julilili42/papers huggingface dataset:
Mining Indonesian Microbial Biodiversity for Novel Natural Compounds by a Combined Genome Mining and Molecular Networking Approach
2021-05-28

Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two thirds of all clinically used antibiotics. Thus, exploiting Indonesia’s microbial diversity for actinomycetes may lead to the discovery of novel antibiotics. A total of 422 actinomycete strains were isolated from three different unique areas in Indonesia and tested for their antimicrobial activity. Nine potent bioactive strains were prioritized for further drug screening approaches. The nine strains were cultivated in different solid and liquid media, and a combination of genome mining analysis and mass spectrometry (MS)-based molecular networking was employed to identify potential novel compounds. By correlating secondary metabolite gene cluster data with MS-based molecular networking results, we identified several gene cluster-encoded biosynthetic products from the nine strains, including naphthyridinomycin, amicetin, echinomycin, tirandamycin, antimycin, and desferrioxamine B. Moreover, 16 putative ion clusters and numerous gene clusters were detected that could not be associated with any known compound, indicating that the strains can produce novel secondary metabolites. Our results demonstrate that sampling of actinomycetes from unique and biodiversity-rich habitats, such as Indonesia, along with a combination of gene cluster networking and molecular networking approaches, accelerates natural product identification.
Discrimination of simple objects decoded from the output of retinal ganglion cells upon sinusoidal electrical stimulation
2021-05-28

Abstract Objective . Most neuroprosthetic implants employ pulsatile square-wave electrical stimuli, which are significantly different from physiological inter-neuronal communication. In case of retinal neuroprosthetics, which use a certain type of pulsatile stimuli, reliable object and contrast discrimination by implanted blind patients remained challenging. Here we investigated to what extent simple objects can be discriminated from the output of retinal ganglion cells (RGCs) upon sinusoidal stimulation. Approach . Spatially confined objects were formed by different combinations of 1024 stimulating microelectrodes. The RGC activity in the ex vivo retina of photoreceptor-degenerated mouse, of healthy mouse or of primate was recorded simultaneously using an interleaved recording microelectrode array implemented in a CMOS-based chip. Main results . We report that application of sinusoidal electrical stimuli (40 Hz) in epiretinal configuration instantaneously and reliably modulates the RGC activity in spatially confined areas at low stimulation threshold charge densities (40 nC mm −2 ). Classification of overlapping but spatially displaced objects (1° separation) was achieved by distinct spiking activity of selected RGCs. A classifier (regularized logistic regression) discriminated spatially displaced objects (size: 5.5° or 3.5°) with high accuracy (90% or 62%). Stimulation with low artificial contrast (10%) encoded by different stimulus amplitudes generated RGC activity, which was classified with an accuracy of 80% for large objects (5.5°). Significance . We conclude that time-continuous smooth-wave stimulation provides robust, localized neuronal activation in photoreceptor-degenerated retina, which may enable future artificial vision at high temporal, spatial and contrast resolution.
131I-GD2-ch14.18 Scintigraphy to Evaluate Option for Radioimmunotherapy in Patients with Advanced Tumors
2021-05-28

