julilili42/papers huggingface dataset:
A reward-learning framework of knowledge acquisition: An integrated account of curiosity, interest, and intrinsic-extrinsic rewards.
2019-06-02

Recent years have seen a considerable surge of research on interest-based engagement, examining how and why people are engaged in activities without relying on extrinsic rewards. However, the field of inquiry has been somewhat segregated into three different research traditions which have been developed relatively independently --- research on curiosity, interest, and trait curiosity/interest. We identify “long-term development” as a critical factor that links different research traditions, and set out an integrative perspective called the reward-learning framework of knowledge acquisition. This framework takes on the basic premise of existing reward-learning models of information seeking: that knowledge acquisition serves as an inherent reward, which reinforces people’s information-seeking behavior through a reward-learning process. Critically, however, the framework reveals how the knowledge-acquisition process is sustained and boosted over a long period of time in real-life settings (i.e., self-boosting effect), allowing us to integrate the different research traditions within reward-learning models. The framework also characterizes the knowledge-acquisition process with three distinct features that are not present in the reward-learning process with extrinsic rewards --- (1) selectivity, (2) vulnerability, and (3) under-appreciation. Finally, we discuss implications of the proposed framework regarding the debate over the conceptualization of broad concepts, namely; curiosity, interest, and intrinsic-extrinsic rewards.
Gluon fusion into Higgs pairs at NLO QCD and the top mass scheme
2019-06-03

We present the calculation of the full next-to-leading order (NLO) QCD corrections to Higgs boson pair production via gluon fusion at the LHC, including the exact top-mass dependence in the two-loop virtual and one-loop real corrections. This is the first independent cross-check of the NLO QCD corrections presented in the literature before. Our calculation relies on numerical integrations of Feynman integrals, stabilised with integration-by-parts and a Richardson extrapolation to the narrow width approximation. We present results for the total cross section as well as for the invariant Higgs-pair-mass distribution at the LHC, including for the first time a study of the uncertainty due to the scheme and scale choice for the top mass in the loops.
Interior-boundary conditions for many-body Dirac operators and codimension-1 boundaries
2019-06-03

We are dealing with boundary conditions for Dirac-type operators, i.e., first\\norder differential operators with matrix-valued coefficients, including in\\nparticular physical many-body Dirac operators. We characterize (what we\\nconjecture is) the general form of reflecting boundary conditions (which\\nincludes known boundary conditions such as the one of the MIT bag model) and,\\nas our main goal, of interior-boundary conditions (IBCs). IBCs are a new\\napproach to defining UV-regular Hamiltonians for quantum field theories without\\nsmearing particles out or discretizing space. For obtaining such Hamiltonians,\\nthe method of IBCs provides an alternative to renormalization and has been\\nsuccessfully used so far in non-relativistic models, where it could be applied\\nalso in cases in which no renormalization method was known. A natural next\\nquestion about IBCs is how to set them up for the Dirac equation, and here we\\ntake first steps towards the answer. For quantum field theories, the relevant\\nboundary consists of the surfaces in -particle configuration space\\n on which two particles have the same location in\\n . While this boundary has codimension 3, we focus here on the\\nmore basic situation in which the boundary has codimension 1 in configuration\\nspace. We describe specific examples of IBCs for the Dirac equation, we prove\\nfor some of these examples that they rigorously define self-adjoint\\nHamiltonians, and we develop the general form of IBCs for Dirac-type operators.\\n
Long noncoding RNA MAGI1-IT1 promoted invasion and metastasis of epithelial ovarian cancer via the miR-200a/ZEB axis
2019-06-03

