gebhart/patrepeval huggingface dataset:
N‐Acetylgucosaminono‐1,5‐lactone oxime and the corresponding (phenylcarbamoyl)oxime (1991)

Using N-acetylglucosaminono-1,5-lactone (1) as the reference, the inhibitory activity of its (formal) derivatives N-acetylglucosaminono-1,5-lactone oxime (2) and N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)-oxime (3) was tested against beta-N-acetylglucosaminidase of different origins (animal, plant, fungus). Displaying inhibition constants of 0.45 microM and 0.62 microM, for the animal and plant enzyme, respectively, the simple oxime 2 was about equally potent as the parent lactone 1, and 50-400 times more efficient than two recently described new beta-N-acetylglucosaminidase inhibitors. The (phenylcarbamoyl)oxime 3 performed even better, particularly with the fungal enzyme (Ki = 40 nM), i.e. was about 350 times more potent than the lactone. In all cases competitive inhibition was observed with 4-nitrophenyl-beta-N-acetylglucosaminide as the substrate. With Ki/Km ratios up to 3300 for 2 and 13,600 for 3, the mode of action of these novel inhibitors is probably that of transition state mimicry. Suggestions are made for their use as a tool in biological research.
Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002)

Osteoblasts mineralize bone matrix by promoting hydroxyapatite crystal formation and growth in the interior of membrane-limited matrix vesicles (MVs) and by propagating the crystals onto the collagenous extracellular matrix. Two osteoblast proteins, tissue-nonspecific alkaline phosphatase (TNAP) and plasma cell membrane glycoprotein-1 (PC-1) are involved in this process. Mutations in the TNAP gene result in the inborn error of metabolism known as hypophosphatasia, characterized by poorly mineralized bones, spontaneous fractures, and elevated extracellular concentrations of inorganic pyrophosphate (PP(i)). PP(i) suppresses the formation and growth of hydroxyapatite crystals. PP(i) is produced by the nucleoside triphosphate pyrophosphohydrolase activity of a family of isozymes, with PC-1 being the only member present in MVs. Mice with spontaneous mutations in the PC-1 gene have hypermineralization abnormalities that include osteoarthritis and ossification of the posterior longitudinal ligament of the spine. Here, we show the respective correction of bone mineralization abnormalities in knockout mice null for both the TNAP (Akp2) and PC-1 (Enpp1) genes. Each allele of Akp2 and Enpp1 has a measurable influence on mineralization status in vivo. Ex vivo experiments using cultured double-knockout osteoblasts and their MVs demonstrate normalization of PP(i) content and mineral deposition. Our data provide evidence that TNAP and PC-1 are key regulators of the extracellular PP(i) concentrations required for controlled bone mineralization. Our results suggest that inhibiting PC-1 function may be a viable therapeutic strategy for hypophosphatasia. Conversely, interfering with TNAP activity may correct pathological hyperossification because of PP(i) insufficiency.
Textured surfaces: Optical storage and other applications (1982)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation H. G. Craighead, R. E. Howard, J. E. Sweeney, D. M. Tennant; Textured surfaces: Optical storage and other applications. Journal of Vacuum Science and Technology 1 March 1982; 20 (3): 316–319. https://doi.org/10.1116/1.571291 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAVS: Science & Technology of Materials Interfaces and ProcessingJournal of Vacuum Science and Technology Search Advanced Search |Citation Search
Nucleotide Metabolism by Endothelium (1985)

Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
SLOCUM: an underwater glider propelled by environmental energy (2001)

SLOCUM is a small gliding AUV of 40 000-km operational range which harvests its propulsive energy from the heat flow between the vehicle engine and the thermal gradient of the temperate and tropical ocean. The design of both the glider and the thermal engine are discussed including the design genesis and approach, field trial results, concept strength, and limitations and potential use.
Oxidative and Nitrative Injury in Periventricular Leukomalacia: A Review (2005)

