gebhart/patrepeval huggingface dataset:
Imbalance of Endothelium-derived Relaxing and Contracting Factors: A New Concept in Hypertension? (1990)

The endothelium has a strategical anatomical position between the circulating blood and vascular smooth muscle cells. It has recently been recognized that endothelial cells play an important regulatory role in the circulation. The cells metabolize or activate vasoactive hormones (ie, norepinephrine, serotonin, bradykinin, angiotensin II), produce substances involved in coagulation and can release endothelium-derived relaxing factors and contracting factors. Nitric oxide and prostacyclin are vasodilators and inhibitors of platelet function. Endothelin is the most potent vasoconstrictor substance known. Thus, the endothelium can profoundly affect platelet adhesion and aggregation, vascular smooth muscle tone and possibly also vascular smooth muscle growth. Under physiological conditions, endothelium-derived relaxing factors appear to dominate. In contrast, in hypertensive and atherosclerotic arteries the release of endothelium-derived relaxing factors and/or the responsiveness of vascular smooth muscle cells to the relaxing factors is reduced, while that of endothelium-derived contracting factors is augmented. This imbalance of endothelium-derived relaxing and contracting factors may be important in the pathogenesis of hypertension and its cardiovascular complications.
Effective sites by sympathetic beta-adrenergic and vagal nonadrenergic inhibitory stimulation in constricted airways. (1985)

In an attempt to identify the site and nature of nonadrenergic inhibitory nervous regulation in airways, we studied the relative effectiveness of the nervous system in reversing bronchoconstriction along various generations of airways by comparing it with that seen during sympathetic (beta-adrenergic) stimulation in 9 cats. After giving atropine (3 mg/kg), airway dimensions were obtained from roentgenograms after insufflation of powdered tantalum. Baseline bronchoconstriction was then induced by an intravenous infusion of serotonin (50 to 250 micrograms/kg/min). Electrical stimulation of the sympathetic nerves inhibited constriction throughout the airways from trachea down to bronchioli less than 0.5 mm in diameter, with the maximal effect in airways 1 to 4 mm in diameter. The vagi were then stimulated after blocking the adrenergic inhibitory nervous system with propranolol (2 mg/kg). The distribution and potency of the remaining nonadrenergic inhibitory nerve's effect on airway constriction induced by serotonin was comparable to that obtained with sympathetic stimulation. We conclude that the nonadrenergic inhibitory nerves preferentially dilate the midsized airways, which essentially correspond to the sites maximally constricted by vagal stimulation without atropine. The largest (tracheal) and the peripheral airways (less than 1 mm in diameter) are only slightly affected by either inhibitory system.
Subcellular localization as a limiting factor for utilization of decoy oligonucleotides (2004)

Transfection of cells with short double-stranded synthetic DNA molecules that contain a transcription factor binding site, known as decoy oligodeoxynucleotides (ODNs), has been proposed as a novel approach in vitro and in vivo for the study of gene regulation and for gene therapy. Once delivered into cells, decoy ODNs are predicted to bind to nuclear transcription factors, preventing their binding to consensus sequences in target genes. Using a fluorescein-labeled decoy ODN containing a consensus sequence for the AP-1 transcription factor, we show that lipid-complexed decoys were readily transfectable into cells, but were consistently detectable in the cytoplasm and not in the nucleus. The same phenomenon was observed in three different cell lines including KB-3, CHO and MDA-MB-231. The AP-1 decoy ODNs failed to inhibit the transcriptional activity of an AP-1-dependent luciferase reporter. The effect of cytoplasmic AP-1 decoy ODNs on the subcellular localization and function of c-Jun induced by the microtubule inhibitor vinblastine, which strongly induced c-Jun expression, was assessed. No difference in protein level or nuclear localization of vinblastine-induced c-Jun, or of one of its target genes, p53, was noted when cells were transfected with wild-type or mutated forms of the decoy ODNs. We suggest that subcellular localization is an unappreciated and key limiting factor for the use of transcription factor decoy ODNs that must be addressed before meaningful data interpretation can be made.
HIERARCHICAL CARBON NANOTUBE-INORGANIC HYBRID STRUCTURES INVOLVING CNT ARRAYS AND CNT FIBERS (2011)

