gebhart/patrepeval huggingface dataset:
Relationships between the N‐glycan structures and biological activities of recombinant human erythropoietins produced using different culture conditions and purification procedures (2003)

Eight preparations of recombinant human erythropoietin (EPO) with differing isoform compositions were produced by using different culture conditions and purification procedures. The N-glycan structures of these EPOs were analysed using a recently developed profiling procedure and identified using matrix-assisted laser desorption ionization mass spectrometry. The specific activities of each of the EPOs were estimated by in vivo and in vitro mouse bioassays. The eight EPOs were found to differ in their isoform compositions (as judged by isoelectric focusing), their N-glycan profiles, and in their in vivo and in vitro bioactivities. N-glycan analyses identified at least 23 different structures among these EPOs, including bi-, tri- and tetra-antennary N-glycans, with or without fucosylation or N-acetyllactosamine extensions, and sialylated to varying degrees. Mass spectrometry also indicated the presence of N-glycans with incomplete outer chains, terminating in N-acetylglucosamine residues, and of molecular masses consistent with phosphorylated or sulphated oligomannoside structures. The tetrasialylated tetra-antennary N-glycan contents of the eight rEPOs were found to be significantly and positively correlated with their specific activities as estimated by mouse in vivo bioassay, and significantly and negatively correlated with their specific activities as estimated by mouse in vitro bioassay. It was concluded that the tetrasialylated tetra-antennary N-glycan content of EPO is a major determinant for its in vivo biological activity in the mouse.
Avant-propos (1987)

Dans le cadre de ses activités anglo-irlandaises, le Centre de recherches des pays de langue anglaise de l’Université de Caen et la RCP d’Etudes irlandaises ont organisé le 7 février 1987 une journée internationale consacrée à Seamus Heaney à laquelle ont collaboré un collègue de University College de Dublin, un autre de l’University of Ulster et des enseignants français tous réunis par la poésie et par l’Irlande. Aux articles ainsi rassemblés s’ajoute une communication donnée lors des atelie...
Identifying and characterizing a second structural domain of protein disulfide isomerase (1999)

Recent protein engineering studies have confirmed the multidomain nature of protein disulfide isomerase previously suggested on the basis of analysis of its amino acid sequence. The boundaries of three domains, denoted a, a' and b, have been determined, and each domain has been expressed as an individual soluble folded protein. In this report, the boundaries of the final structural domain, b', are defined by a combination of restricted proteolysis and protein engineering approaches to complete our understanding of the domain organization of PDI. Using these data an optimized polypeptide construct has been prepared and characterized with a view to further structural and functional studies.
Enhanced Oil Recovery in Rumania (1982)

ABSTRACT The wide oil field experience of the Romanian oil men in producing hydrocarbon reservoirs is based on an old tradition, but only after 1945 reservoir engineering studies were started in Romania. Beginning with 1950 conventional recovery methods expanded continual. During the last 10 years, however, the crude oil, as energy resource, has become of tremendous importance. The need for increasing the ultimate oil recovery has been felt in Romania as everywhere else. To attain this goal EOR methods were and are tested and expanded on a commercial scale. The paper describes the application of the fire-floods to a broad range of Romanian oil reservoirs and crude properties and reviews the field tests of polymer flooding, surfactant flooding and alkaline flooding. A commercial scale project with cyclic steam injection is presented and also the use of the domestic CO2 sources to enhance oil recovery. The results and the difficulties encountered are briefly discussed and also the potential of EOR methods in Romania are presented.
NRF2 Oxidative Stress Induced by Heavy Metals is Cell Type Dependent (2011)

Exposure to metallic environmental toxicants has been demonstrated to induce a variety of oxidative stress responses in mammalian cells. The transcription factor Nrf2 is activated in response to oxidative stress and coordinates the expression of antioxidant gene products. In this study, we describe the development of an Nrf2-specific reporter gene assay that can be used to study the oxidative stress response in multiple cell types. Using five different cell lines, the Nrf2-activating potency of twenty metals was assessed across a range of concentrations. While ten of the metals tested (cadmium, cobalt, copper, gold, iron, lead, mercury, silver, sodium arsenite and zinc) stimulated Nrf2-dependent transcriptional activity in at least three of the engineered cell lines, only three (cadmium, copper and sodium arsenite) were active in all five cell lines. A comparison of metal-induced Nrf2 transcriptional activation revealed significant differences in the absolute magnitude of activation as well as the relative potencies between the cell lines tested. However, there was no direct correlation between activity and potency. Taken together, these results show that the capacity to stimulate Nrf2 activity and relative potencies of these test compounds are highly dependent on the cell type tested. Since oxidative stress is thought to be involved in the mode of action of many toxicological studies, this observation may inform the design of paradigms for toxicity testing for toxicant prioritization and characterization.
[Stduy on flavonoids in Ligustrum lucidum]. (2007)