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and its vulnerability to metastasis contributes to the poor outcomes of EOC patients. Long noncoding RNAs (lncRNAs) were verified to play a pivotal role in EOC metastasis. However, the potential role of lncRNA membrane-associated guanylate kinase inverted 1 (MAGI1) intronic transcript (MAGI1-IT1) in EOC is largely unknown. In this study, the function and mechanisms of MAGI1-IT1 in EOC metastasis were explored profoundly. First, MAGI1-IT1 expression was found to be significantly decreased in overexpressing miR-200a EOC cells. Second, MAGI1-IT1 expression was remarkably increased in metastatic EOC tissues, and high MAGI1-IT1 was dramatically associated with EOC FIGO III-IV stage; in addition, MAGI1-IT1 might be related to EOC dissemination via epithelial-mesenchymal transition (EMT). Next, a series of gain- and loss-of-function assays verified that, although MAGI1-IT1 has no significant role in EOC proliferation and subcutaneous xenograft growth, the upregulation of MAGI1-IT1 can remarkably facilitate EOC EMT phenotype, cells migration and invasion ability and intraperitoneal metastasis in nude mice, while downregulation of MAGI1-IT1 led to the opposite effect <i>in vitro</i>. Moreover, MAGI1-IT1 was validated to promote EOC metastasis through upregulation of ZEB1 and ZEB2 by competitively binding miR-200a, and the restrictive effects of MAGI1-IT1 depletion on EOC metastasis could be reversed by inhibition of miR-200a and upregulation of ZEB1 and ZEB2. Collectively, these results suggest that MAGI1-IT1 may work as a ceRNA in promoting EOC metastasis through miR-200a and ZEB1/2 and may be a potential therapeutic target for EOC.
Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma
2019-06-04

First-line treatment with dabrafenib plus trametinib led to long-term benefit in approximately one third of the patients who had unresectable or metastatic melanoma with a <i>BRAF</i> V600E or V600K mutation. (Funded by GlaxoSmithKline and Novartis; COMBI-d ClinicalTrials.gov number, NCT01584648; COMBI-v ClinicalTrials.gov number, NCT01597908.).
MprF-mediated daptomycin resistance
2019-06-04

Daptomycin has become an important antibiotic for the treatment of serious Methicillin-Resistant Staphylococcus aureus (MRSA) infections. Unlike other approved antibiotics, its mode of action is still under active investigation, as well as the molecular basis of daptomycin resistance, which emerges in some cases during daptomycin treatment. Small nucleotide polymorphisms (SNPs) in the Multiple Peptide Resistance Factor (MprF) appear to play a major role in the resistance mechanism. Until recently, the impact of the SNPs on MprF activity has remained unclear, which is due to conflicting reports on resistance-associated phenotypes and an incomplete understanding of the mode of action of MprF. However, recent structural insights into MprF and studies with isogenic mutants have now led to a new model of MprF-mediated daptomycin resistance, which harmonizes most of the observed phenotypes and provides a basis for challenging biochemical investigations.
Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple‐negative early breast cancer: Primary translational analysis of the WSG‐ADAPT‐TN trial
2019-06-04

In the neoadjuvant WSG‐ADAPT‐TN trial, 12‐week nab‐paclitaxel + carboplatin (nab‐pac/carbo) was highly effective and superior to nab‐paclitaxel + gemcitabine (nab‐pac/gem) in triple‐negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 × nab‐pac 125 mg/m 2 (plus carbo AUC2 or gem 1,000 mg/m 2 d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow‐up. Basal‐like (83.3%) compared to other subtypes was positively associated with pCR (38% vs . 20%, p = 0.015), as was lower HER2 score ( p &lt; 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p &lt; 0.004), higher Ki‐67 (IHC; p &lt; 0.001). For nab‐pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR ( p &lt; 0.05 for all). For nab‐pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05; FGFR4: p = 0.02; VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event‐free survival: 92% vs . 71%, p &lt; 0.001). In early TNBC, basal‐like subtype, higher Ki‐67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches.
Ultrafast Imaging of Cardiomyocyte Contractions by Combining Scanning Ion Conductance Microscopy with a Microelectrode Array
2019-06-04

