julilili42/papers huggingface dataset:
How glyphosate and its associated acidity affect early development in zebrafish (Danio rerio)
2019-06-19

Background Glyphosate is among the most extensively used pesticides worldwide. Following the ongoing highly controversial debate on this compound, its potential impact on non-target organisms is a fundamental scientific issue. In its pure compound form, glyphosate is known for its acidic properties. Methods We exposed zebrafish ( Danio rerio ) embryos to concentrations between 10 μM and 10 mM glyphosate in an unbuffered aqueous medium, as well as at pH 7, for 96 hours post fertilization (hpf). Furthermore, we investigated the effects of aqueous media in the range of pH 3 to 8, in comparison with 1 mM glyphosate treatment at the respective pH levels. Additionally, we exposed zebrafish to 7-deoxy-sedoheptulose (7dSh), another substance that interferes with the shikimate pathway by a mechanism analogous to that of glyphosate, at a concentration of one mM. The observed endpoints included mortality, the hatching rate, developmental delays at 24 hpf, the heart rate at 48 hpf and the malformation rate at 96 hpf. LC 10/50 , EC 10 and, if reasonable, EC 50 values were determined for unbuffered glyphosate. Results The results revealed high mortalities in all treatments associated with low pH, including high concentrations of unbuffered glyphosate (&gt;500 μM), low pH controls and glyphosate treatments with pH &lt; 3.4. Sublethal endpoints like developmental delays and malformations occurred mainly at higher concentrations of unbuffered glyphosate. In contrast, effects on the hatching rate became particularly prominent in treatments at pH 7, showing that glyphosate significantly accelerates hatching compared with the control and 7dSh, even at the lowest tested concentration. Glyphosate also affected the heart rate, resulting in alterations both at pH 7 and, even more pronounced, in the unbuffered system. In higher concentrations, glyphosate tended to accelerate the heart rate in zebrafish embryos, again, when not masked by the decelerating influence of its low pH. At pH &gt; 4, no mortality occurred, neither in the control nor in glyphosate treatments. At 1 mM, 7dSh did not induce any mortality, developmental delays or malformations; only slightly accelerated hatching and a decelerated heart rate were observed. Our results demonstrate that lethal impacts in zebrafish embryos can be attributed mainly to low pH, but we could also show a pH-independent effect of glyphosate on the development of zebrafish embryos on a sublethal level.
Generation of iPSCs by Nonintegrative RNA-Based Reprogramming Techniques: Benefits of Self-Replicating RNA versus Synthetic mRNA
2019-06-19

The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is gaining in importance in the fields of regenerative medicine, tissue engineering, and disease modeling. Patient-specific iPSCs have as an unlimited cell source a tremendous potential for generating various types of autologous cells. For the future clinical applicability of these iPSC-derived cells, the generation of iPSCs via nongenome integrating methods and the efficient reprogramming of patients’ somatic cells are required. In this study, 2 different RNA-based footprint-free methods for the generation of iPSCs were compared: the use of synthetic modified messenger RNAs (mRNAs) or self-replicating RNAs (srRNAs) encoding the reprogramming factors and GFP. Using both RNA-based methods, integration-free iPSCs without genomic alterations were obtained. The pluripotency characteristics identified by specific marker detection and the in vitro and in vivo trilineage differentiation capacity were comparable. Moreover, the incorporation of a GFP encoding sequence into the srRNA enabled a direct and convenient monitoring of the reprogramming procedure and the successful detection of srRNA translation in the transfected cells. Nevertheless, the use of a single srRNA to induce pluripotency was less time consuming, faster, and more efficient than the daily transfection of cells with synthetic mRNAs. Therefore, we believe that the srRNA-based approach might be more appropriate and efficient for the reprogramming of different types of somatic cells for clinical applications.
Effects of Exergaming on Attentional Deficits and Dual-Tasking in Parkinson's Disease
2019-06-19