Compounds II, IV, V were obtained from the fruits of the plant for the first time.
<title>Three-dimensional optical memory using photopolymer, photorefractive crystals, and photochromic materials</title> (1997)

To exceed the capacity limitation of the optical method of data storage, we record and read digital data in three dimension in photorefractive material which is photosensitive for recording and refractile in reading. Experimental results are shown with photopolymers, photorefractive ferroelectric crystals, and photochromic dyes. Thirty layers have been successfully recorded and read in 300 micrometers -thick photopolymer film. Optical systems, including a confocal laser-scanning system and a two-photon laser-scanning system, and photorefractive materials suitable for 3D data storage are discussed with current problems for commercial applications.
Structure of human serum lipoproteins inferred from compositional analysis. (1977)

Analysis of the correlations between size and chemical composition of lipoproteins of normolipidemic human plasma shows that the structure of all circulating lipoproteins is consistent with a spherical model of radius r in which a spherical liquid core of cholesterol esters and triglycerides of radius = r --20.2 A is surrounded by a monolayer of cholesterol and phospholipids with closely hydrophobic ends on the surface of the core. The average molecular areas at this inner surface are Spl = 68.5 A2/molecule for phospholipids and Sc= 39.1 A2/molecule for cholesterol. The proteins are closely packed with the hydrophilic head groups of phospholipids at the outer surface of the particle, with S' pl = 62.7 A2/molecule for phospholipids and Saa = 15.6 A2/amino acid for proteins. The polar head group of free cholesterol does not participate in the packing of the outer layer and thus must be masked by proteins. Free cholesterol is distributed among the circulating lipoproteins--with the exception of very high density lipoprotein and perhaps chylomicrons--according to a thermodynamic equilibrium governed by the curvature of the surface of the particle.
A general regression neural network (1991)

A memory-based network that provides estimates of continuous variables and converges to the underlying (linear or nonlinear) regression surface is described. The general regression neural network (GRNN) is a one-pass learning algorithm with a highly parallel structure. It is shown that, even with sparse data in a multidimensional measurement space, the algorithm provides smooth transitions from one observed value to another. The algorithmic form can be used for any regression problem in which an assumption of linearity is not justified.
Transplantation of transduced chondrocytes protects articular cartilage from interleukin 1-induced extracellular matrix degradation. (1995)

Gene therapy used in the context of delivering a therapeutic gene(s) to chondrocytes offers a new approach for treating chondrocyte-mediated cartilage degradation associated with various human arthropathies including osteoarthritis. In this study, gene delivery to human osteoarthritis chondrocytes in monolayer culture was demonstrated using two adenoviral vectors (Ad.CMVlacZ and Ad.RSVntlacZ) carrying the Escherichia coli beta-galactosidase marker gene, and a third vector (Ad.RSV hIL-1ra) containing the cDNA for human interleukin-1 receptor antagonist. At an moi of 10(3) plaque-forming units/chondrocyte, > 90% of the infected cells stained positive for E. coli beta-galactosidase activity, indicating a high efficiency of transduction. Genetically modified chondrocytes were then transplanted onto the articular surface of osteoarthritic cartilage organ cultures with and without the underlying subchondral bone. Both in situ staining of the cartilage organ cultures for E. coli beta-galactosidase activity and examination by scanning electron microscopy indicated that the transplanted chondrocytes adhered and integrated into the articular surface and continued to express transgenic protein. Chondrocytes transduced with Ad.RSV hIL-1ra and seeded onto the surface of osteoarthritic cartilage secreted high levels of biologically active IL-1 receptor antagonist. The Ad.RSV hIL-1ra-treated cartilage samples were resistant to IL1-induced proteoglycan degradation over 10 d of sustained organ culture. These data demonstrate that transplantation of transduced chondrocytes onto the articular surface protects cartilage from IL-1-induced extracellular matrix degradation.
Sildenafil treatment in established right ventricular dysfunction improves diastolic function and attenuates interstitial fibrosis independent from afterload (2014)

