julilili42/papers huggingface dataset:
Dataset (IV) related to publication: Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors
2021-03-02

MD simulation data of <strong>2</strong> related to the publication Pantsar et al.: <em>Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors.</em> Individual .zip files contain raw-desmond trajectories (-out.cms files and trj-files). All datasets related to this publication: https://doi.org/10.5281/zenodo.4568113(compound <strong>1</strong>; dataset: I) https://doi.org/10.5281/zenodo.4572444 (compound <strong>1</strong>; dataset: II) https://doi.org/10.5281/zenodo.4561797(compound <strong>2</strong>; dataset: III) https://doi.org/10.5281/zenodo.4563896 (compound <strong>2</strong>; dataset: IV) https://doi.org/10.5281/zenodo.5563359 (<strong>SB203580</strong>; dataset: V) https://doi.org/10.5281/zenodo.5563655 (<strong>SB203580</strong>; dataset: VI) https://doi.org/10.5281/zenodo.5564118 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VII) https://doi.org/10.5281/zenodo.5564208 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VIII) https://doi.org/10.5281/zenodo.5564586 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: IX) https://doi.org/10.5281/zenodo.5570882 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: X) https://doi.org/10.5281/zenodo.5571352 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: XI) The datasets include original Desmond raw-trajectories (datasets I–VIII), PDB-coordinates for the energy minimized metastable state derived structures (datasets II, IV and VI) and raw-trajectories of the well-tempered metadynamics simulations (dataset IX–XI).
Dataset (II) related to publication: Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors
2021-03-02

MD simulation data of <strong>1</strong> related to the publication Pantsar et al.: <em>Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors.</em> Individual .zip files contain raw-desmond trajectories (-out.cms files and trj-files). All datasets related to this publication: https://doi.org/10.5281/zenodo.4568113(compound <strong>1</strong>; dataset: I) https://doi.org/10.5281/zenodo.4572444 (compound <strong>1</strong>; dataset: II) https://doi.org/10.5281/zenodo.4561797(compound <strong>2</strong>; dataset: III) https://doi.org/10.5281/zenodo.4563896 (compound <strong>2</strong>; dataset: IV) https://doi.org/10.5281/zenodo.5563359 (<strong>SB203580</strong>; dataset: V) https://doi.org/10.5281/zenodo.5563655 (<strong>SB203580</strong>; dataset: VI) https://doi.org/10.5281/zenodo.5564118 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VII) https://doi.org/10.5281/zenodo.5564208 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VIII) https://doi.org/10.5281/zenodo.5564586 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: IX) https://doi.org/10.5281/zenodo.5570882 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: X) https://doi.org/10.5281/zenodo.5571352 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: XI) The datasets include original Desmond raw-trajectories (datasets I–VIII), PDB-coordinates for the energy minimized metastable state derived structures (datasets II, IV and VI) and raw-trajectories of the well-tempered metadynamics simulations (dataset IX–XI).
Dataset (III) related to publication: Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors
2021-03-02

MD simulation data of <strong>2</strong> related to the publication Pantsar et al.: <em>Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors.</em> Individual .zip files contain raw-desmond trajectories (-out.cms files and trj-files). All datasets related to this publication: https://doi.org/10.5281/zenodo.4568113(compound <strong>1</strong>; dataset: I) https://doi.org/10.5281/zenodo.4572444 (compound <strong>1</strong>; dataset: II) https://doi.org/10.5281/zenodo.4561797(compound <strong>2</strong>; dataset: III) https://doi.org/10.5281/zenodo.4563896 (compound <strong>2</strong>; dataset: IV) https://doi.org/10.5281/zenodo.5563359 (<strong>SB203580</strong>; dataset: V) https://doi.org/10.5281/zenodo.5563655 (<strong>SB203580</strong>; dataset: VI) https://doi.org/10.5281/zenodo.5564118 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VII) https://doi.org/10.5281/zenodo.5564208 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VIII) https://doi.org/10.5281/zenodo.5564586 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: IX) https://doi.org/10.5281/zenodo.5570882 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: X) https://doi.org/10.5281/zenodo.5571352 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: XI) The datasets include original Desmond raw-trajectories (datasets I–VIII), PDB-coordinates for the energy minimized metastable state derived structures (datasets II, IV and VI) and raw-trajectories of the well-tempered metadynamics simulations (dataset IX–XI).
Dataset (I) related to publication: Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors
2021-03-02

