gebhart/patrepeval huggingface dataset:
Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement (2017)

For kinase inhibitors, intracellular target selectivity is fundamental to pharmacological mechanism. Although a number of acellular techniques have been developed to measure kinase binding or enzymatic inhibition, such approaches can fail to accurately predict engagement in cells. Here we report the application of an energy transfer technique that enabled the first broad-spectrum, equilibrium-based approach to quantitatively profile target occupancy and compound affinity in live cells. Using this method, we performed a selectivity profiling for clinically relevant kinase inhibitors against 178 full-length kinases, and a mechanistic interrogation of the potency offsets observed between cellular and biochemical analysis. For the multikinase inhibitor crizotinib, our approach accurately predicted cellular potency and revealed improved target selectivity compared with biochemical measurements. Due to cellular ATP, a number of putative crizotinib targets are unexpectedly disengaged in live cells at a clinically relevant drug dose.
Framework for Computing a Performance Index for Urban Infrastructure Systems Using a Fuzzy Set Approach (2011)

This paper presents a framework for characterizing, analyzing, and computing the performance of urban infrastructure systems. The framework is based on a systems approach and consists of performance indicators classified into three hierarchical levels: indicators, dimensions, and categories. A fuzzy synthetic evaluation technique has been developed to synthesize performance indicators into an index that ranges between 0 and 100. The performance of an individual infrastructure system, in the form of an index, is generated by aggregating the performance indicators in the first three hierarchical levels. The overall performance of the urban infrastructure systems is then obtained by combining the indexes of individual infrastructure systems. The relative importance of the performance indicators during the synthesis process is determined using the analytic hierarchy process technique. The framework demonstrates and measures the performance of the civil infrastructure systems in Kathmandu, Nepal. This framework can be applied to performance analysis of any infrastructure system in an urban area. It enables decision makers to identify the weak and strong components of urban infrastructure systems and to formulate appropriate strategies for infrastructure planning on the basis of performance and investment costs.
Effect of intravenous furosemide on serum theophylline concentration (1981)

The effect of furosemide on the serum theophylline concentration (STC) was investigated in 10 patients at steady state on a continuous i.v. aminophylline infusion. A baseline STC was obtained 48 hours after the initiation of the maintenance infusion. The patients were monitored closely for the last 24 hours of the maintenance period with hourly flow records to assure the same continuous rate. Urine output was measured over four hours, then, a 40-mg dose of furosemide was administered i.v. over two minutes, and the aminophylline infusion was continued at the same rate. Urine output was measured for four hours after the furosemide dose, and then a second STC was obtained. The 40-mg furosemide i.v. bolus injection caused an average increase of 2.9 µg/ml in STC, with a range of 0.5-5.5 µg/ml. The urine volumes increased by an average of 995 ml above the baseline, with a range of 630-1377 ml. Both of the increases were significant at the p < 0.005 level. Patients stabilized on a theophylline dosage regimen should be monitored closely during the addition or discontinuation of furosemide therapy. Furosemide has been shown to be another factor that can alter STC.
A Randomized Trial Comparing the Levonorgestrel Intrauterine System and Thermal Balloon Ablation for Heavy Menstrual Bleeding (2006)

Because hysteroscopic endometrial resection and ablation for menorrhagia require a high level of skill to perform effectively and safely, a variety of global ablation devices have been designed for use by those having limited experience with hysteroscopy. They include ablation using a thermal balloon, microwaves, or diffused laser energy; cryoablation; and instillation of hot saline. The present investigators carried out a prospective, randomized trial comparing thermal balloon ablation with the levonorgestrel intrauterine system (LNG-IUS), an intrauterine device that releases 20 μg levonorgestrel every 24 hours over 5 years. Forty women 25 to 50 years of age with self-described heavy menstrual bleeding were assigned to the LNG-IUS and 39 others to thermal balloon ablation. Menstrual blood loss was estimated using a pictorial bleeding assessment chart after 3, 6, 9, 12, and 24 months. Menstrual blood loss was significantly reduced in both treatment groups, but at 12 and 24 months, bleeding scores were significantly lower in women treated with the LNG-IUS. There was a similar trend in rates of amenorrhea, which, however, was significant only at 24 months. Days of heavy bleeding were significantly reduced in both groups at 3 months. Fewer women had disturbed sleep and more felt able to leave home. More than 80% of women in both groups felt that their treatment had succeeded, and similar numbers of women in the 2 treatment groups would recommend their treatment to a friend. No serious complications were encountered. Self-rated quality of life increased significantly for women in both groups at 3, 12, and 24 months. These findings fail to show that either the LNG-IUS or thermal balloon ablation is superior to the other approach as a means of safely reducing blood loss in women with heavy menstrual bleeding. For this reason, individual preference should form the basis of choosing between these methods.
On the localization of alkaline phosphatase and cyclic phosphodiesterase in Escherichia coli (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the localization of alkaline phosphatase and cyclic phosphodiesterase in Escherichia coliR. W. Brockman and Leon A. HeppelCite this: Biochemistry 1968, 7, 7, 2554–2562Publication Date (Print):July 1, 1968Publication History Published online1 May 2002Published inissue 1 July 1968https://pubs.acs.org/doi/10.1021/bi00847a016https://doi.org/10.1021/bi00847a016research-articleACS PublicationsRequest reuse permissionsArticle Views409Altmetric-Citations100LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Remote Sensing Image Registration Based on Retrofitted SURF Algorithm and Trajectories Generated From Lissajous Figures (2010)