Right ventricular (RV) function is an important determinant of prognosis in congenital heart diseases, pulmonary hypertension, and heart failure. Preventive sildenafil treatment has been shown to enhance systolic RV function and improve exercise capacity in a model of fixed RV pressure load. However, it is unknown whether sildenafil has beneficial effects when treatment is started in established RV dysfunction, which is clinically more relevant. Our aim was to assess the effects of sildenafil treatment on RV function and fibrosis in a model of established RV dysfunction due to fixed afterload. Rats were subjected to pulmonary artery banding (PAB), which induced RV dysfunction after 4 wk, characterized by reduced exercise capacity, decreased tricuspid annular plane systolic excursion, and RV dilatation. From week 4 onward, 50% of rats were treated with sildenafil (100 mg·kg(-1)·day(-1), n = 9; PAB-SIL group) or vehicle (n = 9; PAB-VEH group). At 8 wk, exercise capacity was assessed using cage wheels, and RV function was assessed using invasive RV pressure-volume measurements under anesthesia. Sildenafil treatment, compared with vehicle, improved RV ejection fraction (44 ± 2% vs. 34 ± 2%, P < 0.05, PAB-SIL vs. PAB-VEH groups), reduced RV end-diastolic pressure (2.3 ± 0.5 vs. 5.1 ± 0.9 mmHg, P < 0.05), and RV dilatation (end-systolic volume: 468 ± 45 vs. 643 ± 71 μl, P = 0.05). Sildenafil treatment also attenuated RV fibrosis (30 ± 6 vs. 17 ± 3‰, P < 0.05) but did not affect end-systolic elastance, exercise capacity, or PKG or PKA activity. In conclusion, sildenafil improves RV diastolic function and attenuates interstitial fibrosis in rats with established RV dysfunction, independent from afterload. These results indicate that sildenafil treatment has therapeutic potential for established RV dysfunction.
Occurrence of free ceramide in Acetobacter xylinum. (1986)

We have studied the membrane lipids of acetic acid bacteria, which are capable of growing in an acidic medium near pH 3.0, in an attempt to elucidate the relationship between the lipid composition and the tolerance to acidic pH. So far, as being characteristic of the lipids of the organisms, we have reported an ornithine lipid,1' 2) a tauro-ornithine lipid3A) and a phosphatidyl-
Cytotoxicity against human tumor cells mediated by the conjugate of anti-epidermal growth factor receptor monoclonal antibody to recombinant ricin A chain. (1989)

We have produced monoclonal antibodies against the epidermal growth factor (EGF) receptor which bind to the receptor with high affinity, compete with EGF for binding, block EGF-induced tyrosine kinase activity, and activate internalization and down-regulation of the receptor. These antibodies are cytostatic against cultured A431 cells at concentrations of 5-20 nM. In addition, they prevent the growth of A431 tumor xenografts in athymic mice. In the present experiments, we have attempted to improve the antitumor activity of monoclonal antibody 528 IgG2a against the EGF receptor by linking it to recombinant ricin A chain (rRA). The immunoconjugate (528 IgG-rRA) showed a potent cytotoxic effect on A431 cells in vitro. At a concentration of 10 pM, it inhibited the proliferation of cultured A431 cells by 50% and also inhibited protein synthesis in these cells by 50%. Proliferation was prevented and cell death occurred at 528 IgG-rRA concentrations of 60 pM or greater. Recombinant free ricin A chain was far less toxic. The cytotoxic effect of the immunoconjugate was neutralized by 528 IgG at concentrations 100-fold higher than 528 IgG-rRA. When the cytotoxic effect of 528 IgG-rRA was compared among several human cell lines expressing different numbers of EGF receptors, the capacity to inhibit both proliferation and protein synthesis generally correlated with the number of EGF receptors on the plasma membranes of these cells. Since 528 IgG-rRA is a very potent immunotoxin against A431 cells in culture, we designed experiments to test its in vivo antitumor activity against A431 xenografts in athymic mice. To measure the clearance of 528 IgG-rRA, 50 micrograms of immunotoxin were injected i.p. into athymic mice, blood was collected from the animals at regular intervals, and the level of immunotoxin in the serum was assayed by protein synthesis inhibition in cultured A431 cells. The blood level of active immunoconjugate reached a maximum 6 h after i.p. injection. The half-life of the absorption phase was 2.2 h, the half-life for elimination was 9.2 h, and blood levels which could be potentially cytotoxic were maintained for 48-72 h. We investigated a number of immunotoxin treatment schedules, including every other day for 4 days, based on these data. The results demonstrate that, while 528 IgG-rRA has higher in vivo antitumor activity than 528 IgG against A431 cell xenografts, this is accompanied by toxicity against the murine host.
Z-Selective Homodimerization of Terminal Olefins with a Ruthenium Metathesis Catalyst (2011)

