gebhart/patrepeval huggingface dataset:
Immunologic characterization of a 35-kilodalton recombinant antigen of Mycobacterium tuberculosis (1990)

A 35-kilodalton (kDa) recombinant antigen (35-kDa antigen) produced by Escherichia coli JM107 carrying DNA from Mycobacterium tuberculosis was purified and immunologically examined by in vivo and in vitro methods. A monoclonal antibody (2B2) was produced against the 35-kDa antigen. The protein was purified from the insoluble fraction of the recombinant E. coli strain by either affinity chromatography with the 2B2 monoclonal antibody or preparative isoelectric focusing. In enzyme-linked immunosorbent assay and Western blot (immunoblot) analyses, antibody to 2B2 reacted with whole-cell sonic extracts of M. tuberculosis and other slowly growing mycobacteria but not with two rapid growers, M. chelonae and M. fortuitum. An injection series totaling less than 1 mg of purified protein without adjuvant elicited a humoral response in guinea pigs. In one guinea pig, 10 micrograms of purified protein injected intradermally elicited both a humoral and a cell-mediated response. Results of these studies suggest that the 35-kDa antigen is a membrane-associated protein that stimulates both humoral and cell-mediated immune responses and should be evaluated as a vaccine candidate.
Single-strand conformation polymorphism and heteroduplex analysis for gel-based mutation detection (1999)

Single-strand conformation polymorphism (SSCP) and heteroduplex analysis (HA) are popular electrophoretic methods for the identification of sequences. The principle reasons for the popularity of these two methods are their technical simplicity and their relatively high sensitivity for the detection of mutations. Here we review the theory and practice of SSCP and HA, including the factors contributing to the sensitivity of mutation detection. For SSCP analysis, these factors include: choice of gel matrix, electrophoretic conditions, presence of neutral additives, fragment size, and G+C content For HA, the principle factors influencing sensitivity are the gel matrix and the identity of the base mismatch.
Modifying the ground plane and its effect on planar inverted-F antennas (PIFAs) for mobile phone handsets (2003)

The ground plane of a mobile phone plays an important role on the performance of a planar inverted-F antenna (PIFA). In addition to exploring novel antennas, the effective utilization of the mobile phone ground plane and its associated volume is crucial to a successful design. We propose a uniquely modified ground plane configuration to design ultra-thin PIFAs. Both singleand dual-band design examples are provided. Computed and measured data for 900 and 1900 MHz band cases show that, by utilizing this technique, the height of PIFAs can effectively be reduced by more than 50%, thereby reducing the overall phone thickness.
Thin Films of Macroporous Metal Oxides (2001)

Macroporous materials with void sizes above 200 nm have interesting optical properties in the visible part of the spectrum. Here, a strategy is presented for producing large-area thin films of macroporous titania containing interconnected and close-packed pores (see Figure). Since the pores are highly ordered they possess strong diffractive properties (see also cover).
A SPECTROPHOTOMETRIC METHOD FOR MEASURING THE BREAKDOWN OF HYDROGEN PEROXIDE BY CATALASE (1952)

Several methods have been developed for following the breakdown of hydrogen peroxide catalyzed by catalase, but these either have not been sufficiently quantitative or have not proved rapid enough to yield reliable data during the critical 1st or 2nd minute of the reaction. Chemical procedures in which residual peroxide is titrated with permanganate (l-3) or an excess of permanganate is measured calorimetrically (4) are accurate except for reaction times of less than a minute, although Lemberg and Foulkes (5) developed a micromethod for obtaining data every 10 seconds (see also Ogura et al. (6)). Considerable variability is unavoidable, however, when samples must-be taken at such short intervals. The manometric method for measuring oxygen evolved from the system proved in detailed studies to be unsuited for following the rapid breakdown of peroxide in which a diffusion process across the liquid-air interface becomes limiting. This is manifested by changes in both the order of the reaction and the rate of evolution of oxygen with variations in the rate of agitation of the reaction mixture (7). Direct measurement of hydrogen peroxide by polarography provides good quantitative data during the 1st minute of the reaction which fit first order kinetics (8). However, an elaborate, special, electronic circuit is needed for such measurements. Furthermore, as pointed out by Bonmschen, Chance, and Theorell (8), this method appears to give lower values for catalase activity than do titration techniques. Preliminary experiments for following the breakdown of hydrogen peroxide by observing the decrease in light absorption of peroxide solutions in the ultraviolet were reported by Chance (9) and Chance and Herbert (10). The potentialities of this method have been investigated and a quantitative, spectrophotometric technique for following the breakdown of hydrogen peroxide has been developed for routine studies of catalase kinetics.
Construction of a reporter gene vector for Clostridium beijerinckii using a Clostridium endoglucanase gene. (2000)

