gebhart/patrepeval huggingface dataset:
Tyrosine Kinase Inhibitors. 9. Synthesis and Evaluation of Fused Tricyclic Quinazoline Analogues as ATP Site Inhibitors of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (1996)

Following the discovery of 4-[(3-bromophenyl)amino]-6,7-dimethoxyquinazoline (4; PD 153035) as an extremely potent (IC(50) 0.025 nM) inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), several fused tricyclic quinazoline analogues have been prepared and evaluated for their ability to inhibit the enzyme. The most potent compound was the linear imidazo[4,5-g]quinazoline (8), which exhibited an IC(50) of 0.008 nM for inhibition of phosphorylation of a fragment of phospholipase C-gamma-1 as substrate. While N-methyl analogues of 8 showed similar potency, analogous N-[2-(dimethylamino)ethyl] derivatives were less effective. The next most potent compounds were the linear pyrazoloquinazolines (19 and 20) (IC(50)s 0.34 and 0.44 nM) and pyrroloquinazoline (21) (IC(50) 0.44nM), while several other linear tricyclic ring systems of similar geometry to 8 (triazolo-, thiazolo-, and pyrazinoquinazolines) were less effective. In the imidazo[4,5-g]quinazoline and pyrroloquinazoline series, the corresponding angular isomers were also much less effective than the linear ones. These results are consistent with structure-activity relationship studies previously developed for the 4-[(3-bromophenyl)amino] quinazolines, which suggested that small electron-donating substituents at the 6- and 7-positions were desirable for high potency. Cellular studies of the linear imidazoloquinazoline 8 show that it can enter cells and rapidly and very selectively shut down EGF-stimulated signal transmission by binding competitively at the ATP site of the EGFR.
Polymorphism of the thiopurine S-methyltransferase gene in African- Americans (1999)

The molecular basis for the genetic polymorphism of thiopurine S -methyltransferase (TPMT) has been estab-lished for Caucasians, but it remains to be elucidated in African populations. In the current study, we determined TPMT genotypes in a population of 248 African-Americans and compared it with allele frequencies in 282 Caucasian Americans. TPMT genotype was determined in all individuals with TPMT activity indicative of a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African-Americans, n = 21 Caucasians) and a control group with TPMT activity indicative of a homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23 African-Americans, n = 21 Caucasians). No mutant alleles were found in the high activity control groups. The overall mutant allele frequencies were similar in African-Americans and Caucasians (4.6 and 3.7% of alleles, respectively). However, while TPMT*3C was the most prevalent mutant allele in African-Americans (52.2% of mutant alleles), it represented only 4.8% of mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most prevalent mutant allele in Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing a single nucleotide transition (G644A), leading to an amino acid change at codon 215 (Arg-->His), was found in one African-American with intermediate activity. These data indicate that the same TPMT mutant alleles are found in American black and white populations, but that the predominant mutant alleles differ in these two ethnic groups.
Geminivirus vectors for high‐level expression of foreign proteins in plant cells (2002)

Bean yellow dwarf virus (BeYDV) is a monopartite geminivirus that can infect dicotyledonous plants. We have developed a high-level expression system that utilizes elements of the replication machinery of this single-stranded DNA virus. The replication initiator protein (Rep) mediates release and replication of a replicon from a DNA construct ("LSL vector") that contains an expression cassette for a gene of interest flanked by cis-acting elements of the virus. We used tobacco NT1 cells and biolistic delivery of plasmid DNA for evaluation of replication and expression of reporter genes contained within an LSL vector. By codelivery of a GUS reporter-LSL vector and a Rep-supplying vector, we obtained up to 40-fold increase in expression levels compared to delivery of the reporter-LSL vectors alone. High-copy replication of the LSL vector was correlated with enhanced expression of GUS. Rep expression using a whole BeYDV clone, a cauliflower mosaic virus 35S promoter driving either genomic rep or an intron-deleted rep gene, or 35S-rep contained in the LSL vector all achieved efficient replication and enhancement of GUS expression. We anticipate that this system can be adapted for use in transgenic plants or plant cell cultures with appropriately regulated expression of Rep, with the potential to greatly increase yield of recombinant proteins.
Gastric irritancy of aspirin and its congeners: anti-inflammatory activity without this side-effect (1976)

<P>Abstract copyright UK Data Service and data collection copyright owner.</P>
Discovery and Synthesis of HIV Integrase Inhibitors:  Development of Potent and Orally Bioavailable N-Methyl Pyrimidones (2007)

