gebhart/patrepeval huggingface dataset:
A Rapid Quantitative Bioassay for Evaluating the Effects of Ligands Upon Receptors That Modulate cAMP Levels in a Melanophore Cell Line (1992)

A new method for rapidly evaluating the effects of drugs on receptors that regulate intracellular cAMP in a cell line derived from Xenopus laevis melanophores has been developed. Melanophores were plated into sterile 96 well microtiter plates, and 3 days later the cells were treated with melatonin for 30 min to induce melanosome aggregation. Subsequent exposure to MSH or adrenergic agonists caused dose dependent pigment dispersion that peaked within 30 min. The cumulative pigment displacement from cells could be quantitated by using a microplate reader to measure changes in transmittance of light through the wells. The acquired data enabled detailed and reproducible dose response curves and time course analyses to be generated. In addition, the assay followed for the rapid characterization of the effects of antagonists upon the beta adrenergic receptor (beta AR). The assay has the potential to test the effects of ligands upon any receptor capable of mediating pigment translocation in the melanophore cell line.
TOXICITY OF SELECTED ORGANIC COMPOUNDS TO INSECTS: PART I. TESTS FOR GENERAL TOXICITY ON LARVAE OF MUSCA, TRIBOLIUM, AND EPHESTIA, AND ADULTS OF SITOPHILUS (1948)

The general toxicity of 127 synthetic organic compounds was tested against larvae of Musca domestica, Tribolium confusum, and Ephestia kuehniella, and adults of Sitophilus granarius. The compounds were mixed in the insects' food in graded concentrations, and their toxicity was assessed by determination of the median lethal concentrations (LC 50 ) for each of the four species. The most highly toxic compounds were gammexane (the gamma isomer of hexachlorocyclohexane) and chlordane (obtained by distillation of technical chlordane). The toxicity of DDT was on the average one-half of that of the first two compounds, and it was superior to any of the 12 analogues tested. Four chlorinated aliphatic hydrocarbons, namely hexachloropropene, hexachlorobutadiene, and the symm-and asymm-heptachloropropanes, showed a high toxicity related to their powerful fumigant action. A high level of toxicity was shown by benzyl thiocyanate and its chlorinated derivatives. The nitro compounds dinitro-o-cresol, nitrostyrene, dinitrodimethylbutane and dinitrocyclohexylphenol were especially toxic to Sitophilus adults, but were ineffective against Musca larvae. Certain aromatic semicarbazones recommended by previous workers gave disappointing results. Of 22 derivatives of morpholine tested, only three showed any degree of toxicity to the four species of insects employed.
Oxidative Stress, Plasminogen Activator Inhibitor 1, and Lung Fibrosis (2007)

Fibrosis is characterized by excessive accumulation of extracellular matrix (ECM) in basement membranes and interstitial tissues, resulting from increased synthesis or decreased degradation of ECM or both. The plasminogen activator/plasmin system plays an important role in ECM degradation, whereas the plasminogen activator inhibitor 1 (PAI-1) is a physiologic inhibitor of plasminogen activators. PAI-1 expression is increased in the lung fibrotic diseases and in experimental fibrosis models. The deletion of the PAI-1 gene reduces, whereas the overexpression of PAI-1 enhances, the susceptibility of animals to lung fibrosis induced by different stimuli, indicating an important role of PAI-1 in the development of lung fibrosis. Many growth factors, including transforming growth factor beta (TGF-beta) and tumor necrosis factor alpha (TNF-alpha), as well as other chemicals/agents, induce PAI-1 expression in cultured cells and in vivo. Reactive oxygen and nitrogen species (ROS/RNS) have been shown to mediate the induction of PAI-1 by many of these stimuli. This review summarizes some recent findings that help us to understand the role of PAI-1 in the development of lung fibrosis and ROS/RNS in the regulation of PAI-1 expression during fibrogenesis.
Removal of FKBP12.6 Does Not Alter the Conductance and Activation of the Cardiac Ryanodine Receptor or the Susceptibility to Stress-induced Ventricular Arrhythmias (2007)