The tumor-selective ganglioside antigene GD2 is frequently expressed on neuroblastomas and to a lesser extent on sarcomas and neuroendocrine tumors. The aim of our study was to evaluate the tumor targeting and biodistribution of <sup>131</sup>I-labeled chimeric GD2-antibody clone 14/18 (<sup>131</sup>I-GD2-ch14.18) in patients with late-stage disease in order to identify eligibility for radioimmunotherapy. <b>Methods:</b> Twenty patients (neuroblastoma, <i>n</i> = 9; sarcoma, <i>n</i> = 9; pheochromocytoma, <i>n</i> = 1; and neuroendocrine tumor, <i>n</i> = 1) were involved in this study. A 21- to 131-MBq dose (1-2 MBq/kg) of <sup>131</sup>I-GD2-ch14.18 (0.5-1.0 mg) was injected intravenously. Planar scintigraphy was performed within 1 h from injection (day 0) and on days 1, 2, 3, and 6 or 7 to analyze tumor uptake and tracer biodistribution. Serial blood samples were collected in 4 individuals. Absorbed dose to tumor lesions and organs was calculated using OLINDA software. <b>Results:</b> The tumor-targeting rate on a per-patient base was 65% (13/20), with 6 of 9 neuroblastomas showing uptake of <sup>131</sup>I-GD2-ch14.18. Tumor lesions showed maximum uptake at 20-64 h after injection (effective half-life in tumors, 33-192 h). The tumor-absorbed dose varied between 0.52 and 30.2 mGy/MBq (median, 9.08 mGy/MBq; <i>n</i> = 13). Visual analysis showed prominent blood-pool activity up to day 2 or 3 after injection. No pronounced uptake was observed in the bone marrow compartment or in the kidneys. Bone marrow dose was calculated at 0.09-0.18 mGy/MBq (median, 0.12 mGy/MBq), whereas blood dose was 1.1-4.7 mGy/MBq. Two patients (1 neuroblastoma and 1 pheochromocytoma) with particularly high tumor uptake underwent radioimmunotherapy using 2.3 and 2.9 GBq of <sup>131</sup>I-GD2-ch14.18, both achieving stable disease. Overall survival was 17 and 6 mo, respectively. <b>Conclusion:</b><sup>131</sup>I-GD2-ch14.18 is cleared slowly from blood, not resulting in good tumor-to-background contrast until 2 d after application. With acceptable red marrow and organ dose, radioimmunotherapy is an option for patients with high tumor uptake. However, because of the variable GD2 expression, the decision should depend on pretherapeutic dosimetry.
Randomized Controlled Trials in Medical AI
2021-05-28

Various publications claim that medical AI systems perform as well, or better, than clinical experts. However, there have been very few controlled trials and the quality of existing studies has been called into question. There is growing concern that existing studies overestimate the clinical benefits of AI systems. This has led to calls for more, and higher-quality, randomized controlled trials of medical AI systems. While this a welcome development, AI RCTs raise novel methodological challenges that have seen little discussion. We discuss some of the challenges arising in the context of AI RCTs and make some suggestions for how to meet them.
Tidal effects in the motion of gas clouds around boson stars
2021-05-28

We report simulations regarding tidal disruption clouds orbiting spherically symmetric compact boson stars in two different regimes. First we consider clouds in three different bound orbits close to the boson star and analyze the mechanisms of debris formation for these. We infer from the simulations that the lifetimes of these hot-spots are longer for circularly orbiting clouds than for clouds on eccentric orbits. Next we compare the evolution of more extended and less dense clouds on circular orbits around a boson star and a Schwarzschild black hole. As an outcome of the simulations we observe the formation of a ring-like structure around the boson star endowed with a spiralling shock structure and a constant thermal bremsstrahlung total luminosity. This final configuration contrasts strongly with the black hole scenario where the gas is totally captured behind the event horizon.
A commentary on: ‘Broken, silent and in hiding: tamed endogenous pararetroviruses escape elimination from the genome of sugar beet (Beta vulgaris)’
2021-05-28

This article comments on: Nicola Schmidt, Kathrin M. Seibt, Beatrice Weber, Trude Schwarzacher, Thomas Schmidt, and Tony Heitkam, Broken, silent, and in hiding: tamed endogenous pararetroviruses escape elimination from the genome of sugar beet (Beta vulgaris), Annals of Botany Volume 128, Issue 3, 26 August 2021, Pages 281–291, https://doi.org/10.1093/aob/mcab042
Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes
2021-05-29

Abstract Osteoarthritis (OA) impacts hundreds of millions of people worldwide, with those affected incurring significant physical and financial burdens. Injuries such as focal defects to the articular surface are a major contributing risk factor for the development of OA. Current cartilage repair strategies are moderately effective at reducing pain but often replace damaged tissue with biomechanically inferior fibrocartilage. Here we describe the development, transcriptomic ontogenetic characterization and quality assessment at the single cell level, as well as the scaled manufacturing of an allogeneic human pluripotent stem cell-derived articular chondrocyte formulation that exhibits long-term functional repair of porcine articular cartilage. These results define a new potential clinical paradigm for articular cartilage repair and mitigation of the associated risk of OA.
Characterization of a landslide-triggered debris flow at a rainforest-covered mountain region in Brazil
2021-05-30

