and historical contexts? And, to what extent did Brazil operationalize hedging behavior during the Second World War? Taking these questions, the purpose of this paper is to expand the discourse on hedging twofold: First, to employ it within a South American context; second, to verify hedging historically as a widespread strategic unit-level behavior of small and middle powers amid systemic-level great power competitions. Here, by unboxing Brazil’s hedging behavior during the Second World War, specifically President Getúlio Vargas’s ‘ equidistância pragmática’ (pragmatic equidistance) coping strategy, it is found that Brazil employed hedging behavior with omnidirectional engagement with both the United States and Nazi Germany, yet later abandoned this strategy to fully align with Washington and the Allies in 1942, once Brazilian security and economic interests were aligned.
Report on 2310.17302v1
2023-11-29

The recently proposed center-focused post-processing procedure [Phys.Rev. Research 2, 033476 (2020)] of cellular dynamical mean-field theory suggests that central sites of large impurity clusters are closer to the exact solution of the Hubbard model than the edge sites.In this paper, we systematically investigate results in the spirit of this centerfocused scheme for several cluster sizes up to 8 × 8 in and out of particle-hole symmetry.First we analyze the metal-insulator crossovers and transitions of the half-filled Hubbard model on a simple square lattice.We find that the critical interaction of the crossover is reduced with increasing cluster sizes and the critical temperature abruptly drops for the 4 × 4 cluster.Second, for this cluster size, we apply the center-focused scheme to a system with more realistic tight-binding parameters, investigating its pseudogap regime as a function of temperature and doping, where we find doping dependent metal-insulator crossovers, Lifshitz transitions and a strongly renormalized Fermi-liquid regime.Additionally to diagnosing the real space origin of the suppressed antinodal spectral weight in the pseudogap regime, we can infer hints towards underlying charge ordering tendencies.
The fungal pathogen Ustilago maydis targets the maize corepressor RELK2 to modulate host transcription for tumorigenesis
2023-11-30

Summary Ustilago maydis is a biotrophic fungus that causes tumor formation on all aerial parts of maize. U. maydis secretes effector proteins during penetration and colonization to successfully overcome the plant immune response and reprogram host physiology to promote infection. In this study, we functionally characterized the U. maydis effector protein Topless (TPL) interacting protein 6 (Tip6). We found that Tip6 interacts with the N‐terminus of RELK2 through its two Ethylene‐responsive element binding factor‐associated amphiphilic repression (EAR) motifs. We show that the EAR motifs are essential for the virulence function of Tip6 and critical for altering the nuclear distribution pattern of RELK2. We propose that Tip6 mimics the recruitment of RELK2 by plant repressor proteins, thus disrupting host transcriptional regulation. We show that a large group of AP2/ERF B1 subfamily transcription factors are misregulated in the presence of Tip6. Our study suggests a regulatory mechanism where the U. maydis effector Tip6 utilizes repressive domains to recruit the corepressor RELK2 to disrupt the transcriptional networks of the host plant.
Non-Gaussian Dynamics of Quantum Fluctuations and Mean-Field Limit in Open Quantum Central Spin Systems
2023-11-30

Central spin systems, in which a central spin is singled out and interacts nonlocally with several bath spins, are paradigmatic models for nitrogen-vacancy centers and quantum dots. They show complex emergent dynamics and stationary phenomena which, despite the collective nature of their interaction, are still largely not understood. Here, we derive exact results on the emergent behavior of open quantum central spin systems. The latter crucially depends on the scaling of the interaction strength with the bath size. For scalings with the inverse square root of the bath size (typical of one-to-many interactions), the system behaves, in the thermodynamic limit, as an open quantum Jaynes-Cummings model, whose bosonic mode encodes the quantum fluctuations of the bath spins. In this case, non-Gaussian correlations are dynamically generated and persist at stationarity. For scalings with the inverse bath size, the emergent dynamics is instead of mean-field type. Our Letter provides a fundamental understanding of the different dynamical regimes of central spin systems and a simple theory for efficiently exploring their nonequilibrium behavior. Our findings may become relevant for developing fully quantum descriptions of many-body solid-state devices and their applications.