gebhart/patrepeval huggingface dataset:
Stable Expression of hom-1-thrB in Corynebacterium glutamicum and Its Effect on the Carbon Flux to Threonine and Related Amino Acids (1994)

The hom-1-thrB operon encodes homoserine dehydrogenase resistant to feedback inhibition by L-threonine and homoserine kinase. Stable expression of this operon has not yet been attained in different Corynebacterium glutamicum strains. We studied the use of chromosomal integration and of a low-copy-number vector for moderate expression of the hom-1-thrB operon to enable an analysis of the physiological consequences of its expression in C. glutamicum. Strains carrying one, two, or three copies of hom-1-thrB were obtained. They showed proportionally increased enzyme activity of feedback-resistant homoserine dehydrogenase and of homoserine kinase. This phenotype was stably maintained in all recombinants for more than 70 generations. In a lysine-producing C. glutamicum strain which does not produce any threonine, expression of one copy of hom-1-thrB resulted in the secretion of 39 mM threonine. Additional copies resulted in a higher, although not proportional, accumulation of threonine (up to 69 mM). This indicates further limitations of threonine production. As the copy number of hom-1-thrB increased, increasing amounts of homoserine (up to 23 mM) and isoleucine (up to 34 mM) were secreted. Determination of the cytosolic concentration of the respective amino acids revealed an increase of intracellular threonine from 9 to 100 mM and of intracellular homoserine from 4 to 74 mM as the copy number of hom-1-thrB increased. These results suggest that threonine production with C. glutamicum is limited by the efflux system for this amino acid. Furthermore, the results show the successful use of moderate and stable hom-1-thrB expression for directing the carbon flux from aspartate to threonine.
Studies on Pyridazinone Derivatives. XVI. Analgesic-Antiinflammatory Activities of 3 (2H)-Pyridazinone Derivatives (1994)

In order to examine analgesic and antiinflammatory activities of the position isomers of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (1, emorfazone), an analgesic-antiinflammatory drug, 5-ethoxy-2-methyl-4-morpholino-3(2H)-pyridazinone (2), 6-ethoxy-2-methyl-4-morpholino-3(2H)-pyridazinone (3) and 6-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (4) were prepared. Since 4 showed the most strong activity among the compounds tested, various 6-alkoxy- or 6-allyloxy-2-alkyl- or 2-cyclohexyl- or 2-phenyl-5-substituted amino-3(2H)-pyridazinones (15, 16) were prepared and examined for their activities. As a result, 4 and 2-methyl-5-morpholino-6-n-propoxy- or 6-n-butoxy-3(2H)-pyridazinone (15b, c) and 6-ethoxy-2-ethyl-5-morpholino-3(2H)-pyridazinone (15 l) were revealed to be more potent in analgesic and antipyretic activities than commercial drugs (1, aminopyrine, mepirizole, tiaramide HCl, phenylbutazone, mefenamic acid). On the basis of the available data, the structure-activity relationship in a series of 6-alkoxy-2-alkyl-5-substituted amino-3(2H)-pyridazinones (15, 16) was also discussed.
Electrogenerated Chemiluminescence: An Oxidative‐Reduction Type ECL Reaction Sequence Using Tripropyl Amine (1990)

A new electrogenerated chemiluminescence (ECL) reaction which utilizes tripropyl amine and is presented. The mechanism of light generation appears general enough to include a range of amines and luminophores. An oxidative‐reduction mechanism is proposed. Upon electrochemical oxidation of both the luminophore and amine, a strong emission is observed. Voltammetric analysis reveals the potential for greatest light emission at the tripropyl amine oxidation. The emission is from the excited state of . An electron transfer reaction from the deprotonated tripropyl amine radical and is the central reaction for excited state production. An estimate of the ECL efficiency cannot be made, due to the complex nature of the reaction.
Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. (1992)