<b>Introduction:</b> Impairment of dual-tasking, as an attention-based primary cognitive dysfunction, is frequently observed in Parkinson's Disease (PD). The Training-PD study investigated the efficiency of exergaming, as a novel cognitive-motor training approach, to improve attention-based deficits and dual-tasking in PD when compared to healthy controls. <b>Methods:</b> Eighteen PD patients and 17 matched healthy controls received a 6-week home-based training period of exergaming. Treatment effects were monitored using quantitative motor assessment of gait and cognitive testing as baseline and after 6 weeks of training. <b>Results:</b> At baseline PD patients showed a significantly worse performance in several quantitative motor assessment parameters and in two items of cognitive testing. After 6 weeks of exergames training, the comparison of normal gait vs. dual-tasking in general showed an improvement of stride length in the PD group, without a gait-condition specific improvement. In the direct comparison of three different gait conditions (normal gait vs. dual-tasking calculating while walking vs. dual-tasking crossing while walking) PD patients showed a significant improvement of stride length under the dual-tasking calculating condition. This corresponded to a significant improvement in one parameter of the D2 attention test. <b>Conclusions:</b> We conclude, that exergaming, as an easy to apply, safe technique, can improve deficits in cognitive-motor dual-tasking and attention in PD.
HDMTX-based induction therapy followed by consolidation with conventional systemic chemotherapy and intraventricular therapy (modified Bonn protocol) in primary CNS lymphoma: a monocentric retrospective analysis
2019-06-19

The data of this single center experience suggest that the outcome with a modified Bonn protocol was comparable to that of the previous regimen, showed fewer Ommaya reservoir infections and may have a trend for better outcome with intraventricular therapy.
Amelioration of Behavioral Impairments and Neuropathology by Antiepileptic Drug Topiramate in a Transgenic Alzheimer’s Disease Model Mice, APP/PS1
2019-06-19

Alzheimer’s disease (AD) is a neurodegenerative disease that is the main cause of dementia in the elderly. The aggregation of β-amyloid peptides is one of the characterizing pathological changes of AD. Topiramate is an antiepileptic drug, which in addition, is used in the treatment of many neuropsychiatric disorders. In this study, the therapeutic effects of topiramate were investigated in a transgenic mouse model of cerebral amyloidosis (APP/PS1 mice). Before, during, and after topiramate treatment, behavioral tests were performed. Following a treatment period of 21 days, topiramate significantly ameliorated deficits in nest-constructing capability as well as in social interaction. Thereafter, brain sections of mice were analyzed, and a significant attenuation of microglial activation as well as β-amyloid deposition was observed in sections from topiramate-treated APP/PS1 mice. Therefore, topiramate could be considered as a promising drug in the treatment of human AD.
Rare-Earth Based Chemoresistive CO2 Sensors and Their Operando Investigations
2019-06-19

Rare-earth oxycarbonates have been proposed as promising chemoresistive materials for CO2 sensors. In this contribution we present the results of a broad investigation focused on selecting the best candidates in the rare-earth compounds and, in the case of the best performing material, preliminary results dealing with the understanding of sensing by the operando methods.
Classification of low-luminosity stellar X-ray sources in the field of the Draco dwarf spheroidal galaxy
2019-06-19

Aims . A previous study of the X-ray luminosity function of the X-ray sources in the Draco dwarf spheroidal (dSph) galaxy field indicates the presence of a population of unknown X-ray sources in the soft energy range of 0.5–2 keV. In 2015, there were twenty-six further deep XMM-Newton observations of Draco dSph, providing an opportunity for a new study of the as yet unclassified sources. Methods . We applied the classification criteria presented in our previous multi-wavelength study of the X-ray sources of the Draco dSph to the sources detected in the combined 2009 and 2015 XMM-Newton data set. These criteria are based on X-ray studies and properties of the optical, near-infrared, and mid-infrared counterparts and allows us to distinguish background active galactic nuclei (AGNs) and galaxies from other types of X-ray sources. In this work we performed X-ray spectral and timing analyses for fifteen sources in the field of Draco dSph with stellar counterparts. Results . We present the classification of X-ray sources, for which the counterpart is identified as a stellar object based on our criteria from multi-wavelength data. We identify three new symbiotic stars in the Draco dSph with X-ray luminosities between ∼3.5 × 10 34 erg s −1 and 5.5 × 10 34 erg s −1 . The X-ray spectral analysis shows that two of the classified symbiotic stars are β -type. This is the first identification of this class of symbiotic stars in a nearby galaxy. Eight sources are classified as Galactic M dwarfs in the field of the Draco dSph. These M dwarfs are between ∼140 and 800 pc distant, with X-ray luminosities are between 10 28 and 10 29 erg s −1 and logarithmic ratios of X-ray to bolometric luminosity, log( L X /L bol ), between −3.4 and −2.1. The multiple observations allowed us to investigate flare activity of the M dwarfs. For 5 M dwarfs flare(s) are observed with a significance of &gt; 3 σ level of confidence. Moreover, we classified three foreground sources, located at distances of the order of ∼1–3 kpc in the field of the Draco dSph. Based on both the X-ray luminosities of these foreground sources (&gt; 10 30 erg s −1 ) and their optical counterparts (late type G or K stars), these X-ray sources are classified as candidates of contact binary systems. Conclusions . Our study of X-ray sources of the Draco dSph shows that accreting white dwarfs are the most promising X-ray population of dSphs, which is in line with theoretical expectations. The number of Galactic M dwarfs detected at our X-ray sensitivity limit is consistent with the expectation based on the space density of M dwarfs.
Complete Q-Matrices in General Attribute Structure Models
2019-06-19