MD simulation data of<strong> 1</strong> related to the publication Pantsar et al.: <em>Decisive Role of Water and Protein Dynamics in Residence Time of p38a MAP Kinase Inhibitors.</em> Individual .zip files contain raw-desmond trajectories (-out.cms files and trj-files). All datasets related to this publication: https://doi.org/10.5281/zenodo.4568113(compound <strong>1</strong>; dataset: I) https://doi.org/10.5281/zenodo.4572444 (compound <strong>1</strong>; dataset: II) https://doi.org/10.5281/zenodo.4561797(compound <strong>2</strong>; dataset: III) https://doi.org/10.5281/zenodo.4563896 (compound <strong>2</strong>; dataset: IV) https://doi.org/10.5281/zenodo.5563359 (<strong>SB203580</strong>; dataset: V) https://doi.org/10.5281/zenodo.5563655 (<strong>SB203580</strong>; dataset: VI) https://doi.org/10.5281/zenodo.5564118 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VII) https://doi.org/10.5281/zenodo.5564208 (compound <strong>1</strong> simulated in compound <strong>2</strong> metastable state <strong>2-<em>S</em><sub>3</sub></strong>; dataset: VIII) https://doi.org/10.5281/zenodo.5564586 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: IX) https://doi.org/10.5281/zenodo.5570882 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: X) https://doi.org/10.5281/zenodo.5571352 (well-tempered metadynamics simulations of compounds <strong>1</strong> and <strong>2</strong>; dataset: XI) The datasets include original Desmond raw-trajectories (datasets I–VIII), PDB-coordinates for the energy minimized metastable state derived structures (datasets II, IV and VI) and raw-trajectories of the well-tempered metadynamics simulations (dataset IX–XI).
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma
2021-03-03

Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).
Targeting the Main Protease of SARS‐CoV‐2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors
2021-03-03

Abstract The main protease of SARS‐CoV‐2 (M pro ), the causative agent of COVID‐19, constitutes a significant drug target. A new fluorogenic substrate was kinetically compared to an internally quenched fluorescent peptide and shown to be ideally suitable for high throughput screening with recombinantly expressed M pro . Two classes of protease inhibitors, azanitriles and pyridyl esters, were identified, optimized and subjected to in‐depth biochemical characterization. Tailored peptides equipped with the unique azanitrile warhead exhibited concomitant inhibition of M pro and cathepsin L, a protease relevant for viral cell entry. Pyridyl indole esters were analyzed by a positional scanning. Our focused approach towards M pro inhibitors proved to be superior to virtual screening. With two irreversible inhibitors, azanitrile 8 (k inac /K i =37 500 m −1 s −1 , K i =24.0 n m ) and pyridyl ester 17 (k inac /K i =29 100 m −1 s −1 , K i =10.0 n m ), promising drug candidates for further development have been discovered.
Inactivation of SARS-CoV-2 through Treatment with the Mouth Rinsing Solutions ViruProX® and BacterX® Pro
2021-03-03

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic effects daily dental work. Therefore, infection control measures are necessary to prevent infection of dental personnel during dental treatments. The use of a preprocedural mouth rinse with chlorhexidine (CHX), cetylpyridinium chloride (CPC), or hydrogen peroxide (H2O2) solution for 30–60 s may reduce the viral load and may protect the personnel in a dental practice. In the present study the virucidal effect of the mouth rinsing solutions ViruProX® with 0.05% CPC and 1.5% H2O2 and BacterX® pro containing 0.1% CHX, 0.05% CPC, and 0.005% sodium fluoride (F-) was investigated in vitro. The mouth rinsing solutions successfully inactivated infectious SARS-CoV-2 particles, the causative agent of coronavirus disease 2019 (COVID-19), within 30 s. To determine the effective components, CHX, CPC, H2O2, and a combination of CHX and CPC, were tested against SARS-CoV-2 in addition. While a combination of CPC and CHX as well as CPC alone led to a significant reduction of infectious viral particles, H2O2 and CHX alone had no virucidal effect against SARS-CoV-2. It can be assumed that preprocedural rinsing of the mouth with ViruProX® or BacterX® pro will reduce the viral load in the oral cavity and could thus lower the transmission of SARS-CoV-2 in dental practice.
Biallelic loss-of-function variations in PRDX3 cause cerebellar ataxia
2021-03-03

