gebhart/patrepeval huggingface dataset:
Working outside the protein‐synthesis rules: insights into non‐ribosomal peptide synthesis (2009)

Non-ribosomally synthesized microbial peptides show remarkable structural diversity and constitute a widespread class of the most potent antibiotics and other important pharmaceuticals that range from penicillin to the immunosuppressant cyclosporine. They are assembled independent of the ribosome in a nucleic acids-independent way by a group of multimodular megaenzymes called non-ribosomal peptide synthetases. These biosynthetic machineries rely not only on the 20 canonical amino acids, but also use several different building blocks, including D-configured- and beta-amino acids, methylated, glycosylated and phosphorylated residues, heterocyclic elements and even fatty acid building blocks. This structural diversity leads to a high density of functional groups, which are often essential for the bioactivity. Recent biochemical and structural studies on several non-ribosomal peptide synthetase assembly lines have substantially contributed to the understanding of the molecular mechanisms and dynamics of individual catalytic domains underlying substrate recognition and substrate shuffling among the different active sites as well as peptide bond formation and the regio- and stereoselective product release.
Evidence for field effect cancerization in colorectal cancer (2013)

We compared transcript expression, and chromosomal changes on a series of tumors and surrounding tissues to determine if there is evidence of field cancerization in colorectal cancer. Epithelial cells were isolated from tumors and areas adjacent to the tumors ranging from 1 to 10cm. Tumor abnormalities mirrored those previously reported for colon cancer and while the number and size of the chromosomal abnormalities were greatly reduced in cells from surrounding regions, many chromosome abnormalities were discernable. Interestingly, these abnormalities were not consistent across the field in the same patient samples suggesting a field of chromosomal instability surrounding the tumor. A mutator phenotype has been proposed to account for this instability which states that the genotypes of cells within a tumor would not be identical, but would share at least a single mutation in any number of genes, or a selection of genes affecting a specific pathway which provide a proliferative advantage.
New multivalent cationic lipids reveal bell curve for transfection efficiency versus membrane charge density: lipid–DNA complexes for gene delivery (2005)

Abstract Background Gene carriers based on lipids or polymers—rather than on engineered viruses—constitute the latest technique for delivering genes into cells for gene therapy. Cationic liposome–DNA (CL‐DNA) complexes have emerged as leading nonviral vectors in worldwide gene therapy clinical trials. To arrive at therapeutic dosages, however, their efficiency requires substantial further improvement. Methods Newly synthesized multivalent lipids (MVLs) enable control of headgroup charge and size. Complexes comprised of MVLs and DNA have been characterized by X‐ray diffraction and ethidium bromide displacement assays. Their transfection efficiency (TE) in L‐cells was measured with a luciferase assay. Results Plots of TE versus the membrane charge density (σ M , average charge/unit area of membrane) for the MVLs and monovalent 2,3‐dioleyloxypropyltrimethylammonium chloride (DOTAP) merge onto a universal, bell‐shaped curve. This bell curve leads to the identification of three distinct regimes, related to interactions between complexes and cells: at low σ M , TE increases with increasing σ M ; at intermediate σ M , TE exhibits saturated behavior; and unexpectedly, at high σ M , TE decreases with increasing σ M . Conclusions Complexes with low σ M remain trapped in the endosome. In the high σ M regime, accessible for the first time with the new MVLs, complexes escape by overcoming a kinetic barrier to fusion with the endosomal membrane (activated fusion), yet they exhibit a reduced level of efficiency, presumably due to the inability of the DNA to dissociate from the highly charged membranes in the cytosol. The intermediate, optimal regime reflects a compromise between the opposing demands on σ M for endosomal escape and dissociation in the cytosol. Copyright © 2005 John Wiley & Sons, Ltd.
Novel blends of polylactide with ethylene glycol derivatives of POSS (2014)