In cognitive diagnostic assessment a property of the Q-matrix, usually referred to as completeness, warrants that the cognitive attributes underlying the observed behavior can be assessed uniquely. Characterizations of completeness were first derived under the assumption of independent attributes, and are currently under investigation for interdependent attributes. The dominant approach considers so-called attribute hierarchies, which are conceptualized through a partial order on the set of attributes. The present paper corrects and extends previously published results on this issue obtained for conjunctive attribute hierarchy models. Drawing upon results from knowledge structure theory it provides novel sufficient and necessary conditions for completeness of the -matrix, not only for conjunctive models on attribute hierarchies, but also on more general attribute structures.
Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women
2019-06-19

Abstract Background Cytokines are signaling molecules operating within complex cascade patterns and having exceptional modulatory functions. They impact various physiological processes such as neuroendocrine and metabolic interactions, neurotrophins’ metabolism, neuroplasticity, and may affect behavior and cognition. In our previous study, we found that sex and Cytomegalovirus (CMV)-serostatus may modulate levels of circulating pro- and anti-inflammatory cytokines, metabolic factors, immune cells, and cognitive performance, as well as associations between them. Results In the present study, we used a graph-theoretical approach to investigate the network topology dynamics of 22 circulating biomarkers and 11 measures of cognitive performance in 161 older participants recruited to undergo a six-months training intervention. For network construction, we applied coefficient of determination ( R 2 ) that was calculated for all possible pairs of variables (N = 33) in four groups (CMV − men and women; CMV + men and women). Network topology has been evaluated by clustering coefficient ( CC ) and characteristic path length ( CPL ) as well as local ( E local ) and global ( E global ) efficiency, showing the degree of network segregation ( CC and E local ) and integration ( CPL and E global ). We found that networks under consideration showed small-world networks properties with more random characteristics. Mean CC , as well as local and global efficiency were highest and CPL shortest in CMV − males (having lowest inflammatory status and highest cognitive performance). CMV − and CMV + females did not show any significant differences. Modularity analyses showed that the networks exhibit in all cases highly differentiated modular organization (with Q -value ranged between 0.397 and 0.453). Conclusions In this work, we found that segregation and integration properties of the network were notably stronger in the group with balanced inflammatory status. We were also able to confirm our previous findings that CMV-infection and sex modulate multiple circulating biomarkers and cognitive performance and that balanced inflammatory and metabolic status in elderly contributes to better cognitive functioning. Thus, network analyses provide a useful strategy for visualization and quantitative description of multiple interactions between various circulating pro- and anti-inflammatory biomarkers, hormones, neurotrophic and metabolic factors, immune cells, and measures of cognitive performance and can be in general applied for analyzing interactions between different physiological systems.
Peer Review #3 of "How glyphosate and its associated acidity affect early development in zebrafish (Danio rerio) (v0.1)"
2019-06-19