Abstract Debris flows represent great hazard to humans due to their high destructive power. Understanding their hydrogeomorphic dynamics is fundamental in hazard assessment studies, especially in subtropical and tropical regions where debris flows have scarcely been studied when compared to other mass-wasting processes. Thus, this study aims at systematically analyzing the meteorological and geomorphological factors that characterize a landslide-triggered debris flow at the Pedra Branca catchment (Serra do Mar, Brazil), to quantify the debris flow’s magnitude, peak discharge and velocity. A magnitude comparison with empirical equations (Italian Alps, Taiwan, Serra do Mar) is also conducted. The meteorological analysis is based on satellite data and rain gauge measurements, while the geomorphological characterization is based on terrestrial and aerial investigations, with high spatial resolution. The results indicate that it was a large-sized stony debris flow, with a total magnitude of 120,195 m 3 , a peak discharge of 2146.7 m 3 s −1 and a peak velocity of 26.5 m s −1 . The debris flow was triggered by a 188-mm rainfall in 3 h (maximum intensity of 128 mm h −1 ), with an estimated return period of 15 to 20 years, which, combined with the intense accumulation of on-channel debris (ca. 37,000 m 3 ), indicates that new high-magnitude debris flows in the catchment and the region are likely to occur within the next two decades. The knowledge of the potential frequency and magnitude ( F – M ) can support the creation of F – M relationships for Serra do Mar, a prerequisite for reliable hazard management and monitoring programs.
Data‐driven personalization of a physiologically based pharmacokinetic model for caffeine: A systematic assessment
2021-05-30

Abstract Physiologically based pharmacokinetic (PBPK) models have been proposed as a tool for more accurate individual pharmacokinetic (PK) predictions and model‐informed precision dosing, but their application in clinical practice is still rare. This study systematically assesses the benefit of using individual patient information to improve PK predictions. A PBPK model of caffeine was stepwise personalized by using individual data on (1) demography, (2) physiology, and (3) cytochrome P450 (CYP) 1A2 phenotype of 48 healthy volunteers participating in a single‐dose clinical study. Model performance was benchmarked against a caffeine base model simulated with parameters of an average individual. In the first step, virtual twins were generated based on the study subjects' demography (height, weight, age, sex), which implicated the rescaling of average organ volumes and blood flows. The accuracy of PK simulations improved compared with the base model. The percentage of predictions within 0.8‐fold to 1.25‐fold of the observed values increased from 45.8% (base model) to 57.8% (Step 1). However, setting physiological parameters (liver blood flow determined by magnetic resonance imaging, glomerular filtration rate, hematocrit) to measured values in the second step did not further improve the simulation result (59.1% in the 1.25‐fold range). In the third step, virtual twins matching individual demography, physiology, and CYP1A2 activity considerably improved the simulation results. The percentage of data within the 1.25‐fold range was 66.15%. This case study shows that individual PK profiles can be predicted more accurately by considering individual attributes and that personalized PBPK models could be a valuable tool for model‐informed precision dosing approaches in the future.
Robot Arm Motion Planning Based on Geodesics
2021-05-30

Naturally, finding joint trajectories for robotic manipulators involves competing optimization goals. On the one hand, the end-effector should move along a predictable and short path while on the other hand joint movement and acceleration should be kept to a minimum. Obstacles in the workspace or joint limits complicate the situation even further. Constructing a metric that makes undesired configurations more expensive to travel through, we equip the joint space with a notion of cost. The motion planning task then reduces to the problem of finding cheapest paths connecting two configurations – so-called geodesics. We show how to construct suitable metrics for a variety of typical scenarios and present an efficient algorithm for the computation of the corresponding geodesics. Our approach makes it very easy to balance different optimization goals and produces natural and smooth manipulator movement.
Sample-efficient Reinforcement Learning in Robotic Table Tennis
2021-05-30

