julilili42/papers huggingface dataset:
The preclinical discovery and development of rectal artesunate for the treatment of malaria in young children: a review of the evidence
2020-09-14

Efforts by ministries of health in malaria endemic countries together with international health organizations should establish and enforce guidelines to ensure the correct use of artesunate suppositories only as pre-referral medication in presumed severe malaria cases to minimize the risk of abuse as a monotherapy for treatment of uncomplicated malaria. The priority is to not jeopardize the efficacy of artesunate and to prevent resistance development against this valuable drug class in Africa.
The effect of finite sample thickness in scanning ion conductance microscopy stiffness measurements
2020-09-14

Investigating the mechanical properties of soft biological samples on the single-cell level is of great interest as cell mechanics play a central role in many physiological processes in health and disease. Scanning ion conductance microscopy (SICM) is an emerging technique for measuring cell stiffness on the micro- and nanometer scale in a non-contact fashion. However, as SICM stiffness measurements are based on a localized deformation of the sample, they are affected by the thickness of the sample. We found experimentally and numerically that the apparent stiffness of a thin sample is overestimated. We present a straightforward correction method to account for this effect and derive a thickness-dependent, multiplicative correction factor, which we apply to SICM stiffness mapping of living cells. The correction method allows us to quantitatively measure the stiffness of thin samples with SICM and is, therefore, essential for the comprehensive application of SICM to nanomechanical measurements.
Mapping of safe and early chemo-attenuated livePlasmodium falciparumimmunization identifies immune signature of vaccine efficacy
2020-09-14

Abstract Potent protection against malaria can be induced by attenuated live-immunization with Plasmodium falciparum (Pf) sporozoites (SPZ). However, a better understanding of the critical processes involved in the establishment of protective immunity is needed. We explored the safety and vaccine efficacy of early chemo-attenuation of PfSPZ under atovaquone-proguanil (AP). AP caused early arrest of P. berghei liver stages. Despite the absence of replication, robust protection in mice correlated with parasite-specific effector-memory CD8 + T-cell responses. In a phase I clinical trial a single dose of AP prevented Pf infections in the liver of adult, human subjects who received three doses of 5.12x10 4 or 1.5x10 5 PfSPZ by direct venous inoculation combined with oral AP. However, only 2 of 8 (25%) and 2 of 10 (20%), respectively, were protected against controlled human malaria infection (CHMI) 10 weeks after the last vaccine dose, despite levels of IgG antibodies to the Pf circumsporozoite protein (PfCSP) comparable to those achieved in fully protected volunteers after immunization with 5.12x10 4 PfSPZ with chloroquine chemoprophylaxis active only against subsequent blood stages. We identify lower IgG recognition of the secreted liver stage-specific antigens LISP2 and LSA1 and the multi-stage antigen MSP5 as immune signatures of inferior vaccine efficacy compared to PfSPZ with chloroquine chemoprophylaxis. In conclusion, we show that immune signatures of liver stage antigens, but neither an established rodent malaria model nor concentrations of antibodies against the major surface protein of sporozoites, permit prediction of vaccine efficacy. Thus, this study provides a clear rationale for the development of live sporozoite vaccination protocols that boost exposure to Pf liver stage antigens. Significance Statement Our research demonstrates that attenuation of liver infection of high doses of Plasmodium falciparum sporozoites by concomitant single-dose administration of atovaquone-proguanil is safe in humans. However, vaccine efficacy was modest when compared to an identical protocol using chloroquine that acts only on the subsequent blood infection. Immune signatures of secreted P. falciparum liver stage antigens, but neither an established rodent malaria model nor concentrations of sporozoite antibodies, permit prediction of vaccine efficacy.
The dysphoric body politic, or Seizing the means of imagination
2020-09-14

