gebhart/patrepeval huggingface dataset:
Phytoconstituents, In Vitro Anti-Infective Activity of Buddleja indica Lam., and In Silico Evaluation of its SARS-CoV-2 Inhibitory Potential (2021)

Phytochemical investigation of <i>Buddleja indica</i> Lam. leaves methanol extract (BIT) resulted in the isolation of six known compounds for the first time from the plant, namely, <i>p</i>-hydroxybenzoic acid 1), caffeic acid 2), quercetin 3-O-<i>β-</i>D glucoside-7-O-α-L-rhamnoside 3), kaempferol 3-O-<i>β-</i>D glucoside-7-O-α-L-rhamnoside 4), quercetin 7-O-<i>β-</i>D glucoside 5) and kaempferol 6). BIT extract showed potent antibacterial activity with MIC values ranging between 0.48 and 1.95 μg/ml with <i>Bacillus subtilis</i> was the most susceptible to the BIT effect. It showed a notable antimycobacterial and anti-<i>Helicobacter pylori</i> activity with MIC values of 100 and 80 μg/ml, respectively. Vesicular stomatitis virus (VSV) was more sensitive to the antiviral activity of BIT comparable to herpes simplex virus type 1 (HSV-1), showing 48.38 and 41.85% inhibition of the viral replication at a dose of 50 μg/ml for VSV and HSV-1, respectively. <i>In silico</i> molecular docking of the isolated compounds revealed that caffeic acid 2) showed the highest fitting within the active sites of DNA-gyrase, topoisomerase IV, and SARS-CoV-2 M<sup>Pro</sup>. Quercetin 7-O-<i>β-</i>D glucoside 5) revealed the best fitting in dihydrofolate reductase active site with ∆ G value equals -36.53 Kcal/mol. Kaempferol 6) exhibited the highest fitting towards <i>β</i>-lactamase, SARS-CoV-2PL<sup>pro</sup>, and SARS-CoV-2 3CL<sup>pro</sup> active sites. Thus, <i>B. indica</i> Lam. can be considered as a future source of cheap, substantially safe, and credible antibacterial, antifungal, and antiviral candidate of natural origin that could effectively participate in solving the problem of COVID-19 pandemic. These findings provide a scientific consolidation for the ethnomedicinal uses of <i>Buddleja indica</i> Lam. as a topical antiseptic.
Stimulation of Toll-like receptor 3 and 4 induces interleukin-1β maturation by caspase-8 (2008)

The cytokine interleukin (IL)-1beta is a key mediator of the inflammatory response and has been implicated in the pathophysiology of acute and chronic inflammation. IL-1beta is synthesized in response to many stimuli as an inactive pro-IL-1beta precursor protein that is further processed by caspase-1 into mature IL-1beta, which is the secreted biologically active form of the cytokine. Although stimulation of membrane-bound Toll-like receptors (TLRs) up-regulates pro-IL-1beta expression, activation of caspase-1 is believed to be mainly initiated by cytosolic Nod-like receptors. In this study, we show that polyinosinic:polycytidylic acid (poly[I:C]) and lipopolysaccharide stimulation of macrophages induces pro-IL-1beta processing via a Toll/IL-1R domain-containing adaptor-inducing interferon-beta-dependent signaling pathway that is initiated by TLR3 and TLR4, respectively. Ribonucleic acid interference (RNAi)-mediated knockdown of the intracellular receptors NALP3 or MDA5 did not affect poly(I:C)-induced pro-IL-1beta processing. Surprisingly, poly(I:C)- and LPS-induced pro-IL-1beta processing still occurred in caspase-1-deficient cells. In contrast, pro-IL-1beta processing was inhibited by caspase-8 peptide inhibitors, CrmA or vFLIP expression, and caspase-8 knockdown via RNAi, indicating an essential role for caspase-8. Moreover, recombinant caspase-8 was able to cleave pro-IL-1beta in vitro at exactly the same site as caspase-1. These results implicate a novel role for caspase-8 in the production of biologically active IL-1beta in response to TLR3 and TLR4 stimulation.
Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice (2017)

Â© 2017 Nature America, Inc., part of Springer Nature. All rights reserved. Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time.
Measurements of acoustic pressure at high amplitudes and intensities (2004)

In our research group, we desire measurements of the large pressure amplitudes generated by the shock waves used in shock wave lithotripsy (SWL) and the large acoustic intensities used in High Intensity Focused Ultrasound (HIFU). Conventional piezoelectric or PVDF hydrophones can not be used for such measurements as they are damaged either by cavitation, in SWL applications, or heat, in HIFU applications. In order to circumvent these difficulties, we have utilized optical fiber hydrophones in SWL that do not cavitate, and small glass probes and a scattering technique for measurements of large HIFU intensities. Descriptions of these techniques will be given as well as some typical data.
Neurogranin regulates eNOS function and endothelial activation (2020)