In this letter, we propose a novel remote sensing image registration method by optimizing the Speeded Up Robust Features (SURF) and developing a new similarity measure function based on trajectories generated from Lissajous figures. Compared with SURF which has a low feature-matching rate in some complex cases, the retrofitted SURF algorithm is more robust and accurate. The algorithm greatly improves the correct matching rate to over 80%. Furthermore, the recognition capability of the similarity measure is enhanced by using a trajectory disturbance strategy, which is a significant displacement in the trajectory induced by a minor error of the transformation parameters. Experiments show the promising performance of the proposed image registration method.
Contribution of Citrulline Ureidase to<i>Francisella tularensis</i>Strain Schu S4 Pathogenesis (2009)

The citrulline ureidase (CTU) activity has been shown to be associated with highly virulent Francisella tularensis strains, including Schu S4, while it is absent in avirulent or less virulent strains. A definitive role of the ctu gene in virulence and pathogenesis of F. tularensis Schu S4 has not been assessed; thus, an understanding of the significance of this phenotype is long overdue. CTU is a carbon-nitrogen hydrolase encoded by the citrulline ureidase (ctu) gene (FTT0435) on the F. tularensis Schu S4 genome. In the present study, we evaluated the contribution of the ctu gene in the virulence of category A agent F. tularensis Schu S4 by generating a nonpolar deletion mutant, the Deltactu mutant. The deletion of the ctu gene resulted in loss of CTU activity, which was restored by transcomplementing the ctu gene. The Deltactu mutant did not exhibit any growth defect under acellular growth conditions; however, it was impaired for intramacrophage growth in resting as well as gamma interferon-stimulated macrophages. The Deltactu mutant was further tested for its virulence attributes in a mouse model of respiratory tularemia. Mice infected intranasally with the Deltactu mutant showed significantly reduced bacterial burden in the lungs, liver, and spleen compared to wild-type (WT) Schu S4-infected mice. The reduced bacterial burden in mice infected with the Deltactu mutant was also associated with significantly lower histopathological scores in the lungs. Mice infected with the Deltactu mutant succumbed to infection, but they survived longer and showed significantly extended median time to death compared to that shown by WT Schu S4-infected mice. To conclude, this study demonstrates that ctu contributes to intracellular survival, in vivo growth, and pathogenesis. However, ctu is not an absolute requirement for the virulence of F. tularensis Schu S4 in mice.
Inhibition of Fatty Acid Stimulation of Gluconeogenesis by (+)-Decanoylcarnitine in Perfused Rat Liver (1968)

Oleic acid produced a two- to three-fold stimulation of glucose production from lactate in perfused livers from fasted rats. This effect was completely blocked by (+)-decanoylcarnitine, a known inhibitor of (−)-carnitine palmityltransferase. Activation of fatty acids to the acyl CoA esters was not inhibited. Neither β-oxidation of octanoate, nor its stimulatory effect on gluconeogenesis was blocked by (+)-decanoylcarnitine. The results show that in the intact liver, the oxidation of long-chain but not short-chain fatty acids proceeds almost entirely through carnitine-dependent pathways. Changes in the tissue levels of metabolic intermediates after addition of oleic acid show that the increased rate of gluconeogenesis was caused by a stimulation of the pyruvate carboxylase step. Attendant increases in the levels of acetyl CoA and NADH are consistent with the proposal that the mitochondrial levels of these intermediates control carbohydrate metabolism by diverting pyruvate from oxidation towards the synthesis of glucose. A further control site was identified upon fatty acid addition in the region of the phosphofructokinase and fructose diphosphatase reactions. There was no evidence for control at either of these steps by adenine nucleotides, but a marked rise of citrate was consistent with a postulated inhibition of phosphofructokinase. All the changes in the levels of intermediates of the gluconeogenic pathway and citric acid cycle induced by oleic acid were blocked by (+)-decanoylcarnitine. The failure of oleic acid to increase acetyl CoA and citrate levels in the presence of (+)-decanoylcarnitine explains its failure to stimulate gluconeogenesis under these conditions. It is concluded that the effect of fatty acids on gluconeogenesis is determined by their rate of oxidation and not by their concentration in the perfusion fluid. The significance of these findings in relation to the interactions of carbohydrate and fatty acid metabolism in vivo in the normal, starved and diabetic states is discussed.
A novel genetic-algorithm-based neural network for short-term load forecasting (2003)