Polylactide (PLA), a main biodegradable and biobased candidate for the replacement of petrochemical polymers, is stiff and brittle at room conditions. It is therefore of high interest to formulate new PLA-based materials suitable for applications demanding flexibility and toughness. In this work, novel blends of PLA with polyhedral oligomeric silsesquioxanes (POSS) grafted with longer (P1) and shorter (P2) arms of ethylene glycol derivatives were prepared and studied. It was hypothesized that, owing to their architecture with the central POSS cage grafted with arms, miscibility and stability of the blends could be improved. Indeed, PLA/P1 blends were homogeneous despite P1 relatively high <i>M</i><sub>w</sub> of 9,500 g mol<sup>-1</sup>. The blend with 20 wt% of P1, having <i>T</i><sub>g</sub> at 16 °C, was transparent and flexible, elastomer-like material with excellent drawability. The blend remained homogeneous and retained its good drawability as well as flexibility during 6 months of aging at room temperature: a 2 % secant modulus of elasticity well below 100 MPa, a low yield stress below 2 MPa, and and a large strain at break of 8 (800 %). Contary to that, PLA/P2 blends were only partially miscible. Nevertheless, owing to the liquid state of the dispersed phase, the blend with 15 wt% of P2 was transparent and ductile, with <i>T</i><sub>g</sub> at 49 °C, a relatively high yield strength of 29 MPa, and a large strain at break of 2.3 (230 %). The toughening mechanism involved the initiation of crazes and facilitation of their propagation by the liquid inclusions via the local plasticization effect.
Knowns and Unknowns of the Alveolus (2008)

Our current alveolar paradigm includes three highly specialized cell populations. Alveolar type I cells are flat, elongated cells that presumably enable gas exchange. Alveolar type II cells are small, cuboidal cells with metabolic, secretory, progenitor, and immunologic functions. Alveolar fibroblasts secrete extracellular matrix proteins that support alveolar structure. These cells work together to facilitate respiration. Many years of high-quality research have defined our understanding of alveolar biology. However, there is much to be determined about the factors controlling cellular phenotypes and crosstalk. Moreover, specific questions remain regarding origin, repopulation, and previously unrecognized functions of each cell. This article summarizes the current data for each cell type and highlights areas that would benefit from further investigation.
The historical role of species from the Solanaceae plant family in genetic research (2016)

This article evaluates the main contributions of tomato, tobacco, petunia, potato, pepper and eggplant to classical and molecular plant genetics and genomics since the beginning of the twentieth century. Species from the Solanaceae family form integral parts of human civilizations as food sources and drugs since thousands of years, and, more recently, as ornamentals. Some Solanaceous species were subjects of classical and molecular genetic research over the last 100 years. The tomato was one of the principal models in twentieth century classical genetics and a pacemaker of genome analysis in plants including molecular linkage maps, positional cloning of disease resistance genes and quantitative trait loci (QTL). Besides that, tomato is the model for the genetics of fruit development and composition. Tobacco was the major model used to establish the principals and methods of plant somatic cell genetics including in vitro propagation of cells and tissues, totipotency of somatic cells, doubled haploid production and genetic transformation. Petunia was a model for elucidating the biochemical and genetic basis of flower color and development. The cultivated potato is the economically most important Solanaceous plant and ranks third after wheat and rice as one of the world's great food crops. Potato is the model for studying the genetic basis of tuber development. Molecular genetics and genomics of potato, in particular association genetics, made valuable contributions to the genetic dissection of complex agronomic traits and the development of diagnostic markers for breeding applications. Pepper and eggplant are horticultural crops of worldwide relevance. Genetic and genomic research in pepper and eggplant mostly followed the tomato model. Comparative genome analysis of tomato, potato, pepper and eggplant contributed to the understanding of plant genome evolution.
Indium(III) phthalocyanine <i>eka-conjugated</i> polymer as high-performance optical limiter upon nanosecond laser irradiation (2015)

A novel chloroindium(III) phthalocyanine network polymer (4) was prepared and characterized by energy dispersive X-ray spectrometry, proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermal gravimetric analysis (TGA) and absorption and emission spectroscopies. The non-linear optical (NLO) profile of the prepared phthalocyanine (Pc) network polymer, derived from a nanosecond open-aperture Z-scan technique at 532 nm, shows a clear reverse saturable absorption and a high non-linear absorption coefficient ( α 2 ) of 9.7 × 10 −7 cm W −1 . Optical limiting investigations indicated that the prepared Pc network polymer has a relatively low limiting threshold of 900 mJ cm −2 . According to these results, the prepared Pc polymer is a promising material for many NLO applications.
Membrane properties and cell ultrastructure of taste receptor cells in Necturus lingual slices (1996)