Background.Glyphosate is among the most extensively used pesticides worldwide.Following the ongoing highly controversial debate on this compound, its potential impact on non-target organisms is a fundamental scientific issue.In its pure compound form, glyphosate is known for its acidic properties.Methods.We exposed zebrafish (Danio rerio) embryos to concentrations between 10 μM and 10mM glyphosate in an unbuffered aqueous medium, as well as at pH 7, for 96 hours post fertilisation (hpf).Furthermore, we investigated the effects of aqueous media in the range of pH 3 to pH 8, in comparison with 1 mM glyphosate treatment at the respective pH levels.Additionally, we exposed zebrafish to 7deoxy-sedoheptulose (7dSh), another substance that interferes with the shikimate pathway by a mechanism analogous to that of glyphosate, at a concentration of 1 mM.The observed endpoints included mortality, the hatching rate, developmental delays at 24 hpf, the heart rate at 48 hpf and the malformation rate at 96 hpf.LC 10/50 , EC 10 and, if reasonable, EC 50 values were determined for unbuffered glyphosate.Results.The results revealed high mortalities in all treatments associated with low pH, including high concentrations of unbuffered glyphosate (>500μM), low pH controls and glyphosate treatments with pH < 3.4.Sublethal endpoints like developmental delays and malformations occurred mainly at higher concentrations of unbuffered glyphosate.In contrast, effects on the hatching rate became particularly prominent in treatments at pH7, showing that glyphosate significantly accelerates hatching compared with the control and 7dSh, even at the lowest tested concentration.Glyphosate also affected the heart rate, resulting in alterations both at pH 7 and, even more pronounced, in the unbuffered system.In higher concentrations, glyphosate tended to accelerate the heart rate in zebrafish embryos, again, when not masked by the decelerating influence of its low pH.At pH > 4, no mortality occurred, neither in the control nor in glyphosate treatments.At 1 mM, 7dSh did not induce any mortality, developmental delays or malformations; only slightly accelerated hatching and a decelerated heart rate were observed.Our results demonstrate that lethal impacts in zebrafish embryos can be attributed mainly to low pH, but we could also show a pH-independent effect of glyphosate on the development of zebrafish embryos on a sublethal level.
Peer Review #1 of "How glyphosate and its associated acidity affect early development in zebrafish (Danio rerio) (v0.1)"
2019-06-19

Background.Glyphosate is among the most extensively used pesticides worldwide.Following the ongoing highly controversial debate on this compound, its potential impact on non-target organisms is a fundamental scientific issue.In its pure compound form, glyphosate is known for its acidic properties.Methods.We exposed zebrafish (Danio rerio) embryos to concentrations between 10 μM and 10mM glyphosate in an unbuffered aqueous medium, as well as at pH 7, for 96 hours post fertilisation (hpf).Furthermore, we investigated the effects of aqueous media in the range of pH 3 to pH 8, in comparison with 1 mM glyphosate treatment at the respective pH levels.Additionally, we exposed zebrafish to 7deoxy-sedoheptulose (7dSh), another substance that interferes with the shikimate pathway by a mechanism analogous to that of glyphosate, at a concentration of 1 mM.The observed endpoints included mortality, the hatching rate, developmental delays at 24 hpf, the heart rate at 48 hpf and the malformation rate at 96 hpf.LC 10/50 , EC 10 and, if reasonable, EC 50 values were determined for unbuffered glyphosate.Results.The results revealed high mortalities in all treatments associated with low pH, including high concentrations of unbuffered glyphosate (>500μM), low pH controls and glyphosate treatments with pH < 3.4.Sublethal endpoints like developmental delays and malformations occurred mainly at higher concentrations of unbuffered glyphosate.In contrast, effects on the hatching rate became particularly prominent in treatments at pH7, showing that glyphosate significantly accelerates hatching compared with the control and 7dSh, even at the lowest tested concentration.Glyphosate also affected the heart rate, resulting in alterations both at pH 7 and, even more pronounced, in the unbuffered system.In higher concentrations, glyphosate tended to accelerate the heart rate in zebrafish embryos, again, when not masked by the decelerating influence of its low pH.At pH > 4, no mortality occurred, neither in the control nor in glyphosate treatments.At 1 mM, 7dSh did not induce any mortality, developmental delays or malformations; only slightly accelerated hatching and a decelerated heart rate were observed.Our results demonstrate that lethal impacts in zebrafish embryos can be attributed mainly to low pH, but we could also show a pH-independent effect of glyphosate on the development of zebrafish embryos on a sublethal level.
Peer Review #2 of "How glyphosate and its associated acidity affect early development in zebrafish (Danio rerio) (v0.1)"
2019-06-19