The human immunodeficiency virus type-1 (HIV-1) encodes three enzymes essential for viral replication: a reverse transcriptase, a protease, and an integrase. The latter is responsible for the integration of the viral genome into the human genome and, therefore, represents an attractive target for chemotherapeutic intervention against AIDS. A drug based on this mechanism has not yet been approved. Benzyl-dihydroxypyrimidine-carboxamides were discovered in our laboratories as a novel and metabolically stable class of agents that exhibits potent inhibition of the HIV integrase strand transfer step. Further efforts led to very potent compounds based on the structurally related N-Me pyrimidone scaffold. One of the more interesting compounds in this series is the 2-N-Me-morpholino derivative 27a, which shows a CIC95 of 65 nM in the cell in the presence of serum. The compound has favorable pharmacokinetic properties in three preclinical species and shows no liabilities in several counterscreening assays.
ENHANCED PRACTICAL PHOTOSYNTHETIC CO2 MITIGATION (2001)

This report documents significant achievements in the Enhanced Practical Photosynthetic CO{sub 2} Mitigation project during the period from 10/03/2000 through 10/02/2001. Most of the achievements are milestones in our efforts to complete the tasks and subtasks that constitute the project objectives. This is the fourth quarterly report for this project, so it also serves as a year-1 project review. We have made significant progress on our Phase I objectives, and our current efforts are focused on fulfilling these research objectives ''on time'' relative to the project timeline. Overall, we believe that we are on schedule to complete Phase I activities by 10/2002, which is the milestone date from the original project timeline. Our results to date concerning the individual factors which have the most significant effect on CO{sub 2} uptake are inconclusive, but we have gathered useful information about the effects of lighting, temperature and CO{sub 2} concentration on one particular organism (Nostoc) and significant progress has been made in identifying other organisms that are more suitable for use in the bioreactor due to their better tolerance for the high temperatures likely to be encountered in the flue gas stream. Our current tests are focused on one such thermophilic organism (Cyanidium), and an enlarged bioreactor system (CRF-2) has been prepared for testing this organism. Tests on the enhanced mass transfer CO{sub 2} absorption technique are underway and useful information is currently being collected concerning pressure drop. The solar collectors for the deep-penetration hybrid solar lighting system have been designed and a single solar collector tracking unit is being prepared for installation in the pilot scale bioreactor system currently under construction. Much progress has been made in designing the fiber optic light delivery system, but final selection of the ''optimum'' delivery system design depends on many factors, most significantly the configuration and orientation of the growth surfaces in the bioreactor. For the growth surface subsystem we have identified advantages and disadvantages for several candidate growth surface materials, we have built and tested various ''screen'' systems and fluid delivery systems, and we continue to test compatibility of the candidate materials with the organisms and with the moisture delivery and harvesting system designs. These tests will be ongoing until an ''optimum'' combination of growth surface material/organism type/harvesting system is identified. For the harvesting system, a nozzle-based water jet system has been shown to be effective, but it has disadvantages for the overall system design in terms of space utilization. A streamlined and integrated screen wetting/harvesting system design is currently under development and will be the focus of harvesting system tests in the foreseeable future. This report addresses each of the key project tasks as defined in the statement of work, giving both a summary of key accomplishments over the past year and a plan for future work.
An Enhanced Space-time Equalizer for MIMO Multi-code CDMA Systems (2006)

This paper proposes an enhanced chip-level linear space-time equalizer for multiple-input-multiple-output (MIMO) multi-code CDMA systems. In the MIMO multi-code CDMA systems, the reuse of the same spreading codes in different transmit antennas significantly degrades the equalization performance if the space-time equalizer uses a weighting vector that minimizes the mean squared error of the equalizer output chip sequence. As the CDMA despreader concatenated to a space-time equalizer distorts inter-stream interference components differently from multipath interference and background noise components, the traditional chip-level minimum mean squared error (MMSE) weighting vector usually steers in a sub-optimal direction in the signal space. Therefore, we propose a new MMSE weighting vector that takes the despreading effect into account in this paper. Simulation results show a substantial performance improvement through the new weighting vector.
Simultaneous speaker-independent voice recognition and verification over a telephone network (1993)

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A novel approach to memory power estimation using machine learning (2010)

Reducing power consumption has become a priority in microprocessor design as more devices become mobile and as the density and speed of components lead to power dissipation issues. Power allocation strategies for individual components within a chip are being researched to determine optimal configurations to balance power and performance. Modelling and estimation tools are necessary in order to understand the behaviour of energy consumption in a run time environment. This paper discusses a novel approach to power metering by estimating it using a set of observed variables that share a linear or non-linear correlation to the power consumption. The machine learning approaches exploit the statistical relationship among potential variables and power consumption. We show that Support Vector Machine regression (SVR), Genetic Algorithms (GA) and Neural Networks (NN) can all be used to cheaply and easily predict memory power usage based on these observed variables.
Physical face cloning (2012)