1. Whole cell patch-clamp recordings and electron micrographs were obtained from cells in Necturus taste buds in lingual slices to study their membrane properties and to correlate these properties with cell ultrastructure. 2. Two different populations of taste receptor cells could be identified: one type possessed voltage-gated Na+ and K+ (noninactivating) currents (group 1 cells); the other type possessed only K+ (inactivating) currents (group 2 cells). 3. The zero-current ("resting") potential (Vo) and whole cell resistance (Ro) of these two types of taste cells differed significantly. For group 1 cells, on average, Vo = -75 mV and Ro = 24.6 G omega, and for group 2 cells, Vo = -49 mV and Ro = 48.9 G omega. The difference in Ro was not explained completely by differences in cell sizes, suggesting that intrinsic membrane properties differed between the populations. 4. Cells injected with biocytin were the electron microscope after tissues were reacted with majority (14 of 16) of cells with voltage-gated Na+ and K+ currents (group 1 cells) were characterized by abundant rough endoplasmic reticulum and dense granular packets in the apical process. These are features of dark cells. All the cells that only possessed K+ currents (group 2 cells) were characterize by well-developed smooth endoplasmic reticulum and an absence granular packets. These features characterize light cells. 5. These findings indicate that there is a good, although not exact, correlation between electrophysiological properties and cell morphotype in Necturus taste bud cells. All dark cells possessed Na+ and K+ currents and thus would be expected to be capable of generating action potentials. Most light cells only possessed outward K+ currents and thus would be incapable of generating action potentials.
THE REDUCTION OF THE PERMEABILITY OF GRAPHITE (1959)

Impregnation methods for reducing the permeability of reactor-quality graphite are discussed. The effects produced by the following impregnation processes on the properttes of graphite specimens are tabulated: continuous impregnation using gas; pitch impregnation; and repeated impregnation with a solution of aqueous sugar. A schematic of the equipment used for the gasimpregnation experiments is shown, and a brief discussion is included on the use of impregriated graphite in a nuclear reactor. (J.H.M.)
Vitamin C and blood pressure (1990)

From the Division of Geriatric Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Intrinsic Oxygen Use Kinetics of Transformed Plant Root Culture (2001)

Root meristem oxygen uptake, root tip extension rate, and specific growth rate are assessed as a function of dissolved oxygen level for three transformed root cultures. The influence of hydrodynamic boundary layer was considered for all measurements to permit correlation of oxygen-dependent kinetics with the concentration of oxygen at the surface of the root meristem. Oxygen uptake rate is shown to be saturated at ambient conditions, and a saturation level of approximately 300 micromole O2/(cm(3) tissue.hr) was observed for all three of these morphologically diverse root types. In nearly all cases, the observation of a minimum oxygen pressure, below which respiration, extension, or root growth would not occur, could be accounted for as a boundary layer mass transfer resistance. The critical oxygen pressure below which respiration declines is below saturated ambient oxygen conditions. In contrast, critical oxygen pressures for root tip extension were much higher; extension was nearly linear for the two thicker root types (Hyoscyamus muticus, henbain; Solanum tuberosum, potato) above ambient oxygen levels. The performance of the thinnest root, Brassica juncea (Indian mustard) was consistent with reduced internal limitations for oxygen transport. Extension rates did not correlate with biomass accumulation. The fastest growing henbain culture micro = 0.44 day(-)(1)) displayed the slowest extension rate (0.16 mm/hr), and the slowest growing mustard culture (micro = 0.22 day(-)(1)) had the fastest tip extension rate (0.3 mm/hr). This apparent paradox is explained in terms of root branching patterns, where the root branching ratio is shown to be dependent upon the oxygen-limited mersitem extension rate. The implications of these observations on the performance of root culture in bioreactors is discussed.
New Pathways for Asphaltenes Upgrading Using the Oxy-Cracking Process (2016)