The 12.6-kDa FK506-binding protein (FKBP12.6) is considered to be a key regulator of the cardiac ryanodine receptor (RyR2), but its precise role in RyR2 function is complex and controversial. In the present study we investigated the impact of FKBP12.6 removal on the properties of the RyR2 channel and the propensity for spontaneous Ca(2+) release and the occurrence of ventricular arrhythmias. Single channel recordings in lipid bilayers showed that FK506 treatment of recombinant RyR2 co-expressed with or without FKBP12.6 or native canine RyR2 did not induce long-lived subconductance states. [(3)H]Ryanodine binding studies revealed that coexpression with or without FKBP12.6 or treatment with or without FK506 did not alter the sensitivity of RyR2 to activation by Ca(2+) or caffeine. Furthermore, single cell Ca(2+) imaging analyses demonstrated that HEK293 cells co-expressing RyR2 and FKBP12.6 or expressing RyR2 alone displayed the same propensity for spontaneous Ca(2+) release or store overload-induced Ca(2+) release (SOICR). FK506 increased the amplitude and decreased the frequency of SOICR in HEK293 cells expressing RyR2 with or without FKBP12.6, indicating that the action of FK506 on SOICR is independent of FKBP12.6. As with recombinant RyR2, the conductance and ligand-gating properties of single RyR2 channels from FKBP12.6-null mice were indistinguishable from those of single wild type channels. Moreover, FKBP12.6-null mice did not exhibit enhanced susceptibility to stress-induced ventricular arrhythmias, in contrast to previous reports. Collectively, our results demonstrate that the loss of FKBP12.6 has no significant effect on the conduction and activation of RyR2 or the propensity for spontaneous Ca(2+) release and stress-induced ventricular arrhythmias.
Repair of single base-pair transversion mismatches of Escherichia coli in vitro: correction of certain A/G mismatches is independent of dam methylation and host mutHLS gene functions. (1988)

Six different base-pair transversion mismatches are repaired with different efficiencies in an in vitro mismatch repair system. In particular, the T/T and C/C mismatches appear to be less efficiently repaired than the A/A and G/G mismatches. Four A/G and four C/T mismatches at different positions are repaired to different extents. One of the A/G mismatches is repaired equally efficiently when DNA heteroduplexes are fully methylated or hemi-methylated at the d(GATC) sequences. This type of mismatch repair appears to be unidirectional with A to C conversion by acting at A/G mispairs to restore the C/G pairs. This methylation-independent correction is not controlled by the mutH, mutL, mutS, uvrE, uvrB, phr, recA, recF, and recJ gene products. The independence of the transversion mismatch repair of these genes and methylation distinguishes this from the known mismatch repair pathways.
Host regulation of the cauliflower mosaic virus multiplication cycle. (1990)

The DNA genome of cauliflower mosaic virus (CaMV) replicates in the cytoplasm of infected plant cells by reverse transcription of an RNA template. Viral RNA is generated in the nucleus by transcription of an episomal minichromosome containing supercoiled DNA. We have assessed the relative activities of the nuclear and cytoplasmic phases of the CaMV multiplication cycle by monitoring unencapsidated viral DNA forms and polyadenylylated RNAs in different organs of one host plant and in different host species. Systemically infected leaves of a highly susceptible host, turnip (Brassica rapa), contained abundant 35S RNA and 19S RNA transcripts and unencapsidated reverse transcription products but relatively little supercoiled DNA. In contrast, supercoiled DNA accumulated in roots and other tissues of turnip plants but without significant amounts of steady-state viral RNA. Infected but asymptomatic leaves of a less susceptible CaMV host, kohlrabi (Brassica oleracea), contained supercoiled DNA almost exclusively but negligible viral RNA and DNA products of reverse transcription. An allotetraploid species, rape (Brassica napus), exhibited infection characteristics and minichromosome expression levels intermediate between the other two species from which it was derived. We conclude that expression of the CaMV minichromosome is a key phase of the virus multiplication cycle, which is regulated differentially in organs of a highly susceptible host species. Furthermore, this regulation exhibits genetic variation among different Brassica species and controls host susceptibility to CaMV infection.
<title>Modeling the statistics of image features and associated text</title> (2001)

We present a methodology for modeling the statistics of image features and associated text in large datasets. The models used also serve to cluster the images, as images are modeled as being produced by sampling from a limited number of combinations of mixing components. Furthermore, because our approach models the joint occurrence image features and associated text, it can be used to predict the occurrence of either, based on observations or queries. This supports an attractive approach to image search as well as novel applications such a suggesting illustrations for blocks of text (auto-illustrate) and generating words for images outside the training set (auto-annotate). In this paper we illustrate the approach on 10,000 images of work from the Fine Arts Museum of San Francisco. The images include line drawings, paintings, and pictures of sculpture and ceramics. Many of the images have associated free text whose nature varies greatly, from physical description to interpretation and mood. We incorporate statistical natural language processing in order to deal with free text. We use WordNet to provide semantic grouping information and to help disambiguate word senses, as well as emphasize the hierarchical nature of semantic relationships.
Lipoxin synthase activity of human platelet 12-lipoxygenase (1993)