A beta-1,4-endoglucanase gene (eglA) cloned from C. acetobutylicum P262 was selected for use in the development of a reporter system for C. beijerinckii NCIMB 8052. The reporter plasmid, pER1, was constructed by ligating the promoterless eglA gene into the B subtilis/Clostridium shuttle vector, pFNK1, which can replicate and is stably maintained in C. beijerinckii. The expression of the endoglucanase enzyme from its own promoter was not significantly induced in cells grown in glucose, sucrose or galactose, while growth of cells in cellobiose or fructose resulted in lower levels of activity. The enzyme was efficiently secreted into the culture medium and did not remain associated with the cell in any way. A transcriptional fusion between the glutamine synthetase (glnA) promoter region and the promoterless eglA gene resulted in high levels of endoglucanase expression, which reflected an 11-fold increase in expression levels over the eglA promoter.
Designed Self-Assembly of Molecular Necklaces Using Host-Stabilized Charge-Transfer Interactions (2004)

A novel approach to the noncovalent synthesis of molecular necklaces successfully led to the first quantitative self-assembly of a molecular necklace [6]MN, in which five small rings are threaded on a large ring, from 10 components. Our strategy involves the host-guest complex formation between the molecular host cucurbit[8]uril (CB[8]) and a guest molecule in which an electron donor and an electron acceptor unit are connected by a rigid linker with a proper angle, to form a cyclic oligomer through the host-stabilized intermolecular charge-transfer (CT) complex formation. In the structure of the molecular necklace [6]MN, five molecules of the guest form a cyclic framework by the intermolecular CT interactions, on which five CB[8] molecules are threaded with an arrangement reminiscent of a five-fold propeller. The molecular necklace measures approximately 3.7 nm in diameter and approximately 1.8 nm in thickness.
Design, Synthesis, and Characterization of Novel CXCR4 Antagonists Featuring Cyclic Amines (2020)

Chemokine receptor CXCR4 and its natural ligand CXCL12 (also known as stromal cell-derived factor-1, or SDF-1) regulate a broad range of physiological functions. Dysregulation of the CXCL12/CXCR4 axis is involved in numerous pathological conditions such as HIV infection, inflammation and cancer. Herein, we report the design, synthesis, and characterization of novel CXCR4 antagonists based on cyclic amine scaffolds. Compound 24 was identified as a potent CXCR4 receptor antagonist (competitive inhibition of 12G5 binding, IC<sub>50</sub> =24 nM; functional inhibition of CXCL12-induced cytosolic calcium increase, IC<sub>50</sub> =0.1 nM). In addition, compound 24 potently inhibited cell migration in CXCR4/CXCL12-mediated chemotaxis in a matrigel invasion assay. The absolute configuration of compound 24 was elucidated by X-ray crystallography.
Voltage-gated sodium channel blockers as cytostatic inhibitors of the androgen-independent prostate cancer cell line PC-3. (2003)

The recent discovery of sodium (Na(+)) channel expression in human prostate cancer (PCa) cells led us to investigate the potential use of neuronal Na(+) channel blockers as inhibitors of PCa cells. Our initial studies discovered two classes of Na(+) channel blockers that were effective inhibitors of PCa cell proliferation. Both hydroxyamides (compounds 1 and 4) and a hydantoin (compound 5) were shown to inhibit the androgen-independent PCa cell line PC-3 in vitro. Electrophysiology showed that all compounds functionally block brain type II voltage-gated Na(+) channels (Nav1.2) expressed in Xenopus laevis oocytes. Long-term growth assays in androgen-independent PC-3 cells showed remarkable inhibition of cell growth, with cells growing to a maximum of 30% of controls with analogue 1. Further, our analogues demonstrated only marginal impact on cell viability over the same treatment interval.
Player goal recognition in open-world digital games with long short-term memory networks (2016)