We propose a complete process for designing, simulating, and fabricating synthetic skin for an animatronics character that mimics the face of a given subject and its expressions. The process starts with measuring the elastic properties of a material used to manufacture synthetic soft tissue. Given these measurements we use physics-based simulation to predict the behavior of a face when it is driven by the underlying robotic actuation. Next, we capture 3D facial expressions for a given target subject. As the key component of our process, we present a novel optimization scheme that determines the shape of the synthetic skin as well as the actuation parameters that provide the best match to the target expressions. We demonstrate this computational skin design by physically cloning a real human face onto an animatronics figure.
ChemInform Abstract: TOTAL SYNTHESIS OF (.+‐.)‐FLAVIPUCINE (1976)

Abstract Das Natriumsalz (IIIa) entsteht quantitativ aus (I) und (II).
Influenza: The Vaccines (1976)

The extreme antigenic lability of the influenza A viruses accounts for the less-than-ideal immune responses to them. With a possible swine flu pandemic in the offing, the "vaccine strategy" required is critical, particularly as the medical and public health communities in the United States embark on the first systematic attempt in history to blunt preemptively the impact of a pandemic.
Learning the consensus on visual quality for next-generation image management (2007)

While personal and community-based image collections grow by the day, the demand for novel photo management capabilities grows with it. Recent research has shown that it is possible to learn the consensus on visual quality measures such as aesthetics with a moderate degree of success. Here, we seek to push this performance to more realistic levels and use it to (a) help select high-quality pictures from collections, and (b) eliminate low-quality ones, introducing appropriate performance metrics in each case. To achieve this, we propose a sequential arrangement of a weighted linear least squares regressor and a naive Bayes' classifier, applied to a set of visual features previously found useful for quality prediction. Experiments on real-world data for these tasks show promising performance, with significant improvements over a previously proposed SVM-based method.
Overview of interference cancellation for CDMA wireless systems (2002)

The paper gives an overview of interference cancellation (IC) methods, in terms of implementation and performance, for third generation CDMA communications systems. The signal processing of each method is outlined and the advantages and challenges are discussed. An exemplary IC application at the mobile receiver and its performance are presented for the WCDMA system setup.
Metalorganic deposition of superconducting E sub u -B sub a -C sub u O thin films by rapid thermal annealing (1990)

This patent describes a method for producing films of superconductor materials. It comprises: forming a solution from the neodecanoates of europium, barium, and copper metals, the metals form an oxide mixture exhibiting superconductive properties, the solution comprises a solvent having at least approximately 10 volume percent pyridine in xylene; depositing a film of the solution onto a substrate, the substrate selected from the group consisting of strontium titanate, barium titanate, and sapphire; pyrolyzing the film in an oxygen-containing environment at a first temperature of approximately 500{degrees}C. for up to approximately 5 minutes and heating the oxide film at a second temperature ranging between about 850{degrees}C. and 1000{degrees}C. for a duration of up to approximately 2 minutes.
Phosphorus and arsenic profile control for high performance epitaxial base bipolar junction devices (1999)

In this study, we report on the incorporation behavior of n-type species in undoped layers grown subsequent to doped layers at low temperature (700–750 °C) reduced pressure chemical vapor deposition of silicon/silicon germanium (Si/Si1−xGex) performed in a single wafer epitaxial deposition system. Significant amounts of these species are observed even in an undoped layer grown subsequent to the doped layer. The presence of these dopants in the subsequently grown undoped layer is attributed to segregation at the moving growth interface. The arsenic segregation is confirmed to be significantly higher than phosphorus. In addition, an increase in both the phosphorus and arsenic incorporation is observed in the presence of a highly doped boron layer.
Engineering nanostructured thermal spray coatings: process–property–performance relationships of ceramic based materials (2007)

Nanostructured powders were deposited using thermal spraying to produce coatings having internal features of nanosized dimensions. Several ceramic based materials were studied, including WC–12 wt-%Co, TiO2, hydroxyapatite, Al2O3–13 wt-%TiO2 and yttria stabilised zirconia. The effect of the thermal spray conditions on the microstructure, phase composition, properties and performance was investigated. Key nanostructural features of the coatings were identified and their potential benefit in contributing to enhanced behaviour explored. Issues relating to design strategies and process control for engineering these types of coatings with performance characteristics tailored for targeted applications are discussed.
Development of open (Broken) conductor detection system for high resistivity areas (2017)

