gebhart/patrepeval huggingface dataset:
Multiple Length Peptide-Pheromone Variants Produced by Streptococcus pyogenes Directly Bind Rgg Proteins to Confer Transcriptional Regulation (2014)

Streptococcus pyogenes, a human-restricted pathogen, accounts for substantial mortality related to infections worldwide. Recent studies indicate that streptococci produce and respond to several secreted peptide signaling molecules (pheromones), including those known as short hydrophobic peptides (SHPs), to regulate gene expression by a quorum-sensing mechanism. Upon transport into the bacterial cell, pheromones bind to and modulate activity of receptor proteins belonging to the Rgg family of transcription factors. Previously, we reported biofilm regulation by the Rgg2/3 quorum-sensing circuit in S. pyogenes. The aim of this study was to identify the composition of mature pheromones from cell-free culture supernatants that facilitate biofilm formation. Bioluminescent reporters were employed to detect active pheromones in culture supernatants fractionated by reverse-phase chromatography, and mass spectrometry was used to characterize their properties. Surprisingly, multiple SHPs that varied by length were detected. Synthetic peptides of each variant were tested individually using bioluminescence reporters and biofilm growth assays, and although activities differed widely among the group, peptides comprising the C-terminal eight amino acids of the full-length native peptide were most active. Direct Rgg/SHP interactions were determined using a fluorescence polarization assay that utilized FITC-labeled peptide ligands. Peptide receptor affinities were seen to be as low as 500 nm and their binding affinities directly correlated with observed bioactivity. Revelation of naturally produced pheromones along with determination of their affinity for cognate receptors are important steps forward in designing compounds whose purpose is positioned for future therapeutics aimed at treating infections through the interference of bacterial communication.
Abstract 5510: Tamoxifen induces estrogen receptor-independent bioenergetic stress: A synthetic lethality approach to target tumor metabolism (2015)

Abstract Tamoxifen, a selective estrogen receptor modulator (SERM) is clinically used for adjuvant treatment of estrogen receptor (ER) positive breast cancer. Recent data from our lab has shown that tamoxifen inhibits oxygen consumption at high, yet clinically relevant, doses. We hypothesize that this occurs through a non-ER dependent, direct effect on the mitochondria, and causes metabolic and signaling changes that can be exploited for therapeutic benefit. ER+, MCF7 breast cancer cells have a higher basal respiratory rate and lower glycolytic rate than ER, MDA231, cells. However, tamoxifen inhibited oxygen consumption to a similar degree in both cell lines Pharmacological inhibition of ERα expression or CRISPR-Cas9 mediated knock out of the ERα did not affect the ability of tamoxifen to decrease oxygen consumption. In response to tamoxifen inhibition of oxygen consumption, tumor cells increased dependence on glycolysis. Glucose deprivation or treatment with glycolytic inhibitors, 2-deoxy glucose (2DG) or 3-bromo-pyruvate significantly sensitized breast cancer cells to tamoxifen treatment. Tamoxifen combined with glucose deprivation or treatment with 2-DG led to robust activation of the AMPK signaling pathway. Knockout of AMPKα1 in breast cancer cells ameliorated cytotoxicity. Based on these data we’ve also demonstrated clinical usefulness of tamoxifen in a non-breast cancer model. BRAF inhibitor resistant melanoma exhibits a higher rate of oxidative phosphorylation over to the BRAF inhibitor sensitive melanoma cells. Tamoxifen-induced inhibition of oxygen consumption increased cytotoxicity in the OxPhos-addicted, BRAF inhibitor-resistant, population compared to the BRAF inhibitor sensitive cells. Our results indicate a new and unanticipated mechanism of action for tamoxifen in ER+ and ER-breast cancers. Moreover, since this effect is not ER dependent, tamoxifen may have clinical use in a wider spectrum of cancers especially when combined with inhibitors of glycolysis. Citation Format: Natalie A. Daurio, Stephen Tuttle, Constantinos Koumenis. Tamoxifen induces estrogen receptor-independent bioenergetic stress: A synthetic lethality approach to target tumor metabolism. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5510. doi:10.1158/1538-7445.AM2015-5510
Identification of ASF/SF2 as a Critical, Allele-Specific Effector of the Cyclin D1b Oncogene (2010)