Although escapism has been used pejoratively in describing fandom, it might be reframed as a reaction to untenable external circumstances. This reformulation of escapism is a starting point for examining how fan fiction is a political practice. In light of the political upheaval in the United States as well as the existential threat of climate change, this is a topical, even urgent, collective project for producing survivable conditions. Fan fiction uniquely diagnoses and imagines alternatives to oppressive political conditions. The lens of political dysphoria, adapted from critical transgender studies and used here to describe the dissonance between dominant political structures and desiring subjects, permits exploration of how fan fiction enables subjects to acknowledge oppressive political conditions, engage in coalitional rebellion, and reimagine societal structures for collective liberation.
Full-field numerical simulations of temperate ice viscoplastic deformation and dynamic recrystallization [Data set]
2020-09-14

&lt;p&gt;This data set corresponds to the scientific article Llorens, M.-G., Griera, A., Bons, P.D., Gomez-Rivas, E., Weikusat, I., Prior, D., Kerch, J. and Lebensohn, R.A. Seismic anisotropy of temperate ice in polar ice sheets. Journal of Geophysical Research: Earth Surface.&lt;/p&gt; &lt;p&gt;This data set contains (i) the output files with the crystal orientation and phase data of each simulation presented in the article (run using the open-source software platform ELLE; Bons et al., 2008; Piazolo et al., 2019), and (ii) a code to plot the crystallographic orientation density function (ODF) using the open-source code MTEX (Mainprice et al., 2015). For the visualization of seismic wave velocities the information contained in these output files can be loaded (in radians) to the software package AEH-EBSD Analysis Toolbox (Naus-Thijseen, 2011; Vel et al., 2016). The output files are provided for time steps 50 (shear strain of 1), 100 (shear strain of 2), 200 (shear strain of 4), 300 (shear strain of 6) and 400 (shear strain of 8).&lt;/p&gt; &lt;p&gt;Each file has eight columns and multiple rows. Each row stores the output data for an unode of the model, and the model has 256x256 unodes. The first three columns correspond to the three Euler angles (&lt;em&gt;&alpha;&lt;/em&gt;, &lt;em&gt;&beta;&lt;/em&gt;, &lt;em&gt;&gamma;&lt;/em&gt;) in degrees, the fourth and fifth column are the &lt;em&gt;x&lt;/em&gt; and &lt;em&gt;y&lt;/em&gt; coordinates of each unode, the sixth and seventh columns contain attributes not used in these simulations and column eight shows the phase number corresponding to each unode (1 for solid ice and 2 for water).&lt;/p&gt; &lt;p&gt;Three simulations are presented and analyzed in this article, and thus their results stored in this data set:&lt;/p&gt; &lt;p&gt;Simulation 1: purely solid ice (melt fraction &lt;em&gt;φ&lt;/em&gt;=0)&lt;/p&gt; &lt;p&gt;Simulation 2: ice including 5% water (melt fraction &lt;em&gt;φ&lt;/em&gt;=5)&lt;/p&gt; &lt;p&gt;Simulation 3: ice including 15% water (melt fraction &lt;em&gt;φ&lt;/em&gt;=15)&lt;/p&gt;
System Identification with Biophysical Constraints: A Circuit Model of the Inner Retina
2020-09-14

Visual processing in the retina has been studied in great detail at all levels such that a comprehensive picture of the retina’s cell types and the many neural circuits they form is emerging. However, the currently best performing models of retinal function are black-box CNN models which are agnostic to such biological knowledge. In particular, these models typically neglect the role of the many inhibitory circuits involving amacrine cells and the biophysical mechanisms underlying synaptic release. Here, we present a computational model of temporal processing in the inner retina, including inhibitory feedback circuits and realistic synaptic release mechanisms. Fit to the responses of bipolar cells, the model generalized well to new stimuli including natural movie sequences, performing on par with or better than a benchmark black-box model. In pharmacology experiments, the model replicated in silico the effect of blocking specific amacrine cell populations with high fidelity, indicating that it had learned key circuit functions. Also, more in depth comparisons showed that connectivity patterns learned by the model were well matched to connectivity patterns extracted from connectomics data. Thus, our model provides a biologically interpretable data-driven account of temporal processing in the inner retina, filling the gap between purely black-box and detailed biophysical modeling.
Full-field numerical simulations of temperate ice viscoplastic deformation and dynamic recrystallization [Data set]
2020-09-14

