gebhart/patrepeval huggingface dataset:
Copper Influences the Antibacterial Outcomes of a β-Lactamase-Activated Prochelator against Drug-Resistant Bacteria (2018)

The unabated rise in bacterial resistance to conventional antibiotics, coupled with collateral damage to normal flora incurred by overuse of broad-spectrum antibiotics, necessitates the development of new antimicrobials targeted against pathogenic organisms. Here, we explore the antibacterial outcomes and mode of action of a prochelator that exploits the production of β-lactamase enzymes by drug-resistant bacteria to convert a nontoxic compound into a metal-binding antimicrobial agent directly within the microenvironment of pathogenic organisms. Compound PcephPT (phenylacetamido-cephem-pyrithione) contains a cephalosporin core linked to 2-mercaptopyridine N-oxide (pyrithione) via one of its metal-chelating atoms, which minimizes its preactivation interaction with metal ions and its cytotoxicity. Spectroscopic and chromatographic assays indicate that PcephPT releases pyrithione in the presence of β-lactamase-producing bacteria. The prochelator shows enhanced antibacterial activity against strains expressing β-lactamases, with bactericidal efficacy improved by the presence of low-micromolar copper in the growth medium. Metal analysis shows that cell-associated copper accumulation by the prochelator is significantly lower than that induced by pyrithione itself, suggesting that the location of pyrithione release influences biological outcomes. Low-micromolar (4-8 μg/mL) minimum inhibitory concentration (MIC) values of PcephPT in ceftriaxone-resistant bacteria compared with median lethal dose (LD<sub>50</sub>) values greater than 250 μM in mammalian cells suggests favorable selectivity. Further investigation into the mechanisms of prochelators will provide insight for the design of new antibacterial agents that manipulate cellular metallobiology as a strategy against infection.
Quinquedentate Coordination of 6-Methyl-1,11-dithia-4,8-diazacyclotetradecan-6-amine to Cobalt(III). X-Ray Crystal Structure of the [Co(N3S2)(OOCCH3)] (ClO4)2.H2O Complex (1991)

The pendant arm macrocycle 6-methyl-1,11-dithia-4,8-diazacyclotetradecan-6-amine (7) can coordinate to cobalt(III) as a quinquedentate N3S2 ligand . Spectroscopy indicated a geometry with the macrocycle folded and the pendant amine and the unidentate donor in cis dispositions for the [Co(7) Cl ]2+ and [Co(7)(OOCCH3)]2+ products isolated. An X-ray crystal structure analysis of [Co(7)(OOCCH3)](ClO4)2.H2O characterized the cis stereochemistry. The complex crystallized in the Pbca space group, a 10.620(9), b 13.926(9), c 32.35(2)?, and analysis defined a distorted octahedral geometry with the primary and two secondary nitrogen donors occupying an octahedral face with relatively short Co-N bonds [1.937(7)-1.950(7)?], the acetate ion [Co-O 1.905(6)?] trans to one of the secondary amine donors and thioether donors [Co-S 2.223(3), 2.227(3)?] trans to the other nitrogen donors. Significant angle distortions occur around the metal ion. Base hydrolysis of the chloro complex is slow and stereoretentive , with a rate constant of 1.08×103 dm3 mol-1 s-1 at 25°C, 15-fold faster than for the pentaaza analogue.
Refined Phase Diagram of Boron Nitride (1999)

The equilibrium phase diagram of boron nitride thermodynamically calculated by Solozhenko in 1988 has been now refined on the basis of new experimental data on BN melting and extrapolation of heat capacities of BN polymorphs into high-temperature region using the adapted pseudo-Debye model. As compared with the above diagram, the hBN ⇆ cBN equilibrium line is displaced by 60 K toward higher temperatures. The hBN−cBN−L triple point has been calculated to be at 3480 ± 10 K and 5.9 ± 0.1 GPa, while the hBN−L−V triple point is at T = 3400 ± 20 K and p = 400 ± 20 Pa, which indicates that the region of thermodynamic stability of vapor in the BN phase diagram is extremely small. It has been found that the slope of the cBN melting curve is positive whereas the slope of hBN melting curve varies from positive between ambient pressure and 3.4 GPa to negative at higher pressures.
The β- and δ-Thalassemia Repository (Eighth Edition) (1995)