Periventricular leukomalacia (PVL) is the major substrate of cerebral palsy in survivors of prematurity. Its pathogenesis is complex and likely involves ischemia/reperfusion in the critically ill premature infant, with impaired regulation of cerebral blood flow, as well as inflammatory mechanisms associated with maternal and/or fetal infection. During the peak period of vulnerability for PVL, developing oligodendrocytes (OLs) predominate in the white matter. We hypothesize that free radical injury to the developing OLs underlies, in part, the pathogenesis of PVL and the hypomyelination seen in long-term survivors. In human PVL, free radical injury is supported by evidence of oxidative and nitrative stress with markers to lipid peroxidation and nitrotyrosine, respectively. Evidence in normal human cerebral white matter suggests an underlying vulnerability of the premature infant to free radical injury resulting from a developmental mismatch of antioxidant enzymes (AOE) and subsequent imbalance in oxidant metabolism. In vitro studies using rodent OLs suggest that maturational susceptibility to reactive oxygen species is dependent, not only on levels of individual AOE, but also on specific interactions between these enzymes. Rodent in vitro data further suggest 2 mechanisms of nitric oxide damage: one involving the direct effect of nitric oxide on OL mitochondrial integrity and function, and the other involving an activation of microglia and subsequent release of reactive nitrogen species. The latter mechanism, while important in rodent studies, remains to be determined in the pathogenesis of human PVL. These observations together expand our knowledge of the role that free radical injury plays in the pathogenesis of PVL, and may contribute to the eventual development of therapeutic strategies to alleviate the burden of oxidative and nitrative injury in the premature infant at risk for PVL.
A malaria merozoite surface protein (MSP1)-structure, processing and function (1992)

Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.
Conversion of Nicotine in Tobacco Smoke to Its Volatile and Available Free-Base Form through the Action of Gaseous Ammonia (1997)

Ammonia-forming compounds are routinely added to cigarette tobacco. The U.S. Food and Drug Administration (FDA) has argued that this is done to promote the formation of the volatile free-base form of nicotine in mainstream smoke (MSS) particles, thus increasing its availability to the smoker. The presence of ammonia in tobacco smoke may also be expected to promote the volatilization of nicotine from environmental tobacco smoke (ETS) particles in indoor air. The gas/particle partitioning of nicotine can be parameterized in terms of the gas/particle partitioning constant Kp = cp/cg, where cp (ng/μg) is the concentration in the particle phase and cg (ng/m3) is the concentration in the gas phase. The ability of ammonia to increase the amount of nicotine in the gas phase, as compared to the particle phase, was measured and confirmed. A gas-phase am monia pressure of pNH3 of ∼100 × 10-6 atm (100 ppmV) was found to reduce the Kp value for the partitioning of nicotine to tobacco smoke particulate matter by more than 100-fold. The agreement between ETS and MSS at pNH3 ≈ 100 ppmV was excellent, suggesting that the overall physical properties (e.g., polarity and number-average molecular weight) of ETS and MSS particulate material are very similar. Because gas-phase nicotine deposits more readily in the respiratory tract than does particle-phase nicotine and because free-base nicotine is more lipid soluble than is protonated nicotine, such a reduction in Kp will increase the availability of nicotine from MSS as well as from freshly formed ETS particles. At 20 °C and a relative humidity of 60%, the partitioning constant for the free-base form of nicotine is estimated to be Kp,fb = cp,fb/cg = 10-4.94. Cor rection to a body temperature of 37 °C yields Kp,fb = 10-5.97. Calculations using this Kp,fb value indicate that about 25% of the nicotine will be in the gas phase at a temperature of 37 °C for inhaled MSS under the full ammonia effect at a total suspended smoke particulate matter level of 3 × 106 μg/m3.
Fatty Acid Composition of Tobacco Seed Oil and Synthesis of Alkyd Resin (2007)