This paper presents a neural network with a novel neuron model. In this model, the neuron has two activation functions and exhibits a node-to-node relationship in the hidden layer. This neural network provides better performance than a traditional feedforward neural network, and fewer hidden nodes are needed. The parameters of the proposed neural network are tuned by a genetic algorithm with arithmetic crossover and nonuniform mutation. Some applications are given to show the merits of the proposed neural network.
NavTracks: Supporting Navigation in Software (2005)

Any modification to a software system involves investigating the source code with the goal of understanding it. In turn, this investigation usually requires significant navigation effort. However, relatively little research has been conducted on software developer navigation patterns and tool support for improving navigation. Our research addresses this issue. We present NavTracks, a tool that supports browsing through software. NavTracks keeps track of the navigation history of software developers, forming associations between related files. These associations are then used as the basis for recommending potentially related files as a developer browses the software system.
Hierarchical Event Streams and Event Dependency Graphs: A New Computational Model for Embedded Real-Time Systems (2006)

One of the important aspects of schedulability analysis is the model used to describe the system and its timing behavior. On one side, the accuracy of the test strongly depends on the accuracy of the model. On the other side, a detailed model could lead to an unaccaptable evaluation time. In this paper we propose a new model, the hierarchical event streams, which allows a high accuracy. We provide an efficient feasibility test for the model based on the context of demand and request bound function. Additionally we will provide a methodology to extract this model out of a control-flow graph efficiently. Together this allows a more accurate and efficient schedulability analysis of event driven real-time systems
A self-guided theorem proving system (2003)

There are so many possible strategies for theorem provers to use that it becomes a problem to know how to combine them in the best way. Choosing appropriate strategies for solving a given problem may require the knowledge of different strategies or may involve a lot of painstaking trial-and-errors. To encourage the widespread use of computer reasoning systems, it is important that a reasoning system be usable by those with no knowledge of problem solving strategies, since few users have such knowledge. One possible approach is to get a lot of intelligence into a theorem proving system by having a collection of strategies and let the system by itself alternate between them. Such a system solves problems for the user automatically, freeing the user from the necessity of understanding the system or the merits of different strategies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Influence of bone‐derived matrices on generation of bone in an ectopic rat model (2009)

Most bone regeneration experimental models that test bone-derived matrices take place in conjunction with the native bone. Here, we compared the relative effectiveness of bone matrix components on bone-marrow-directed osteogenesis in an ectopic model. Cortical bone cylinders consisted of diaphysis of DA rat femurs. They were either demineralized (DBM), deproteinized (HABM), or nontreated (MBM). Fresh bone marrow was placed into cylinders and implanted at subcutaneous thoracic sites of 2-month-old DA rats. At designated times the cylinders were surgically removed from the animals. Microradiographs of DBM and histology of DBM and MBM cylinders demonstrated progressive increase in mineralized bone volume and its trabecular configuration. Bone filled the inner volume of DBM and MBM cylinders within 4 weeks, while in HABM cylinders mostly granulation tissue developed. In the DBM cylinders cartilage deposited within 10 days, while in the MBM cylinders bone was directly deposited. As early as day 3 after marrow transplantation, marrow cells interacting with DBM increased significantly the genes that express the cartilage and the bone phenotype. In conclusion, organic components of bone are needed for marrow-directed osteogenesis.
Continuous-time leapfrog filter with precise successive approximation tuning (2002)

The design of a tunable continuous-time active-RC leapfrog filter whose precise response is controlled by means of a novel successive approximation tuning technique independent of tight circuit components matching. An RLC prototype ladder is described, together with the tunable active-RC leapfrog architecture. Experimental results are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Vibrational Perturbations and Ligand–Layer Coupling in a Single Crystal of Au<sub>144</sub>(SC<sub>2</sub>H<sub>4</sub>Ph)<sub>60</sub> Nanocluster (2014)