The cyclin D1b oncogene arises from alternative splicing of the CCND1 transcript, and harbors markedly enhanced oncogenic functions not shared by full-length cyclin D1 (cyclin D1a). Recent studies showed that cyclin D1b is selectively induced in a subset of tissues as a function of tumorigenesis; however, the underlying mechanism(s) that control tumor-specific cyclin D1b induction remain unsolved. Here, we identify the RNA-binding protein ASF/SF2 as a critical, allele-specific, disease-relevant effector of cyclin D1b production. Initially, it was observed that SF2 associates with cyclin D1b mRNA (transcript-b) in minigene analyses and with endogenous transcript in prostate cancer (PCa) cells. SF2 association was altered by the CCND1 G/A870 polymorphism, which resides in the splice donor site controlling transcript-b production. This finding was significant, as the A870 allele promotes cyclin D1b in benign prostate tissue, but in primary PCa, cyclin D1b production is independent of A870 status. Data herein provide a basis for this disparity, as tumor-associated induction of SF2 predominantly results in binding to and accumulation of G870-derived transcript-b. Finally, the relevance of SF2 function was established, as SF2 strongly correlated with cyclin D1b (but not cyclin D1a) in human PCa. Together, these studies identify a novel mechanism by which cyclin D1b is induced in cancer, and reveal significant evidence of a factor that cooperates with a risk-associated polymorphism to alter cyclin D1 isoform production. Identification of SF2 as a disease-relevant effector of cyclin D1b provides a basis for future studies designed to suppress the oncogenic alternative splicing event.
Amplification of bleomycin-mediated degradation of DNA by polyamines. (1988)

The degradation of calf thymus DNA by a ferrous complex of bleomycin A2 or Blenoxane (a mixture consisting mainly of BLM-A2 and BLM-B2) is enhanced by polyamines higher than ethylenediamine. The QSAR analysis gave excellent correlation between the experimental amplification results and calculated valence molecular connectivity indices of the third order and path type for the protonated polyamines. A new amplifier of bleomycin activity has been synthesized and its interaction with DNA has been studied. This compound contains a DNA-intercalating moiety and a polyamine portion, two independent amplification systems in the same molecule. The role of the C-terminus of bleomycin as the intramolecular amplifier for the degradation of DNA is discussed.
Applications and method development in the simulation of ligands binding to drug targets - eScholarship (2012)

The role of computation in drug discovery has increased considerably in the past few decades. As of 2004 about 50 compounds discovered with computational approaches had entered human clinical trials and some are FDA approved(1). Computational methods can be employed to effectively guide medicinal chemists and discover and optimize active compounds(2). Here we have focused on two protein targets, which are medically important, to inhibit with novel compounds that we have discovered virtually. In chapter 2 we describe the discovery of the first inhibitors of the Akt phosphatase PHLPP, (PH domain Leucine-rich repeat Protein Phosphatase). This enzyme opposes the effects of two kinases, Akt and PKC, which play a major role in cell growth and survival making it an attractive drug target in the treatment of diabetes and heart disease(3, 4). We have used a combination of in silico and chemical screening tools to find new inhibitor compounds of PHLPP. In chapter 3 we describe drug discovery efforts towards inhibitors of the second target, which is undecaprenyl pyrophosphate synthase, (UPPS) an enzyme necessary for bacterial cell wall synthesis. This recently discovered enzyme is substantially different than the analogous human enzyme making it an attractive target for anti-bacterial drug discovery(5). However UPPS is highly flexible target showing great changes in the active site upon substrate, product, or inhibitor binding, thus making it challenging for structure based drug design. Therefore we have characterized these changes using molecular dynamics simulations, and extracted rare conformations important to drug design. In addition to applying existing methods to new drug targets we have worked on developing a new form of enhanced sampling MD described in chapter 4. This method relies on the same approach as Hamelberg et al. took in accelerated MD simulations but the mathematical equations modifying the potential energy surface increase the recovery of statistics from the simulation. This new boost equation has been applied to statistically rigorous free energy calculations that incorporate solvent, entropy, and dynamics, and are among the most computationally accurate yet costly calculations of ligand-protein binding free energy
The synthesis of 1,8-disubstituted 10,11-dihydrodibenz[b,f]oxepin-10-ones. analogues of anaesthetic steroids (1991)