Carbon nanotube-inorganic hybrid materials have stimulated a new boost in CNT research as a new class of multifunctional materials with properties distinct from the well-known CNT composites. Synergistic effects based on interfacial charge and heat transfer processes commend these hybrids for use in photocatalysis, gas sensors and in electrochemical devices. A major challenge is the synthesis of hybrids with hierarchical architectures and controlled interfaces. Common wet-chemical techniques have the major drawback that the CNT array typically collapses upon drying due to stresses imposed by the surface tension of the solvent. In this work, we synthesized hierarchical hybrids with coherent 3D architectures using unique CNT fibers, based on the "Cambridge process" as well as vertical arrays of CNTs ("carpets"). We demonstrate that separating the liquid reactants from the CNT array is key to preserving the hybrid's architecture. In addition, we show that the presence of benzyl alcohol as a linking agent is beneficial to maximizing the interfacial area in TiO 2 -coated CNT fibers.
A micromachined interface for airborne sample-to-liquid transfer and its application in a biosensor system (2006)

A novel micromachined interface for airborne sample-to-liquid adsorption and droplet-to-liquid transfer was designed and fabricated. It enables a robust sheet liquid flow serving as an adsorption site. The interface was characterised for flow and pressure properties and tested successfully for the transfer/adsorption of different samples. A qualitative theoretical model of the device characteristics is presented. We also used the interface to introduce a novel method and system for fast detection of dust- and vapour-based narcotics and explosives traces. The microfluidic vapour-to-liquid adsorption interface was coupled to a set of downstream QCM sensors. The system was tested successfully, with 50 ng cocaine samples rendering 15 Hz frequency shifts and with 100 ng heroine samples rendering 50 Hz frequency shifts. Gravitation invariance of the open liquid interface was demonstrated successfully, with the interface mounted upside down as well as vertically. The detection time was reduced to half of the time needed in previous systems. Machine size, weight and cost were reduced.
TGF-ß Signaling in Renal Disease (2002)

Since discovery over a decade ago of a role for the cytokine TGF-beta as key mediator of glomerular and tubulointerstitial pathobiology in chronic kidney diseases, studies of TGF-beta signaling in the kidney have focused on the molecular biology of fibrogenesis. In recent years, glomerular and tubular epithelial cell apoptosis and cellular transdifferentiation have been proposed as putative primary pathomechanisms that may underlie progression of renal disease. This review describes evidence in support of nonlinear models and functional roles of TGF-beta signaling in mediating apoptosis and epithelial-to-mesenchymal transdifferentiation (EMT) in chronic progressive renal disease. Emphasis is placed on cell context-dependent models of TGF-beta signaling providing a conceptual framework to consolidate seemingly distinct pathomechanisms of progression of glomerular and tubulointerstitial disease.
Novel Enzymatically Degradable Polymers Comprising α-Amino Acid, 1,2-Ethanediol, and Adipic Acid (1991)

Abstract Novel water-insoluble polymers, which are degraded and solubilized by the action of specific proteolytic enzymes, were successfully synthesized from α-amino acid, 1,2-ethanediol, and adipic acid.
Cellular Mechanisms for Human Procollagenase-3 (MMP-13) Activation (1996)