This data set corresponds to the scientific article Llorens, M.-G., Griera, A., Bons, P.D., Gomez-Rivas, E., Weikusat, I., Prior, D., Kerch, J. and Lebensohn, R.A. Seismic anisotropy of temperate ice in polar ice sheets. Journal of Geophysical Research: Earth Surface. This data set contains (i) the output files with the crystal orientation and phase data of each simulation presented in the article (run using the open-source software platform ELLE; Bons et al., 2008; Piazolo et al., 2019), and (ii) a code to plot the crystallographic orientation density function (ODF) using the open-source code MTEX (Mainprice et al., 2015). For the visualization of seismic wave velocities the information contained in these output files can be loaded (in radians) to the software package AEH-EBSD Analysis Toolbox (Naus-Thijseen, 2011; Vel et al., 2016). The output files are provided for time steps 50 (shear strain of 1), 100 (shear strain of 2), 200 (shear strain of 4), 300 (shear strain of 6) and 400 (shear strain of 8). Each file has eight columns and multiple rows. Each row stores the output data for an unode of the model, and the model has 256x256 unodes. The first three columns correspond to the three Euler angles (<em>α</em>, <em>β</em>, <em>γ</em>) in degrees, the fourth and fifth column are the <em>x</em> and <em>y</em> coordinates of each unode, the sixth and seventh columns contain attributes not used in these simulations and column eight shows the phase number corresponding to each unode (1 for solid ice and 2 for water). Three simulations are presented and analyzed in this article, and thus their results stored in this data set: Simulation 1: purely solid ice (melt fraction <em>φ</em>=0) Simulation 2: ice including 5% water (melt fraction <em>φ</em>=5) Simulation 3: ice including 15% water (melt fraction <em>φ</em>=15)
Testing spacetime symmetry through gravitational waves from extreme-mass-ratio inspirals
2020-09-15

One of the primary aims of upcoming spaceborne gravitational wave detectors is to measure radiation in the mHz range from extreme-mass-ratio inspirals. Such a detection would place strong constraints on hypothetical departures from a Kerr description for astrophysically stable black holes. The Kerr geometry, which is unique in general relativity, admits a higher-order symmetry in the form of a Carter constant, which implies that the equations of motion describing test particle motion in a Kerr background are Liouville-integrable. In this article, we investigate whether the Carter symmetry itself is discernible from a generic deformation of the Kerr metric in the gravitational waveforms for such inspirals. We build on previous studies by constructing a new metric which respects current observational constraints, describes a black hole, and contains two non-Kerr parameters, one of which controls the presence or absence of the Carter symmetry, thereby controlling the existence of chaotic orbits, and another which serves as a generic deformation parameter. We find that these two parameters introduce fundamentally distinct features into the orbital dynamics, and evince themselves in the gravitational waveforms through a significant dephasing. Although only explored in the quadrupole approximation, this, together with a Fisher metric analysis, suggests that gravitational wave data analysis may be able to test, in addition to the governing theory of gravity, the underlying symmetries of spacetime.
Defining diagnostic cutoffs in neurological patients for serum very long chain fatty acids (VLCFA) in genetically confirmed X-Adrenoleukodystrophy
2020-09-15