(1995). The β- and δ-Thalassemia Repository (Eighth Edition) Hemoglobin: Vol. 19, No. 3-4, pp. 213-236.
Physiology and molecular aspects of <i>Verticillium</i> wilt diseases caused by <i>V. dahliae</i> and <i>V. albo‐atrum</i> (2006)

Kingdom: Fungi, phylum: Ascomycota, subphylum, Pezizomycotina, class: Sordariomycetes, order: Phyllachorales, genus: Verticillium. Host range and disease symptoms: Over 200 mainly dicotyledonous species including herbaceous annuals, perennials and woody species are host to Verticillium diseases. As Verticillium symptoms can vary between hosts, there are no unique symptoms that belong to all plants infected by this fungus. Disease symptoms may comprise wilting, chlorosis, stunting, necrosis and vein clearing. Brown vascular discoloration may be observed in stem tissue cross-sections. Pathogenicity: Verticillium spp. have been reported to produce cell-wall-degrading enzymes and phytotoxins that all have been implicated in symptom development. Nevertheless, evidence for a crucial role of toxins in pathogenicity is inconsistent and therefore not generally accepted. Microsclerotia and melanized mycelium play an important role in the disease cycle as they are a major inoculum source and are the primary long-term survival structures. Resistance: Different defence responses in the prevascular and the vascular stage of Verticillium wilt diseases determine resistance. Although resistance physiology is well established, the molecular processes underlying this physiology remain largely unknown. Resistance against Verticillium largely depends on the isolation of the fungus in contained parts of the xylem tissues followed by subsequent elimination of the fungus. Although genetic resistance has been described in several plant species, only one resistance locus against Verticillium has been cloned to date. Useful website: http://cbr-rbc.nrc-cnrc.gc.ca/services/cogeme/
The <i>AeAct‐4</i> gene is expressed in the developing flight muscles of female <i>Aedes aegypti</i> (2004)

Population reduction of mosquitoes is an effective method for controlling dengue fever and malaria transmission. Recent developments in control techniques include proposals to construct transgenic strains of mosquitoes carrying dominant, conditional-lethal genes under the control of sex- and stage-specific promoters. In order to identify such promoters, subtractive cDNA libraries derived from male and female pupal mRNA of the yellow fever mosquito, Aedes aegypti, were constructed and screened. A cDNA clone, F49, corresponds to a gene expressed specifically in female pupae. Sequence analyses revealed that this gene belongs to the actin gene family, and therefore was designated Aedes Actin-4 (AeAct-4). Transcription analyses demonstrated that this gene is expressed predominantly in the indirect flight muscles and, to a lesser extent, the legs of developing female mosquitoes. The promoter of this gene may be a useful tool for developing conditional lethal strains of mosquitoes.
Steroidal Saponins from <i>Disporopsis pernyi</i> (2004)

