gebhart/patrepeval huggingface dataset:
The role of structure in kinase-targeted inhibitor design. (2004)

Protein kinases are attractive targets for rational drug design against a wide range of diseases. From detailed knowledge of the structure-function relationships underlying protein kinase activity and regulation, a number of methods for achieving kinase inhibition have been suggested and explored using structure-aided drug discovery. Attaining selective protein kinase inhibition in a cellular context, and converting the large number of known potent kinase inhibitors into effective drugs, are outstanding problems in this area and, from a structural perspective, the challenges presented by modulating pharmacokinetics and minimizing the incidence of resistant mutations in the target are of particular interest.
A Model of Force Generation by Locust Skeletal Muscle in Response to Individual Stimuli (2009)

A mathematical model of the locust hind leg extensor muscle is presented. The model accounts for the force response of the muscle due to individual stimuli under isometric conditions. Experimental data was collected by stimulating the muscle directly and force measured at the tibia. Joint dimensions were calculated, enabling tibial force to be converted into muscle force. In developing a model it was assumed that the response to a single isolated stimulus was linear, but no assumptions were made about the model order. Models of various order were fitted using time and frequency domain methods to data obtained from well-separated input pulses. The response could be approximated as an impulse response, with the response to each stimulus best described by a linear third-order system. Responses where input pulses were not well-separated, so that summation of subsequent pulses occurred, were also investigated. As has been observed in mammalian muscle, both facilitation and force depression were evident in locust muscle. The linear third-order model was found to provide an adequate fit to data in which depression and facilitation were evident if the parameters describing the system were allowed to vary between each response.
Cellulose as an inert matrix for presenting cytokines to target cells: production and properties of a stem cell factor–cellulose-binding domain fusion protein (1999)

A chimaera of stem cell factor (SCF) and a cellulose-binding domain from the xylanase Cex (CBDCex) effectively immobilizes SCF on a cellulose surface. The fusion protein retains both the cytokine properties of SCF and the cellulose-binding characteristics of CBDCex. When adsorbed on cellulose, SCF-CBDCex is up to 7-fold more potent than soluble SCF-CBDCex and than native SCF at stimulating the proliferation of factor-dependent cell lines. When cells are incubated with cellulose-bound SCF-CBDCex, activated receptors and SCF-CBDCex co-localize on the cellulose matrix. The strong binding of SCF-CBDCex to the cellulose surface permits the effective and localized stimulation of target cells; this is potentially significant for long-term perfusion culturing of factor-dependent cells. It also permits the direct analysis of the effects of surface-bound cytokines on target cells.
DC electrical conductivity of XLPE cable models aged under multiple thermal-electrical stresses (2003)

The DC electrical properties (conductivity, charging, and discharging currents) of XLPE (cross-linked polyethylene) cable models aged under multiple thermal-electrical stresses for different aging times are investigated over the temperature range 55 to 90 degrees C. The conductivity of the cables aged under thermoelectrical stresses exhibits a nonmonotonic behavior with aging time, similar to that of other investigated properties, such as density, crystallinity, and electric strength; however, its variations are much greater, indicating a higher sensitivity to degradation phenomena due to aging. This could provide an effective diagnostic tool for monitoring cable behavior in service. A relaxation process, which may be ascribed to an interfacial polarization of the Maxwell-Wagner-Sillars type, is observed at the intermediate aging times, for which conductivity exhibits its maximum value. In the range of temperature and electric field studied, ionic charge carriers seem to make the most contribution to both the conduction and relaxation processes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Gamifying the Media Classroom (2017)

Gamification, or the use of game elements in non-game contexts, has become a popular and increasingly accepted method of engaging learners in educational settings. However, there have been few comparisons of different kinds of courses and students, particularly in terms of discipline and content. Additionally, little work has reported on course instructor/designer perspectives. Finally, few studies on gamification have used a conceptual framework to assess the impact on student engagement. This paper reports on findings from evaluating two gamified multimedia and social media undergraduate courses over the course of one semester. Findings from applying a multidimensional framework suggest that the gamification approach taken was moderately effective for students overall, with some elements being more engaging than others in general and for each course over time." Post-term questionnaires posed to the instructors/course designers revealed congruence with the student perspective and several challenges pre- and post-implementation, despite the use of established rules for gamifying curricula.
Intraoral pressure and its relationship to velopharyngeal inadequacy. (1988)