Abstract X-linked Adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene resulting in the accumulation of very long chain fatty acids (VLCFA). X-ALD is the most common peroxisomal disorder with adult patients (male and female) presenting with progressive spastic paraparesis with bladder disturbance, sensory ataxia with impaired vibration sense, and leg pain. 80% of male X-ALD patients have an adrenal failure, while adrenal dysfunction is rare in women with X-ALD. The objective of this study was to define optimal serum VLCFA cutoff values in patients with X-ALD-like phenotypes for the differentiation of genetically confirmed X-ALD and Non-X-ALD individuals. Three groups were included into this study: a) X-ALD cases with confirmed ABCD1 mutations (n = 34) and two Non-X-ALD cohorts: b) Patients with abnormal serum VCLFA levels despite negative testing for ABCD1 mutations (n = 15) resulting from a total of 1,953 VLCFA tests c) Phenotypically matching patients as Non-X-ALD controls (n = 104). Receiver operating curve analysis was used to optimize VLCFA cutoff values, which differentiate patients with genetically confirmed X-ALD and Non-X-ALD individuals. The serum concentration of C26:0 was superior to C24:0 for the detection of X-ALD. The best differentiation of Non-X-ALD and X-ALD individuals was obtained with a cutoff value of &lt; 1.0 for the C24:0/C22:0 ratio resulting in a sensitivity of 97%, a specificity of 94.1% and a positive predictive value (PPV) of 83.8% for true X-ALD. Our findings further suggested a cutoff of &lt; 0.02 for the ratio C26:0/C22:0 leading to a sensitivity of 90.9%, a specificity of 95.0%, and a PPV of 80.6%. Pearson correlation indicated a significant positive association between total blood cholesterol and VLCFA values. Usage of serum VLCFA are economical and established biomarkers suitable for the guidance of genetic testing matching the X-ALD phenotype. We suggest using our new optimized cutoff values, especially the two ratios (C24:0/C22:0 and C26:0/C22:0), in combination with standard lipid profiles.
Questionable research practices may have little effect on replicability
2020-09-15

This article examines why many studies fail to replicate statistically significant published results. We address this issue within a general statistical framework that also allows us to include various questionable research practices (QRPs) that are thought to reduce replicability. The analyses indicate that the base rate of true effects is the major factor that determines the replication rate of scientific results. Specifically, for purely statistical reasons, replicability is low in research domains where true effects are rare (e.g., search for effective drugs in pharmacology). This point is under-appreciated in current scientific and media discussions of replicability, which often attribute poor replicability mainly to QRPs.
Combining implicit geological modeling, field surveys, and hydrogeological modeling to describe groundwater flow in a karst aquifer
2020-09-15

Abstract In three-dimensional (3-D) implicit geological modeling, the bounding surfaces between geological units are automatically constructed from lithological contact data (position and orientation) and the location and orientation of potential faults. This approach was applied to conceptualize a karst aquifer in the Middle Triassic Muschelkalk Formation in southwest Germany, using digital elevation data, geological maps, borehole logs, and geological interpretation. Dip and strike measurements as well as soil-gas surveys of mantel-borne CO 2 were conducted to verify the existence of an unmapped fault. Implicit geological modeling allowed the straightforward assessment of the geological framework and rapid updates with incoming data. Simultaneous 3-D visualizations of the sedimentary units, tectonic features, hydraulic heads, and tracer tests provided insights into the karst-system hydraulics and helped guide the formulation of the conceptual hydrogeological model. The 3-D geological model was automatically translated into a numerical single-continuum steady-state groundwater model that was calibrated to match measured hydraulic heads, spring discharge rates, and flow directions observed in tracer tests. This was possible only by introducing discrete karst conduits, which were implemented as high-conductivity features in the numerical model. The numerical groundwater flow model was applied to initially assess the risk from limestone quarrying to local water supply wells with the help of particle tracking.
A New Method for In-Situ Skin Penetration Analysis by Confocal Raman Microscopy
2020-09-15

In the development of dermal drug formulations and cosmetics, understanding the penetration properties of the active ingredients is crucial. Given that widespread methods, including tape stripping, lack in spatial resolution, while being time- and labour-intensive, Confocal Raman Microscopy is a promising alternative. In optimizing topically applied formulations, or the development of generic formulations, comparative in-situ measurements have a huge potential of saving time and resources. In this work, we show our approach to in-situ skin penetration analysis by confocal Raman Microscopy. To analyse feasibility of the approach, we used caffeine solutions as model vehicles and tested the effectiveness of 1,2-pentanediol as a penetration enhancer for delivery to the skin.
Phoenician lime for Phoenician wine: Iron Age plaster from a wine press at Tell el-Burak, Lebanon
2020-09-15

Despite the importance of wine in the Iron Age Mediterranean, known structures associated with its production are rare. Recent excavations at Phoenician Tell el-Burak have now revealed the first Iron Age wine press in Lebanon. Its remarkable state of preservation enables a systematic study of its plaster to be made as well as a comparison with two other plastered installations at the site. Archaeometric analyses offer new data concerning the composition and technology of Iron Age lime-plaster production, confirming the existence of a local and innovative tradition of plaster production in southern Phoenicia. These results contribute to the wider discussion of Phoenician technology in the broader Iron Age Mediterranean.
Multiscalar Gauss-Bonnet gravity: Hairy black holes and scalarization
2020-09-15