Human platelets and megacaryocytes generate lipoxins from exogenous leukotriene A4 (LTA4). We examined the role of human 12-lipoxygenase (12-LO) in lipoxin generation with recombinant histidine-tagged human platelet enzyme (6His-12-LO), partially purified 12-LO from human platelets (HPL 12-LO) and, for the purposes of direct comparison, permeabilized platelets. Recombinant and HPL 12-LO catalysed the conversion of intact LTA4 into both lipoxin A4 (LXA4) and lipoxin B4 (LXB4). In contrast, only negligible quantities of LXA4 were generated when recombinant 12-LO was incubated with the non-enzymic hydrolysis products of LTA4.6His-12-LO also converted a non-allylic epoxide, 5(6)-epoxy-(8Z,11Z,14Z)-eicosatrienoic acid. The apparent Km and Vmax. for lipoxin synthase activity of 6His-12-LO were estimated to be 7.9 +/- 0.8 microM and 24.5 +/- 2.5 nmol/min per mg respectively, and the LXB4 synthase activity of this enzyme was selectively regulated by suicide inactivation. Aspirin gave a 2-fold increase in lipoxin formation by platelets but did not enhance the conversion of LTA4 by the recombinant 12-LO. These results provide direct evidence for LXA4 and LXB4 synthase activity of human platelet 12-LO. Moreover, they suggest that 12-LO is a dual-function enzyme that carries both oxygenase and lipoxin synthase activity.
A Convenient Method for the Preparation of Fluorous Tin Derivatives for the Fluorous Labeling Strategy (2008)

A convenient method for the preparation of fluorous aryl stannanes was developed as a means of expanding the general utility of the fluorous labeling strategy (FLS). Following the synthesis of a novel fluorous distannane, a palladium-catalyzed cross-coupling reaction was used to prepare the target compounds from aryl halides. The scope of the reaction was investigated by preparing a small library of model compounds where the reaction yields were similar to those reported for the analogous procedures employing hexamethyl- or hexabutyldistannanes. The utility of the reported methodology was demonstrated through the successful synthesis of fluorous precursors to two established molecular imaging and therapy agents (FIAU, IUdR). These were radiolabeled with iodine-125 and the desired products isolated in high yield and effective specific activity.
Unique and common protective epitopes among different serotypes of group A streptococcal M proteins defined with hybridoma antibodies (1984)

A set of four monoclonal antibodies was produced against a highly purified pepsin extract of type 5 streptococcal M protein. Three of the four antibodies cross-reacted with purified M proteins from heterologous serotypes and opsonized the respective heterologous organisms. Our studies suggest that monoclonal antibodies may be useful in identifying subpeptides of various M proteins containing common, protective epitopes that are capable of evoking antibodies that would protect against several different potentially "rheumatogenic" serotypes.
DNA probe detection of periodontal pathogens in HIV‐associated periodontal lesions (1991)

Recent studies have shown that an atypical gingivitis and a rapidly progressive periodontal disease may be early-occurring opportunistic infections associated with human immunodeficiency virus (HIV) infection. This study examined the prevalence of selected periodontal pathogens associated with these HIV-related periodontal lesions. Subgingival plaque samples were obtained from both HIV-seronegative and HIV-seropositive homosexual men and from presumably uninfected heterosexual men. DNA probes were used to detect Actinobacillus actinomycetemcomitans, Bacteroides intermedius, Bacteroides gingivalis, Eikenella corrodens and Wolinella recta in the plaque. The healthy sites in both the seronegative and seropositive homosexual groups showed a greater prevalence of all test bacteria, except for E. corrodens, than did the heterosexual group. HIV-associated periodontitis sites showed a microbial profile qualitatively similar to that of conventional periodontitis, except that B. gingivalis was more prevalent in conventional periodontitis. In contrast, HIV-associated gingivitis sites exhibited a greater prevalence of all bacteria tested than conventional gingivitis sites. In fact, HIV gingivitis generally showed a bacterial profile similar to that of the HIV periodontitis lesions, except that W. recta was significantly more prevalent in HIV periodontitis. These data suggest that the HIV gingivitis lesion is a precursor to HIV periodontitis. Thus, early identification and prophylactic treatment of high-risk individuals may prevent the destruction of periodontal tissues.
Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of HumansWith Type 2 Diabetes (2000)

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFalpha, and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes.
Ziv-aflibercept: A novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer (2013)

Current clinical data are insufficient to directly compare ziv-aflibercept and bevacizumab when used with standard combination chemotherapy as first- or second-line regimens for mCRC. The role of ziv-aflibercept is currently limited to the second-line setting in combination with irinotecan-based regimens in mCRC patients who have not received irinotecan previously. The role of ziv-aflibercept in chemotherapy for other tumor types is yet to be determined.
Premature Infants 750–1,250 g Birth Weight Supplemented with a Novel Human Milk-Derived Cream Are Discharged Sooner (2016)

Very preterm infants who received an HM-derived cream supplement were discharged earlier. Infants with BPD may have benefited the most.
Factor inducing Agrobacterium tumefaciens vir gene expression is present in monocotyledonous plants (1988)