Gelatinase A and membrane-type metalloproteinase (MT1-MMP) were able to process human procollagenase-3 (Mr 60,000) to the fully active enzyme (Tyr85 N terminus; Mr 48,000). MT1-MMP activated procollagenase-3 via a Mr 56,000 intermediate (Ile36 N terminus) to 48,000 which was the result of the cleavage of the Glu84-Tyr85 peptide bond. We have established that the activation rate of procollagenase-3 by MT1-MMP was enhanced in the presence of progelatinase A, thereby demonstrating a unique new activation cascade consisting of three members of the matrix metalloproteinase family. In addition, procollagenase-3 can be activated by plasmin, which cleaved the Lys38-Glu39 and Arg76-Cys77 peptide bonds in the propeptide domain. Autoproteolysis then resulted in the release of the rest of the propeptide domain generating Tyr85 N-terminal active collagenase-3. However, plasmin cleaved the C-terminal domain of collagenase-3 which results in the loss of its collagenolytic activity. Concanavalin A-stimulated fibroblasts expressing MT1-MMP and fibroblast-derived plasma membranes were able to process human procollagenase-3 via a Mr 56,000 intermediate form to the final Mr 48,000 active enzyme which, by analogy with progelatinase A activation, may represent a model system for in vivo activation. Inhibition experiments using tissue inhibitor of metalloproteinases, plasminogen activator inhibitor-2, or aprotinin demonstrated that activation in the cellular model system was due to MT1-MMP/gelatinase A and excluded the participation of serine proteinases such as plasmin during procollagenase-3 activation. We have established that progelatinase A can considerably potentiate the activation rate of procollagenase-3 by crude plasma membrane preparations from concanavalin A-stimulated fibroblasts, thus confirming our results using purified progelatinase A and MT1-MMP. This new activation cascade may be significant in human breast cancer pathology, where all three enzymes have been implicated as playing important roles.
Gene regulation in parthenocarpic tomato fruit (2009)

Parthenocarpy is potentially a desirable trait for many commercially grown fruits if undesirable changes to structure, flavour, or nutrition can be avoided. Parthenocarpic transgenic tomato plants (cv MicroTom) were obtained by the regulation of genes for auxin synthesis (iaaM) or responsiveness (rolB) driven by DefH9 or the INNER NO OUTER (INO) promoter from Arabidopsis thaliana. Fruits at a breaker stage were analysed at a transcriptomic and metabolomic level using microarrays, real-time reverse transcription-polymerase chain reaction (RT-PCR) and a Pegasus III TOF (time of flight) mass spectrometer. Although differences were observed in the shape of fully ripe fruits, no clear correlation could be made between the number of seeds, transgene, and fruit size. Expression of auxin synthesis or responsiveness genes by both of these promoters produced seedless parthenocarpic fruits. Eighty-three percent of the genes measured showed no significant differences in expression due to parthenocarpy. The remaining 17% with significant variation (P <0.05) (1748 genes) were studied by assigning a predicted function (when known) based on BLAST to the TAIR database. Among them several genes belong to cell wall, hormone metabolism and response (auxin in particular), and metabolism of sugars and lipids. Up-regulation of lipid transfer proteins and differential expression of several indole-3-acetic acid (IAA)- and ethylene-associated genes were observed in transgenic parthenocarpic fruits. Despite differences in several fatty acids, amino acids, and other metabolites, the fundamental metabolic profile remains unchanged. This work showed that parthenocarpy with ovule-specific alteration of auxin synthesis or response driven by the INO promoter could be effectively applied where such changes are commercially desirable.
Principles and Practice of Recombinant DNA Research with Yeast (1982)

