julilili42/papers huggingface dataset:
Ginkgolic Acid is a Multi-Target Inhibitor of Key Enzymes in Pro-Inflammatory Lipid Mediator Biosynthesis
2019-07-17

<b>Introduction:</b> Lipid mediators (LMs) comprise bioactive metabolites of polyunsaturated fatty acids, including pro-inflammatory prostaglandins (PGs), thromboxanes (TXs), and leukotrienes (LTs), as well as specialized pro-resolving mediators (SPMs). They are essentially biosynthesized <i>via</i> cyclooxygenase (COX) and lipoxygenase (LO) pathways in complex networks and regulate the progression as well as the resolution of inflammatory disorders including inflammation-triggered cancer. Ginkgolic acid (GA) is a phenolic acid contained in <i>Ginkgo biloba</i> L. with neuroprotective, antimicrobial, and antitumoral properties. Although LMs regulate microbial infections and tumor progression, whether GA affects LM biosynthesis is unknown and was investigated here in detail. <b>Methods:</b> Pharmacophore-based virtual screening was performed along with docking simulations. Activity assays were conducted for isolated human recombinant 5-LO, cytosolic phospholipase (PLA)<sub>2</sub>α, COX-2, and ovine COX-1. The activity of human mPGES-1 and thromboxane A<sub>2</sub> synthase (TXAS) was determined in crude cellular fractions. Cellular LM formation was studied using human monocytes, neutrophils, platelets, and M1- and M2-like macrophages. LMs were identified after (ultra)high-performance liquid chromatography by UV detection or ESI-tandem mass spectrometry. <b>Results:</b> GA was identified as virtual hit in an mPGES-1 pharmacophore-based virtual screening. Cell-free assays revealed potent suppression of mPGES-1 activity (IC<sub>50</sub> = 0.7 μM) that is fully reversible and essentially independent of the substrate concentration. Moreover, cell-free assays revealed COX-1 and TXAS as additional targets of GA with lower affinity (IC<sub>50</sub> = 8.1 and 5.2 μM). Notably, 5-LO, the key enzyme in LT biosynthesis, was potently inhibited by GA (IC<sub>50</sub> = 0.2 μM) in a reversible and substrate-independent manner. Docking simulations support the molecular interaction of GA with mPGES-1 and 5-LO and suggest concrete binding sites. Interestingly, interference of GA with mPGES-1, COX-1, TXAS, and 5-LO was evident also in intact cells with IC<sub>50</sub> values of 2.1-3.8 μM; no radical scavenging or cytotoxic properties were obvious. Analysis of LM profiles from bacteria-stimulated human M1- and M2-like macrophages confirmed the multi-target features of GA and revealed LM redirection towards the formation of 12-/15-LO products including SPM. <b>Conclusions:</b> We reveal GA as potent multi-target inhibitor of key enzymes in the biosynthesis of pro-inflammatory LMs that contribute to the complex pharmacological and toxicological properties of GA.
Mobile Monitoring—Open-Source Based Optical Sensor System for Service-Oriented Turbidity and Dissolved Organic Matter Monitoring
2019-07-17

