gebhart/patrepeval huggingface dataset:
Tyrosine Kinase Inhibitors. 13. Structure−Activity Relationships for Soluble 7-Substituted 4-[(3-Bromophenyl)amino]pyrido[4,3-<i>d</i>]pyrimidines Designed as Inhibitors of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (1997)

The general class of 4-(phenylamino)quinazolines are potent (some members with IC50 values << 1 nM) and selective inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), via competitive binding at the ATP site of the enzyme, but many of the early analogues had poor aqueous solubility (<< 1 mM). A series of 7-substituted 4-[(3-bromophenyl)-amino]pyrido[4,3-d]pyrimidines, together with selected (3-methylphenyl)amino analogues, were prepared by reaction of the analogous 7-fluoro derivatives with appropriate amine nucleophiles in 2-BuOH or aqueous 1-PrOH. All of the compounds were evaluated for their ability to inhibit the tyrosine-phosphorylating action of EGF-stimulated full-length EGFR enzyme. Selected analogues were also evaluated for their inhibition of autophosphorylation of the EGF receptor in A431 human epidermoid carcinoma cells in culture and against A431 tumor xenografts in mice. Analogues bearing a wide variety of polyol, cationic, and anionic solubilizing substituents retained activity, but the most effective in terms of both increased aqueous solubility (> 40 mM) and retention of overall inhibitory activity (IC50's of 0.5-10 nM against isolated enzyme and 8-40 nM for inhibition of EGFR autophosphorylation in A431 cells) were weakly basic amine derivatives. These results are broadly consistent with a proposed model for the binding of these compounds to EGFR, in which the 6- and 7-positions of the pyridopyrimidine ring are in a largely hydrophobic binding region of considerable steric freedom, at the entrance of the adenine binding cleft. The most active cationic analogues have a weakly basic side chain where the amine moiety is three or more carbon atoms away from the nucleus. Two of the compounds (bearing weakly basic morpholinopropyl and strongly basic (dimethylamino)butyl solubilizing groups) produced in vivo tumor growth delays of 13-21 days against advanced stage A431 epidermoid xenografts in nude mice, when administered i.p. twice per day on days 7-21 posttumor implant. Treated tumors did not increase in size during therapy and resumed growth at the termination of therapy, indicating an apparent cytostatic effect for these compounds under these treatment conditions. The data suggest that continuous long-term therapy with these compounds may result in substantial tumor growth inhibition.
Non-Silver Amplification Processes: Part 3. Catalytic Thermal Decomposition of Te(<sub>II</sub>) Coordination Complexes via Internal Redox Reactions (1982)

A series of tellurium(II) coordination complexes of the general formulas [TeL2,X2] TeL4]X2 (L = thiourea or substituted thiourea; X = CI, Br, SCN) and [Te(S2X)2] (X = COR, CN(C2H5), P(OCH3),P(OCH3)2 P(OC2H5)2 P(C6H11)2 have been prepared and evaluated as image precursors in solution and dry amplification elements. Non-aqueous solutions of the thiourea complexes depit Te(0) at room temperature, Te(0), Pd(0) and Ag(0) being effective catalysts for the reaction. The Te(n) xanthates, Te(S2COR)2(R=CH3,C2H5, i-C3H7,n-C3H7,n-C5H11,C12H25), undergo facile catalytic thermal decomposition to Te(0), Ag(0), Pd(0) and Te(0) being effective catalysts for such processes. The mechanism of the thermal decomposition of [Te(s2CO-i-C3H7)2], has been shown by X-ray photoelectron spectroscopy to involve an intramolecular thermal ligand reduction reaction to give oxidized sulphur ligand (i.e. i-C3H7O-C(S)SSC(S)O-i-C3H7) and Te(0), ESCA experiments have also demonstrated that the amplification process is autocatalytic.
Non-Stoichiometric Liquid Enclosure Compounds ("Liquid Clathrates") (1976)