Endothelial nitric oxide (NO) is a critical mediator of vascular function and vascular remodeling. NO is produced by endothelial nitric oxide synthase (eNOS), which is activated by calcium (Ca<sup>2+</sup>)-dependent and Ca<sup>2+</sup>-independent pathways. Here, we report that neurogranin (Ng), which regulates Ca<sup>2+</sup>-calmodulin (CaM) signaling in the brain, is uniquely expressed in endothelial cells (EC) of human and mouse vasculature, and is also required for eNOS regulation. To test the role of Ng in eNOS activation, Ng knockdown in human aortic endothelial cells (HAEC) was performed using Ng SiRNA along with Ng knockout (Ng <sup>-/-</sup>) in mice. Depletion of Ng expression decreased eNOS activity in HAEC and NO production in mice. We show that Ng expression was decreased by short-term laminar flow and long-them oscillating flow shear stress, and that Ng siRNA with shear stress decreased eNOS expression as well as eNOS phosphorylation at S1177. We further reveled that lack of Ng expression decreases both AKT-dependent eNOS phosphorylation, NF-κB-mediated eNOS expression, and promotes endothelial activation. Our findings also indicate that Ng modulates Ca<sup>2+</sup>-dependent calcineurin (CaN) activity, which suppresses Ca<sup>2+</sup>-independent AKT-dependent eNOS signaling. Moreover, deletion of Ng in mice also reduced eNOS activity and caused endothelial dysfunction in flow-mediated dilation experiments. Our results demonstrate that Ng plays a crucial role in Ca<sup>2+</sup>-CaM-dependent eNOS regulation and contributes to vascular remodeling, which is important for the pathophysiology of cardiovascular disease.
Magnetoresistance and magnetic properties of Co/Ir multilayers on MgO(110) substrates (1997)

A Co(12 Å)/Ir(16 Å) multilayer deposited on MgO(110) is found to have a strong uniaxial anisotropy, comparable to bulk hcp-Co. Experimental results suggests the crystallographic relation of (100)[001]Co/(110)[001]Ir/(110)[001]MgO. A remarkable difference is seen between easy and hard axis magnetization processes, due to competition between the in-plane anisotropy and the exchange coupling. Considering the characteristics of the MH loops and magnetoresistance curves, we simulate the magnetization and magnetoresistance processes numerically. The results of our simulation indicate the existence of biquadratic coupling in Co/Ir(110).
INFLUENCE OF SINTERING CONDITIONS ON DOPED PZT CERAMICS FOR BASE-METAL ELECTRODE MULTILAYER ACTUATORS (2012)

The influence of sintering atmosphere and copper addition on the microstructural and piezoelectric properties of Mn -doped lead zirconate titanate ceramics (PZT) was investigated. This ceramic powder densifies below 1000°C, enabling the use of copper inner electrodes for a multilayer actuator setup. To simulate the influence of oxidized inner electrodes during sintering, different CuO contents (0 and 1 mol.%) were mixed to the precalcined Mn -doped PZT powder. Ceramic discs were sintered at 950°C in air and analogously in N 2 , or in steam containing N 2 (25 vol.% water vapor content). The electrical characterization of the discs showed that the piezoelectric properties are influenced by the CuO addition as well as by the sintering atmospheres. The large signal piezoelectric constant [Formula: see text] shows an improvement of at least 20% when CuO is added. CuO acts as a sintering aid, and especially when the ceramics are fired in steam-containing N 2 , anomalous grain growth occurs.
ChemInform Abstract: REDUCTION OF Δ2‐ISOXAZOLINES. 2. A FACILE SYNTHESIS OF 3(2H)‐FURANONES (1983)

Abstract Bei der Umsetzung mit dem Nitriloxid (II) erhält man aus dem Vinylether (I) das ISOX′.
Electrically Heated Oxide Ceramic Tubes for High Temperature Reactions (2023)

Abstract Endothermic high temperature reactions are usually carried out in metal tubes heated by gas burners. Electrical heating allows substantial reduction of CO 2 emissions. We propose the usage of a composite tube, where a thin metallic layer is embedded between an inner and outer ceramic layer. While monolithic ceramics suffer from brittleness and low tolerance to thermal stress, only the inner layer is made from monolithic ceramics, while the outer layer is made of fiber reinforced oxide ceramics. In first tests the hybrid ceramic tube was electrically heated to 1250 °C with a maximum heat release of 85 kW m −2 .
Effects of food starvation on digestive activities, energy reserves and reproductive outcomes in Gammarus fossarum (2013)