Abstract The fatty acid composition of tobacco seed oil revealed that the oil is rich in unsaturated fatty acids, having linoleic acid (71.63%), oleic acid (13.46%) and palmitic acid (8.72%) as the most abundant unsaturated and saturated fatty acids respectively. So the tobacco oil was characterized as semi‐drying type on the basis of fatty acid composition. The synthesis of alkyd resin was carried out by alcoholysis or monoglyceride process using an alkali refined tobacco seed oil, pentaerythritol, cis ‐1,2,3,6‐tetrahydrophthalic anhydride along with lithium hydroxide as catalyst. The alkyd resin so prepared was found to be bright and of low color with high gloss. The drying and hardness properties and adhesion of the tobacco seed oil derived alkyd resin were also found a bit superior to those of other alkyd resins of the same oil length. In addition, the water and acid resistance of the said alkyd was also found comparable to the other alkyds.
Prevention of Influenza Pneumonitis by Sialic Acid–Conjugated Dendritic Polymers (2002)

Influenza A viral infection begins by hemagglutinin glycoproteins on the viral envelope binding to cell membrane sialic acid (SA). Free SA monomers cannot block hemagglutinin adhesion in vivo because of toxicity. Polyvalent, generation 4 (G4) SA-conjugated polyamidoamine (PAMAM) dendrimer (G4-SA) was evaluated as a means of preventing adhesion of 3 influenza A subtypes (H1N1, H2N2, and H3N2). In hemagglutination-inhibition assays, G4-SA was found to inhibit all H3N2 and 3 of 5 H1N1 influenza subtype strains at concentrations 32-170 times lower than those of SA monomers. In contrast, G4-SA had no ability to inhibit hemagglutination with H2N2 subtypes or 2 of 5 H1N1 subtype strains. In vivo experiments showed that G4-SA completely prevented infection by a H3N2 subtype in a murine influenza pneumonitis model but was not effective in preventing pneumonitis caused by an H2N2 subtype. Polyvalent binding inhibitors have potential as antiviral therapeutics, but issues related to strain specificity must be resolved.
Review and Hypothesis: Vulnerable plaque formation from obstruction of Vasa vasorum by homocysteinylated and oxidized lipoprotein aggregates complexed with microbial remnants and LDL autoantibodies. (2009)

Little attention has been paid to the function of lipoproteins as part of a nonspecific immune defense system that binds and inactivates microbes and their toxins effectively by complex formation. Because of high extra-capillary tissue pressure, aggregates of such complexes may be trapped in vasa vasorum of the major arteries. This complex formation and aggregation may be enhanced by hyperhomocysteinemia, because homocysteine thiolactone reacts with the free amino groups of apo-B to form homocysteinylated low-density lipoprotein (LDL), which is subject to spontaneous precipitation in vitro. Obstruction of the circulation in vasa vasorum, caused by the aggregated complexes, may result in local ischemia in the arterial wall, intramural cell death, bursting of the capillary, and escape of microorganisms into the intima, all of which lead to inflammation and creation of vulnerable plaques. The presence of homocysteinylated LDL and oxidized LDL stimulates production of LDL autoantibodies, which may start a vicious circle by increasing the complex formation and aggregation of lipoproteins. The content of necrotic debris and leukocytes and the higher temperature than its surroundings give the vulnerable plaque some characteristics of a micro-abscess that by rupturing may initiate an occluding thrombosis. This suggested chain of events explains why many of the clinical symptoms and laboratory findings in acute myocardial infarction are similar to those seen in infectious diseases. It explains the presence of microorganisms in atherosclerotic plaques and why bacteriemia and sepsis are often seen in myocardial infarction complicated with cardiogenic shock. It explains the many associations between infections and cardiovascular disease. And it explains why cholesterol accumulates in the arterial wall. Some risk factors may not cause vascular disease directly, but they may impair the immune system, promote microbial growth, or cause hyperhomocysteinemia, leading to vulnerable plaques.
Output of neurogliaform cells to various neuron types in the human and rat cerebral cortex (2007)