Compounds of the general formulation M[Al2(CH3)6X]— where M = alkali metal, tetraalkylammonium ion and X = N3-, SCN-, SeCN-, Cl-, Br-, I-—react in a visually dramatic fashion with small aromatic molecules to form non-stoichiometric liquid complexes. In the most favorable situation, as many as 16 benzene molecules are trapped per anionic unit. Because of similarity to the well known solid-state clathrates, the designation "liquid clathrate" is used for the new substances. The term is not meant to imply order as in the solid state, but to convey the method of interaction of M[Al2(CH3)6X] with aromatic molecules. The liquid clathrate may consist of either roughly spherical or hyerlike domains; the latter is supported by the x-ray crystallographically determined structure of K[CH3Se{Al(CH3)3}3] · 2C6H6.
Safe Reinforcement Learning with Scene Decomposition for Navigating Complex Urban Environments (2019)

Navigating urban environments represents a complex task for automated vehicles. They must reach their goal safely and efficiently while considering a multitude of traffic participants. We propose a modular decision making algorithm to autonomously navigate intersections, addressing challenges of existing rule-based and reinforcement learning (RL) approaches. We first present a safe RL algorithm relying on a model-checker to ensure safety guarantees. To make the decision strategy robust to perception errors and occlusions, we introduce a belief update technique using a learning based approach. Finally, we use a scene decomposition approach to scale our algorithm to environments with multiple traffic participants. We empirically demonstrate that our algorithm outperforms rule-based methods and reinforcement learning techniques on a complex intersection scenario.
B‐lymphocyte contributions to human autoimmune disease (2008)

Autoimmunity results from abnormal B- and T-cell recognition of self-antigens, which leads to autoantibody production in many cases. Autoantibodies produced by B-cell-derived plasma cells provide diagnostic markers for autoimmunity but also contribute significantly to disease pathogenesis. As discussed in this review, the therapeutic benefit of depleting B cells in mice and humans has refocused attention on B cells and their role in autoimmunity beyond autoantibody production. B cells specifically serve as cellular adjuvants for CD4(+) T-cell activation, while regulatory B cells, including those that produce interleukin-10 (B10 cells), function as negative regulators of inflammatory immune responses. The emerging picture is that B cells, autoantibodies, and T cells are all important components of abnormal immune responses that lead to tissue pathology unique to each autoimmune disease, with their relative contributions changing during disease progression. Autoimmune diseases where B-cell functions are closely correlated with disease activity include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, type 1 diabetes, and multiple sclerosis. Understanding the overlapping roles of B cells as mediators of autoimmune disease will facilitate the development of more precisely directed therapies and combination therapies with broader clinical efficacy than current depletion strategies that remove all B cells.
A Scanning Spot-Beam Satellite System (1977)

We propose a satellite with a high gain, movable spot beam to communicate with individual earth stations time-sharing a single channel in the tdma (Time-Division Multiple Access) mode. It is estimated that this approach could readily save some 20 dB in the link budget while still providing full U.S. coverage. When this 20 dB is apportioned with the objectives of reducing the earth-station antenna size, increasing the satellite capacity, and reducing transmitter power, the effects are dramatic. This technique can be combined with a fixed-spot beam system serving major traffic areas. This combination can provide both full area coverage as well as multiple reuse of the frequency band. A tdma burst organization is proposed, and estimates of burst lengths, beam switching intervals, and buffer storage size are made for a 100-earth-station network operating on a 600 Mb/s channel. A phased array antenna with each element irradiating the entire U.S. is employed to form the movable spot-beam. This provides an attractive solution even though a closed-loop beam-forming algorithm may be required. It appears feasible to construct such an antenna with nearly 50-dB gain capable of forming a spot beam toward any position within the continental United States with a switching time of a few nanoseconds.
Enabling Gate Dielectric Design for All Solution-Processed, High-Performance, Flexible Organic Thin-Film Transistors (2006)

A novel solution-processed, compositionally and structurally stable dual-layer gate dielectric composed of a UV-cured poly(4-vinyl phenol)-co-poly(methyl methacrylate) bottom layer and a thermally cross-linked poly(methyl silsesquioxane) top layer for organic thin-film transistors is described. This gate dielectric design, coupled with compatible solution-processable semiconductor and conductor materials, has enabled fabrication of all solution-processed, high-performance organic thin-film transistors on flexible substrates. High field-effect mobility and current on/off ratio, together with other desirable transistor properties, are demonstrated.
Development of Steam Quality Measurement and Monitoring Technique Using Absorption Spectroscopy With Diode Lasers (2010)