The protection and sustainable use of aquatic resources require a better understanding of fresh water sources, limnic ecosystems, and oceans. The effects of global change, intensive use of natural resources and the complex interactions between humans and the environment show different effects at different scales. Current research approaches are not sufficient to appropriately take account of the heterogeneity and dynamics of aquatic ecosystems. A major challenge in applied environmental research is to extend methods for holistic monitoring and long-term observation technologies with enhanced resolution over both space and time. In this study, turbidity and the content of dissolved organic matter (DOM) are key parameters, as they are of importance for assessing the health of aquatic ecosystems and the state of ecosystem services (e.g., the provision of drinking water). Photonics and optical sensors as well as integrated circuits and open-source based components open interesting possibilities to overcome the current lack of adaptive and service-oriented sensor systems. An open source based optical sensor system was developed, which enables a user-specific, modular and adaptive in-situ monitoring of the turbidity and the dissolved organic substance content almost in real time. Quantification is based on attenuation or transmission measurements with two narrowband LEDs and corresponding detectors in the ultraviolet (DOM content) and infrared range (turbidity) of the electromagnetic spectrum. The developed in-situ sensor system shows a very high agreement with the results obtained using a laboratory photometer but with less methodological effort. First tests carried out in the area close to the city of Leipzig (Saxony, Germany) show promising results. The in-situ sensor system is able to acquire the optical attenuation with a sampling rate up to 0.1 Hz. Due to the fact that data is visualized directly with the help of web services, even the quality of data collection can be improved by assisting the selection of sampling points or a direct spatio-temporal data feedback. What this approach illustrates is the fact that open-source technologies and microelectronics can now be used to implement resilient and promising sensor systems that can set new standards in terms of performance and usability within applied environmental research.
Optimal measurement strategies for fast entanglement detection
2019-07-17

With the advance of quantum information technology, the question of how to\\nmost efficiently test quantum circuits is becoming of increasing relevance.\\nHere we introduce the statistics of lengths of measurement sequences that\\nallows one to certify entanglement across a given bi-partition of a multi-qubit\\nsystem over the possible sequence of measurements of random unknown states, and\\nidentify the best measurement strategies in the sense of the (on average)\\nshortest measurement sequence of (multi-qubit) Pauli measurements. The approach\\nis based on the algorithm of truncated moment sequences that allows one to deal\\nnaturally with incomplete information, i.e. information that does not fully\\nspecify the quantum state. We find that the set of measurements corresponding\\nto diagonal matrix elements of the moment matrix of the state are particularly\\nefficient. For symmetric states their number grows only like the third power of\\nthe number of qubits. Their efficiency grows rapidly with , leaving\\nalready for less than a fraction of randomly chosen entangled\\nstates undetected.\\n
A pooled analysis of the duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine: data & analysis output
2019-07-17

Data files and analysis output associated with the medRxiv preprint article: Bretscher et al. 2019 A pooled analysis of the duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine.
Timing matters! Explaining between study phases enhances students’ learning.
2019-07-18

Previous research has shown that explaining is an effective activity to enhance learning.In prior studies, students were instructed to explain the contents after completing an entire learning phase.Explaining at the end of a learning phase, however, may be less apt to support comprehension monitoring and subsequent regulation activities.In two experiments, we investigated whether explaining in earlier phases of studying (i.e., in-between explaining) would foster learning more than explaining after the entire study phase (i.e., after-study explaining).In Experiment 1, university students (N = 91) read a text about combustion engines and either explained the contents between the study phases or at the end of the entire study phase.A third group recalled the learning contents aloud at the end of the study phase to control for retrieval-processes that may also be involved in explaining.Results showed no overall effect of explaining in comparison to retrieval practice.However, in-between explaining enhanced students' conceptual knowledge as compared to after-study explaining.Verbal protocol analyses showed that this effect was due to students' increased monitoring.Experiment 2 (N = 126), had a 2×2-factorial design with between-subjects factors timing (inbetween versus after-study) and learning activity (explaining versus written retrieval practice).We found a cascaded trend: In-between learning activities were more effective than after-study learning activities, whereas explaining was more effective than written retrieval practice.These findings suggest that the timing of learning activities is crucial to improve learning.Additionally, our findings reveal that explaining is not simply a result of retrieval practice.
On the semantics of nonwords and their lexical category.
2019-07-18