Agrobacterium tumefaciens harboring the tumor-inducing Ti plasmid incites crown gall tumor on dicotyledonous species. Upon infection of these plants, Ti plasmid DNA sequence is stably transferred (T-DNA) by unknown mechanisms to plant cells to be integrated into nuclear DNA. The T-DNA processing and transfer require the expression of vir (virulence) genes on the Ti plasmid, which are known to be induced by certain phenolic compounds released from cells at the wounded inoculation site. The results of the present study demonstrate that wheat and oats contain a substance(s) that induces vir gene expression, yet the inducing substance of wheat differs from the phenolic inducers in that it is hydrophilic and has a molecular weight of several thousand. The novel inducer was not detectable in the exudates of seedlings of these plants but was found in an extract from the transition region between shoot and root of the seedlings and also in extracts from the seeds, bran, and germ. This finding suggests that T-DNA processing and possibly its transfer should take place when Agrobacterium invades suitable tissues of monocotyledonous plants.
DASH-2: Flexible, Low-Cost, and High-Throughput SNP Genotyping by Dynamic Allele-Specific Hybridization on Membrane Arrays (2003)

Genotyping technologies need to be continually improved in terms of their flexibility, cost-efficiency, and throughput, to push forward genome variation analysis. To this end, we have leveraged the inherent simplicity of dynamic allele-specific hybridization (DASH) and coupled it to recent innovations of centrifugal arrays and iFRET. We have thereby created a new genotyping platform we term DASH-2, which we demonstrate and evaluate in this report. The system is highly flexible in many ways (any plate format, PCR multiplexing, serial and parallel array processing, spectral-multiplexing of hybridization probes), thus supporting a wide range of application scales and objectives. Precision is demonstrated to be in the range 99.8-100%, and assay costs are 0.05 USD or less per genotype assignment. DASH-2 thus provides a powerful new alternative for genotyping practice, which can be used without the need for expensive robotics support.
In Vitro and In Vivo Characterization of Irreversible Mutant-Selective EGFR Inhibitors That Are Wild-Type Sparing (2014)

Patients with non-small cell lung carcinoma (NSCLC) with activating mutations in epidermal growth factor receptor (EGFR) initially respond well to the EGFR inhibitors erlotinib and gefitinib. However, all patients relapse because of the emergence of drug-resistant mutations, with T790M mutations accounting for approximately 60% of all resistance. Second-generation irreversible EGFR inhibitors are effective against T790M mutations in vitro, but retain affinity for wild-type EGFR (EGFR(WT)). These inhibitors have not provided compelling clinical benefit in T790M-positive patients, apparently because of dose-limiting toxicities associated with inhibition of EGFR(WT). Thus, there is an urgent clinical need for therapeutics that overcome T790M drug resistance while sparing EGFR(WT). Here, we describe a lead optimization program that led to the discovery of four potent irreversible 2,4-diaminopyrimidine compounds that are EGFR mutant (EGFR(mut)) selective and have been designed to have low affinity for EGFR(WT). Pharmacokinetic and pharmacodynamic studies in H1975 tumor-bearing mice showed that exposure was dose proportional resulting in dose-dependent EGFR modulation. Importantly, evaluation of normal lung tissue from the same animals showed no inhibition of EGFR(WT). Of all the compounds tested, compound 3 displayed the best efficacy in EGFR(L858R/T790M)-driven tumors. Compound 3, now renamed CO-1686, is currently in a phase I/II clinical trial in patients with EGFR(mut)-advanced NSCLC that have received prior EGFR-directed therapy.
Chitosan Derivatives Killed Bacteria by Disrupting the Outer and Inner Membrane (2006)

Six kinds of water-soluble chitosan were prepared by grafting aminofunctionality onto chitosan at the C-6 position, and their antimicrobial activities were investigated against three Gram-negative and three Gram-positive bacteria. Among the derivatives, dimethylaminoethyl-chitosan (DMAEC) has the highest potential to suppress the growth of bacteria. To elucidate detailed antimicrobial modes of action against bacteria, cell integrity, outer membrane (OM), and inner membrane (IM) permeabilization assays were investigated. When treated with DMAEC, the release of 260 nm absorbing materials quickly increased for both Escherichia coli and Staphylococcus aureus, but the absorbance value was different due to the difference in cell structures. In OM and IM permeabilization assays, DMAEC rapidly increased 1-N-phenylnaphthylamine uptake and the release of cytoplasmic beta-galactosidase via an increase in the permeability of OM and IM. Moreover, DMAEC90 prepared from 90% deacetylated chitosan had more activity than DMAEC50 prepared from 50% deacetylated chitosan, and these results revealed that the antimicrobial action of water-soluble chitosans was dependent on the degree of deacetylation and the substituted group.
Alkaloid Biosynthesis: Molecular Aspects (1994)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More