Intraoral pressure measurements were made during multiple productions of the word "hamper" by each of 267 patients who manifested differing degrees of velopharyngeal inadequacy. The results indicate that intraoral pressure diminishes as the extent of velopharyngeal impairment increases. However, pressure remained above 3 cm H2O in the majority of subjects, even when the impairment was such that intraoral and intranasal pressures were essentially equal. Comparison of these results with model simulations suggests that speakers make adjustments to velopharyngeal impairment that tend to maintain pressures at levels thought to be necessary for obstruent consonant production. Variations in pressure as a function of gender and age parallel those observed in normal children and adults.
Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis (2009)

Elevated levels of serum unconjugated bilirubin (UCB) in the first weeks of life may lead to long-term neurologic impairment. We previously reported that an early exposure of developing neurons to UCB, in conditions mimicking moderate to severe neonatal jaundice, leads to neuritic atrophy and cell death. Here, we have further analyzed the effect of UCB on nerve cell differentiation and neuronal development, addressing how UCB may affect the viability of undifferentiated neural precursor cells and their fate decisions, as well as the development of hippocampal neurons in terms of dendritic and axonal elongation and branching, the axonal growth cone morphology, and the establishment of dendritic spines and synapses. Our results indicate that UCB reduces the viability of proliferating neural precursors, decreases neurogenesis without affecting astrogliogenesis, and increases cellular dysfunction in differentiating cells. In addition, an early exposure of neurons to UCB decreases the number of dendritic and axonal branches at 3 and 9 days in vitro (DIV), and a higher number of neurons showed a smaller growth cone area. UCB-treated neurons also reveal a decreased density of dendritic spines and synapses at 21 DIV. Such deleterious role of UCB in neuronal differentiation, development, and plasticity may compromise the performance of the brain in later life.
Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast Cancer by Targeting BET Family Bromodomains (2020)

Therapeutics such as lapatinib that target ERBB2 often provide initial clinical benefit but resistance frequently develops. Adaptive responses leading to lapatinib resistance involve reprogramming of the kinome through reactivation of ERBB2/ERBB3 signaling and transcriptional upregulation and activation of multiple tyrosine kinases. The heterogeneity of induced kinases prevents their targeting by a single kinase inhibitor, underscoring the challenge of predicting effective kinase inhibitor combination therapies. We hypothesized that to make the tumor response to single kinase inhibitors durable, the adaptive kinome response itself must be inhibited. Genetic and chemical inhibition of BET bromodomain chromatin readers suppresses transcription of many lapatinib-induced kinases involved in resistance including ERBB3, IGF1R, DDR1, MET, and FGFRs, preventing downstream SRC/FAK signaling and AKT reactivation. Combining inhibitors of kinases and chromatin readers prevents kinome adaptation by blocking transcription, generating a durable response to lapatinib and overcoming the dilemma of heterogeneity in the adaptive response.
Interpretations of Fundus Autofluorescence from Studies of the Bisretinoids of the Retina (2010)

Elevated fundus autofluorescence signals can reflect enhanced lipofuscin in RPE cells, augmented fluorescence due to photooxidation, and/or excess bisretinoid fluorophores in photoreceptor cells due to mishandling of vitamin A aldehyde by dysfunctional cells.
Cell biology of heart failure (2016)