The cross-metathesis of terminal olefins using a novel ruthenium catalyst results in excellent selectivity for the Z-olefin homodimer. The reaction was found to tolerate a large number of functional groups, solvents, and temperatures while maintaining excellent Z-selectivity, even at high reaction conversions.
Nonanticoagulant Protective Effect of Heparin in Chronic Aminonucleoside Nephrosis (1986)

Aminonucleoside nephrosis progresses over an 18-week period to focal and segmental glomerulosclerosis (FSGS). Whole heparin has been shown to blunt the extent of renal injury in another model of FSGS, renal ablation; however, the precise mechanism of protection has remained uncertain. Since heparin has a variety of physiologic actions unrelated to anticoagulation, we administered three different heparin compounds, each with a distinct profile of biological properties, to groups of rats given a single intravenous dose of puromycin aminonucleoside (PA). In the absence of a prolongation of the activated partial thromboplastin time (aPTT), both whole heparin (WH) and a 7,000- to 11,000-dalton-molecular-weight nonanticoagulant heparin (NAH) ameliorated the functional and histologic abnormalities of chronic aminonucleoside nephrosis as evidenced by significant reductions in 24-hour urine protein excretion while preserving the glomerular filtration rate and blunting the rise in serum creatinine as compared to untreated PA control animals at the conclusion of the study. In addition, the NAH and WH groups exhibited significantly fewer glomeruli with either segmental mesangial proliferative areas or glomerulosclerosis/hyalinosis lesions 18 weeks after PA administration. A fragment of heparin (HF) was ineffective. We conclude that heparin may exert its beneficial effect in chronic aminonucleoside nephrosis through a biologic action, other than anticoagulation, perhaps by inhibition of mesangial cell proliferation.
Sorption and diffusion of alcohols in amorphous polymers (1981)

Abstract The effects of polymer composition and penetrant molecular size on the solubility and diffusivity of alcohol vapors in a series of well characterized isoprene‐methyl methacrylate copolymers and their corresponding homopolymers has been investigated at room temperature. The rate of sorption behavior changes progressively from Fickian to non‐Fickian, to Case II to “Super Case II” transport with increasing methyl methacrylate (MMA) content in the polymers. The equilibrium solubility of the alcohols increases linearly with increasing penetrant molecular size for polymers which are above their glass transition temperature and decreases for polymers which are below their T g . The solubility also initially increases as an approximately linear function of MMA content in the copolymers. At about 55 mole percent MMA, the sorbed concentration either levels off or passes through a maximum depending on the size of the penetrant. The apparent “diffusion coefficients” (D) decrease with increasing molecular volume of the penetrants. An exponential dependence was found between these two variables for PMMA. These “diffusion coefficients” also decrease exponentially with increasing MMA content in these polymers. However, at 55 mole percent MMA the copolymer undergoes a rubber to glass transition at the temperature of the experiments. On this basis, it is suggested that the hindered chain segmental motion contributes to the sorption process in addition to strictly thermodynamic considerations. Free volume theory can be used to explain the mechanism of diffusion through the rubbery polymers while the “hole” theory can be applied to explain the transport of the penetrants through the glassy polymers.
Altered function of pulmonary surfactant in fatty acid lung injury (1990)