Beating cardiomyocytes undergo fast morphodynamics during the contraction-relaxation cycle. However, imaging these morphodynamics with a high spatial and temporal resolution is difficult, owing to a lack of suitable techniques. Here, we combine scanning ion conductance microscopy (SICM) with a microelectrode array (MEA) to image the three-dimensional (3D) topography of cardiomyocytes during a contraction-relaxation cycle with 1 μm spatial and 1 ms time resolution. We record the vertical motion of cardiomyocytes at many locations across a cell by SICM and synchronize these data using the simultaneously recorded action potential by the MEA as a time reference. This allows us to reconstruct the time-resolved 3D morphology of cardiomyocytes during a full contraction-relaxation cycle with a raw data rate of 200 μs/frame and to generate spatially resolved images of contractile parameters (maximum displacement, time delay, asymmetry factor). We use the MEA-SICM setup to visualize the effect of blebbistatin, a myosin II inhibitor, on the morphodynamics of contractions. Further, we find an upper limit of 0.02% for cell volume changes during an action potential. The results show that MEA-SICM provides an ultrafast imaging platform for investigating the functional interplay of cardiomyocyte electrophysiology and mechanics.
Cooperative Use of Brønsted Acids and Metal Catalysts in Tandem Isomerization Reactions of Olefins
2019-06-04

Abstract Dual catalysis constitutes a growing field of the organic synthesis. It is a useful methodology, which allows for a discovery of new and more efficient transformations. This concept article describes tandem reactions, which comprise of an isomerization of the double bond and following transformation, whereby a combination of a homogeneous metal catalyst and Brønsted acid is used. The aim is to highlight the versatility of this catalyst combination.
Empirical random phase transitions between free flow and synchronized flow at highway bottlenecks
2019-06-04

Based on a study of probe vehicle data measured on different highways during different days we have revealed some common empirical microscopic characteristic features of sequences of phase transitions from free flow to synchronized flow and back from synchronized flow to free flow occurring before traffic breakdown at a highway bottleneck predicted theoretically by Kerner. Following common empirical features of sequences of these phase transitions have been found: (i) Sequences of empirical phase transitions from free flow to synchronized flow and back from synchronized flow to free flow are observed on different highways at different bottlenecks. (ii) Empirical sequences of the phase transitions exhibit a random character, in particular, at different days very different sequences of phase transitions from free flow to synchronized flow and back from synchronized flow to free flow have been observed at the same bottleneck. (iii) Time durations between the transition from free flow to synchronized flow and the subsequent transition from synchronized flow to free flow within a sequence of the phase transitions are random values. Time intervals between subsequent sequences of the phase transitions are also random values. (iv) Regions of dissolving synchronized flow that result from sequences of phase transitions from free flow to synchronized flow and back from synchronized flow to free flow exhibit random characteristics. (v) Several following each other sequences of phase transitions from free flow to synchronized flow and back from synchronized flow to free flow can lead to waves of synchronized flow between free flow.
Astin C Production by the Endophytic Fungus Cyanodermella asteris in Planktonic and Immobilized Culture Conditions
2019-06-04

The fungal endophyte Cyanodermella asteris ( C. asteris ) has been recently isolated from the medicinal plant Aster tataricus ( A. tataricus ). This fungus produces astin C, a cyclic pentapeptide with anticancer and anti‐inflammatory properties. The production of this secondary metabolite is compared in immobilized and planktonic conditions. For immobilized cultures, a stainless steel packing immersed in the culture broth is used as a support. In these conditions, the fungus exclusively grows on the packing, which provides a considerable advantage for astin C recovery and purification. C. asteris metabolism is different according to the culture conditions in terms of substrate consumption rate, cell growth, and astin C production. Immobilized‐cell cultures yield a 30% increase of astin C production, associated with a 39% increase in biomass. The inoculum type as spores rather than hyphae, and a pre‐inoculation washing procedure with sodium hydroxide, turns out to be beneficial both for astin C production and fungus development onto the support. Finally, the influence of culture parameters such as pH and medium composition on astin C production is evaluated. With optimized culture conditions, astin C yield is further improved reaching a five times higher final specific yield compared to the value reported with astin C extraction from A. tataricus (0.89 mg g −1 and 0.16 mg g −1 respectively).
The Game Theory of Politeness in Language: A Formal Model of Polite Requests
2019-06-04