Abstract In many etiologies of heart failure there is a reduction of the normal number of cardiac myocotes, and the syndrome is consistently associated with both qualitative and quantitative changes in these cells. This chapter describes the triggers, phenomena, and mechanisms associated with the transitions away from normal cardiac myocyte structure and function during pathological remodeling of the heart. Morphological adaptations of cardiac myocytes, the regulation of cardiac contractility, cardiac metabolism, and alternative cell death pathways activated in failing hearts are considered. The reversibility of cardiac myocyte hypertrophy and dysfunction that has been demonstrated in in recent years is also highlighted. These reverse remodeling phenomena demonstrate the substantial plasticity of the severely failing heart, providing insights into factors driving and sustaining pathological adaptations and attesting to the potential benefit of importance of therapeutic interventions targeting the failing heart.
Assymmetry of the α-laser emitted in far-field radiation (1999)

The main feature of a semiconductor (alpha) -laser is the codirectional small angle Bragg-reflection in a medium with gain. Within the framework of the coupled wave formalism for Bragg reflection an asymmetrical filtering characteristic occurs in dependence on the coupling constant, the ground gain and the gain coupling coefficient. The asymmetric far- field distribution of (alpha) -lasers is comparable with that filtering process.
Supplementary Methods from Quantitative Whole Genome Sequencing of Circulating Tumor Cells Enables Personalized Combination Therapy of Metastatic Cancer (2023)

&lt;p&gt;This file contains descriptions of all of the bioinformatic analyses used in the paper.&lt;/p&gt;
Stereo‐ and Enantioselective Synthesis of Both cis‐Chrysanthemic Acid Methyl Esters in High Optical Purity (1985)

The insecticidal activity of pyrethroids depends strongly upon their configuration. A novel synthesis of the highly active title compounds 1 and ent-1 does not require separation of racemates or diastereomers nor microbiological or enzymatic reactions.
Urban Aerosol Particulate Matter Promotes Necrosis and Autophagy via Reactive Oxygen Species-Mediated Cellular Disorders that Are Accompanied by Cell Cycle Arrest in Retinal Pigment Epithelial Cells (2021)

Urban particulate matter (UPM) is recognized as a grave public health problem worldwide. Although a few studies have linked UPM to ocular surface diseases, few studies have reported on retinal dysfunction. Thus, the aim of the present study was to evaluate the influence of UPM on the retina and identify the main mechanism of UPM toxicity. In this study, we found that UPM significantly induced cytotoxicity with morphological changes in ARPE-19 human retinal pigment epithelial (RPE) cells and increased necrosis and autophagy but not apoptosis. Furthermore, UPM significantly increased G2/M arrest and simultaneously induced alterations in cell cycle regulators. In addition, DNA damage and mitochondrial dysfunction were remarkably enhanced by UPM. However, the pretreatment with the potent reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) effectively suppressed UPM-mediated cytotoxicity, necrosis, autophagy, and cell cycle arrest. Moreover, NAC markedly restored UPM-induced DNA damage and mitochondrial dysfunction. Meanwhile, UPM increased the expression of mitophagy-regulated proteins, but NAC had no effect on mitophagy. Taken together, although further studies are needed to identify the role of mitophagy in UPM-induced RPE injury, the present study provides the first evidence that ROS-mediated cellular damage through necrosis and autophagy is one of the mechanisms of UPM-induced retinal disorders.
Enhanced Methane Recovery from Waste-Activated Sludge by Alginate-Degrading Consortia: The Overlooked Role of Alginate in Extracellular Polymeric Substances (2020)

The hydrolysis of extracellular polymeric substances (EPS) in waste-activated sludge (WAS) is considered as the rate-limiting step in anaerobic digestion. Uronic acids such as alginate are one of main polysaccharide components in EPS; however, their roles on WAS conversion are overlooked until now. Previously, we described alginate-degrading consortia (ADC) that have high activity for alginate conversion. In this work, ADC was studied for polysaccharide hydrolysis and methane production from WAS for the first time, which increased the methane production by 115%–185%. Dosing ADC also increased the values of biological methane potential from 131 to 172 mL/gVSS. An alginate-like exopolysaccharide was extracted from WAS, and the content was 65 mg/g-VSS. Then, the molecular weight profiles at UV254nm showed that disaccharides were the final hydrolysates of alginate by ADC enzyme. Extracted EPS could be utilized by ADC for methane production with acetate as the main intermediate. The mechanism was proposed that ADC played a key role in WAS conversion. These results indicated that alginate in EPS shall not be overlooked, which offers a new microbial method to enhance methane recovery from WAS. The microbial changes in ADC for the stability of WAS digestion should be investigated in the future.
Stereotaktische Laser‐Neurochirurgie (1993)