Degradation of proteoglycans is an initial change in osteoarthritic cartilage. Matrix metalloproteinase-3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen was immunolocalized in osteoarthritic and normal cartilage. Immunohistochemical studies showed MMP-3 in chondrocytes of the superficial and transition zones in approximately 90% of osteoarthritic cartilage (60 of 67 samples) and in 31% of those of the superficial zone in some normal cartilage (4 of 13 samples). MMP-3 staining correlated directly with the histological histochemical scores of Mankin and with proteoglycan depletion, up to a certain grade of severity. Chondrocytes in the deep radial zone, clusters, and osteophytes were immunostained only when proteoglycan depletion and fissures affected them. Culture media from osteoarthritic cartilage contained significantly higher levels of metalloproteinase activity that was identified as MMP-3 by immunoblotting and lower amounts of tissue inhibitor of metalloproteinases compared with those in the control samples. MMP-3 was also immunolocalized in the lining cells of most osteoarthritic synovium (20 of 23 specimens, 87%) with a direct correlation with scores of inflammatory cell infiltration in the synovium, but it was not detected in the normal synovium. Light and electron microscopic studies demonstrated that MMP-3 digests proteoglycan aggregates in human articular cartilage. Treatment of normal and osteoarthritic cartilage slices with tumor necrosis factor-alpha and/or interleukin-1 alpha increased the number of MMP-3-immunoreactive chondrocytes and the intensity of the staining. These data suggest that MMP-3 produced by the chondrocytes and synovial lining cells under stimulation with these cytokines may be important in proteoglycan degradation in human ostoearthritic cartilage.
Structure and serological characteristics of the capsular K4 antigen of Escherichia coli O5:K4:H4, a fructose-containing polysaccharide with a chondroitin backbone (1988)

The chemical structure of the K4-specific capsular polysaccharide (K4 antigen) of Escherichia coli O5:K4:H4 was elucidated by composition, carboxyl reduction periodate oxidation methylation nuclear-magnetic-resonance spectroscopy and enzymatic cleavage. The polysaccharide consists of a backbone with the structure----3)-beta-D-glucuronyl-(1,4)-beta-D-N-acetylgalactosaminyl(1- to which beta-fructofuranose is linked at C-3 of glucuronic acid. Mild acid hydrolysis liberated fructose and converted the K4 antigen into a polysaccharide which has the same structure as chondroitin. The defructosylated polysaccharide was a substrate for hyaluronidase and chondroitinase. The serological reactivity of the K4 polysaccharide was markedly reduced after defructosylation.
Regulation of interactions of endotoxin with host cells (2003)

Potent Toll-like receptor 4 (TLR4)-dependent cell activation by endotoxin requires lipopolysaccharide-binding protein (LBP) and CD14-dependent delivery of endotoxin to cells containing MD-2 and TLR4. We have used metabolically labeled [(14)C] meningococcal lipooligosaccharide (LOS), purified recombinant endotoxin-binding proteins, and cultured endothelial cells to better define protein:endotoxin intermediates key in cell activation in the absence of functional membrane (m) CD14. Protein:endotoxin complexes or aggregates (agg) were purified by gel sieving and characterized by immunocapture and bio-assays. Cell activation closely correlated with LBP, albumin and soluble (s) CD14-dependent conversion of endotoxin agg (M(r) > or = 20 x 10(6)) to monomeric (M(r) approximately 55 x 10(3)) endotoxin:sCD14 complexes. Ordered interaction of LBP (+ albumin) and sCD14 with LOSagg was required for the efficient formation of a bioactive endotoxin:sCD14 complex and potent cell activation. Increasing the ratio of LBP/sCD14 or addition of bactericidal/permeability-increasing protein (BPI) reduced accumulation of endotoxin:sCD14 complexes and instead yielded aggregates of endotoxin (M(r) approximately 1-20 x 10(6)) containing LBP or BPI that were taken up by cells in a CD14- and TLR4-independent manner without inducing pro-inflammatory responses. These findings strongly suggest that host machinery linked to TLR4-dependent cellular activation or TLR4-independent cellular clearance of endotoxin selectively recognizes different protein:endotoxin complexes. At the outset of infection, the low concentrations of LBP present and absence of extracellular BPI favor formation of pro-inflammatory endotoxin:CD14 complexes. The mobilization of LBP and BPI that is triggered by inflammation directs endotoxin for clearance and hence resolution of endotoxin-triggered inflammation.
Prevention of Iatrogenic Atrial Tachycardia After Ablation of Atrial Fibrillation (2004)