Recent years have seen a growing interest in player modeling for digital games. Goal recognition, which aims to accurately recognize players' goals from observations of low-level player actions, is a key problem in player modeling. However, player goal recognition poses significant challenges because of the inherent complexity and uncertainty pervading gameplay. In this paper, we formulate player goal recognition as a sequence labeling task and introduce a goal recognition framework based on long short-term memory (LSTM) networks. Results show that LSTM-based goal recognition is significantly more accurate than previous state-of-the-art methods, including n-gram encoded feedforward neural networks pre-trained with stacked denoising autoencoders, as well as Markov logic network-based models. Because of increased goal recognition accuracy and the elimination of labor-intensive feature engineering, LSTM-based goal recognition provides an effective solution to a central problem in player modeling for open-world digital games.
Contribution of phosphatidylinositol 3-kinase to radiation resistance in human melanoma cells (1999)

The activity of phosphatidylinositol 3-kinase (PI3K), a key component of multiple signal transduction pathways, was investigated in early- and late-stage melanoma cells that have varying degrees of radiation resistance. Analysis of PI3K biproducts (PI-3,4-P2 and PI-3,4,5-triphosphate) revealed a direct correlation between radiation resistance and levels of PI3K activity. Treating melanoma cells with wortmanin or LY294002, two different PI3K inhibitors, decreased PI3K activity and caused a dose-dependent decrease in resistance to ultraviolet radiation. Lower resistance to radiation elicited by LY294002 coincided with increased apoptosis. To further establish the role of PI3K in radiation resistance, we transfected early-stage melanoma cells with the cDNA of p85, the regulatory subunit of PI3K. Clones that constitutively overexpressed p85 exhibited a higher degree of PI-3,4-P2 synthesis and a corresponding increase in their resistance to ultraviolet radiation. The results of this study point to the role of PI3K and its biproducts in radiation resistance of human melanoma cells.
Targeted Inactivation of the 25-Hydroxyvitamin D3-1α-Hydroxylase Gene (CYP27B1) Creates an Animal Model of Pseudovitamin D-Deficiency Rickets* (2001)

Pseudovitamin D-deficiency rickets is caused by mutations in the cytochrome P450 enzyme, 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-OHase). Patients with the disease exhibit growth retardation, rickets, and osteomalacia. Serum biochemistry is characterized by hypocalcemia, secondary hyperparathyroidism, and undetectable levels of 1alpha,25-dihydroxyvitamin D(3). We have inactivated the 1alpha-OHase gene in mice after homologous recombination in embryonic stem cells. Serum analysis of homozygous mutant animals confirmed that they were hypocalcemic, hypophosphatemic, hyperparathyroidic, and that they had undetectable 1alpha,25-dihydroxyvitamin D(3). Histological analysis of the bones from 3-week-old mutant animals confirmed the evidence of rickets. At the age of 8 weeks, femurs from 1alpha-OHase-ablated mice present a severe disorganization in the architecture of the growth plate and marked osteomalacia. These results show that we have successfully inactivated the 1alpha-OHase gene in mice and established a valid animal model of pseudovitamin D-deficiency rickets.
Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity (2016)

Osimertinib may represent a clinically significant treatment option for patients with EGFRm NSCLC and brain metastases. Further investigation of osimertinib in this patient population is ongoing. Clin Cancer Res; 22(20); 5130-40. ©2016 AACR.
IL-2 binding activates a tyrosine-phosphorylated phosphatidylinositol-3-kinase (1991)