Solvent deasphalting of the bottom of vacuum distillation columns (vacuum residue, VR) is a process practiced worldwide. In Northern Alberta, a solvent deasphalting plant was designed to process up to 4000 tons/day of the asphaltenic pitch. Asphaltenes oxy-cracking in liquid phase could be a new approach to asphaltenes upgrading and conversion into valuable chemicals. Oxy-cracking is a combination of oxidation and cracking in basic aqueous media at moderate temperatures (170–225 °C) and pressures (300–500 psi). This process could act very selectively producing smaller amounts of greenhouse gases like CO2, thus being considered environmentally friendly. In this work, a mild oxy-cracking treatment of C5-asphaltenes solid from Athabasca vacuum residue was investigated. The reaction kinetics and possible reaction mechanism for C5-asphaltenes oxy-cracking in water under alkali conditions were studied. Products solubilized under different severities were characterized using Fourier transform infrared and nuclear magnetic resonance spectroscopies, simulated distillation, elemental analysis, and ultraviolet–visible spectrophotometry to investigate the structure of solubilized products and changes in asphaltenes structures after the reaction. A model based on sequential-parallel reactions from the asphaltenes to water-soluble products and CO2 was found to describe the process successfully. Products of oxidized functionalities like carboxylic acids, their salts, methyl ethers and esters, and sulfur-oxidized forms plus phenolics were determined as the most significant fractions soluble in water. Solubilization of asphaltenes in water could also decrease challenges regarding facilities and pipelines plugging.
Dynamic Models in Multiphase Flow (2012)

Transport of oil and gas mixtures in pipelines involves flow dynamics on a wide range of time and length scales. Liquid slugs and waves occur at scales extending from diameters (“hydrodynamic slug flow”) and up to riser lengths (“severe slugging”). The approach in one-dimensional dynamic multiphase flow models for analysis of flow dynamics depends upon the scale to be resolved. Types of models are discussed, and a hybrid two-fluid model and a slug tracking model are in particular described. A two-fluid model is applied on a stationary grid in the gas–liquid stratified flow region until a slug is formed (or initiated), when a slug tracking method with a moving grid takes over. The performance of the model is demonstrated in relation to three types of cases with different time and length scales: Two- and three-phase severe slugging, hydrodynamic slugging after a bend, and a pigging case to simulate the rapid release of a hydrate plug. The computations are compared to experimental laboratory data.
Effects of adenosine phosphates and nicotinamide nucleotides on pyruvate carboxylase from baker's yeast (1969)

1. Pyruvate carboxylase from baker's yeast is inhibited by ADP, AMP and adenosine at pH8.0 in the presence of magnesium chloride concentrations equal to or higher than the ATP concentration. The adenine moiety is essential for the inhibitory effect. 2. In the absence of acetyl-CoA (an allosteric activator) ADP, AMP and adenosine are competitive inhibitors with respect to ATP. In the presence of acetyl-CoA, besides the effect with respect to ATP, AMP competes with acetyl-CoA, whereas ADP and adenosine are non-competitive inhibitors with respect to the activator. 3. Pyruvate carboxylase is inhibited by NADH. The inhibition is competitive with respect to acetyl-CoA and specific with respect to NADH, since NAD(+), NADP(+) and NADPH do not affect the enzyme activity. In the absence of acetyl-CoA, NAD(+), NADH, NADP(+) and NADPH do not inhibit pyruvate carboxylase. 4. Pyruvate carboxylase is inhibited by ADP, AMP and NADH at pH6.5, in the presence of 12mm-Mg(2+), 0.75mm-Mn(2+) and 0.5mm-ATP, medium conditions similar to those existing inside the yeast cell. The ADP and NADH effects are consistent with a regulation of enzyme activity by the intracellular [ATP]/[ADP] ratio and secondarily by NADH concentration. These mechanisms would supplement the already known control of yeast pyruvate carboxylase by acetyl-CoA and l-aspartate. Inhibition by AMP is less marked and its physiological role is perhaps limited.
Evaluation of Metabolite Profiles of Ginseng Berry Pomace Obtained after Different Pressure Treatments and Their Correlation with the Antioxidant Activity (2021)