INTRODUCTION Recombinant DNA research shows great promise in furthering understanding of yeast biology by making possible the analysis and manipulation of yeast genes not only in the test tube but also in yeast cells. The intent of this paper is to summarize the major features of current technology and to outline some implications for the immediate future of yeast molecular biology. There now exist simple and general methods for isolating and amplifying virtually any yeast gene, although these methods generally require an intermediate step in Escherichia coli. Powerful and exquisitely sensitive hybridization methods have been developed that allow direct physical analysis of any chromosomal region containing a gene that has been molecularly cloned. Most importantly, it is now possible to return to yeast, by transformation with DNA, cloned genes using a variety of selectable marker systems developed for this purpose. These technological advances have combined to make feasible truly molecular as well as classical genetic manipulation and analysis in yeast. The many uses to which these new tools have already been put have recently been reviewed by Olson (1981), and the results that have been obtained are to be found scattered in many of the papers in this volume. The biological problems that have been most effectively addressed by recombinant DNA technology are ones that have the structure and organization of individual genes as their central issue. Thus, the reader will find elsewhere in this volume that many signal advances in the understanding of such diverse subjects as the switching...
BindingDB Entry 2158: Tumor suppression by a rationally designed reversible inhibitor of methionine aminopeptidase-2. (2007)

Methionine aminopeptidase (MetAP)-2 has been suggested as a novel target for cancer therapy because the anticancer agent TNP-470 irreversibly inactivates the catalytic activity of this enzyme. However, the importance of MetAP2 in cell growth and tumor progression was uncertain because previous data were based on the chemically reactive TNP-470. Here we show that a rationally designed reversible MetAP2 inhibitor, A-357300, suppresses tumor growth preclinically without the toxicities observed with TNP-470. We have synthesized this bestatin-type MetAP2 inhibitor with the aid of crystal structures of the enzyme-inhibitor complexes and parallel synthesis. A-357300 induces cytostasis by cell cycle arrest at the G(1) phase selectively in endothelial cells and in a subset of tumor cells, but not in most primary cells of nonendothelial type. A-357300 inhibits angiogenesis both in vitro and in vivo and shows potent antitumor efficacy in carcinoma, sarcoma, and neuroblastoma murine models. These data affirm that MetAP2 plays a pivotal role in cell growth and establish that reversible MetAP2 inhibitors are promising novel cancer therapeutic agents.
Stromal expression of platelet-derived growth factor beta-receptor and platelet-derived growth factor B-chain in colorectal cancer. (1993)

The presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively, i.e., expression of the receptor and its ligand, fulfills two of the prerequisites for a role of PDGF in the activation of stromal cells in colorectal cancers. The data suggest that stromal activation, characterized by clusters of PDGF beta-receptor expressing cells, is of importance for the formation of tumor stroma per se. However, the expression of the PDGF beta-receptor has no potential as a prognostic marker.
Organocatalytic Living Ring-Opening Polymerization of Cyclic Carbosiloxanes (2006)

[reaction: see text] An organocatalytic route to narrowly dispersed poly(carbosiloxanes) of predictable molecular weight and end group fidelity is described. N-Heterocyclic carbenes (NHC) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyze the ring opening of cyclic carbosiloxanes. The pK(b) of the catalyst is important in preventing adverse transetherification reactions and obtaining well-defined polymers. Mechanistic studies indicate that hydrogen bonding to TBD or the NHC activates alcohols or silanols for ring-opening reactions.
Necdin, A Postmitotic Neuron-specific Growth Suppressor, Interacts with Viral Transforming Proteins and Cellular Transcription Factor E2F1 (1998)

Necdin is a nuclear protein expressed in virtually all postmitotic neurons, and ectopic expression of this protein strongly suppresses the proliferation of NIH3T3 cells. Simian virus 40 large T antigen targets both p53 and the retinoblastoma protein (Rb) for cellular transformation. By analogy with the interactions of the large T antigen with these nuclear growth suppressors, we examined the ability of necdin to bind to the large T antigen. Necdin was co-immunoprecipitated with the large T antigen from the nuclear extract of necdin cDNA-transfected COS-1 cells. Yeast two-hybrid and in vitro binding analyses revealed that necdin bound to an amino-terminal region of the large T antigen, which encompasses the Rb-binding domain. Moreover, necdin bound to adenovirus E1A, another viral oncoprotein that forms a specific complex with Rb. We then examined the ability of necdin to bind to the transcription factor E2F1, a cellular Rb-binding factor involved in cell-cycle progression. Intriguingly, necdin, like Rb, bound to a carboxyl-terminal domain of E2F1, and repressed E2F-dependent transactivation in vivo. In addition, necdin suppressed the colony formation of Rb-deficient SAOS-2 osteosarcoma cells. These results suggest that necdin is a postmitotic neuron-specific growth suppressor that is functionally similar to Rb.
Influence of Chemical Structures in Sulfurized Fats on Antiwear Behavior (1971)