Reinforcement learning (RL) has achieved some impressive recent successes in various computer games and simulations. Most of these successes are based on having large numbers of episodes from which the agent can learn. In typical robotic applications, however, the number of feasible attempts is very limited. In this paper we present a sample-efficient RL algorithm applied to the example of a table tennis robot. In table tennis every stroke is different, with varying placement, speed and spin. An accurate return therefore has to be found depending on a high-dimensional continuous state space. To make learning in few trials possible the method is embedded into our robot system. In this way we can use a one-step environment. The state space depends on the ball at hitting time (position, velocity, spin) and the action is the racket state (orientation, velocity) at hitting. An actor-critic based deterministic policy gradient algorithm was developed for accelerated learning. Our approach performs competitively both in a simulation and on the real robot in a number of challenging scenarios. Accurate results are obtained without pre-training in under episodes of training. The video presenting our experiments is available at https://youtu.be/uRAtdoL6Wpw.
Information Ethics
2021-05-30

Information ethics is a branch of applied ethics that focusses on web applications, information management, and the general use of computers. It is concerned with questions of a just and free distribution of information, with questions of autonomy and power on the internet or a value-oriented design of Information Technology (IT) systems. Information technologies shape many of the essential factors of interaction in a data-driven society. The implementation of values such as privacy, freedom from discrimination or participation in the development of a digital society is therefore a necessary prerequisite for a democratic and sustainable course of action. Digital information technologies make it possible to disseminate information in two ways: via the users, and about the users. Increasingly, information about the behavior and the communication of users can be collected through digital platforms. The vast amount of economically used data and also the exchange of information on social media platforms calls for evaluation, orientation and governance. Only in this way can we ensure that freedom of information is not a privilege, but a shared resource in a lively pluralistic and democratic society.
Alterations in the CO2 availability induce alterations in the phosphoproteome of the cyanobacterium Synechocystis sp. PCC 6803
2021-05-31

Summary Cyanobacteria are the only prokaryotes that perform plant‐like oxygenic photosynthesis. They evolved an inorganic carbon‐concentrating mechanism to adapt to low CO 2 conditions. Quantitative phosphoproteomics was applied to analyze regulatory features during the acclimation to low CO 2 conditions in the model cyanobacterium Synechocystis sp. PCC 6803. Overall, more than 2500 proteins were quantified, equivalent to c . 70% of the Synechocystis theoretical proteome. Proteins with changing abundances correlated largely with mRNA expression levels. Functional annotation of the noncorrelating proteins revealed an enrichment of key metabolic processes fundamental for maintaining cellular homeostasis. Furthermore, 105 phosphoproteins harboring over 200 site‐specific phosphorylation events were identified. Subunits of the bicarbonate transporter BCT1 and the redox switch protein CP12 were among phosphoproteins with reduced phosphorylation levels at lower CO 2 , whereas the serine/threonine protein kinase SpkC revealed increased phosphorylation levels. The corresponding Δ spkC mutant was characterized and showed decreased ability to acclimate to low CO 2 conditions. Possible phosphorylation targets of SpkC including a BCT1 subunit were identified by phosphoproteomics. Collectively, our study highlights the importance of posttranscriptional regulation of protein abundances as well as posttranslational regulation by protein phosphorylation for the successful acclimation towards low CO 2 conditions in Synechocystis and possibly among cyanobacteria.
Morphology of the temporal skull region in tetrapods: research history, functional explanations, and a new comprehensive classification scheme
2021-05-31