Abstract Peroxiredoxin 3 (PRDX3) belongs to a superfamily of peroxidases that function as protective antioxidant enzymes. Among the six isoforms (PRDX1–PRDX6), PRDX3 is the only protein exclusively localized to the mitochondria, which are the main source of reactive oxygen species. Excessive levels of reactive oxygen species are harmful to cells, inducing mitochondrial dysfunction, DNA damage, lipid and protein oxidation and ultimately apoptosis. Neuronal cell damage induced by oxidative stress has been associated with numerous neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. Leveraging the large aggregation of genomic ataxia datasets from the PREPARE (Preparing for Therapies in Autosomal Recessive Ataxias) network, we identified recessive mutations in PRDX3 as the genetic cause of cerebellar ataxia in five unrelated families, providing further evidence for oxidative stress in the pathogenesis of neurodegeneration. The clinical presentation of individuals with PRDX3 mutations consists of mild-to-moderate progressive cerebellar ataxia with concomitant hyper- and hypokinetic movement disorders, severe early-onset cerebellar atrophy, and in part olivary and brainstem degeneration. Patient fibroblasts showed a lack of PRDX3 protein, resulting in decreased glutathione peroxidase activity and decreased mitochondrial maximal respiratory capacity. Moreover, PRDX3 knockdown in cerebellar medulloblastoma cells resulted in significantly decreased cell viability, increased H2O2 levels and increased susceptibility to apoptosis triggered by reactive oxygen species. Pan-neuronal and pan-glial in vivo models of Drosophila revealed aberrant locomotor phenotypes and reduced survival times upon exposure to oxidative stress. Our findings reveal a central role for mitochondria and the implication of oxidative stress in PRDX3 disease pathogenesis and cerebellar vulnerability and suggest targets for future therapeutic approaches.
Alpha entrainment drives pain relief using visual stimulation in a sample of chronic pain patients: a proof-of-concept controlled study
2021-03-03

One-third of the population in the UK and worldwide struggle with chronic pain. Entraining brain alpha activity through noninvasive visual stimulation has been shown to reduce experimental pain in healthy volunteers. Neural oscillations entrainment offers a potential noninvasive and nonpharmacological intervention for patients with chronic pain, which can be delivered in the home setting and has the potential to reduce use of medications. However, evidence supporting its use in patients with chronic pain is lacking. This study explores whether (a) alpha entrainment increase alpha power in patients and (b) whether this increase in alpha correlates with analgesia. In total, 28 patients with chronic pain sat in a comfortable position and underwent 4-min visual stimulation using customised goggles at 10 Hz (alpha) and 7 Hz (control) frequency blocks in a randomised cross-over design. 64-channel electroencephalography and 11-point numeric rating scale pain intensity and pain unpleasantness scores were recorded before and after stimulation. Electroencephalography analysis revealed frontal alpha power was significantly higher when stimulating at 10 Hz when compared to 7 Hz. There was a significant positive correlation between increased frontal alpha and reduction in pain intensity ( r = 0.33; P &lt; 0.05) and pain unpleasantness ( r = 0.40; P &lt; 0.05) in the 10 Hz block. This study provides the first proof of concept that changes in alpha power resulting from entrainment correlate with an analgesic response in patients with chronic pain. Further studies are warranted to investigate dose–response parameters and equivalence to analgesia provided by medications.
Comparative analysis of TMPA and IMERG precipitation datasets in the arid environment of El- Qaa Plain, Sinai
2021-03-03

&amp;lt;p&amp;gt;The replenishment of aquifers depends mainly on precipitation rates, which is of vital 19 importance for determining water budgets in arid and semi-arid regions. El-Qaa Plain in Sinai 20 Peninsula is such a region which experiences a constant population growth. The local water budget 21 equilibrium is negatively affected by relatively frequent light rain events. This study compares the 22 performance of two sets of satellite-based data of precipitation and in situ rainfall measurements. The 23 dates selected refer to rainfall events between 2015 and 2018. For this purpose, 0.1&amp;amp;#176; and 0.25&amp;amp;#176; spatial 24 resolution TMPA (TRMM Multi-satellite Precipitation Analysis) and IMERG (Integrated Multi-25 satellitE Retrievals for GPM) data were retrieved and analyzed, employing appropriate statistical 26 metrics. The best-performing data set was determined as the data source capable to most accurately 27 bridge gaps in the limited rain gauge records, embracing both frequent light-intensity rain events 28 and rarer heavy-intensity events. With light-intensity events the corresponding satellite-based data 29 sets differ the least and correlate more, while the greatest differences and weakest correlations are 30 noted for the heavy-intensity events. The satellite-based records best match those of the rain gauges 31 during light-intensity events, when compared to the heaviest ones. IMERG data exhibit a superior 32 performance than TMPA, in all rainfall intensities.&amp;lt;/p&amp;gt;
Sleep Facilitates Problem Solving With No Additional Gain Through Targeted Memory Reactivation
2021-03-03