Techniques using a tunable diode laser (TDL) and multiple broadband lasers have been developed and tested for measuring the steam quality or steam wetness fraction. The steam wetness fraction was estimated using a ratiometric technique combining measured absorbance of water and water vapor overtone transitions in the near infrared spectral band. Using these techniques we were able to measure a wide variation in steam quality ranging from saturated steam condition to 80% mass fraction of steam with less than 1% error. Our sensor can be tailor-made to suit cost, sensitivity, and operating conditions as per requirements, and could be used eventually for measuring the quality of steam in the low pressure stage of steam turbines.
Learning Early Exit Strategies for Additive Ranking Ensembles (2021)

Modern search engine ranking pipelines are commonly based on large machine-learned ensembles of regression trees. We propose LEAR, a novel - learned - technique aimed to reduce the average number of trees traversed by documents to accumulate the scores, thus reducing the overall query response time. LEAR exploits a classifier that predicts whether a document can early exit the ensemble because it is unlikely to be ranked among the final top-k results. The early exit decision occurs at a sentinel point, i.e., after having evaluated a limited number of trees, and the partial scores are exploited to filter out non-promising documents. We evaluate LEAR by deploying it in a production-like setting, adopting a state-of-the-art algorithm for ensembles traversal. We provide a comprehensive experimental evaluation on two public datasets. The experiments show that LEAR has a significant impact on the efficiency of the query processing without hindering its ranking quality. In detail, on a first dataset, LEAR is able to achieve a speedup of 3x without any loss in NDCG1@0, while on a second dataset the speedup is larger than 5x with a negligible NDCG@10 loss (< 0.05%).
Three-dimensional integrated circuits for lab-on-chip dielectrophoresis of nanometer scale particles (2007)

In this paper, we present a mixed-technology micro-system for electronically manipulating and optically detecting virusscale particles in fluids that is designed using 3D integrated circuit technology. During the 3D fabrication process, the top-most chip tier is assembled upside down and the substrate material is removed. This places the polysilicon layer, which is used to create geometries with the process' minimum feature size, in close proximity to a fluid channel etched into the top of the stack. By taking advantage of these processing features inherent to "3D chip-stacking" technology, we create electrode arrays that have a gap spacing of 270 nm. Using 3D CMOS technology also provides the ability to densely integrate analog and digital control circuitry for the electrodes by using the additional levels of the chip stack. We show simulations of the system with a physical model of a Kaposi's sarcoma-associated herpes virus, which has a radius of approximately 125 nm, being dielectrophoretically arranged into striped patterns. We also discuss how these striped patterns of trapped nanometer scale particles create an effective diffraction grating which can then be sensed with macro-scale optical techniques.
Erbium doped fibres for efficient optical amplifiers (1990)

The authors report that erbium doped Al2O3−P2O5−SiO2 based fibres can be used as efficient optical amplifiers provided the concentration of erbium is kept low. Small signal gains of 35 dB at 1.55 μm and a 3 dB bandwidth of 35 nm have been measured using 70 mW pump power at 1.475 μm. Even when driven heavily into saturation, 16 dB gain was achieved with a resultant signal output power of 15.6 dBm.
Hydroxydiether Lipid Structures in <i>Methanosarcina</i> spp. and <i>Methanococcus voltae</i> (1993)

Hydroxylated diether lipids are the most abundant lipids in Methanosarcina acetivorans, Methanosarcina thermophila, and Methanosarcina barkeri MS and Fusaro, regardless of the substrate used for growth. Structural analysis of the lipid moiety freed of polar head groups revealed that the hydroxydiether lipids of all the Methanosarcina strains were hydroxylated at position 3 of sn-2 phytanyl chains. The finding that Methanosarcina strains synthesize the same hydroxydiether structure suggests that this is a taxonomic characteristic of the genus. Methanococcus voltae produced minor amounts of the 3-hydroxydiether characteristic of Methanosarcina spp. and also the 3'-hydroxydiether described previously for Methanosaeta concilii.
Synthesis and structure of a water-soluble nitrosyl iron complex with cysteamine ligand (2009)