Abstract Die bisher entwickelten Bestrahlungstechniken von Hirntumoren sollen durch die Einführung eines stereotaktischen Lasersystems zur Ablation und Absaugung eines massiven Tumors ergänzt werden.
Probing the Reactivity of Oxomanganese−Salen Complexes: An Electrospray Tandem Mass Spectrometric Study of Highly Reactive Intermediates (2001)

Electrospray ionization in combination with tandem mass spectrometric techniques has been employed to study the formation of oxomanganese-salen complexes upon oxidation of [Mn(III)(salen)]+ cations as well as the properties and reactions of the oxidized species in the gas phase. Two species could be characterized as the principal oxidation products: the oxomanganese(v) complex, [Mn=O(salen)]+, which is the actual oxygen-transfer agent in epoxidation reactions, and the dinuclear, mu-oxo bridged [L(salen)Mn-O-Mn(salen)L]2+ with two terminal ligands L; the latter acts as a reservoir species. The effects of various substituents in the 5- and 5'-positions, respectively, of the salen ligand on the reactivity of the epoxidation catalyst were determined quantitatively from CID (collision-induced dissociation) experiments and B3LYP density functional calculations. Accordingly, the effect of axial donor ligands on the reactivity of the epoxidation catalyst was studied. Electron-withdrawing substitutents on the salen ligand and additional axial ligands decrease the stability and thus enhance the reactivity of the Mn=O moiety, while electron-donating salen substituents have a strong stabilizing effect.
Beam Slice-Based Recognition Method for Acoustic Landmark With Multi-Beam Forward Looking Sonar (2017)

Autonomous underwater vehicles (AUVs) have been widely used for many risky underwater tasks. For these tasks, AUVs require navigational aids, such as active beacon-type underwater acoustic landmarks, which are the most widely used. It requires heavy installation loads and regular maintenance with high price sensors. In this paper, we propose a novel localization method in shallow water with a multi-beam forward looking sonar (MFLS), where positioning is based on passive-type acoustic landmarks. The proposed landmark comprises a combination of concrete pillars with a highly reliable and efficient recognition method for the real-time use of AUVs. The proposed landmark system has many advantages in the practical use, such as no maintenance, being strong on the marine bio-fouling, and light installation load with low price concrete pillars. The proposed recognition method is divided into two processes to verify the landmark. First, a pillarlike object is separated from the background, and the height of the pillar is calculated by the length of the shadow, which has a very high recognition rate and accuracy. Through modeling, the distance from the landmark to the MFLS can be calculated. The proposed method stochastically updates the navigation data based on the positional relationship with the landmark. The performance of the proposed landmark and its recognition method is verified through a water tank and field experiments using the AUV (Cyclops). The recognition rate and accuracy are also discussed.
Efficacy of Patient Selection for Diagnostic Coronary Angiography in Suspected Coronary Artery Disease (2015)

In this study, less than a quarter of the patients referred for coronary angiography with suspected CAD had the diagnosis confirmed. A better clinical and non-invasive assessment is necessary, to improve the efficacy of patient selection for coronary angiography.
Improved NOx Submodel for In-Cylinder CFD Simulation of Low- and Medium-Speed Compression Ignition Engines (2001)