ABSTRACT The morphology of the temporal region in the tetrapod skull traditionally has been a widely discussed feature of vertebrate anatomy. The evolution of different temporal openings in Amniota (mammals, birds, and reptiles), Lissamphibia (frogs, salamanders, and caecilians), and several extinct tetrapod groups has sparked debates on the phylogenetic, developmental, and functional background of this region in the tetrapod skull. This led most famously to the erection of different amniote taxa based on the number and position of temporal fenestrae in their skulls. However, most of these taxa are no longer recognised to represent natural groupings and the morphology of the temporal region is not necessarily an adequate trait for use in the reconstruction of amniote phylogenies. Yet, new fossil finds, most notably of parareptiles and stem‐turtles, as well as modern embryological and biomechanical studies continue to provide new insights into the morphological diversity of the temporal region. Here, we introduce a novel comprehensive classification scheme for the various temporal morphotypes in all Tetrapoda that is independent of phylogeny and previous terminology and may facilitate morphological comparisons in future studies. We then review the history of research on the temporal region in the tetrapod skull. We document how, from the early 19th century with the first recognition of differences in the temporal region to the first proposals of phylogenetic relationships and their assessment over the centuries, the phylogenetic perspective on the temporal region has developed, and we highlight the controversies that still remain. We also compare the different functional and developmental drivers proposed for the observed morphological diversity and how the effects of internal and external factors on the structure of the tetrapod skull have been interpreted.
BOLD sensitivity and vessel size specificity along CPMG and GRASE echo trains
2021-05-31

Purpose To assess the vessel size specificity and sensitivity of rapid CPMG and GRASE for functional BOLD imaging for different echo train lengths, echo spacings, field strength, and refocusing flip angle schemes. In addition, the behavior of signals acquired before and after the refocusing time points is analyzed. Methods Evolution of magnetization within a network of artificial cylinders is simulated with Monte Carlo methods for all relevant coherence pathways. In addition, measurements on microspheres were performed to confirm some of the theoretical results. Results For reduced refocusing flip angles, the peak of the vessel size sensitivity curve is shifting toward larger radii with increasing echo time. Furthermore, the BOLD‐related signal change along the echo train depends on the chosen refocusing flip angle scheme and in general does not follow corresponding echo amplitudes. Conclusion CPMG or GRASE can be used with low refocusing flip angles without significant loss of sensitivity to BOLD. The evolution of BOLD signal changes along the echo train can be used to design optimal k‐space reordering schemes. Signals acquired before or after the spin echo time point show contributions from larger vessels similar to gradient echo sequences. Short echo spacing (time between refocusing pulses) suppresses gradient echo‐related contributions from larger vessels, whereas the spin echo‐related contribution from small vessels remains constant and is independent of the echo spacing.
The Plant-Like Structure of Lance Sea Urchin Spines as Biomimetic Concept Generator for Freeze-Casted Structural Graded Ceramics
2021-05-31

The spine of the lance sea urchin (Phyllacanthus imperialis) is an unusual plant-akin hierarchical lightweight construction with several gradation features: a basic core–shell structure is modified in terms of porosities, pore orientation and pore size, forming superstructures. Differing local strength and energy consumption features create a biomimetic potential for the construction of porous ceramics with predetermined breaking points and adaptable behavior in compression overload. We present a new detailed structural and failure analysis of those spines and demonstrate that it is possible to include at least a limited number of those features in an abstracted way in ceramics, manufactured by freeze-casting. This possibility is shown to come from a modified mold design and optimized suspensions.
Center-surround interactions underlie bipolar cell motion sensing in the mouse retina
2021-05-31

Motion is a critical aspect of vision. We studied the representation of motion in mouse retinal bipolar cells and found, surprisingly, that some bipolar cells possess motion-sensing capabilities that rely on their center-surround receptive fields. Using a glutamate sensor, we directly observed motion-sensitive bipolar cell synaptic output, which was strongest for local motion and dependent on the motion’s origin. We characterized bipolar cell receptive fields and found that there are motion and non-motion sensitive bipolar cell types, the majority being motion sensitive. Next, we used these bipolar cell receptive fields along with connectomics to design biophysical models of downstream cells. The models and experiments demonstrated that bipolar cells pass motion-sensitive excitation to starburst amacrine cells through direction-specific signals mediated by bipolar cells’ center-surround receptive field structure. As bipolar cells provide excitation to most amacrine and ganglion cells, their motion sensitivity may contribute to motion processing throughout the visual system.