Background.Glyphosate is among the most extensively used pesticides worldwide.Following the ongoing highly controversial debate on this compound, its potential impact on non-target organisms is a fundamental scientific issue.In its pure compound form, glyphosate is known for its acidic properties.Methods.We exposed zebrafish (Danio rerio) embryos to concentrations between 10 μM and 10mM glyphosate in an unbuffered aqueous medium, as well as at pH 7, for 96 hours post fertilisation (hpf).Furthermore, we investigated the effects of aqueous media in the range of pH 3 to pH 8, in comparison with 1 mM glyphosate treatment at the respective pH levels.Additionally, we exposed zebrafish to 7deoxy-sedoheptulose (7dSh), another substance that interferes with the shikimate pathway by a mechanism analogous to that of glyphosate, at a concentration of 1 mM.The observed endpoints included mortality, the hatching rate, developmental delays at 24 hpf, the heart rate at 48 hpf and the malformation rate at 96 hpf.LC 10/50 , EC 10 and, if reasonable, EC 50 values were determined for unbuffered glyphosate.Results.The results revealed high mortalities in all treatments associated with low pH, including high concentrations of unbuffered glyphosate (>500μM), low pH controls and glyphosate treatments with pH < 3.4.Sublethal endpoints like developmental delays and malformations occurred mainly at higher concentrations of unbuffered glyphosate.In contrast, effects on the hatching rate became particularly prominent in treatments at pH7, showing that glyphosate significantly accelerates hatching compared with the control and 7dSh, even at the lowest tested concentration.Glyphosate also affected the heart rate, resulting in alterations both at pH 7 and, even more pronounced, in the unbuffered system.In higher concentrations, glyphosate tended to accelerate the heart rate in zebrafish embryos, again, when not masked by the decelerating influence of its low pH.At pH > 4, no mortality occurred, neither in the control nor in glyphosate treatments.At 1 mM, 7dSh did not induce any mortality, developmental delays or malformations; only slightly accelerated hatching and a decelerated heart rate were observed.Our results demonstrate that lethal impacts in zebrafish embryos can be attributed mainly to low pH, but we could also show a pH-independent effect of glyphosate on the development of zebrafish embryos on a sublethal level.
Design, Synthesis and Biological Evaluation of 7-Chloro-9H-pyrimido[4,5-b]indole-based Glycogen synthase kinase-3β inhibitors
2019-06-19

The dataset related to the publication: Andreev et al.Design, Synthesis and Biological Evaluation of 7 Chloro-9H-pyrimido[4,5-b]indole-based Glycogen synthase kinase-3&amp;beta; inhibitors. The files include: 1) Movies of the MD simulations of compounds 14b (Cmpd14b.mpg) and24 (Cmpd24.mpg). 2) Raw trajectory files of the Desmond MD simulations of the compounds14b (14b.zip),24 (24.zip) and 24 (3aR, 7aS) (24_3aR_7aS.zip)(contains out.cms and the full trj files). 3)Output conformations of the QM Tautomer &amp;amp; Conformation Predictor of Maestro (Schr&amp;ouml;dinger, LLC, New York, NY, 2019) of the compounds 14b (Cmpd14b_QMconftauto_output.mae;Cmpd14b_QMconftauto_output.sdf), 24(Cmpd24_QMconftauto_output.mae;Cmpd24_QMconftauto_output.sdf) and 24 (3aR, 7aS)(Cmpd24_3aR_7aS_QMconftauto_output.mae;Cmpd24_3aR_7aS_QMconftauto_output.sdf) 4) Jaguar pKa calculation (conformations) output-files for compounds 14b, 14c,14d,14e,14f,14g,14h,14i,14j,14k,14l,14m,14n pKa.zip (contains conformation in .mae file and Final weighted pKa value in .out file).