The NOx submodels currently used in the CFD-based simulation of engines have been developed for conditions where homogeneous and stoichiometric mixtures of fuel and air are burned. Such conditions apply well for spark ignition engines (SIE) but not for compression ignition engines (CIE), where combustion takes place in a highly heterogeneous environment. As a consequence, current NOx submodels do not satisfactorily describe the fate of nitrogen oxides in CIE. The aim of this work was to determine, by detailed chemical kinetic investigation, the mechanisms leading to in-cylinder NOx in low- and medium-speed CIE and to develop a more accurate submodel for the prediction of NOx in CIE by means of CFD. Calculations at constant pressure (1−150 bar) and constant temperature (1500−2200 °C) under ideal plug flow conditions show that, relative to the proportion of NO, the proportion of NO2 in NOx is negligible and that the formation and destruction of NO occurs mainly via 10 reactions. These reactions can be organized into three NO mechanisms: thermal, N2O intermediate, and N2O extension, the latter being a set of five reactions that oxidize N2O to NO via NH and HNO intermediates. To our knowledge, the importance of the N2O-extension mechanism is reported here for the first time. An improved NOx submodel was developed taking into account all three mechanisms, after introducing approximations relevant to CIE. According to our kinetic investigations, partial equilibrium approximation can be applied to O, OH, and H and a quasi-steady-state approximation to N2O, N, NH, and HNO. The performance of the improved submodel is illustrated by comparing its NOx predictions with those of a detailed kinetic scheme and a NO submodel currently used in CFD. The comparison shows that the improved submodel always produces more accurate predictions of NOx than does the current submodel.
A new amino acid derivative of ursodeoxycholate, (N-L-Glutamyl)-UDCA (UDCA-Glu), to selectively release UDCA in the colon. (2009)

Conjugation of UDCA to glutamic acid reduces its intestinal absorption and biotransformation resulting in increased colonic delivery of UDCA. UDCA-Glu may have potential application as a pro-drug for enhancing the action of UDCA in the treatment of colonic diseases.
Production of Pseudomonas aeruginosa Rhamnolipid Biosurfactants in Heterologous Hosts (1995)

The high-level production of rhamnolipid biosurfactants is a unique feature of Pseudomonas aeruginosa and is strictly regulated in response to environmental conditions. The final step in rhamnolipid biosynthesis is catalyzed by the rhlAB genes encoding a rhamnosyltransferase. The expression of the cloned rhlAB genes was studied in heterologous hosts, either under the control of the rhlR and rhlI rhamnolipid regulatory elements or under the control of the tac promoter. A recombinant P. fluorescens strain harboring multiple plasmid-encoded copies of the rhamnolipid gene cluster produced rhamnolipids (0.25 g liter(sup-1)) when grown under nitrogen-limiting conditions. The highest yields (0.6 g liter(sup-1)) and productivities (24 mg liter(sup-1) h(sup-1)) were obtained in a recombinant Pseudomonas putida strain, KT2442, harboring promoterless rhlAB genes fused to the tac promoter on a plasmid. Active rhamnosyltransferase was synthesized, but no rhamnolipids were produced, by recombinant Escherichia coli upon induction of rhlAB gene expression.
Depth-based patch scaling for content-aware stereo image completion (2014)

A number of recent algorithms have been proposed for working with stereo image pairs in ways that are already familiar to users of single-image editing tools. In particular, Morse, et al. (2012) have proposed a method for performing image completion in stereo images so as to maintain stereoscopic consistency. Like prior work in stereo completion, this method drew source texture only from regions at the same depth as the target region, which while helping the result can sometimes overly limit the pool of suitable source textures. Other methods such as the Generalized PatchMatch approach of Barnes, et al. (2010) have used scaled (and otherwise transformed) source texture to improve the quality of the completed target region, but these methods rely on randomly sampling the scale (or transformation) space without knowledge of scene geometry. This paper extends stereo image completion to include source textures scaled according to the relative differences in depth between image regions. Limited random sampling is used to make the method robust to minor errors in the stereo disparities and to provide for non-uniform aspect ratios, but with far fewer random samples than prior unrestrained sampling of scale. A preference for unscaled or downsampled source textures rather than upsampled ones is incorporated into the objective function and avoids an inherent matching bias towards low-frequency regions. Results demonstrate that using scene geometry to drive scale selection results in improved image completion compared to either single-image completion or prior methods for stereo completion.