Using computational simulations, this work demonstrates that it is possible to learn a systematic relation between words' sound and their meanings. The sound-meaning relation was learned from a corpus of phonologically transcribed child-directed speech by using the linear discriminative learning (LDL) framework (Baayen, Chuang, Shafaei-Bajestan, & Blevins, 2019), which implements linear mappings between words' form vectors and semantic vectors. Presented with the form vectors of 16 nonwords, taken from a study on word learning (Fitneva, Christiansen, & Monaghan, 2009), the network generated the estimated semantic vectors of the nonwords. As half of these nonwords were created to phonologically resemble English nouns and the other half were phonologically similar to English verbs, we assessed whether the estimated semantic vectors for these nonwords reflect this word category difference. In 7 different simulations, linear discriminant analysis (LDA) successfully discriminated between noun-like nonwords and verb-like nonwords, based on their semantic relation to the words in the lexicon. Furthermore, how well LDA categorized a nonword correlated well with a phonological typicality measure (i.e., the degree of its form being noun-like or verb-like) and with children's performance in an entity/action discrimination task. On the one hand, the results suggest that children can infer the implicit meaning of a word directly from its sound. On the other hand, this study shows that nonwords do land in semantic space, such that children can capitalize on their semantic relations with other elements in the lexicon to decide whether a nonword is more likely to denote an entity or an action. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Implications of Indenyl Substitution for the Structural Chemistry of Rare-Earth Metal (Half-)Sandwich Complexes and Performance in Living Isoprene Polymerization
2019-07-18

Lanthanum indenyl half-sandwich complexes of the composition (IndR)La(AlMe4)2 were synthesized in high crystalline yields by a salt-metathesis protocol applying La(AlMe4)3 and Li(IndR). In the solid state, the parent indenyl (Ind) and 2-ethylindenyl (IndEt) complexes exhibit a dimeric structural motif with the methyl groups of the linearly aligned La(μ-CH3)Al moieties being cis-positioned to the indenyl ligand. In contrast, 1-trimethylsilyl indenyl (IndSi) directs the η1-coordinated methyl group of the bridging aluminato ligand into a trans-position, while 2-tert-butyl indenyl afforded the monomeric half-sandwich complex (IndtBu)La(AlMe4)2. The reactions of Lu(AlMe4)3 with 1 or 2 equiv of Li(IndR) gave predominantly bis(indenyl) sandwich complexes (IndR)2Lu(AlMe4). All (half-)sandwich complexes were characterized by X-ray structure analysis, 1H/13C{1H} NMR and FTIR spectroscopy, and microanalysis. The performance of all half-sandwich complexes in isoprene polymerization was assessed upon activation with [Ph3C][B(C6F5)4], [PhNMe2H][B(C6F5)4], or B(C6F5)3. The choice of indenyl ligand and cocatalyst had a major impact on the polymerization efficiency and stereospecificity. The highest selectivities could be achieved with the binary catalyst systems (IndEt)La(AlMe4)2/[Ph3C][B(C6F5)4] (cis/trans content 10.4/85.9) and (IndSi)La(AlMe4)2/B(C6F5)3 (cis/trans content 77.0/13.0).
Mobilisation and transport of dissolved organic carbon and iron in peat catchments—Insights from the Lehstenbach stream in Germany using generalised additive models
2019-07-18

Abstract During the last decades, increasing exports of both dissolved organic carbon (DOC) and iron were observed from peat catchments in North America and Europe with potential consequences for water quality of streamwater and carbon storages of soils. As mobilisation and transport processes of DOC and iron in peat catchments are only partly understood, the purpose of this study was to elucidate these processes in an intensively monitored and studied system. Specifically, it was hypothesised that dissimilatory iron reduction in riparian peatland soils mobilises DOC initially adsorbed to iron minerals. During stormflow conditions, both DOC and iron will be transported into the stream network. Ferrous iron may be reoxidised at redox interfaces on its way to the stream, and subsequently, ferric iron could be transported together with DOC as complexes. To test these hypotheses, generalised additive models (GAMs) were applied to 14 years of weekly time series of discharge and concentrations of selected solutes measured in a German headwater stream called Lehstenbach. This stream drains a 4.19‐km 2 forested mountain catchment; one third of which is covered by riparian peatland soils. We interpreted results of different types of GAM in the way that (a) iron reduction drove the mobilisation of DOC from peatland soils and that (b) both iron and DOC were transported as complexes after their joint mobilisation to and within the steam. It was speculated that low nitrate availability in the uppermost wetland soil layer, particularly during the growing season, promoted iron reduction and thus the mobilisation of DOC. However, the influence of nitrate on the DOC mobilisation remains relatively uncertain. This influence could be further investigated using methods similar to the GAM analysis conducted here for other catchments with long‐term data as well as detailed measurements of the relevant species in riparian wetland soils and the adjacent stream network.
Face perception inherits low-level binocular adaptation
2019-07-18