IL-2 was shown to induce phosphatidylinositol-3-kinase activity in the CTLL-2 murine lymphocyte line. Tyrosine phosphorylation of phosphatidylinositol-3-kinase was demonstrated by immunoabsorption with antiphosphotyrosine antibody and was coincident with activation of an IL-2R-associated tyrosine kinase. Half-maximal activation of this enzyme, and of cell proliferation, occurred at 30 pM IL-2. Incubation of cells with genistein, a selective tyrosine kinase inhibitor, blocked IL-2-dependent activation of receptor-associated tyrosine kinase and phosphatidylinositol-3-kinase activities, suggesting that tyrosine phosphorylation-dependent activation of phosphatidylinositol-3-kinase is a component of the IL-2R signal transduction process.
Dissecting Physiological Roles of Estrogen Receptor α and β with Potent Selective Ligands from Structure-Based Design (2004)

The distinct roles of the two estrogen receptor (ER) isotypes, ERalpha and ERbeta, in mediating the physiological responses to estrogens are not completely understood. Although knockout animal experiments have been aiding to gain insight into estrogen signaling, additional information on the function of ERalpha and ERbeta will be provided by the application of isotype-selective ER agonists. Based on the crystal structure of the ERalpha ligand binding domain and a homology model of the ERbeta-ligand binding domain, we have designed steroidal ligands that exploit the differences in size and flexibility of the two ligand binding cavities. Compounds predicted to bind preferentially to either ERalpha or ERbeta were synthesized and tested in vitro using radio-ligand competition and transactivation assays. This approach directly led to highly ER isotype-selective (approximately 200-fold) and potent ligands. To unravel physiological roles of the two receptors, in vivo experiments with rats were conducted using the ERalpha- and ERbeta-selective agonists in comparison to 17beta-estradiol. The ERalpha agonist induced uterine growth, caused bone-protective effects, reduced LH and FSH plasma levels, and increased angiotensin I, whereas the ERbeta agonist did not at all or only at high doses lead to such effects, despite high plasma levels. It can thus be concluded that estrogen effects on the uterus, pituitary, bone, and liver are primarily mediated via ERalpha. Simultaneous administration of the ERalpha and ERbeta ligand did not lead to an attenuation of ERalpha-mediated effects on the uterus, pituitary, and liver parameters.
Epitope prediction algorithms for peptide-based vaccine design (2004)

Peptide-based vaccines, in which small peptides derived from target proteins (eptiopes) are used to provoke an immune reaction, have attracted considerable attention recently as a potential means both of treating infectious diseases and promoting the destruction of cancerous cells by a patient's own immune system. With the availability of large sequence databases and computers fast enough for rapid processing of large numbers of peptides, computer aided design of peptide-based vaccines has emerged as a promising approach to screening among billions of possible immune-active peptides to find those likely to provoke an immune response to a particular cell type. In this paper, we describe the development of three novel classes of methods for the prediction problem. We present a quadratic programming approach that can be trained on quantitative as well as qualitative data. The second method uses linear programming to counteract the fact that our training data contains mostly positive examples. The third class of methods uses sequence profiles obtained by clustering known epitopes to score candidate peptides. By integrating these methods, using a simple voting heuristic, we achieve improved accuracy over the state of the art.
Mechanistic Insights Into the Cross-Feeding of Ruminococcus gnavus and Ruminococcus bromii on Host and Dietary Carbohydrates (2018)

Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities. Here, we focused on two major human gut symbionts, the mucin-degrader <i>Ruminococcus gnavus</i> ATCC 29149, and <i>R. bromii</i> L2-63, a keystone species for the degradation of resistant starch (RS) in human colon. Using anaerobic individual and co-cultures of <i>R. bromii</i> and <i>R. gnavus</i> grown on mucin or starch as sole carbon source, we showed that starch degradation by <i>R. bromii</i> supported the growth of <i>R. gnavus</i> whereas <i>R. bromii</i> did not benefit from mucin degradation by <i>R. gnavus</i>. Further we analyzed the growth (quantitative PCR), metabolite production (<sup>1</sup>H NMR analysis), and bacterial transcriptional response (RNA-Seq) of <i>R. bromii</i> cultured with RS or soluble starch (SS) in the presence or absence of <i>R. gnavus</i>. In co-culture fermentations on starch, <sup>1</sup>H NMR analysis showed that <i>R. gnavus</i> benefits from transient glucose and malto-oligosaccharides released by <i>R. bromii</i> upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products. Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of <i>R. bromii</i> induced changes in <i>R. gnavus</i> transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of <i>R. gnavus</i> to utilize <i>R. bromii</i> starch degradation products. In the RS co-culture, <i>R. bromii</i> showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of <i>R. gnavus</i>. Together this study showed a direct competition between <i>R. bromii</i> and <i>R. gnavus</i> on RS, suggesting that <i>in vivo</i>, the <i>R. gnavus</i> population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.
Rapid and selective modification of phosphoserine residues catalysed by Ba2+ ions for their detection during peptide microsequencing (1991)