1,8-Disubstituted 10,11-dihydrodibenz[b,f]oxepin-10-ones 4a, b and 5a, b have been synthesised as analogues of steroid anaesthetics 2 and 3 respectively. The novel partial Ullmann reaction between methyl 2,6-dichlorophenylacetate 7 and 4-substituted phenols 8e, b gave diphenyl ether derivatives 9a, b. The latter were then hydrolysed and cyclodehydrated to give 1,8-disubstituted 10,11-dihydrodibenz[b,f] oxepin-10-ones 11a, b which underwent selective functional group transformations to give 4a, 5a and 4b, 5b respectively. Lithium borohydride reduction of the ester 13b to the benzyl alcohol 14b proceeded without reduction of the enol ether function.
Impairment of Gamma Interferon Signaling in Human Neutrophils Infected with<i>Anaplasma phagocytophilum</i> (2009)

Anaplasma phagocytophilum, the causative agent of tick-borne human granulocytic anaplasmosis (HGA), is an intracellular bacterium which survives and multiplies inside polymorphonuclear neutrophil granulocytes (PMN). Increased bacterial burden in gamma interferon (IFN-gamma)-deficient mice suggested a major role of IFN-gamma in the control of A. phagocytophilum. Here we investigated whether infection of human PMN with A. phagocytophilum impairs IFN-gamma signaling thus facilitating intracellular survival of the bacterium. The secretion of the IFN-gamma-inducible chemokines IP-10/CXCL10 and MIG/CXCL9 was markedly inhibited in infected neutrophils. Molecular analyses revealed that, compared to uninfected PMN, A. phagocytophilum decreased the expression of the IFN-gamma receptor alpha-chain CD119, diminished the IFN-gamma-induced phosphorylation of STAT1, and enhanced the expression of SOCS1 and SOCS3 in PMN. Since IFN-gamma activates various antibacterial effector mechanisms of PMN, the impaired IFN-gamma signaling in infected cells likely contributes to the survival of A. phagocytophilum inside PMN and to HGA disease development.
SIMULATION OF NUCLEATION KINETICS: THE DEVELOPMENT OF THE KINETIC ORRECTION FACTOR FOR THE URVIVAL THEORY (1980)

From several simulations of nucleation kinetics, the number of surviving nuclei were found to differ from that predicted by the survival theory. This difference led to the development of a kinetic correction factor to be applied to the survival theory. This correction factor depends upon the relaxation behavior of the nucleation rate which in turn depends upon the supersaturation and the distribution function of the disturbance. This study was extended to non gaussian shaped disturbance functions
Inward-Rectifying K+ Channels in Root Hairs of Wheat (A Mechanism for Aluminum-Sensitive Low-Affinity K+ Uptake and Membrane Potential Control) (1994)