We have determined vibrational signatures and optical gap of the Au144(PET)60 (PET: phenylethylthiol, SC2H4Ph) nanocluster solvated in deuterated dichloromethane (DCM-D2, CD2Cl2) and in a single crystal. For crystals, solid-state (13)C NMR and X-ray diffraction were also measured. A revised value of 2200 cm(-1) (0.27 eV) was obtained for the optical gap in both phases. The vibrational spectra of solvated AU144(PET)60 closely resembles that of neat PET, while the crystalline-state spectrum exhibits significant inhomogeneous spectral broadening, frequency shifts, intensity transfer between vibrational modes, and an increase in the overtone and combination transition intensities. Spectral broadening was also observed in the (13)C NMR spectrum. Changes in the intensity are explained due to vibrational coupling of the normal modes induced by the crystal packing, and the vibrational broadening is caused by ligand-environment inhomogeneity in the crystal. This indicates a pseudocrystalline state where the cluster cores are arranged in periodic fashion, while the ligand-layer molecules between the cores form amorphous structures.
Application of Hybrid Genetic Algorithm in Power System Parameter Measurement (2007)

Existing power system parameter measuring methods often aim at only one error factor,which makes it difficult to obtain accurate results when data sampled from the power system is influenced by several errors.In view of this problem,a parameter extremum optimization model is developed,in which such error factors as the decaying DC components,nonsynchronous sampling and harmonics are precisely depicted.A new measuring method based on the hybrid genetic algorithm(HGA)is developed to use this model for finding accurate power system parameters such as the amplitude,phase,frequency and harmonics.As the ordinary genetic algorithm(GA)converges slowly and the classic method is sensitive to initial guess,the HGA combines the GA operator and hybrid quasi-Newton operator together and,with the GA operator performing global searching in the solution space,the hybrid operator carrying out the strongly local searching at the same time to achieve fast calculation of the power parameters.Simulations show that the HGA method can effectively improve the efficiency and accuracy of power parameter measurement,laying a solid foundation for further monitoring and control of power systems.
Mutagenesis directed by phosphotriester analogues of oligonucleotides: A way to site‐specific mutagenesis in vivo (1988)

A new approach to induce directed mutations in genes of study through simple cotransfection of E. coli cells by the mixture of primer and template was developed. This method is based on the use of synthetic phosphotriester analogues of oligonucleotides as site-specific mutagenic primers. The achieved yield of mutant clones was 2-3%.
Respiration gating and Bloch fitting improve pH measurements with acidoCEST MRI in an ovarian orthotopic tumor model (2016)

We have developed a MRI method that can measure extracellular pH in tumor tissues, known as acidoCEST MRI. This method relies on the detection of Chemical Exchange Saturation Transfer (CEST) of iopamidol, an FDA-approved CT contrast agent that has two CEST signals. A log<sub>10</sub> ratio of the two CEST signals is linearly correlated with pH, but independent of agent concentration, endogenous T<sub>1</sub> relaxation time, and B<sub>1</sub> inhomogeneity. Therefore, detecting both CEST effects of iopamidol during <i>in vivo</i> studies can be used to accurately measure the extracellular pH in tumor tissues. Past <i>in vivo</i> studies using acidoCEST MRI have suffered from respiration artifacts in orthotopic and lung tumor models that have corrupted pH measurements. In addition, the non-linear fitting method used to analyze results is unreliable as it is subject to over-fitting especially with noisy CEST spectra. To improve the technique, we have recently developed a respiration gated CEST MRI pulse sequence that has greatly reduced motion artifacts, and we have included both a prescan and post scan to remove endogenous CEST effects. In addition, we fit the results by parameterizing the contrast of the exogenous agent with respect to pH via the Bloch equations modified for chemical exchange, which is less subject to over-fitting than the non-linear method. These advances in the acidoCEST MRI technique and analysis methods have made pH measurements more reliable, especially in areas of the body subject to respiratory motion.
In vivo labeling of neuronal nicotinic acetylcholine receptors with radiolabeled isomers of norchloroepibatidine (1995)

In vitro binding studies have shown that epibatidine and its norchloro analogues have high affinities for the cholinergic nicotinic receptor. In this study, the in vivo binding characteristics of [3H](+)norchloroepibatidine (NCEPB) and [3H](-)NCEPB in mice were examined. After injection of [3H](+)NCEPB, radioactivity levels in all brain regions examined increased and then decreased, with different regions accumulating different levels of radioactivity. The regional distribution of radioactivity at later times paralleled the distribution of nicotinic receptor binding in vitro. The ratio of radioactivity in the superior colliculus to that in the cerebellum, a reflection or estimate of total: non-specific binding, was strikingly high at 8 h (about 35). Drugs known to bind to nicotinic receptors reduced [3H](+)NCEPB binding, while atropine and spiperone, muscarinic and dopaminergic drugs respectively, did not. [3H](-)NCEPB had a similar regional distribution to [3H](+)NCEPB. Pretreatment with increasing doses of non-radioactive (-)NCEPB resulted in saturation of in vivo binding of [3H](-)NCEPB. These data indicate that [3H](+) and (-)NCEPB are useful in vivo binding ligands for the cholinergic nicotinic receptor.