A water-soluble nitrosyl complex of iron {Fe2[S(CH2)2NH3]2(NO)4}SO4·2.5H2O, belonging to a structural type ‘μ2-S’ and containing a ligand of natural origin, cysteamine, was synthesised and studied by X-ray crystallography, IR and Mössbauer spectroscopy.
Synthesis, absolute configuration, stereoselectivity, and receptor selectivity of (.alpha.R,.beta.S)-.alpha.,.beta.-dimethylhistamine. A novel highly potent histamine H3 receptor agonist (1992)

Depending on the selected synthetic pathway, structural variations of the neurotransmitter histamine led to mixtures of alpha,beta-dimethylhistamines as well as to the corresponding pure optical isomers. One of these isomers, namely (alpha R,beta S)-alpha,beta-dimethylhistamine, proved to be a highly potent H3 receptor agonist with exceptional receptor selectivity. The absolute configuration of the compound was determined by X-ray structure analysis of its dihydrobromide using the anomalous dispersion of bromine. The optical purity of both enantiomers of erythro-alpha,beta-dimethylhistamine was checked by 1HNMR investigations after acylation of the amines with (R)-2-methoxy-2-phenylacetyl chloride. As expected H3 receptors distinguish in a very strong way between the title compound and its alpha S,beta R-configured enantiomer. The agonistic potency of the latter is 2 orders of magnitude lower than the potency of (alpha R,beta S)-alpha,beta-dimethylhistamine.
Development of a Neutron Scatter Camera for Fission Neutrons (2006)

Special nuclear material (SNM) emits high energy radiation during active and passive interrogation. This radiation can be imaged thus allowing visualization of shielded and/or smuggled SNM. Although gamma-ray imaging is appropriate for many cases, neutrons are much more penetrating through hi-Z materials, and are thus preferred in certain scenarios (e.g. weapons grade Pu or HEU smuggled inside a lead pig several inches thick). Techniques for thermal neutron imaging have already been developed, but these approaches only image the moderating material, not the true SNM source. Traditional neutron detectors such as He3 tubes and scintillators simply count neutrons. We are developing an instrument that will directly image the fast fission neutrons from an SNM source using a neutron scatter camera. This technique has been shown to be 10 times more sensitive for solar neutrons over traditional neutron counting techniques. In addition to being a 4pi neutron imager, this instrument will also be an excellent neutron spectrometer, and will be able to differentiate between different types of neutron sources (e.g. fission, gamma-n, cosmic ray, and dd or dt fusion). Our instrument will be able to pinpoint the source location. We will present results from a prototype detector and discuss key parameters that determine detector performance.
Skew estimator method for alignment of troposcatter antennas and synchronization of master clocks (1982)

Microprocessor-based instrumentation for optimum alignment of troposcatter antennas and simultaneous synchronization of transmitter and receiver oscillators is discussed. The instrument estimates various spectral moments of the Doppler spectrum of the received signal. When the third central moment or skew is zero, the antennas are properly aligned. Tests of this method indicate that alignment to within 1/10 beam width within a time period of 10 min or less is possible.
B‐Cell Chronic Lymphocytic Leukemia, a Clonal Disease of B Lymphocytes with Receptors that Vary in Specificity for (Auto)antigens (2005)

B-Cell chronic lymphocytic leukemia (B-CLL) is an incurable disease that is relatively common among aging Caucasians. Patients with this leukemia can be divided into prognostic categories using clinical staging parameters, as well as molecular features [presence or absence of IgVH mutations in rearranged VHDJH segments that code for the leukemic B cell's receptor for antigen (BCR)]. In addition, the deduced amino acid structure of the BCRs from patients that fall into different prognostic categories is shared, to varying degrees, within these groups. In this paper, the molecular features of the genes that code for the BCRs of B-CLL patients are reviewed, and these are compared to antibodies of known specificity. These comparisons suggest that the BCRs of many cases resemble autoantibodies, and in some cases, antibodies to microbial antigens. Antigen-binding analyses confirm these impressions, and also indicate that polyreactivity appears to distinguish cases with worse clinical outcomes differ from those with better outcomes. The persistence of autoreactivity and polyreactivity is somewhat surprising, because IgV DNA sequence analyses suggest that many of the B cells that become leukemic have undergone one form or another of receptor editing. Thus, B-CLL appears to be a disease of B-cell clones that have undergone various types of receptor reconfiguration and yet retain inappropriate antigen-binding properties.
Demethylation-Induced Developmental Pleiotropy in <b> <i>Arabidopsis</i> </b> (1996)