Modified CPVA is as effective as CPVA in preventing AF but is associated with a lower risk of developing incessant AT.
Anti‐N‐glycolylneuraminic acid antibodies identified in healthy human serum (2002)

The first and major clinical obstacle in xenotransplantation is antibody-mediated hyperacute rejection. Although human natural antibodies against Galalpha1,3Gal (Gal) antigens, which are common on porcine cells and organs, have been identified to play a major role in hyperacute rejection, other natural antibodies against non-Gal epitopes may be also involved in the process. Here, we present evidence suggesting that the majority of human anti-non-Gal antibodies are specific for carbohydrate structures carrying terminally linked N-glycolylneuraminic acid (NeuGc), a xenoantigen existing in almost all animals except humans. Furthermore, this anti-NeuGc activity is detectable in 85% of healthy humans, implicating the involvement of NeuGc in hyperacute rejection and the importance of developing strategies for removing NeuGc for clinical xenotransplantation.
Measurement of particle size distribution in multilayered skin phantoms using polarized light spectroscopy (2002)

We report on the ability to use polarized light to measure the particle size distribution of thin layers of polystyrene microspheres on top of a solid Intralipid phantom. The optical properties of each layer were adjusted to match the absorption and scattering properties of the epidermis (polystyrene layer) and dermis (Intralipid layer). Polarized light was used to discriminate between light scattered from the top layer of polystyrene and the lower layer of Intralipid. In this paper we also study the effect of the thickness of the top layer on the ability to reconstruct the polystyrene size distribution.
Mullerian Inhibiting Substance: A Gonadal Hormone with Multiple Functions* (1993)

Mullerian inhibiting substance (MIS) is the gonadal hormone that causes regression of the Mullerian ducts, the anlagen of the female internal reproductive structures, during male embryogenesis. MIS is a member of the large transforming growth factor-beta (TGF beta) multigene family of glycoproteins that are involved in the regulation of growth and differentiation. The proteins in this gene family are all produced as dimeric precursors and undergo posttranslational processing for activation, requiring cleavage and dissociation to release bioactive C-terminal fragments. Similarly, the 140 kilodalton (kDa) disulfide-linked homodimer of MIS is proteolytically cleaved to generate its active C-terminal fragments. The sexually dimorphic expression of MIS in Sertoli cells of the testis and granulosa cells of the ovary is critical for normal differentiation of the internal reproductive tract structures. A number of extra-Mullerian functions such as control of germ cell maturation and gonadal morphogenesis, induction of the abdominal phase of testicular descent, suppression of lung maturation, and growth inhibition of transformed cells have also been proposed for this growth-inhibitory hormone and will be discussed. This article will summarize the current understanding of the biology and multiple functions of MIS including its activation, regulation, and mechanism of action and discuss areas of interest in ongoing research.
ALLELIC ASSOCIATION OF THE D2 DOPAMINE RECEPTOR GENE IN COCAINEDEPENDENCE. (1992)

*Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA. **Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX.
The spindle kinesin‐like protein HsEg5 is an autoantigen in systemic lupus erythematosus (1996)

Autoantibodies to MSA fall into 2 major classes: those reactive with NuMA and those reactive with HsEg5. Autoantibodies to HsEg5 are found in a lower frequency than NuMA in sera that demonstrate the MSA pattern of staining and appear to be specifically associated with SLE. HsEg5 can be distinguished from NuMA by indirect immunofluorescence and Western blotting.
Influence of β2-Adrenergic Receptor Genotypes on Signal Transduction in Human Airway Smooth Muscle Cells (1995)