Sulfurized methyl 10-undecenoate was used as the substance typifying sulfurized fatty extreme-pressure lubricant additives. The characteristic chemical structures in sulfurized methyl un-decenoate are sulfur-bridged long-chain di-esters, of which 1,20-dicarbomelhoxy-9,12-dimethyl-10,11 -dithiaeicosane is an example. The antiwear performance of this dithio-ester with respect to hardened AISI1095 steel in a pin-and-disk apparatus was indistinguishable from that of sulfurized methyl undecenoate. Esters such as methyl laurate and 1,18-dicarbomethoxyocta-decane did not show the antiwear behavior typical of sulfurized methyl undecenoate. Organic sulfides—-di-n-octyl monosulfide, di-n-octyl disulfide, di-n-octyl tetrasulfide, di-sec-octyl disulfide, d-t-octyl disulfide—behaved much differently than sulfurized methyl undecenoate. A mixture of methyl laurate and di-sec-octyl disulfide showed the same kind of antiwear behavior as sulfurized methyl undecenoate.
An analysis of the changes in soluble hydrogenase and global gene expression in Cupriavidus necator (Ralstonia eutropha) H16 grown in heterotrophic diauxic batch culture (2015)

We report the first full transcriptome analysis of C. necator H16 grown heterotrophically on fructose and glycerol in diauxic batch culture, which permits expression of soluble hydrogenase under heterotrophic conditions. The data presented deepens our understanding of the changes in global gene expression patterns that occur during the switch to growth on glycerol and suggests that energy deficit is a key driver for induction of hydrogenase expression in this organism.
Tat–Human Immunodeficiency Virus-1 Induces Human Monocyte Chemotaxis by Activation of Vascular Endothelial Growth Factor Receptor-1 (1997)

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti-VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody anti-phosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.
Influence of High Cycle Thermal Loads on Thermal Fatigue Behavior of Thick Thermal Barrier Coatings (1997)

Thick thermal barrier coating systems in a diesel engine experience severe thermal Low Cycle Fatigue (LCF) and High Cycle Fatigue (HCF) during engine operation. In the present study, the mechanisms of fatigue crack initiation and propagation, as well as of coating failure, under thermal loads which simulate engine conditions, are investigated using a high power CO2 laser. In general, surface vertical cracks initiate early and grow continuously under LCF and HCF cyclic stresses. It is found that in the absence of interfacial oxidation, the failure associated with LCF is closely related to coating sintering and creep at high temperatures, which induce tensile stresses in the coating after cooling. Experiments show that the HCF cycles are very damaging to the coating systems. The combined LCF and HCF tests produced more severe coating surface cracking, microspallation and accelerated crack growth, as compared to the pure LCF test. It is suggested that the HCF component cannot only accelerate the surface crack initiation, but also interact with the LCF by contributing to the crack growth at high temperatures. The increased LCF stress intensity at the crack tip due to the HCF component enhances the subsequent LCF crack growth. Conversely, since a faster HCF crack growth rate will be expected with lower effective compressive stresses in the coating, the LCF cycles also facilitate the HCF crack growth at high temperatures by stress relaxation process. A surface wedging model has been proposed to account for the HCF crack growth in the coating system. This mechanism predicts that HCF damage effect increases with increasing temperature swing, the thermal expansion coefficient and the elastic modulus of the ceramic coating, as well as the HCF interacting depth. A good agreement has been found between the analysis and experimental evidence.