Among freshwater species intensively used in ecotoxicology, Gammarus fossarum is a relevant test species. Many sub-individual and individual responses are studied in gammarids in order to monitor and predict effects of chemical water quality on aquatic life. In this framework, energetic metabolism variations appear to be a good predictive tool to detect physiological disturbance of organisms linked to ecosystem quality. Among biological processes involving energy uptake, digestive enzymes play a key role. Some papers clearly demonstrated that the activity of these enzymes may be disturbed by pollutants. Consequently digestive enzymes can be proposed as relevant indicators of health organisms. In this way, the monitoring of digestive responses was recently successfully applied with caged organisms for the diagnosis of aquatic system. However, confounding factors may highly influence activity levels of these enzymes, consequently the impact of these parameters should be known and taken into account for an accurate interpretation of activity levels in term of toxicity. The use of control organisms for experiments allows preventing the impact of these biotic factors. However, some other factors as the amount of available food or the food eaten by organisms cannot be easily controlled. The present study aimed to show the influence of food availability on digestive enzyme activities (amylase and trypsin) on both gender of the freshwater amphipod Gammarus fossarum, throughout their reproductive cycle. Organisms were exposed to 3 levels of food available. First data showed a decrease of amylase activity correlated with the food availability. In contrast, for trypsin no effect of starvation was observed on enzyme activity for the both gender. In female, an interaction effect between moult cycle and level food available was also observed on digestive enzyme activities. So male appears as a better biological matrix for using digestive enzymes in biomonitoring survey. Moreover results indicated in starved female a delay in reproductive cycle compared to ad libitum fed organisms which demonstrated the diet stress effect on physiological responses. The digestive capacity inhibition may induce changes in energy allocation. These results concerning digestive capacities (both gender) and reproductive cycle (female) will be discussed in regard to energy reserve measurements and reproductive outcomes (fertility and fecundity).
ChemInform Abstract: Carotenoid Synthesis. Part 2. Strategies for Building the Carbon Skeleton (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Influence of Experimental Uncertainty on Prediction of Holistic Multi-Scale Data Center Energy Efficiency (2011)

As the energy footprint of data centers continues to increase, models that allow for “what-if” simulations of different data center design and management paradigms will be important. Prior work by the authors has described a multi-scale energy efficiency model that allows for evaluating the coefficient of performance of the data center ensemble (COPGrand), and demonstrated the utility of such a model for purposes of choosing operational set-points and evaluating design trade-offs. However, experimental validation of these models poses a challenge because of the complexity involved with tailoring such a model for implementation to legacy data centers, with shared infrastructure and limited control over IT workload. Further, test facilities with dummy heat loads or artificial racks in lieu of IT equipment generally have limited utility in validating end-to-end models owing to the inability of such loads to mimic phenomena such as fan scalability, etc. In this work, we describe the experimental analysis conducted in a special test chamber and data center facility. The chamber, focusing on system level effects, is loaded with an actual IT rack, and a compressor delivers chilled air to the chamber at a preset temperature. By varying the load in the IT rack as well as the air delivery parameters — such as flow rate, supply temperature, etc. — a setup which simulates the system level of a data center is created. Experimental tests within a live data center facility are also conducted where the operating conditions of the cooling infrastructure are monitored — such as fluid temperatures, flow rates, etc. — and can be analyzed to determine effects such as air flow recirculation, heat exchanger performance, etc. Using the experimental data a multi-scale model configuration emulating the data center can be defined. We compare the results from such experimental analysis to a multi-scale energy efficiency model of the data center, and discuss the accuracies as well as inaccuracies within such a model. Difficulties encountered in the experimental work are discussed. The paper concludes by discussing areas for improvement in such modeling and experimental evaluation. Further validation of the complete multi-scale data center energy model is planned.
Bringing text input beyond the desktop (2000)

This paper describes the T9 Text Input® product (T9), which can be used by small device designers to meet the text-entry needs of diverse populations of users. Examples are provided illustrating how this technology has been applied to Chinese text input and to augmentative and alternative communication (AAC).
Utilization of an Active Site Mutant Receptor for the Identification of Potent and Selective Atypical 5-HT2CReceptor Agonists (2017)