Linguistic Politeness (LP) is a fascinating domain of language, as it directly interfaces with human social behavior. Here, we show how game theory, as a higher-order theory of behavior, can provide the tools to understand and model LP phenomena. We show this for the specific case of requests, where the magnitude of request and the resultant Rate of Imposition are subsumed under a more powerful explanatory principle: alignment of interests. We put forward the Politeness Equilibrium Principle (PEP), whereby the more disalignment there is between the interests of Speaker and Hearer, the more LP Speaker needs to offset the imbalance. In the second part of our paper, we flesh out our ideas by means of a formal model inspired by evolutionary signaling theory, and provide a mathematical proof showing that the model follows the PEP. We see this work as an important first step in the direction of reconciling theories of language with signaling theory, by incorporating language into more general models of communication.
Quantitative Rodent Brain Receptor Imaging
2019-06-05

Positron emission tomography (PET) is a non-invasive imaging technology employed to describe metabolic, physiological, and biochemical processes in vivo. These include receptor availability, metabolic changes, neurotransmitter release, and alterations of gene expression in the brain. Since the introduction of dedicated small-animal PET systems along with the development of many novel PET imaging probes, the number of PET studies using rats and mice in basic biomedical research tremendously increased over the last decade. This article reviews challenges and advances of quantitative rodent brain imaging to make the readers aware of its physical limitations, as well as to inspire them for its potential applications in preclinical research. In the first section, we briefly discuss the limitations of small-animal PET systems in terms of spatial resolution and sensitivity and point to possible improvements in detector development. In addition, different acquisition and post-processing methods used in rodent PET studies are summarized. We further discuss factors influencing the test-retest variability in small-animal PET studies, e.g., different receptor quantification methodologies which have been mainly translated from human to rodent receptor studies to determine the binding potential and changes of receptor availability and radioligand affinity. We further review different kinetic modeling approaches to obtain quantitative binding data in rodents and PET studies focusing on the quantification of endogenous neurotransmitter release using pharmacological interventions. While several studies have focused on the dopamine system due to the availability of several PET tracers which are sensitive to dopamine release, other neurotransmitter systems have become more and more into focus and are described in this review, as well. We further provide an overview of latest genome engineering technologies, including the CRISPR/Cas9 and DREADD systems that may advance our understanding of brain disorders and function and how imaging has been successfully applied to animal models of human brain disorders. Finally, we review the strengths and opportunities of simultaneous PET/magnetic resonance imaging systems to study drug-receptor interactions and challenges for the translation of PET results from bench to bedside.
Volume Path Guiding Based on Zero-Variance Random Walk Theory
2019-06-05

The efficiency of Monte Carlo methods, commonly used to render participating media, is directly linked to the manner in which random sampling decisions are made during path construction. Notably, path construction is influenced by scattering direction and distance sampling, Russian roulette, and splitting strategies. We present a consistent suite of volumetric path construction techniques where all these sampling decisions are guided by a cached estimate of the adjoint transport solution . The proposed strategy is based on the theory of zero-variance path sampling schemes, accounting for the spatial and directional variation in volumetric transport. Our key technical contribution, enabling the use of this approach in the context of volume light transport, is a novel guiding strategy for sampling the particle collision distance proportionally to the product of transmittance and the adjoint transport solution (e.g., in-scattered radiance). Furthermore, scattering directions are likewise sampled according to the product of the phase function and the incident radiance estimate. Combined with guided Russian roulette and splitting strategies tailored to volumes, we demonstrate about an order-of-magnitude error reduction compared to standard unidirectional methods. Consequently, our approach can render scenes otherwise intractable for such methods, while still retaining their simplicity (compared to, e.g., bidirectional methods).
Alpha‐synuclein at the nexus of genes and environment: the impact of environmental enrichment and stress on brain health and disease
2019-06-05