Neurogliaform cells in the rat elicit combined GABAA and GABAB receptor-mediated postsynaptic responses on cortical pyramidal cells and establish electrical synapses with various interneuron types. However, the involvement of GABAB receptors in postsynaptic effects of neurogliaform cells on other GABAergic interneurons is not clear. We measured the postsynaptic effects of neurogliaform cells in vitro applying simultaneous whole-cell recordings in human and rat cortex. Single action potentials of human neurogliaform cells evoked unitary IPSPs composed of GABAA and GABAB receptor-mediated components in various types of inteneuron and in pyramidal cells. Slow IPSPs were combined with homologous and heterologous electrical coupling between neurogliaform cells and several human interneuron types. In the rat, single action potentials in neurogliaform cells elicited GABAB receptor-mediated component in responses of neurogliaform, regular spiking, and fast spiking interneurons following the GABAA receptor-mediated component in postsynaptic responses. In conclusion, human and rat neurogliaform cells elicit slow IPSPs and reach GABAA and GABAB receptors on several interneuron types with a connection-specific involvement of GABAB receptors. The electrical synapses recorded between human neurogliaform cells and various interneuron types represent the first electrical synapses recorded in the human cortex.
A Study of Parylene C Polymer Deposition Inside Microscale Gaps (2007)

Parylene C is a biocompatible polymer that has been investigated as an encapsulation material for implantable microsystems. Since parylene C is deposited directly on the substrate from the vapor phase it can conform to a wide range of geometries. However, the thickness of the deposited layer tends to decrease in microscale gaps, which might lead to an insulation failure. To ensure more robustness of the coating, the changes in parylene C coating thickness have been investigated experimentally using simple gaps of known dimensions. In an attempt to better understand these experimental findings, two theoretical models have been developed. The first one, which is based on a diffusion approximation, is able to reproduce and extrapolate the experimental results, leading to a useful design rule for practical applications involving parylene C coating. As an example, we present the substrate design of a flexible sieve electrode for a peripheral nerve interface. The second model aims at an appropriate microscopic description of the coating process in terms of kinetic theory of gases.
Lubrication and wear properties of grafted polyelectrolytes, hyaluronan and hylan, measured in the surface forces apparatus (2004)

Hyaluronan is believed to have an important function in the boundary biolubrication of articular cartilage. Using a Surface Forces Apparatus, we tested the tribological properties of surface bound, rather than "free" hyaluronan. The grafting process of the polyelectrolyte included either a biological route via an HA-binding protein or a chemical reaction to covalently bind the polymer to a lipid bilayer coated surface. In another reaction, we constructed a surface with covalently grafted hylan (crosslinked hyaluronan). We studied the normal and shear forces between these surfaces. None of the systems demonstrated comparable lubrication to that found between cartilage surfaces except at very low loads. Both grafted hyaluronan and hylan generated coefficients of friction between 0.15 and 0.3. Thus, the polysaccharide, which is a constituent of the lamina splendens (outermost cartilage layer), is not expected to be the responsible molecule for the great lubricity of cartilage; however, it may contribute to the load bearing and wear protection of these surfaces. This was concluded from the results with hylan, where a thin gel layer was sufficient to shield the underlying surfaces from damage even at applied pressures of over 200 atmospheres during shear. Our study shows that a low coefficient of friction is not a requirement for, or necessarily a measure of, wear protection.
Effective Backscatter Approximation for Photometry in Murky Water (2016)

Shading-based approaches like Photometric Stereo assume that the image formation model can be effectively optimized for the scene normals. However, in murky water this is a very challenging problem. The light from artificial sources is not only reflected by the scene but it is also scattered by the medium particles, yielding the backscatter component. Backscatter corresponds to a complex term with several unknown variables, and makes the problem of normal estimation hard. In this work, we show that instead of trying to optimize the complex backscatter model or use previous unrealistic simplifications, we can approximate the per-pixel backscatter signal directly from the captured images. Our method is based on the observation that backscatter is saturated beyond a certain distance, i.e. it becomes scene-depth independent, and finally corresponds to a smoothly varying signal which depends strongly on the light position with respect to each pixel. Our backscatter approximation method facilitates imaging and scene reconstruction in murky water when the illumination is artificial as in Photometric Stereo. Specifically, we show that it allows accurate scene normal estimation and offers potentials like single image restoration. We evaluate our approach using numerical simulations and real experiments within both the controlled environment of a big water-tank and real murky port-waters.
A Framework for Modelling the Electronic Medical Record (1993)