According to the active systems consolidation theory, memories undergo reactivation during sleep that can give rise to qualitative changes of the representations. These changes may generate new knowledge such as gaining insight into solutions for problem solving. targeted memory reactivation (TMR) uses learning-associated cues, such as sounds or odors, which have been shown to improve memory consolidation when re-applied during sleep. Here we tested whether TMR during slow wave sleep (SWS) and/or rapid eye movement (REM) sleep increases problem solving. Young healthy volunteers participated in one of two experiments. Experiment 1 tested the effect of natural sleep on problem solving. Subjects were trained in a video game-based problem solving task until being presented with a non-solved challenge. Followed by a ~10-h incubation interval filled with nocturnal sleep or daytime wakefulness, subjects were tested on the problem solving challenge again. Experiment 2 tested the effect of TMR on problem solving, with subjects receiving auditory TMR either during SWS (SWSstim), REM sleep (REMstim), or wakefulness (Wakestim). In Experiment 1, sleep improved problem solving, with 62% of subjects from the Sleep group solving the problem compared to 24% of the Wake group. Subjects with higher amounts of SWS in the Sleep group had a higher chance to solve the problem. In Experiment 2, TMR did not change the sleep effect on problem solving: 56 and 58% of subjects from the SWSstim and REMstim groups solved the problem compared to 57% from the Wakestim group. These findings indicate that sleep, and particularly SWS, facilitates problem solving, whereas this effect is not further increased by TMR.
Bayesian ODE solvers: the maximum a posteriori estimate
2021-03-03

Abstract There is a growing interest in probabilistic numerical solutions to ordinary differential equations. In this paper, the maximum a posteriori estimate is studied under the class of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>ν</mml:mi> </mml:math> times differentiable linear time-invariant Gauss–Markov priors, which can be computed with an iterated extended Kalman smoother. The maximum a posteriori estimate corresponds to an optimal interpolant in the reproducing kernel Hilbert space associated with the prior, which in the present case is equivalent to a Sobolev space of smoothness <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>ν</mml:mi> <mml:mo>+</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> </mml:math> . Subject to mild conditions on the vector field, convergence rates of the maximum a posteriori estimate are then obtained via methods from nonlinear analysis and scattered data approximation. These results closely resemble classical convergence results in the sense that a <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>ν</mml:mi> </mml:math> times differentiable prior process obtains a global order of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>ν</mml:mi> </mml:math> , which is demonstrated in numerical examples.
Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI
2021-03-03

ABSTRACT Laminar BOLD-fMRI has been applied to better depict the neuronal input and output circuitry and functional connectivity across cortical layers by measuring local hemodynamic changes. Despite extensive studies detecting laminar fMRI signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across different cortical regions remain to be fully investigated in both evoked and resting states. Here, we developed a multi-slice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 μm) and temporal resolution (100 ms) in anesthetized rats. Across different scanning trials, we detected both laminar-specific positive and negative BOLD responses in the surrounding cortical region adjacent to the most activated cortex under evoked condition. Specifically, in contrast to the typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for the trials with negative BOLD in adjacent regions, which indicate a brain state-dependent laminar-fMRI responses based on cortiocotical interaction from different trials. Also, we acquired the laminar-specific rs-fMRI signals across different cortical regions, of which the high spatiotemporal resolution allows us to estimate lag times based on the maximal cross-correlation of laminar-specific rs-fMRI signals. In contrast to the larger variability of lag times in L1 and 6, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from the caudal to the rostral slice. In summary, our work provides a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity with MS-LS, presenting layer-specific spatiotemporal variation of both evoked and rs-fMRI signals.
Fabric beats in radar data across the NEGIS ice stream
2021-03-03

&amp;lt;p&amp;gt;Crystal anisotropy of ice causes slight birefringence for electromagnetic waves. At the same time, the mechanical anisotropy amounts to several orders of magnitude, thus making fabric properties highly-relevant for internal deformation. To date, bulk anisotropy of glaciers and ice sheets can be determined by geophysical methods, such as polarimetric radar, or direct sampling from ice cores. A shortcoming has been so far that changes of bulk anisotropy could mainly be inferred at single point observations, but less so as continuous profiles. Here, we exploit the effect of birefringence caused by bulk anisotropy in co-polarized airborne radar data to determine the horizontal anisotropy across the North-East Greenland Ice Stream. We base our analysis on the fact that birefringence causes a second-order effect on radar amplitudes, which leads to a beat frequency in the low and medium frequency range (O(100 kHz)), which is proportional to the horizontal anisotropy. Complementing our radar analysis with direct fabric and dielectric property observations we can constrain the range of all three fabric eigenvalues as a function of space across and along the ice stream. Finally, we assess the effect of the inferred fabric distribution on the overall ice rheology in the context of ice stream dynamics. Our overall approach has the advantage that it can be applied to co-polarized radar systems, as commonly used in profiling surveys, and does not require dedicated cross-polarized radar set-up. This provides the opportunity to revisit older data, especially from Greenland and Antarctica, to map fabric anisotropy in ice-dynamically interesting regions.&amp;lt;/p&amp;gt;