gebhart/patrepeval huggingface dataset:
Fibroblast growth factor‐2 is selectively modulated in the rat brain by E‐5842, a preferential sigma‐1 receptor ligand and putative atypical antipsychotic (2001)

Fibroblast growth factor-2 (FGF-2) is a member of a large family of trophic factors whose expression is regulated under several conditions in different areas of the brain. The goal of our experiments was to determine whether the administration of 4-(4-fluorophenyl)-1,2,3,6-tetrahydro-1-[4-(1,2,4-triazol-1-il)butyl] pyridine citrate (E-5842), a sigma-1 receptor ligand and putative atypical antipsychotic, could regulate the expression of FGF-2. After chronic treatment with E-5842 (21 days, and the animals killed 24 h after the last administration), an up-regulation was observed of the expression of FGF-2 mRNA in the prefrontal cortex and the striatum, and a down-regulation of the expression of FGF-2 mRNA in the hypothalamus of the rat brain. Acute treatment with E-5842 (one single administration and animals killed 6 h later) up-regulated FGF-2 expression in the prefrontal cortex, the striatum, the hypothalamus and the hippocampus in a dose-dependent manner. The acute up-regulation was transient and disappeared 24 h after E-5842 administration. The induction of FGF-2 in the striatum after repeated administration has been described for clozapine, but our data concerning regulation in the prefrontal cortex suggest that this effect is unique to E-5852 among other antipsychotics. Given the neuroprotective activity of FGF-2, the data presented here might be relevant to the deficit in cognition and other symptoms that appear in schizophrenia.
Proteolytic formation and properties of gamma-carboxyglutamic acid-domainless protein C. (1983)

Protein C activation is catalyzed by a complex between thrombin and an endothelial cell surface receptor, thrombomodulin.To investigate the function of the y-carboxyglutamic acid (Gla) residues in the calciumdependent activation of protein C, residues 1-41 were removed from the protein C light chain by selective proteolysis with chymotrypsin, and the Gla-domainless protein C was purified to homogeneity.Activated Gladomainless protein C and activated protein C hydrolyzed H-D-Phe-pipecolyl-Arg-p-nitroanilide at the same rate.Unlike activated protein C, Gla-domainless activated protein C did not function as an anticoagulant.Calcium ions were required for Gla-domainless protein C activation by the thrombin-thrombomodulin complex.At 2 p~ substrate, half-maximal rates of activation were achieved at 250 2 50 p~ Ca2+ for protein C and 60 k 5 p~ Ca2+ for Gla-domainless protein C. At saturating levels of Ca2+, the activation properties of these two substrates were identical; Vmax = 250 mol/ min/mol and K,,, = 8 PM.In the absence of thrombomodulin, calcium inhibits thrombin-catalyzed activation of both Gla-domainless protein C and protein C. Half-maximal inhibition of protein C activation occurs at 250 p~ Ca2+, while half-maximal inhibition of Gladomainless protein c activation occurs at 60 CM Ca".Over the surface of rabbit endothelial cells, Gla-domainless protein C, at physiological concentrations, was activated at less than 5% the rate of protein C. Endothelial cell-mediated protein C activation exhibited sites with both high and low affinity for protein C, while only low affinity sites were observed for Gladomainless protein C.These results indicate that protein C possesses a Glaindependent high affinity calcium-binding site that is required for recognition by the thrombin-thrombomodulin complex and that metal ion interaction with this same site is responsible for Ca2+ inhibition of protein C activation by thrombin alone.These studies further show that the Gla domain of protein C is essential for optimal protein C activation at the endothelial cell surface.
Incorporation of the catalytic domain of a hammerhead ribozyme into antisense RNA enhances its inhibitory effect on the replication of human immunodeficiency virus type 1 (1993)

The catalytic domain of a hammerhead ribozyme was incorporated into a 413 nucleotides long antisense RNA directed against the 5'-leader/gag region of the human immunodeficiency virus type 1 (HIV-1) (pos. +222 to +634). The resulting catalytic antisense RNA was shown to cleave its target RNA in vitro specifically at physiological ion strength and temperature. We compared the antiviral effectiveness of this catalytic antisense RNA with that of the corresponding unmodified antisense RNA and with a mutated catalytic antisense RNA, which did not cleave the substrate RNA in vitro. Each of these RNAs was co-transfected into human SW480 cells together with infectious complete proviral HIV-1 DNA, followed by analysis of HIV-1 replication. The presence of the catalytically active domain resulted in 4 to 7 fold stronger inhibition of HIV-1 replication as compared to the parental antisense RNA and the inactive mutant. Kinetic and structural studies performed in vitro indicated that the ability for double strand formation was not changed in catalytic antisense RNA versus parental antisense RNA. Together, these data suggest that the ability to cleave target RNA is a crucial prerequisite for the observed increase of inhibition of the replication of HIV-1.
N-Acetylgalactosamine-6-Sulfate Sulfatase in Human Placenta: Purification and Characteristics1 (1991)