K+ is the most abundant cation in cells of higher plants, and it plays vital roles in plant growth and development. Extensive studies on the kinetics of K+ uptake in roots have shown that K+ uptake is mediated by at least two transport mechanisms, one with a high and one with a low affinity for K+. However, the precise molecular mechanisms of K+ uptake from soils into root epidermal cells remain unknown. In the present study we have pursued the biophysical identification and characterization of mechanisms of K+ uptake into single root hairs of wheat (Triticum aestivum L.), since root hairs constitute an important site of nutrient uptake from the soil. These patch-clamp studies showed activation of a large inward current carried by K+ ions into root hairs at membrane potentials more negative than -75 mV. This K+ influx current was mediated by hyperpolarization-activated K+-selective ion channels, with a selectivity sequence for monovalent cations of K+ > Rb+ [almost equal to] NH4+ >> Na+ [almost equal to] Li+ > Cs+. Kinetic analysis of K+ channel currents yielded an apparent K+ equilibrium dissociation constant (Km) of [almost equal to]8.8 mM, which closely correlates to the major component of low-affinity K+ uptake. These channels did not inactivate during prolonged stimulation and would thus enable long-term K+ uptake driven by the plasma membrane proton-extruding pump. Aluminum, which is known to inhibit cation uptake at the root epidermis, blocked these inward-rectifying K+ channels with half-maximal current inhibition at [almost equal to]8 [mu]M free Al3+. Aluminum block of K+ channels at these Al3+ concentrations correlates closely to Al3+ phytotoxicity. It is concluded that inward-rectifying K+ channels in root hairs can function as both a physiologically important mechanism for low-affinity K+ uptake and as regulators of membrane potential. The identification of this mechanism is a major step toward a detailed molecular characterization of the multiple components involved in K+ uptake, transport, and membrane potential control in root epidermal cells.
Light-Activated Pest Control (1995)

Upon illumination, some photoactive molecules have been shown to cause toxic reactions in living cells. This is especially significant when the photoactive chemical is taken up or ingested by arthropods, many of which are agricultural or medical pests. The structures of these molecules are diverse and range from visible dyes to allelochemicals. The common aspect of the toxic reaction involves illumination by photons of light and the presence of oxygen. Over many decades, laboratory and small scale field tests have proven the efficacy of the approach in many pesticidal applications. Most of the dye applications have utilized the halogenated xanthene series of dyes, while the allelochemical applications have utilized a broad search for new chemical structures capable of catalyzing these photochemical reactions. There are current efforts aimed primarily at developing suitable bait technologies for large scale control of commercially important insects.
Influence of age and body size on intestinal permeability and absorption in healthy dogs (2002)

These results indicate that age and body size should be considered when assessing intestinal permeability by use of the L:R urinary excretion test in dogs. High intestinal permeability could be a possible cause of poor fecal quality in large dogs.
Post etch killer defect characterization and reduction in a self-aligned double patterning technology (2011)

This paper identifies post etch killer defects, e.g., core bridging, small particle and tiny bridging, and investigates the possible solutions in a SADP module. Among the killer defect adders, core bridging and small particle are commonly observed after the oxide core removal by BOE. Core bridging adder is a carbon-containing polymeric by-product during nitride spacer open; by introducing additional diluted HF (DHF) treatment could effectively eliminate such bridging adder. Small particle adder is found to peel from the poly-Si hard mask-1 (HM1) damaged location, where is eroded during the wafer backside cleaning. It is useful for suppressing the formation of small particle by skipping the wafer backside cleaning process. Tiny bridging adder is block of etched poly-Si HM1 causing short between lines. One possibility of blocked etch adder creating is the fine micromasking formed on the opening of BARC during poly-Si HM1 etching. The effective suppression of tiny bridging adder is using high energetic F-/O-radicals to break through the micromasking in the poly-Si HM1 patterning. The reductions of above killer defects successfully boost up the sorting yield in our 45 nm charge-trapping flash memory.
Pesticide Residues, Residual Properties of the Systemic Insecticide O,O-Dimethyl 1-Carbomethoxy-1-propen-2-yl Phosphate (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPesticide Residues, Residual Properties of the Systemic Insecticide O,O-Dimethyl 1-Carbomethoxy-1-propen-2-yl PhosphateJ. E. Casida, P. E. Gatterdam, L. W. Getzin Jr., and R. K. ChapmanCite this: J. Agric. Food Chem. 1956, 4, 3, 236–243Publication Date (Print):March 1, 1956Publication History Published online1 May 2002Published inissue 1 March 1956https://pubs.acs.org/doi/10.1021/jf60061a003https://doi.org/10.1021/jf60061a003research-articleACS PublicationsRequest reuse permissionsArticle Views66Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
MLP, muscle lim protein is a component of a mechano-sensor pathway in cardiac myocytes (2003)