In the present paper we consider multi-scalar extension of Einstein-Gauss-Bonnet gravity. We focus on multi-scalar Einstein-Gauss-Bonnet models whose target space is a three-dimensional maximally symmetric space, namely either , or , and in the case when the map is nontrivial. We prove numerically the existence of black holes in this class of models for several Gauss-Bonnet coupling functions, including the case of scalarization. We also perform systematic study of a variety of black hole characteristics and the space-time around them, such as the area of the horizon, the entropy and the radius of the photon sphere. One of the most important properties of the obtained solutions is that the scalar charge is zero and thus the scalar dipole radiation is suppressed which leads to much weaker observational constraints compared to the majority of modified theories possessing a scalar degree of freedom. For one of the coupling functions we could find branches of scalarized black holes which have a nontrivial structure -- there is non-uniqueness of the scalarized solutions belonging to a single branch and there is a region of the parameter space where most probably stable scalarized black holes coexist with the stable Schwarzschild black holes. Such a phenomena can have a clear observational signature.
Reovirus σ1 Conformational Flexibility Modulates the Efficiency of Host Cell Attachment
2020-09-15

Nonenveloped virus entry is an incompletely understood process. For reovirus, the functional significance of conformational rearrangements in the attachment protein, σ1, that occur during entry and particle uncoating are unknown. We engineered and characterized reoviruses containing cysteine mutations that cross-link σ1 monomers in nonreducing conditions. We found that the introduction of a cysteine pair in the receptor-binding domain of σ1 yielded a virus that replicates with faster kinetics than the parental virus and forms larger plaques. Using functional assays, we found that cross-linking the σ1 receptor-binding domain modulates reovirus attachment but not uncoating or transcription. These data suggest that σ1 conformational rearrangements mediate the efficiency of reovirus host cell binding.
Impacts of Fertilization on Biologically Cycled P in Xylem Sap of Fagus sylvatica L. Revealed by Means of the Oxygen Isotope Ratio in Phosphate
2020-09-15

Studies on the effect of high atmospheric N deposition report inconsistent results on forest productivity and N cycling which might be related to P availability in soil and subsequently affect tree P nutrition. We wanted to test the effects of (i) site i.e., a P-poor versus a P-rich site and of (ii) fertilization (N,P,N+P) on inorganic P (Pi) and organic P (Po) concentrations as well as on biologically cycled phosphate (inferred from the O isotope signature after adding an 18O-enriched label) in xylem sap. We measured Pi and Po concentrations and the O isotope signature in phosphate (δ18OPi) in xylem sap of beech (Fagus sylvatica L.) trees two and 14 days after addition of 18O-enriched water to the organic layer in a full factorial fertilization experiment (control, +N, +P, +NP) at two sites differing in P availability. Higher P concentrations in xylem sap at the P-rich than at the P-poor site originated from accelerated biological P cycling indicated by incorporation of 18O from the isotope label into phosphate in xylem sap shortly after labeling. At this site, δ18OW values of xylem sap after label application remained close to background δ18OW values of soil solution. We speculate that in contrast to P uptake, trees took up water from deeper (non-18O-labeled) soil layers. At the P-poor site, the 18O label was recovered both in xylem sap water and phosphate in xylem sap, the latter only after 14 days. These results imply that trees relied on the organic layer for P acquisition and water uptake. However, biological processes associated with an incorporation of 18O from the label were slower at the P-poor than at the P-rich site. P addition (P,NP) increased Pi concentrations in xylem sap at the P-rich site. Based on δ18OPi values in xylem sap, the additional P originated both from the fertilizer and from accelerated biological P cycling in soil. We conclude that P-poor sites likely suffer more from climate change in case of an increased frequency of droughts because as opposed to P-rich sites both water and nutrient uptake will be affected.