Abstract Four new steroidal saponins, named disporosides A–D ( 1 – 4 ), corresponding to (3 β ,25 R )‐3‐[( β ‐ D ‐glucopyranosyl‐(1→2)‐[ β ‐ D ‐glucopyranosyl‐(1→6)]‐ β ‐ D ‐glucopyranosyl)oxy]‐5 β ‐spirostan ( 1 ), (3 β ,25 R )‐3‐[( β ‐ D ‐glucopyranosyl‐(1→2)‐[6‐ O ‐hexadecanoyl‐ β ‐ D ‐glucopyranosyl‐(1→6)]‐ β ‐ D ‐glucopyranosyl)oxy]‐5 β ‐spirostan ( 2 ), (3 β ,22 R ,25 R )‐26‐[( β ‐ D ‐glucopyranosyl)oxy]‐3‐[( β ‐ D ‐glucopyranosyl‐(1→2)‐ β ‐ D ‐glucopyranosyl)oxy]‐5 β ‐furostan ( 3 ), and (3 β ,22 R ,25 R )‐26‐[( β ‐ D ‐glucopyranosyl)oxy]‐3‐[( β ‐ D ‐glucopyranosyl‐(1→2)‐[ β ‐ D ‐glucopyranosyl‐(1→6)]‐ β ‐ D ‐glucopyranosyl)oxy]‐5 β ‐furostan ( 4 ), have been isolated from the fresh rhizomes of Disporopsis pernyi , together with the three known compounds Ys‐I, agavoside B, and (3 β ,25 R )‐3‐[( β ‐ D ‐xylopyranosyl‐(1→3)‐ β ‐ D ‐glucopyranosyl‐(1→4)‐ β ‐ D ‐galactopyranosyl)oxy]‐5 α ‐spirostan‐12‐one. Their structures were elucidated by spectroscopic analyses, chemical transformations (acid hydrolysis), and comparison with literature data.
Effects of Multiple Deletions of Murein Hydrolases on Viability, Septum Cleavage, and Sensitivity to Large Toxic Molecules in <i>Escherichia coli</i> (2002)

The multiplicity of murein hydrolases found in most bacteria presents an obstacle to demonstrating the necessity of these potentially autolytic enzymes. Therefore, Escherichia coli mutants with deletions in multiple murein hydrolases, including lytic transglycosylases, amidases, and DD-endopeptidases, were constructed. Even a mutant from which seven different hydrolases were deleted was viable and grew at a normal rate. However, penicillin-induced lysis was retarded. Most of the mutants were affected in septum cleavage, which resulted in the formation of chains of cells. All three enzymes were shown to be capable of splitting the septum. Failure to cleave the septum resulted in an increase in outer membrane permeability, and thus the murein hydrolase mutants did not grow on MacConkey agar plates. In addition, the hydrolase mutants not only could be lysed by lysozyme in the absence of EDTA but also were sensitive to high-molecular-weight antibiotics, such as vancomycin and bacitracin, which are normally ineffective against E. coli.
NaH-Mediated One-Pot Cyclocondensation of 6-Nitroquinoline with Aromatic Hydrazones To Form [1.2.4]Triazino[6,5-<i>f</i>]quinolines and/or Pyrazolo[3,4-<i>f</i>]quinolines (2000)

[reaction: see text] 6-Nitroquinoline undergoes direct cyclocondensation with aromatic hydrazones in the presence of sodium hydride in DMF at -10 degrees C, giving the corresponding 3-aryl-1(3)H-pyrazolo[3,4-f]quinolines and/or 3-aryl[1.2.4]triazino[6,5-f]quinolines in low to moderate yield. The mode of cyclocondensation is considerably dependent on the electronic nature of ring substituent of hydrazones, an electron-donating substituent favoring the formation of the latter heterocycles.
Remarkably Efficient Enantioselective Titanium(IV)−(<i>R</i>)-H<sub>8</sub>-BINOLate Catalyst for Arylations to Aldehydes by Triaryl(tetrahydrofuran)aluminum Reagents (2006)

Novel asymmetric triarylaluminum AlAr3(THF) additions to aldehydes catalyzed by 10 mol % of the titanium(IV) complex of (R)-H8-BINOL ligand are reported. The catalytic system is extremely efficient with reactions completing within 10 min. The system applies to the most diversified aldehydes to date, and more than 20 aldehydes were examined to afford diarylmethanols having an electron-donating or an electron-withdrawing group at the 2-, 3-, or 4-position on the aryl moiety, linear or branched 1-aryl aliphatic alcohols, aryl furyl methanols, 1-aryl allylic alcohols, and, especially, 1-aryl propargylic alcohols in excellent enantioselectivities of >/=90% ee, except for the case of 1-naphthyl addition to benzaldehyde. Noteworthily, diarylmethanols in both R- and S-configurations can be obtained.
The human brain mannose 6‐phosphate glycoproteome: A complex mixture composed of multiple isoforms of many soluble lysosomal proteins (2005)