This paper presents a model for an electronic medical record which satisfies the requirements for a faithful and structured record of patient care set out in a previous paper in this series. The model underlies the PEN & PAD clinical workstation, and it provides for a permanent, completely attributable record of patient care and the process of medical decision making. The model separates the record into two levels: direct observations of the patient and meta-statements about the use of observations in decision making and the clinical dialogue. The model is presented in terms of "descriptions" formulated in the Structured Meta Knowledge (SMK) formalism, but many of its features are more general than the specific implementation. The use of electronic medical records based on the model for decision support and the analysis of aggregated data are discussed along with potential use of the model in distributed information systems.
Immunostimulatory, but not antiendotoxin, activity of lipid X is due to small amounts of contaminating N,O-acylated disaccharide-1-phosphate: in vitro and in vivo reevaluation of the biological activity of synthetic lipid X (1991)

Lipid X, a precursor in the biosynthesis of lipid A, has been claimed to possess most of the immunostimulatory activity but none of the toxicity of endotoxin. However, recent work shows that synthetic lipid X can be contaminated with small amounts of N,O-acylated disaccharide-1-phosphate (H. Aschauer, A. Grob, J. Hildebrandt, E. Schuetze, and P. Steutz, J. Biol. Chem. 265:9159-9164, 1990). Because the impurities themselves exhibit immunostimulatory properties, it was necessary to establish whether chemically pure synthetic lipid X exhibits any of the endotoxinlike biological activities previously attributed to the native compound extracted from the Escherichia coli MN7 mutant. In the present study, two batches of synthetic lipid X were used: batch A contained the contaminating disaccharide, and batch B was pure lipid X. Batch A, previously believed to be pure on the basis of spectroscopic and microanalysis data, induced murine peritoneal macrophages to secrete tumor necrosis factor, interleukin-1, and prostaglandin E2 at a minimal dose of 10 micrograms/ml in vitro. Batch B, further purified by Sephadex LH 20 chromatography, was found virtually inactive in these in vitro assays. Furthermore, batch A was pyrogenic in rabbits at a dose of 0.05 mg/kg, whereas batch B was not pyrogenic at doses of up to greater than or equal to 2 mg/kg. However, both batches were equally tolerated by galactosamine-loaded mice at doses of up to 100 mg/kg. Surprisingly, while only batch A protected neutropenic mice against lethal infection with Pseudomonas aeruginosa (50% effective dose, 12.4 mg/kg), both batches were equally protective against infection with herpes simplex virus type 1 in mice and guinea pigs, even when lipid X was administered therapeutically. Interestingly, both batches of lipid X blocked endotoxin-induced expression of monocyte procoagulant activity and priming of human neutrophils for superoxide anion release. Similarly, both batches protected galactosamine-sensitized mice from otherwise lethal endotoxemia when administered prophylactically or simultaneously with the lipopolysaccharide challenge. Thus, our findings suggest that chemically pure lipid X (batch B) is devoid of the immunostimulatory properties of lipid A or endotoxin. Rather, it behaves as a competitive inhibitor of lipopolysaccharide. We conclude, therefore, that previous studies which attributed immunostimulatory activities to any batch of synthetic lipid X should be interpreted with caution.
Natural Toxins for Use in Pest Management (2010)

Natural toxins are a source of new chemical classes of pesticides, as well as environmentally and toxicologically safer molecules than many of the currently used pesticides. Furthermore, they often have molecular target sites that are not exploited by currently marketed pesticides. There are highly successful products based on natural compounds in the major pesticide classes. These include the herbicide glufosinate (synthetic phosphinothricin), the spinosad insecticides, and the strobilurin fungicides. These and other examples of currently marketed natural product-based pesticides, as well as natural toxins that show promise as pesticides from our own research are discussed.