In previous work (May & Zhaoping, 2016; May, Zhaoping, & Hibbard, 2012), we have provided evidence that the visual system efficiently encodes binocular information using separately adaptable binocular summation and differencing channels. In that work, binocular test stimuli delivered different grating patterns to the two binocular channels; selective adaptation of one of the binocular channels made participants more likely to see the other channel's grating pattern. In the current study, we extend this paradigm to face perception. Our test stimuli delivered different face images to the two binocular channels, and we found that selective adaptation of one binocular channel biased the observer to perceive the other channel's face image. We show that the perceived identity, gender, emotional expression, or direction of 3-D rotation of a facial test image can be influenced by pre-exposure to binocular random-noise patterns that contain no meaningful spatial structure. Our results provide compelling evidence that face-processing mechanisms can inherit adaptation from low-level sites. Our adaptation paradigm targets the low-level mechanisms in such a way that any response bias or inadvertent adaptation of high-level mechanisms selective for face categories would reduce, rather than produce, the measured effects of adaptation.
Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis
2019-07-19

Abstract Most antineoplastic chemotherapies eliminate cancer cells through activation of the mitochondria-controlled intrinsic apoptotic pathway. Therein, BAX, BAK, and/or BOK function as the essential pore-forming executioners of mitochondrial outer membrane permeabilization (MOMP). The activation threshold of BAX and BAK also correlates inversely with the required strength of an apoptotic stimulus to induce MOMP and thereby effectively determines a cell’s readiness to undergo apoptosis. Consequently, the ‘gatekeepers’ BAX and BAK emerged as therapeutic targets, but functional or genetic loss renders BAX/BAK-targeting strategies prone to fail. Here, we show that the small molecule Raptinal overcomes this limitation by triggering cytochrome c release in a BAX/BAK/BOK-independent manner. Raptinal exerts a dual cytotoxic effect on cancer cells by rapid activation of the intrinsic apoptotic pathway and simultaneous shutdown of mitochondrial function. Together with its efficacy to eliminate cancer cells in vivo, Raptinal could be useful in difficult-to-treat cancer entities harboring defects in the intrinsic apoptosis pathway.
APEX2‐mediated proximity labeling resolves protein networks in Saccharomyces cerevisiae cells
2019-07-19

Enzyme‐catalyzed proximity labeling (PL) with the engineered ascorbate peroxidase APEX2 is a novel approach to map organelle compartmentalization and protein networks in living cells. Current procedures developed for mammalian cells do not allow delivery of the cosubstrate, biotin‐phenol, into living yeast cells. Here, we present a new method based on semipermeabilized yeast cells. Combined with stable isotope labeling by amino acids in cell culture (SILAC), we demonstrate proteomic mapping of a membrane‐enclosed and a semiopen compartment, the mitochondrial matrix and the nucleus. APEX2 PL revealed nuclear proteins that were previously not identified by conventional techniques. One of these, the Yer156C protein, is highly conserved but of unknown function. Its human ortholog, melanocyte proliferating gene 1, is linked to developmental processes and dermatological diseases. A first characterization of the Yer156C neighborhood reveals an array of proteins linked to proteostasis and RNA binding. Thus, our approach establishes APEX2 PL as another powerful tool that complements the methods palette for the model system yeast.
Implementation and Evaluation of Activity-Based Congestion Management Using P4 (P4-ABC)
2019-07-19