The lysosome is a membrane delimited cytoplasmic organelle that contains at least 50 hydrolytic enzymes and associated cofactors. The biomedical importance of these enzymes is highlighted by the many lysosomal storage disorders that are associated with mutations in genes encoding lysosomal proteins, and there is also evidence that lysosomal activities may be involved in more widespread human diseases. The aim of this study was to characterize the human brain lysosomal proteome with the goal of establishing a reference map to investigate human diseases of unknown etiology and to gain insights into the cellular function of the lysosome. Proteins containing mannose 6-phosphate (Man6-P), a carbohydrate modification used for targeting resident soluble lysosomal proteins to the lysosome, were affinity-purified using immobilized Man6-P receptor. Fractionation by two-dimensional electrophoresis resolved a complex mixture comprising approximately 800 spots. Constituent proteins in each spot were identified using a combination of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (both peptide mass fingerprinting and tandem mass spectrometry) [corrected] on in-gel tryptic digests and N-terminal sequencing. In a complementary analysis, we also analyzed a tryptic digest of the unfractionated mixture by liquid chromatography MS/MS. In total, 61 different proteins were identified. Seven were likely contaminants associated with true Man6-P glycoproteins. Forty-one were known lysosomal proteins of which 11 have not previously been reported to contain Man6-P. An additional nine proteins were either uncharacterized or proteins not previously reported to have lysosomal function. We found that the human brain Man6-P-containing lysosomal proteome is highly complex and contains more proteins with a much greater number of individual isoforms than found in previous studies of Man6-P glycoproteomes.
Experimental Esophageal Lye Burns (1973)

. MADDEN, JOHN W M.D.; DAVIS, WILLIAM M. M.D.; BUTLER, COOLEY II M.D.; PEACOCK, ERLE E. JR. M.D. Author Information
Synthesis and Characterization of Pt Dendrimer-Encapsulated Nanoparticles: Effect of the Template on Nanoparticle Formation (2008)

In this article, we provide a detailed description of the synthesis and properties of Pt dendrimer-encapsulated nanoparticles (DENs) prepared using sixth-generation, hydroxyl-terminated, poly(amidoamine) (PAMAM) dendrimers (G6−OH) and three different PtCl42−/G6−OH ratios: 55, 147, and 240. Results obtained from UV−vis spectroscopy, X-ray photoelectron spectroscopy, electron microscopy, X-ray absorption spectroscopy, and high-energy X-ray diffraction show that only a fraction of the Pt2+/dendrimer precursors are reduced by BH4− and that the reduction process is highly heterogeneous. That is, after reduction each Pt2+/dendrimer precursor complex is either fully reduced, to yield a DEN having a size and structure consistent with the original PtCl42−/dendrimer ratio used for the synthesis, or the precursor is not reduced at all. This result is consistent with an autocatalytic process that entails slow formation of a nascent catalytic Pt seed within the dendrimer, followed by rapid, catalytic reduction of nearby Pt2+ ions. Details concerning the formation of the Pt2+/dendrimer precursor are also discussed.
Spectral encoding method for measuring the relative arrival time between x-ray/optical pulses (2014)