Agonism of the 5-HT<sub>2C</sub> receptor represents one of the most well-studied and clinically proven mechanisms for pharmacological weight reduction. Selectivity over the closely related 5-HT<sub>2A</sub> and 5-HT<sub>2B</sub> receptors is critical as their activation has been shown to lead to undesirable side effects and major safety concerns. In this communication, we report the development of a new screening paradigm that utilizes an active site mutant D134A (D3.32) 5-HT<sub>2C</sub> receptor to identify atypical agonist structures. We additionally report the discovery and optimization of a novel class of nonbasic heterocyclic amide agonists of 5-HT<sub>2C</sub>. SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT<sub>2C</sub> with high selectivity over the related 5-HT<sub>2A</sub> and 5-HT<sub>2B</sub> receptor subtypes. Further optimization through replacement of the amide with a variety of five- and six-membered heterocycles led to the identification of 6-(1-ethyl-3-(quinolin-8-yl)-1H-pyrazol-5-yl)pyridazin-3-amine (69). Oral administration of 69 to rats reduced food intake in an ad libitum feeding model, which could be completely reversed by a selective 5-HT<sub>2C</sub> antagonist.
Electrowetting-based droplet mixers for microfluidic systemsElectronic supplementary information (ESI) available: six mpeg videos showing some mixing schemes used in Fig. 7. See http://www.rsc.org/suppdata/lc/b2/b210825a/ (2003)

Mixing of analytes and reagents is a critical step in realizing a lab-on-a-chip. However, mixing of liquids is very difficult in continuous flow microfluidics due to laminar flow conditions. An alternative mixing strategy is presented based on the discretization of liquids into droplets and further manipulation of those droplets by electrowetting. The interfacial tensions of the droplets are controlled with the application of voltage. The droplets act as virtual mixing chambers, and mixing occurs by transporting the droplet across an electrode array. We also present an improved method for visualization of mixing where the top and side views of mixing are simultaneously observed. Microliters of liquid droplets are mixed in less than five seconds, which is an order of magnitude improvement in reported mixing times of droplets. Flow reversibility hinders the process of mixing during linear droplet motion. This mixing process is not physically confined and can be dynamically reconfigured to any location on the chip to improve the throughput of the lab-on-a-chip.
Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mice model of autism Shank3B (2020)

Abstract Background: Partial or an entire deletion of SHANK3 are considered as major drivers in the Phelan McDermid syndrome, in which 75% of patients are diagnosed with autism spectrum disorder (ASD). During the recent years, there was an increasing interest in stem cell therapy in ASD, and specifically, mesenchymal stem cells (MSC). Moreover, it has been suggested that the therapeutic effect of the MSC is mediated mainly via the secretion of small extracellular-vesicle that contain important molecular information of the cell and are used for cell-to cell communication. Within the fraction of the extracellular-vesicles, exosomes were highlighted as the most effective ones to convey the therapeutic effect.Methods: Exosomes derived from MSC (MSC-exo) were purified, characterized and given via intranasal administration to Shank3B KO mice (in concentration of 10 7 particals/ml). Three weeks post treatment the mice were tested for behavioral scoring and their results were compared to control saline treated and to their wild type littermates. Results: Intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization and reduces repetitive behaviors. We also observed an increase of GABARB1 in the prefrontal cortex.Conclusions: Herein, we hypothesized that MSC-exo would have a direct beneficial effect on the behavioral autistic-like phenotype of the genetically modified Shank3B KO mice model of autism. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of this mouse model autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.
Orlando espino, Carlos santamaría, Enrique Meseguer and Manuel carreiras (universidad de la laguna) early and late processes in syllogistic reasoning: Evidence from eye-movements, b1–b9 (2006)

Intra-protein information is transmitted over distances via allosteric processes. This ubiquitous protein process allows for protein function changes due to ligand binding events. Understanding protein allostery is essential to understanding protein functions. In this study, allostery in the second PDZ domain (PDZ2) in the human PTP1E protein is examined as model system to advance a recently developed rigid residue scan method combining with configurational entropy calculation and principal component analysis. The contributions from individual residues to whole-protein dynamics and allostery were systematically assessed via rigid body simulations of both unbound and ligand-bound states of the protein. The entropic contributions of individual residues to whole-protein dynamics were evaluated based on covariance-based correlation analysis of all simulations. The changes of overall protein entropy when individual residues being held rigid support that the rigidity/flexibility equilibrium in protein structure is governed by the La Châtelier's principle of chemical equilibrium. Key residues of PDZ2 allostery were identified with good agreement with NMR studies of the same protein bound to the same peptide. On the other hand, the change of entropic contribution from each residue upon perturbation revealed intrinsic differences among all the residues. The quasi-harmonic and principal component analyses of simulations without rigid residue perturbation showed a coherent allosteric mode from unbound and bound states, respectively. The projection of simulations with rigid residue perturbation onto coherent allosteric modes demonstrated the intrinsic shifting of ensemble distributions supporting the population-shift theory of protein allostery. Overall, the study presented here provides a robust and systematic approach to estimate the contribution of individual residue internal motion to overall protein dynamics and allostery.