Activity-Based Congestion management (ABC) is a novel domain-based QoS mechanism providing more fairness among customers on bottleneck links. It avoids per-flow or per-customer states in the core network and is suitable for application in future 5G networks. However, ABC cannot be configured on standard devices. P4 is a novel programmable data plane specification which allows defining new headers and forwarding behavior. In this work, we implement an ABC prototype using P4 and point out challenges experienced during implementation. Experimental validation of ABC using the P4-based prototype reveals the desired fairness results.
Revealing Suppressed Intermolecular Coupling Effects in Aggregated Organic Semiconductors by Diluting the Crystal: Model System Perfluoropentacene:Picene
2019-07-19

In order to investigate the effects of intermolecular interactions on the optical properties of organic semiconductors, we employ mixing of the organic semiconductor perfluoropentacene (PFP; C22F14) with the wide band-gap organic semiconductor picene (PIC; C22H14). The binary mixed thin films are prepared by simultaneous coevaporation of PIC and PFP in vacuum. We determine the optical properties of the blends by differential reflectance spectroscopy (absorption) and photoluminescence (emission). PFP:PIC thin films are a rare case of mixed thin films with a known molecular packing. The formation of equimolar mixed domains with a crystal structure clearly different from that of the pure compounds is, in the case of nonequimolar blends, accompanied by pure domains of the excess compound. Due to the wide band gap of PIC, the effect of reduced intermolecular interactions between PFP molecules can be studied in detail without any direct contributions of PIC to the spectra. We find a strongly enhanced emission from PFP in the mixed thin films, which can be explained by decoupling. Real-time investigations of the absorption spectra during growth provide further insight into intermolecular coupling effects on optical properties.
Minor deviations from randomness have huge repercussions on the functional structuring of sequence space
2019-07-20

Approaches based on molecular evolution have organized natural proteins into a hierarchy of families, superfamilies, and folds, which are often pictured as islands in a great sea of unrealized and generally non-functional polypeptides. In contrast, approaches based on information theory have substantiated a mostly random scatter of natural proteins in global sequence space. We evaluate these opposing views by analyzing fragments of a given length derived from either a natural dataset or different random models. For this, we compile distances in sequence space between fragments within each dataset and compare the resulting distance distributions between sets. Even for 100-mers, more than 95% of distances can be accounted for by a random sequence model that incorporates the natural amino acid frequency of proteins. When further accounting for the specific residue composition of the respective fragments, which would include biophysical constraints of protein folding, more than 99% of all distances can be modeled. Thus, while the local space surrounding a protein is almost entirely shaped by common descent, the global distribution of proteins in sequence space is close to random, only constrained by divergent evolution through the requirement that all intermediates connecting two forms in evolution must be functional. Significance Statement When generating new proteins by evolution or design, can the entire sequence space be used, or do viable sequences mainly occur only in some areas of this space? As a result of divergent evolution, natural proteins mostly form families that occupy local areas of sequence space, suggesting the latter. Theoretical work however indicates that these local areas are highly diffuse and do not dramatically affect the statistics of sequence distribution, such that natural proteins can be considered to effectively cover global space randomly, though extremely sparsely. By comparing the distance distribution of natural sequences to that of various random models, we find that they are indeed distributed largely randomly, provided that the amino acid composition of natural proteins is respected.
A pooled analysis of the duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine
2019-07-20

Abstract Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly-used treatments against Plasmodium falciparum malaria in Africa. The lumefantrine and amodiaquine partner drugs may provide differing durations of post-treatment prophylaxis, an important additional benefit to patients. Analyzing 4214 individuals from clinical trials in 12 sites, we estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ after allowing for transmission intensity. However, the duration varied substantially between sites: where wild type pfmdr1 86 and pfcrt 76 parasite genotypes predominated, AS-AQ provided ∼2-fold longer protection than AL. Conversely, AL provided up to 1.5-fold longer protection than AS-AQ where mutants were common. We estimate that choosing AL or AS-AQ as first-line treatment according to local drug sensitivity could alter population-level clinical incidence of malaria by up to 14% in under-five year olds where malaria transmission is high.