Genetically engineered mice which harbor a deficiency in MLP (muscle lim protein) display cardiac pump failure with chamber dilation and extensive disorganization of myocyte cytoarchitecture. To identify the pathways by which mechanical stress leads to heart failure in the MLP deficient mice (MLPKO), cross-breeding was performed with phospholamban deficient mice (PLBKO), that have the enhanced cardiac performance with positive inotropy and markedly accelerated relaxation. Releasing mechanical stress by PLB ablation resulted in dramatic improvement of functional abnormalities, as well as reversal of histological defects and the induction of embryonic gene markers observed in MLPKO animals. Direct mechanical strain was applied to isolated cardiac myocytes from MLPKO animals using a stretch device equipped with a silicon elastic membrane, revealing that mechanical stress-induced hypertrophic response is selectively blunted in MLPKO cells, while responses to agonists such as endothelin-1 are preserved. These observations strongly support the concept that MLP is an essential molecular component of a mechanosensor pathway in cardiomyocytes.
1605 Behavior of debris in processing of metal using femtosecond pulse laser(2) (2006)

In processing of metal using femtosecond pulse laser, we discovered a novel phenomenon of behavior of debris. The process has five phases: in the first phase, no debris are generated even under irradiation of the femtosecond laser; in the second phase, smoke-like debris burst out from the processed point; in the third phase, large debris blast off in a radial pattern from the processed point; in the forth phase, the splattered debris decelerate its velocities and some debris already scattered around the outside of the visualized area reverses the motion direction, rushing toward the center of the processed point; in the fifth phase, all scattered debris rush toward the processing point.
Whole-body voxel phantoms of paediatric patients—UF Series B (2006)

Following the previous development of the head and torso voxel phantoms of paediatric patients for use in medical radiation protection (UF Series A), a set of whole-body voxel phantoms of paediatric patients (9-month male, 4-year female, 8-year female, 11-year male and 14-year male) has been developed through the attachment of arms and legs from segmented CT images of a healthy Korean adult (UF Series B). Even though partial-body phantoms (head-torso) may be used in a variety of medical dose reconstruction studies where the extremities are out-of-field or receive only very low levels of scatter radiation, whole-body phantoms play important roles in general radiation protection and in nuclear medicine dosimetry. Inclusion of the arms and legs is critical for dosimetry studies of paediatric patients due to the presence of active bone marrow within the extremities of children. While the UF Series A phantoms preserved the body dimensions and organ masses as seen in the original patients who were scanned, comprehensive adjustments were made for the Series B phantoms to better match International Commission on Radiological Protection (ICRP) age-interpolated reference body masses, body heights, sitting heights and internal organ masses. The CT images of arms and legs of a Korean adult were digitally rescaled and attached to each phantom of the UF series. After completion, the resolutions of the phantoms for the 9-month, 4-year, 8-year, 11-year and 14-year were set at 0.86 mm x 0.86 mm x 3.0 mm, 0.90 mm x 0.90 mm x 5.0 mm, 1.16 mm x 1.16 mm x 6.0 mm, 0.94 mm x 0.94 mm x 6.00 mm and 1.18 mm x 1.18 mm x 6.72 mm, respectively.
Provably competitive adaptive routing (2005)

An ad hoc wireless network is an autonomous self-organizing system of mobile nodes connected by wireless links where nodes not in direct range communicate via intermediary nodes. Routing in ad hoc networks is a challenging problem as a result of highly dynamic topology as well as bandwidth and energy constraints. In addition, security is critical in these networks due to the accessibility of the shared wireless medium and the cooperative nature of ad hoc networks. However, none of the existing routing algorithms can withstand a dynamic proactive adversarial attack. The routing protocol presented in this work attempts to provide throughput-competitive route selection against an adaptive adversary. A proof of the convergence time of our algorithm is presented as well as preliminary simulation results.