Abstract Accumulation of alpha‐synuclein protein aggregates is the hallmark neuropathologic feature of synucleinopathies such as Parkinson’s disease. Rare point mutations and multiplications in SNCA , the gene encoding alpha‐synuclein, as well as other genetic alterations are linked to familial Parkinson’s disease cases with high penetrance and hence constitute major genetic risk factors for Parkinson’s disease. However, the preponderance of cases seems sporadic, most likely based on a complex interplay between genetic predispositions, aging processes and environmental influences. Deciphering the impact of these environmental factors and their interactions with the individual genetic background in humans is challenging and often requires large cohorts, complicated study designs, and longitudinal set‐ups. In contrast, rodent models offer an ideal system to study the influence of individual environmental aspects under controlled genetic background and standardized conditions. In this review, we highlight findings from studies examining effects of environmental enrichment mimicking stimulation of the brain by its physical and social surroundings as well as of environmental stressors on brain health in the context of Parkinson’s disease. We discuss possible internal molecular transducers of such environmental cues in Parkinson’s disease rodent models and emphasize their potential in developing novel avenues to much‐needed therapies for this still incurable disease. image This article is part of the Special Issue “Synuclein”
Fragility Fractures of the Pelvis Classification
2019-06-05

Background: The fragility fractures of the pelvis (FFP) classification was established to address the specific fracture morphology and dynamic instability in the elderly. Although this system is frequently used, data on the intra-rater and inter-rater reliabilities are lacking. Methods: Six experienced and 6 inexperienced surgeons and 1 surgeon trained by the originator of the FFP classification (“gold standard”) each used the FFP classification 3 times to grade the computed tomography (CT) scans of 60 patients from 6 hospitals. We assessed intra-rater and inter-rater reliabilities using Fleiss kappa statistics and the percentage of agreement using the “gold standard,” the submitting hospital, and the majority vote as references. Results: The intra-rater reliability for the FFP classification was mainly moderate, with a mean Fleiss kappa coefficient (and 95% confidence interval) of 0.46 (0.40 to 0.50) for the complete classification (i.e., both the main-group FFP ratings [I through III] and the subgroup ratings [a, b, and c]) and 0.60 (0.53 to 0.65) for the main group only. The inter-rater reliability was substantial for the main group classification (0.61 [0.54 to 0.66]) and moderate for the complete classification (0.53 [0.48 to 0.58]). The percentage of agreement was 68% to 80%. The lowest agreement was found for FFP II and III. Conclusions: The FFP classification displayed moderate and substantial intra-rater and inter-rater reliabilities. Clinical Relevance: With moderate to substantial intra-rater and inter-rater reliabilities, the FFP classification forms a solid basis for future clinical investigations. The differentiation of FFP II from FFP III should be evaluated thoroughly, as the initial treatment changes from nonoperative for II to operative for III.
Synthesis, Structure, and Electronic Properties of Sn(CN2) and Sn4Cl2(CN2)3
2019-06-05

A solid-state metathesis reaction between equimolar amounts of Li<sub>2</sub>(CN<sub>2</sub>) and SnCl<sub>2</sub> revealed the formation of two new compounds, Sn<sub>4</sub>Cl<sub>2</sub>(CN<sub>2</sub>)<sub>3</sub> and Sn(CN<sub>2</sub>). Thermal analysis of this reaction indicated that Sn<sub>4</sub>Cl<sub>2</sub>(CN<sub>2</sub>)<sub>3</sub> forms exothermically near 200 °C and subsequently transforms into Sn(CN<sub>2</sub>) at higher temperatures. The crystal structures of both compounds are presented. According to optical measurements and band structure calculations, Sn(CN<sub>2</sub>) can be considered as a semiconductor with a band gap on the order of 2 eV. The presence of Sn<sup>2+</sup> ions in the structure of Sn(CN<sub>2</sub>) with a toroidally shaped lone pair is indicated by electron localization function calculations. The structure of Sn(CN<sub>2</sub>) is shown to be related to the structures of FeS<sub>2</sub> and CaC<sub>2</sub>.