In the Kingdom of Saudi Arabia, some distribution lines feed loads that are located in remote desert areas. Such distribution systems, including medium and low voltage networks, face difficulties regarding fault detection and localization as compared with high voltage transmission systems. High impedance fault (HIF) resulting from an open (or broken) conductor in medium voltage (MV) overhead lines represents the most challenging problem in such an environment. The aim of this paper is to report on a new method to detect and locate such high impedance faults generated by downed conductors. These faults usually produce very low fault currents that are usually not detectable by the feeder conventional over-current protection schemes. The proposed Open Conductor Detection (OCD) system is based on distributed voltage measurements performed at low voltage (LV) sides of distribution transformers throughout the distribution network with GSM network communication to locate the faulty line section. The OCD detects the fault by activating all units downstream of the fault. The network operator locates the fault by searching for the last active and the first inactive unit, and then performs the necessary line sectionalizing to prevent incidents and minimize downtime. The OCD has been successfully piloted and has received patents.
Stereoselective total synthesis of (+)-artemisinin, the antimalarial constituent of Artemisia annua L (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective total synthesis of (+)-artemisinin, the antimalarial constituent of Artemisia annua LMitchell A. Avery, Wesley K. M. Chong, and Clive Jennings-WhiteCite this: J. Am. Chem. Soc. 1992, 114, 3, 974–979Publication Date (Print):January 1, 1992Publication History Published online1 May 2002Published inissue 1 January 1992https://pubs.acs.org/doi/10.1021/ja00029a028https://doi.org/10.1021/ja00029a028research-articleACS PublicationsRequest reuse permissionsArticle Views5559Altmetric-Citations213LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Biochemical and Structural Insights into the Preference of Nairoviral DeISGylases for Interferon-Stimulated Gene Product 15 Originating from Certain Species (2016)

Viral ovarian tumor domain proteases (vOTUs) are one of the two principal classes of viral proteases observed to reverse posttranslational modification of host proteins by ubiquitin and interferon-stimulated gene product 15 (ISG15), subsequently facilitating downregulation of IFN-I signaling pathways. Unlike the case with ubiquitin, the amino acid sequences of ISG15s from various species are notably divergent. We illustrate that vOTUs have clear preferences for ISG15s from certain species. In addition, these observations are related to the molecular insights acquired via the first X-ray structure of the vOTU from the Erve nairovirus in complex with the first structurally resolved nonhuman ISG15. This information implicates certain amino acids that drive the preference of vOTUs for ISG15s from certain species.
Design and Synthesis of Novel Dual‐Action Compounds Targeting the Adenosine A<sub>2A</sub> Receptor and Adenosine Transporter for Neuroprotection (2011)

A novel compound, N⁶-(4-hydroxybenzyl)adenosine, isolated from Gastrodia elata and which has been shown to be a potential therapeutic agent for preventing and treating neurodegenerative disease, was found to target both the adenosine A(2A) receptor (A(2A) R) and the equilibrative nucleoside transporter 1 (ENT1). As A(2A) R and ENT1 are proximal in the synaptic crevice of striatum, where the mutant huntingtin aggregate is located, the dual-action compounds that concomitantly target these two membrane proteins may be beneficial for the therapy of Huntington's disease. To design the desired dual-action compounds, pharmacophore models of the A(2A) R agonists and the ENT1 inhibitors were constructed. Accordingly, potentially active compounds were designed and synthesized by chemical modification of adenosine, particularly at the N⁶ and C⁵' positions, if the predicted activity was within an acceptable range. Indeed, some of the designed compounds exhibit significant dual-action properties toward both A(2A) R and ENT1. Both pharmacophore models exhibit good statistical correlation between predicted and measured activities. In agreement with competitive ligand binding assay results, these compounds also prevent apoptosis in serum-deprived PC12 cells, rendering a crucial function in neuroprotection and potential utility in the treatment of neurodegenerative diseases.
EGFRvIII‐Targeted Vaccination Therapy of Malignant Glioma (2009)

Given the highly infiltrative growth pattern of malignant glioma and the lack of specificity associated with currently available treatment regimens, alternative strategies designed to eradicate cancer cells while limiting collateral toxicity in normal tissues remain a high priority. To this end, the development of specific immunotherapies against targeted neoplastic cells represents a promising approach. The epidermal growth factor receptor class III variant (EGFRvIII), a constitutively activated mutant of the wild-type tyrosine kinase, is present in a substantial proportion of malignant gliomas and other human cancers, yet completely absent from normal tissues. This receptor variant consists of an in-frame deletion, the translation of which produces an extracellular junction with a novel glycine residue, flanked by amino acid sequences that are not typically adjacent in the normal protein. In this review, both preclinical and early clinical development of a peptide vaccine directed against this portion of the EGFRvIII antigenic domain are recapitulated. Following vaccination, our group has demonstrated potent, redirected cellular and humoral immunity against cancer cells expressing the mutant receptor without significant toxicity. Additionally, the corresponding therapeutic outcomes observed in these studies lend credence to the potential role of peptide-based vaccination strategies among emerging antitumor immunotherapies in patients with malignant glioma.