The phenotypic relevance of allelic variation in the structure of the beta 2-adrenergic receptor (beta 2AR) expressed in lung cells is unknown. In particular, altered responsiveness of the beta 2AR expressed on airway smooth muscle, which are responsible for bronchodilation in the treatment of asthma, may be an important factor in the ultimate physiologic response to agonist. To approach this, we established primary cultures of human airway smooth muscle cells obtained at autopsy and developed a method to determine the beta 2AR genotype at the polymorphic loci of codons 16 and 27, using allele-specific polymerase chain reactions. Radioligand binding studies revealed that these cells expressed approximately 70 fmol/mg of receptor which was exclusively of the beta 2AR subtype. All cell lines obtained (n = 10) exhibited normal agonist binding and receptor-mediated activation of the adenylyl cyclase second messenger pathway. However, distinct differences were found in the response to long-term agonist exposure between the different beta 2AR genotypes. Cells expressing Arg at codon 16 (Arg16) traditionally referred to as wild-type, underwent 77.8 +/- 8.1% downregulations of beta 2AR following prolonged (24-h) exposure to the beta 2AR agonist isoproterenol (10 microM). In contrast, cells expressing Gly16 beta 2AR underwent enhanced agonist-promoted downregulation (95.6 +/- 1.7%, P < 0.05 versus Arg16), whereas cells expressing Glu27 beta 2AR were relatively resistant to such downregulation (29.5 +/- 12.7%, P < 0.01 versus Arg16). For cells expressing Glu27 beta 2AR, this difference resulted in a significant attenuation of agonist-promoted functional desensitization (33 +/- 7 versus 90 +/- 5% desensitization for Arg16, P < 0.001) following preincubation with 1 microM isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural Diversity in Domains of the Immunoglobulin Superfamily (1989)

In recent years, it has become clear that structures related to antibodies function at cell surfaces to control the movement and differentiation of many types of vertebrate cells (for review, see Williams and Barclay 1988; Hunkapiller and Hood 1989). It seems likely that the primitive function of the Ig-related molecules was concerned with cell-cell interactions unrelated to immune mechanisms and that T- and B-cell immunity developed when molecular elements of a self-self recognition system became involved in non-self recognition (Williams 1982, 1987).
Advances and challenges in the molecular biology and treatment of glioblastoma-is there any hope for the future? (2015)

Malignant gliomas, such as glioblastoma multiforme (GBM), present some of the greatest challenges in the management of cancer patients worldwide. Even with aggressive surgical resections and recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal and quality of life is poor. Although new molecular pathways crucial to the biology and invasive ability of GBM are coming to light, translation of basic science achievements into clinical practice is slow. Optimal management requires a multidisciplinary approach and knowledge of potential complications arising from both disease and treatment. To help illustrate "where we are going" with GBM, we here include a detailed depiction of the molecular alterations underlying this fatal disease, as well as intensive research over the past two decades that has led to considerable advances in the understanding of basic GBM biology, pathogenesis and therapeutic approaches.
Molecular cloning of promoter-containing fragments from Bacillus stearothermophilus and their expression in Escherichia coli and Bacillus subtilis (1984)

Bacillus stearothermophilus DNA fragments containing a promoter were isolated in Escherichia coli using a shuttle promoter-probe vector. The molecular sizes of the isolated fragments ranged from 0.78 to 10 kb. The 0.78 and 1.1 kb fragments were selected and examined in some detail for promoter activity in both E. coli and Bacillus subtilis by analysis of expression of erythromycin-resistance (Emr) and β-galactosidase. The results showed that the two fragments exhibit a high promoter activity in both bacteria. In vitro promoter activity of the 1.1 kb fragment was also shown by RNA syntheses catalyzed by RNA polymerases prepared from E. coli, B. subtilis and B. stearothermophilus.
Rapid prototyping of functional ceramic composites (1996)

Laminated object manufacturing (LOM{reg_sign}) is one of several manufacturing systems developed recently to produce a solid part directly from a 3D CAD drawing, without the use of hard tooling or dies. These systems begin with a conventional 3-D CAD file--solid model or wire-form model--that is converted to a de facto standard format for flexible manufacturing (.STL file) and sliced into thin cross sections by a separate computer program. These slices are then used to control the equipment that produces the component slice-by-slice. This paper describes an application of the CerLOM approach to produce multilayered composites of ZrO{sub 2} and Al{sub 2}O{sub 3}. The choice of materials is based on previous studies that showed that a beneficial increase in toughness can be achieved with multilayered microstructures in this system. The toughness increase is due to martensitic transformation in the ZrO{sub 2}phase. Because the CerLOM process produces the component directly from a CAD file without tooling, dies or molds, the production is rapid and cost effective. Components of complex shape can be fabricated readily, and design changes can be made easily.
The Effects of Titanium and Hydroxyapatite on Osteoblastic Expression and Proliferation in Rat Parietal Bone Cultures (1993)