The advent of few femtosecond x-ray light sources brings promise of x-ray/optical pump-probe experiments that can measure chemical and structural changes in the 10-100 fs time regime. Widely distributed timing systems used at x-ray Free-Electron Laser facilities are typically limited to above 50 fs fwhm jitter in active x-ray/optical synchronization. The approach of single-shot timing measurements is used to sort results in the event processing stage. This has seen wide use to accommodate the insufficient precision of active stabilization schemes. In this article, we review the current technique for "measure-and-sort" at the Linac Coherent Light Source at the SLAC National Accelerator Laboratory. The relative arrival time between an x-ray pulse and an optical pulse is measured near the experimental interaction region as a spectrally encoded cross-correlation signal. The cross-correlation provides a time-stamp for filter-and-sort algorithms used for real-time sorting. Sub-10 fs rms resolution is common in this technique, placing timing precision at the same scale as the duration of the shortest achievable x-ray pulses.
Polarization Holography (2009)

Current research into holography is concerned with applications in optically storing, retrieving, and processing information. Polarization holography has many unique properties compared to conventional holography. It gives results in high efficiency, achromaticity, and special polarization properties. This books reviews the research carried out in this field over the last 15 years. The authors provide basic concepts in polarization and the propagation of light through anisotropic materials, before presenting a sound theoretical basis for polarization holography. The fabrication and characterization of azobenzene based materials, which remain the most efficient for the purpose, is described in detail. This is followed by a description of other materials that are used in polarization holography. An in-depth description of various applications, including display holography and optical storage, is given, and the book concludes with perspectives for the future. This book is an important reference for researchers.
The Bayesian Structural EM Algorithm (2013)

In recent years there has been a flurry of works on learning Bayesian networks from data. One of the hard problems in this area is how to effectively learn the structure of a belief network from incomplete data- that is, in the presence of missing values or hidden variables. In a recent paper, I introduced an algorithm called Structural EM that combines the standard Expectation Maximization (EM) algorithm, which optimizes parameters, with structure search for model selection. That algorithm learns networks based on penalized likelihood scores, which include the BIC/MDL score and various approximations to the Bayesian score. In this paper, I extend Structural EM to deal directly with Bayesian model selection. I prove the convergence of the resulting algorithm and show how to apply it for learning a large class of probabilistic models, including Bayesian networks and some variants thereof.
Combined coenzyme-substrate analog of various dehydrogenases. Synthesis of (3S)- and (3R)-5-(3-carboxy-3-hydroxypropyl)nicotinamide adenine dinucleotide and their interaction with (S)- and (R)-lactate-specific dehydrogenases (1978)

Two diastereomeric nicotinamide adenine dinucleotide (NAD+) derivatives were synthesized in which the substrates of (S)-and (R)-lactate-specific dehydrogenases are covalently attached via a methylene spacer at position 5 of the nicotinamide ring. The corresponding nicotinamide derivatives were obtained stereospecifically by enzymatic reduction of 5-(2-oxalylethyl)nicotinamide. (3S)-5-(3-Carboxy-3-hydroxypropyl)-NAD+ undergoes and intramolecular hydride transfer in the presence of pig heart lactate dehydrogenase, forming the corresponding coenzyme-substrate analogue composed of pyruvate and NADH. No cross-reaction products resulting from an intermolecular reaction are observed. Two (R)-lactate specific dehydrogenases, however, do not catalyze a similar reaction in either one of the two diastereomers. A possible arrangement of the substrates in the active centers of these enzymes is proposed. 5-Methyl-NAD+ and 5-methyl-NADH are active coenzymes of pig heart lactate dehydrogenase in contrast to reports in the literature. (S)-Lactate binds to this enzyme in the absence of coenzyme, exhibiting a dissociation constant of 11 mM.
Chemoenzymatic modification of silk fibroin with poly(2,6-dimethyl-1,5-phenylene ether) using horseradish peroxidase (2016)

Hydrophobic modification of silk fibroin with poly(2,6-dimethyl-1,5-phenylene ether) (PPE) chains is achieved by the chemoenzymatic polymerization of 2,6-dimethylphenol.
The Inhalation Device Influences Lung Deposition and Bronchodilating Effect of Terbutaline (1996)