To determine whether acute fatty acid lung injury impairs pulmonary surfactant function, we studied anesthetized ventilated rabbits given oleic acid (55 mg/kg iv, n = 11) or an equivalent volume of saline (n = 8). Measurements of pulmonary mechanics indicated a decrease in dynamic compliance within 5 min of injury and a decrease in lung volume that was disproportionately large at low pressures, consistent with diminished surfactant activity in vivo. Bronchoalveolar lavage fluid obtained 1 h after injury had significantly increased erythrocytes and total leukocytes, largely polymorphonuclear cells. The phospholipid content and composition of the cell-free fraction had only minor changes from those of controls, but the protein content was increased 35-fold. Measurements of lavage surface activity in vitro showed an increase in average minimum surface tension from 1.3 +/- 0.4 (SE) dyn/cm in controls to 20.2 +/- 3.9 dyn/cm in injured animals. The alterations in static pressure-volume curves and decrease in lavage surface activity suggest a severe alteration of surfactant function in this form of lung injury that occurs despite the presence of normal amounts of surfactant phospholipids.
Medicinal Chemistry Strategies to Reduce CYP2D6 Inhibitory Activity of Lead Candidates (2009)

Among the various human cytochrome P450s (CYP450s) that catalyze the biotransformation of xenobiotics, CYP450 2D6 (CYP2D6) is one of the most important based on the number and wide variety of its drug substrates. CYP2D6 shows a high degree of interindividual variability, which is primarily due to the extensive genetic polymorphism that influences its expression and function. A number of drugs have been clinically implicated in major drug-drug interactions (DDI) via CYP2D6 inhibition. In order to avoid or minimize issues related to CYP2D6-mediated DDIs, pharmaceutical companies routinely screen for potential CYP2D6 liability of lead candidates in the early stage of the drug discovery process. This review summarizes the medicinal chemistry tactics employed to mitigate inhibitory activity at CYP2D6, identified through an extensive literature survey covering the 1998-2008 period.
Synthetic Lipoteichoic Acid fromStaphylococcus aureusIs a Potent Stimulus of Cytokine Release (2002)

We recently purified lipoteichoic acid (LTA) from Staphylococcus aureus to more than 99% purity by a novel preparation method and deduced its structure with the first nuclear magnetic resonance (NMR) of a complete LTA. In contrast to Gram-negative lipopolysaccharides, this LTA requires the toll-like receptor (TLR)-2 and not TLR-4 for cytokine induction in monocytes and macrophages. To elucidate the structure-function relationships for LTA from S. aureus, the lipid anchor was prepared by either acidic hydrolysis of native LTA or chemical synthesis (gentiobiosyl-sn-dimyristoylglycerol). Next, a complete LTA molecule with six glycerophosphate units carrying four alanine plus one N-acetyl-glucosamine substituent was synthesized, which displayed the same potency to activate monocytes as native LTA. However, 100-1,000 times higher concentrations of the lipid anchor were required for cytokine induction. It is worthy to note that replacing D-alanine with L-alanine blunted the effect indicating stereoselective recognition. The structure identification of this synthesized and biologically active LTA was proven by NMR and matrix-assisted laser desorption-ionization mass spectrometry. We concluded that the lipid anchor, with its fatty acids, represents an integral part of the immunostimulatory activity of LTA, but requires additional structural components on the polyglycerophosphate backbone.
New and Generic Anticoagulants and Biosimilars: Safety Considerations (2010)

The recent health care changes and approval of a generic low-molecular-weight heparin (LMWH) by the US Food and Drug Administration (FDA) merit a review of the facts regarding the new and generic anticoagulants. Fatal hypotension from anaphylactoid type reactions following heparin administration was responsible for more than 149 deaths all over the world. Researchers detected a heparin-like semisynthetic contaminant, over-sulfated chondroitin sulfate (OSCS), that appeared to be intentional. Low-molecular-weight heparins are produced using unfractionated heparin and OSCS has been found in various batches of LMWHs. Some newer anticoagulants are claiming to be free from the need to monitor for therapeutic effect and bleeding risk. Therefore, monitoring assays are not being developed and there is no antidote to reverse bleeding. In addition, there are concerns about reproducibility, product variation, and quality. In conclusion, although the generic LMWHs and newer anticoagulants may appear to be effective for qualified indications, their safety remains to be a concern.