Ginseng berry pomace (GBP) is a byproduct of ginseng berry processing and is rich in numerous bioactive components, including ginsenosides and their derivatives. The application of GBP as a beneficial biomaterial is currently limited. In this study, we aimed to evaluate their potential as a promising source of bioactive compounds using metabolite profiling. The GBP obtained after different ultra-high-pressure (UHP) treatments was analyzed by GC-TOF-MS and UHPLC-LTQ-Orbitrap-MS/MS. In multivariate analyses, we observed a clear demarcation between the control and UHP-treated groups. The results demonstrated that the relative abundance of primary metabolites and a few ginsenosides was higher in the control, whereas UHP treatment contained higher levels of fatty acids and sugars. Furthermore, GBPs were fractionated using different solvents, followed by UHPLC-LTQ-Orbitrap-MS/MS analyses. The heatmap revealed that phenolics (e.g., quercetin, kaempferol) and fewer polar ginsenosides (e.g., F4, Rh2) were abundant in the ethyl acetate fraction, whereas the levels of lignans (e.g., 7-hydroxysecoisolariciresinol, syringaresinol) and fatty acids (e.g., trihydroxy-octadecenoic acid, oxo-dihydroxy-octadecenoic acid) were high in chloroform. Correlation analysis showed that phenolics, less polar ginsenosides, and fatty acids were positively correlated with the antioxidant activity of GBP. Our study highlights GBP as a functional ingredient for the development of high-quality ginseng berry products.
In Vitro Antibacterial Activity of Bismuth Subsalicylate (1990)

This study was undertaken to determine the in vitro activity of bismuth subsalicylate (BSS) and sodium salicylate (SS) against various groups of pathogenic bacteria. BSS had the greatest activity against Clostridium difficile, which had a minimal inhibitory concentration for 90% of the strains (MIC90) of 128 micrograms/mL. The Bacteroides fragilis group also had a relatively low MIC90 of 512 micrograms/mL. BSS had the least activity against Pseudomonas (MIC90, 6,144 micrograms/mL). SS was as active as BSS against aerobic bacteria but was less active against anaerobic bacteria. The MIC90 values of SS for C. difficile and the B. fragilis group were greater than 8,192 and 4,096 micrograms/mL, respectively. This study demonstrates that BSS has antibacterial activity in vitro at levels that should be achievable in the gastrointestinal tract.
Double-blind, placebo-controlled trial of toremifene for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (2005)

1003 Background: Toremifene, a selective estrogen receptor modulator (SERM) marketed for the treatment of breast cancer, appears to have promise in preventing prostate cancer. A randomized, double-blind, placebo-controlled study was conducted to determine the incidence of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (PIN) treated with toremifene. Methods: 514 patients with high-grade PIN and no evidence of prostate cancer at study entry were randomized to oral toremifene 20, 40, or 60 mg or placebo QD for 12 months. Patients were rebiopsied at 6 and 12 months (minimum 8 cores per biopsy). Initial and subsequent biopsies were evaluated by a central pathologist (Bostwick Laboratories) for diagnosis of high-grade PIN and prostate cancer. Cumulative risk reduction and 12-month point-estimate risk reduction were compared between each toremifene group and placebo with Mantel-Cox and Cochran-Mantel-Haenszel, respectively, stratified by study center. Results: The number of evaluable patients (defined as having one on-study biopsy and being compliant with the protocol) was 447. Prostate cancer was diagnosed among significantly fewer patients taking toremifene 20 mg compared with placebo during the study based upon both 6-month and 12-month biopsy data (24.4% vs. 31.2% cumulative incidence, p<0.05). The cumulative incidence of cancer with 40 mg and 60 mg doses was lower than with placebo but not statistically different (28.2% and 28.1%, respectively). The number of cancers prevented per year with toremifene 20 mg over placebo was 6.8 per 100 persons treated. Among patients with no evidence of prostate cancer on baseline and 6-month biopsies, the incidence of prostate cancer was reduced by 48% with toremifene 20 mg compared with placebo on 12-month biopsy (9.1% vs. 17.4% 12 month point estimate, p<0.05). For the 40-mg and 60-mg doses, cancer incidence at 12 months was reduced by 14.3% and 13.0%, respectively, compared with placebo (not statistically significant). Conclusions: Toremifene 20 mg significantly reduced the incidence of prostate cancer at 1 year in a high-risk population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GTx