The development of new inhalation devices for asthma drugs raises the issue of the relationship between pulmonary deposition and therapeutic effect of inhaled drugs in patients with obstructive lung diseases. We thus conducted a randomized, double-blind and double-dummy, four-period crossover study in 13 patients with moderate asthma (mean age 36 yr; FEV1 59% of predicted), who inhaled 0.25 and 0.5 mg terbutaline sulphate on separate occasions either via a pressurized metered dose inhaler (pMDI) or Turbuhaler (TBH). Pulmonary deposition was 8.1 +/- 2.7% and 8.3 +/- 2.3%, respectively, of the nominal dose for pMDI and 19.0 +/- 7.3%, and 22.0 +/- 8.1% for TBH. The FEV1 increase after 0.25 mg terbutaline sulphate via TBH was significantly greater than after 0.25 mg via pMDI. No significant differences in FEV1 increase were observed between 0.25 mg via TBH, 0.5 mg via pMDI, or 0.5 mg via TBH. Other lung function variables showed similar dose- and device-related changes. We concluded that: (1) the dose of terbutaline sulphate deposited in the lungs is dependent on which inhalation system is used; (2) TBH delivers about twice the amount of drug to the lungs as the pMDI; and (3) the observed difference in deposition is reflected in the bronchodilating effect.
Regional distribution of mRNA encoding the long form of leptin receptor in the mouse brain (1997)

The distribution of the long form leptin receptor mRNA as examined in the mouse brain using in situ hybridization histochemistry with two independent [35S]labeled oligonucleotide probes. Analysis of film autoradiograms showed that the long form leptin receptor mRNA was widely expressed throughout the mouse brain. A strong hybridization signal was detected through the olfactory bulb, the pyramidal layer of the piriform cortex, the medial amygdala, the hippocampus, the medial habenula and the cerebellum. Additionally, several subdivisions of the hypothalamus, namely the arcuate, the ventromedial and dorsomedial nuclei, also displayed a high level of labeling. The specific labeling detected in other brain areas was low and generally more diffuse. Overall, these anatomical findings suggest that the role of leptin in the central nervous system is not confined to the control of energy balance. © 1997 John Wiley & Sons, Ltd.
Chemical genomics identifies compounds affecting <i>Xenopus laevis</i> pigment cell development (1900)

A forward chemical genomic screen was carried out using Xenopus laevis embryos to identify compounds disrupting pigmented cell development, including the retinal pigment epithelial (RPE) layer of the eye and the melanophores (melanocytes). Phenotypes showing changes in cell migration, morphology and pigmentation were observed. The screen also identified compounds affecting other aspects of Xenopus development including general patterning and morphogenesis, eye development and edema formation. Evidence is presented for the molecular targets of three of the compounds identified. Xenopus melanophore and human melanoma cell lines were also utilised in follow-up cell morphology assays. Chemical genomic screens of this type have an important role to play in the identification of novel compounds providing new molecular tools, and biological information, along with identification of new protein targets and leads for potential therapeutic agents.
Transfer-matrix analysis of the intensity and phase noise of multisection DFB semiconductor lasers (1991)

A general small-signal model for the intensity and phase noise spectra of multisection distributed feedback (DFB) semiconductor lasers is developed by using the transfer-matrix approach based on the Green's function method. The spontaneous emission enhancements due to nonuniform longitudinal field distribution and the effective amplitude-phase coupling effect (the effective linewidth enhancement factor) are taken into account in the formulation. Analytical expressions for the spectra of the relative intensity noise and the FM noise of the main mode in the multimode operation are presented by using the transfer functions in a flow-graph representation. Facet reflectivities and external optical feedback are included in the model. The effects of the grating coupling coefficient, the random grating-phase at the facets, the phase-shift position, the external optical feedback, and the side mode on the noise spectra are analyzed systematically for a lambda /4-shifted DFB laser.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>