The function of DNA methylation in higher plants was investigated by expression of a complementary DNA encoding a cytosine methyltransferase (MET1) from Arabidopsis thaliana as an antisense RNA in transgenic plants. This expression resulted in a 34 to 71 percent reduction in total genomic cytosine methylation. Loss of methylation was observed in both repetitive DNA and single-copy gene sequences. Developmental effects included altered heterochrony, changes in meristem identity and organ number, and female sterility. Cytosine demethylation prolonged both vegetative and reproductive phases of development. These findings implicate DNA methylation in establishing or maintaining epigenetic developmental states in the meristem.
The mechanism of energy decrease in the XeBr laser (1979)

The xenon bromide discharge laser utilizes the reaction of Xe* with HBr to produce XeBr* in a dilute mixture with He or Ne buffer gas. XeBr lasers previously reported suffer from a high gas usage rate under static fill conditions. This is caused by the decomposition of HBr in the laser discharge to bromine and hydrogen. This reaction can be reversed using a catalyst in an external gas circulating system. We demonstrate a tenfold reduction in the consumption of the laser mix, namely 126 shots per liter of gas mix for decay of laser energy to 75% of maximum.
Low‐Thermal‐Conductivity Rare‐Earth Zirconates for Potential Thermal‐Barrier‐Coating Applications. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Tandem repeats of Sushi3 peptide with enhanced LPS-binding and -neutralizing activities (2003)

Endotoxin, also known as lipopolysaccharide (LPS), is the major mediator of septic shock due to Gram-negative bacterial infection. Chemically synthesized S3 peptide, derived from Sushi3 domain of Factor C, which is the endotoxin-sensitive serine protease of the limulus coagulation cascade, was previously shown to bind and neutralize LPS activity. For large-scale production of this peptide and to mimick other pathogen-recognizing molecules, tandem multimers of the S3 gene were constructed and expressed in Escherichia coli. The recombinant tetramer of S3 (rS3-4mer) was purified by anion exchange and digested into monomers (rS3-1mer). Both the rS3-4mer and rS3-1mer were functionally analyzed for their ability to bind LPS by an ELISA-based method and surface plasmon resonance. The LAL inhibition and TNFalpha-release test showed that rS3-1 mer can neutralize the LPS activity as effectively as the synthetic S3 peptide, while rS3-4mer displays an enhanced inhibitory effect on LPS-induced activities. Both recombinant peptides exhibited low cytotoxicity and no haemolytic activity on human cells. This evidence suggests that the recombinant sushi peptides have potential use for the detection, removal of endotoxin and/or anti-endotoxin strategies.
Data from Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma (2023)

<div>Abstract<p>Esophageal adenocarcinoma is an increasingly common disease with a dismal 5-year survival rate of 10% to 15%. In the first systematic evaluation of the PD-1 pathway in esophageal adenocarcinoma, we identify expression of PD-L2 in cancer cells in 51.7% of esophageal adenocarcinomas. Epithelial PD-L1 was expressed on only 2% of cases, although PD-L1<sup>+</sup> immune cells were observed in 18% of esophageal adenocarcinomas. We also evaluated expression in the precursor lesion of esophageal adenocarcinoma, Barrett's esophagus, which emerges following gastric reflux–induced esophageal inflammation, and found PD-L2 expression in Barrett's esophagus but not in non–Barrett's esophagus esophagitis. Because the progression from squamous esophagitis to Barrett's esophagus is accompanied by a transition from a T<sub>H</sub>1 to T<sub>H</sub>2 immune response, we hypothesized that the T<sub>H</sub>2 cytokines IL4/IL13 could contribute to PD-L2 induction. We confirmed that these cytokines can augment PD-L2 expression in esophageal adenocarcinoma cell lines. These results suggest that the inflammatory environment in Barrett's esophagus and esophageal adenocarcinoma may contribute to the expression of PD-L2. Furthermore, the potential for PD-1 receptor blockade to be effective in esophageal adenocarcinomas with epithelial PD-L2 or immune cell PD-L1 expression should be evaluated in clinical trials. <i>Cancer Immunol Res; 3(10); 1123–9. ©2015 AACR</i>.</p></div>