The beta-elimination of phosphoserine residues by dilute alkali is catalysed by the presence of group II metal ions. The use of 0.1 M-Ba (OH)2 catalysed the rate of beta-elimination of phosphoserine by more than two orders of magnitude compared with the use of NaOH at the same OH-ion concentration. Serine and threonine residues are unaffected by this treatment. Free thiol groups and disulphide bonds are labile to these conditions, but carboxymethylcysteine is stable. The rate of beta-elimination of O-glycosidically linked moieties is not catalysed under these conditions, and the rate of reaction is thus two orders of magnitude slower than for phosphoserine. This specific catalysis was readily exploited in the rapid and selective modification of phosphoserine residues under mildly alkaline conditions with the nucleophile methylamine via the alpha beta-desaturated dehydroalanine intermediate to yield the beta-methylaminoalanine residue. This modified residue could be easily detected on sequence analysis and in amino acid compositions.
Specific Capture and Release of Circulating Tumor Cells Using Aptamer‐Modified Nanosubstrates (2013)

A platform for capture and release of circulating tumor cells (CTCs) is demonstrated by utilizing aptamer grafted silicon nanowires. Here, single-stranded DNA-aptamers are generated via the Cell-SELEX process to serve as capture agents, allowing specific capture and release of non-small cell lung cancer (NSCLC) CTCs from whole-blood samples with minimum contamination and negligible disruption to CTC viability and functions.
Learning to extract information from semi-structured text using a discriminative context free grammar (2005)

In recent work, conditional Markov chain models (CMM) have been used to extract information from semi-structured text (one example is the Conditional Random Field [10]). Applications range from finding the author and title in research papers to finding the phone number and street address in a web page. The CMM framework combines a priori knowledge encoded as features with a set of labeled training data to learn an efficient extraction process. We will show that similar problems can be solved more effectively by learning a discriminative context free grammar from training data. The grammar has several distinct advantages: long range, even global, constraints can be used to disambiguate entity labels; training data is used more efficiently; and a set of new more powerful features can be introduced. The grammar based approach also results in semantic information (encoded in the form of a parse tree) which could be used for IR applications like question answering. The specific problem we consider is of extracting personal contact, or address, information from unstructured sources such as documents and emails. While linear-chain CMMs perform reasonably well on this task, we show that a statistical parsing approach results in a 50% reduction in error rate. This system also has the advantage of being interactive, similar to the system described in [9]. In cases where there are multiple errors, a single user correction can be propagated to correct multiple errors automatically. Using a discriminatively trained grammar, 93.71% of all tokens are labeled correctly (compared to 88.43% for a CMM) and 72.87% of records have all tokens labeled correctly (compared to 45.29% for the CMM).
Some Derivatives of 1-Benzazepine. Part II (1974)

We have investigated the ring expansion of some substituted 1,4-naphthoquinones by hydrazoic acid to yield new 1-benzazepine derivatives of the "azatropolone" type. Ring contraction of those products, which are 2,5-dihydro-3-hydroxy-2,5-dioxo-1-benzazepines, gives 4-quinolone-2-carboxylic acids. Some of the reactions of the new benzazepine system were investigated. Attempts to prepare substituted derivatives suitable for making 1-benzazatrop-5-one were not successful.The effect of substituents on the ring expansion reaction is discussed and an anomalous ring expansion to a 2,5-dihydro-4-hydroxy-2,5-dioxo-1-benzazepine is described and explained mechanistically.