Titanium and hydroxyapatite are used for the fabrication of dental and orthopedic implants. The longevity of these implants depends on the amount and rate of bone formation that occurs around their surfaces. In the present study, the effects of titanium, hydroxyapatite, and polystyrene (control) on the proliferation of rat calvarial cells, and on their capacity to express alkaline phosphatase and respond to parathyroid hormone (PTH) stimulation, were studied. The nature of the substrate did not affect the DNA and protein contents of experimental and control cultures throughout the experimental period. Alkaline phosphatase expression and PTH response, as assessed by DNA synthesis and adenylate cyclase activity, were higher in cultures grown on hydroxyapatite and polystyrene than in those grown on titanium. These results indicate that hydroxyapatite was a more favorable substrate than titanium for the growth and differentiation of osteoblast-like cells in vitro.
Design, Synthesis, and Biological Evaluation of Fluoroneplanocin A as the Novel Mechanism-Based Inhibitor of S-Adenosylhomocysteine Hydrolase (2002)

Fluoroneplanocin A (12) was designed as a novel mechanism-based inhibitor of S-adenosylhomocysteine hydrolase (SAH) and efficiently synthesized via an electrophilic vinyl fluorination reaction (n-BuLi, N-fluorobenzenesulfonimide at -78 degrees C). Fluoroneplanocin A exhibited 2-fold more potent SAH inhibitory activity than the parent neplanocin A. A new mechanism of irreversible inhibition discovered in this work might provide new alternatives in the design of a different class of antiviral agents operating via SAH inhibition.
Monitoring the hybridization of the components of oligonucleotide mixtures to immobilized DNA via matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (1998)

Reported here is how the hybridization of individual components of oligonucleotide mixtures to solid-phase bound complementary strands can be monitored simultaneously by quantitative matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Three oligonucleotides, a DNA heptamer, a DNA octamer and a DNA octamer with a terminal cholic acid appendage were used as the test mixture. Upon cooling in the presence of a complementary undecamer on controlled pore glass, depletion of the components from the solution was observed. The resulting hybridization curves show the same relative affinities as traditional UV melting curves with single components and their complement. Assays of the kind described here may be used to select high affinity binders from combinatorial libraries of modified antisense oligonucleotides. © 1998 John Wiley & Sons, Ltd.
ADP-RIBOSYLATION (1985)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Evidence that sulphated polysaccharides inhibit tumour metastasis by blocking tumour‐cell‐derived heparanases (1987)

Recent studies in this laboratory demonstrated that several sulphated polysaccharides can inhibit metastasis of the rat mammary adenocarcinoma 13762 MAT, probably by preventing the passage of tumour cells through the walls of blood vessels. In order to directly test this possibility, 13762 MAT cells were cultured with (35S)O4(=)-labelled subendothelial extracellular matrices (ECM) and ECM degradation was monitored in either the presence or absence of different sulphated polysaccharides. Degradation products were detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis and subsequent autoradiography. The 5 sulphated polysaccharides that had previously been shown to possess anti-metastatic activity were potent inhibitors of the degradation of subendothelial ECM by 13762 MAT cells. In contrast, of the 4 polysaccharides tested that failed to inhibit metastasis, 3 had no effect on ECM breakdown and one (carrageenan-kappa) was substantially less effective at inhibiting ECM degradation than the anti-metastatic preparations. It was also shown that 13762 MAT cells produce a heparan sulphate-specific glycosidase (heparanase) that degrades the heparan sulphate side-chains of the ECM, the action of this enzyme rather than that of other ECM-solubilizing enzymes being inhibited by the antimetastatic sulphated polysaccharides. Additional experiments indicated that the anti-coagulant activity of the polysaccharides probably plays a minor role in their anti-metastatic effects since heparin, almost completely depleted (98-99.5%) of heparin molecules with anti-coagulant activity by passage over an anti-thrombin III column, retained its ability to inhibit 13762 MAT heparanases and was almost as effective as unfractionated heparin at inhibiting tumour-cell metastasis. Collectively, these data suggest that sulphated polysaccharides inhibit the metastasis of 13762 MAT cells by inhibiting tumour-cell-derived heparanases involved in the penetration of the vascular endothelium and its underlying basement membrane by tumour cells.