N-Acetylgalactosamine-6-sulfate sulfatase from human placenta was purified 33,600-fold using beta-N-acetyl-D-galactosamine 6-sulfate-(1----4)-beta-D-glucuronic acid-(1----3)-N-acetyl-D-[3H]galactosaminitol 6-sulfate as the substrate. This enzyme is an oligomer with a molecular mass of 120 kDa and consists of polypeptides of 40 and 15 kDa. The 15 kDa polypeptide is a glycoprotein. This purified protein has activities of N-acetylgalactosamine-6-sulfate sulfatase and galactose-6-sulfate sulfatase. Rabbit antiserum was raised against the purified protein. The antibody titrated N-acetylgalactosamine-6-sulfate sulfatase and galactose-6-sulfate sulfatase. The size of the precursor of the enzyme is 60 kDa, as determined by cell-free translation. The optimal pH values of the N-acetylgalactosamine-6-sulfate sulfatase and galactose-6-sulfate sulfatase activities are pH 3.8-4.0, and the Kms are 8 and 13 microM, respectively. Sulfate and phosphate ions are potent competitive inhibitors for the enzyme and their inhibition constants are 35 and 200 microM, respectively. Cross-reactive materials of 40 and 15 kDa were detected by immunoblot analysis, in the placenta, liver, and normal fibroblasts, but not in fibroblasts from a patient with Morquio disease.
Dynamics of Pathogenic and Suppressor T Cells in Autoimmune Diabetes Development (2003)

In the nonobese diabetic (NOD) mouse, pathogenic and suppressor CD4(+) T cells can be distinguished by the constitutive expression of CD25. In this study, we demonstrate that the progression of autoimmune diabetes in NOD mice reflects modifications in both T cell subsets. CD4(+)CD25(+) suppressor T cells from 8-, but not 16-wk-old NOD mice delayed the onset of diabetes transferred by 16-wk-old CD25-depleted spleen cells. These results were paralleled by the inhibition of alloantigen-induced proliferation of CD4(+)CD25(-) cells, indicating an age-dependent decrease in suppressive activity. In addition, CD4(+)CD25(-) pathogenic T cells became progressively less sensitive to immunoregulation by CD4(+)CD25(+) T cells during diabetes development. CD4(+)CD25(-) T cells showed a higher proliferation and produced more IFN-gamma, but less IL-4 and IL-10, whereas CD4(+)CD25(+) T suppressor cells produced significantly lower levels of IL-10 in 16- compared with 8-wk-old NOD mice. Consistent with these findings, a higher frequency of Th1 cells was observed in the pancreas of 16-wk-old compared with 8-wk-old NOD mice. An increased percentage of CD4(+)CD25(-) T cells expressing CD54 was present in 16-wk-old and in diabetic NOD, but not in BALB/c mice. Costimulation via CD54 increased the proliferation of CD4(+)CD25(-) T cells from 16-, but not 8-wk-old NOD mice, and blocking CD54 prevented their proliferation, consistent with the role of CD54 in diabetes development. Thus, the pathogenesis of autoimmune diabetes in NOD mice is correlated with both an enhanced pathogenicity of CD4(+)CD25(-) T cells and a decreased suppressive activity of CD4(+)CD25(+) T cells.
Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature (2013)

Pancreatic cancer (PC) has a poor prognosis, with a 5-year survival of 3-4%. This is mainly due to late diagnosis because of diffuse symptoms, where 80-85% of the patients are inoperable. Consequently, early diagnosis would be of significant benefit, resulting in a potential 5-year survival of 30-40%. However, new technologies must be carefully evaluated concerning effectiveness and healthcare costs. We have developed a framework for modelling cost and health effects from early detection of PC, which for the first time allowed us to analyse its cost-effectiveness. A probabilistic cohort model for estimating costs and quality adjusted life-years (QALY) arising from screening for PC, compared to a "wait-and-see"-approach, was designed. The test accuracy, Swedish survival and costs by tumour stage, expected life gain from early detection and pretest probabilities in risk groups, were retrieved from previous investigations. In a cohort of newly diagnosed diabetic patient (incidence 0.71%) the incremental cost per QALY gained (ICER) was €13,500, which is considered cost-effective in Europe. Results were mainly sensitive to the incidence with the ICER ranging from €315 to €204,000 (familial PC 35% and general population 0.046%, respectively). This is the first study focusing on clinical implementation of advanced testing and what is required for novel technologies in cancer care to be cost-effective. The model clearly demonstrated the potential of multiplexed proteomic-testing of PC and also identified the requirements for test accuracy. Consequently, it can serve as a model for assessing the possibilities to introduce advanced test platforms also for other cancer indications.
Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. (1996)

Oncogenic activation of Abl proteins due to structural modifications can occur as a result of viral transduction or chromosomal translocation. The tyrosine protein kinase activity of oncogenic Abl proteins is known to be essential for their transforming activity. Therefore, we have attempted to identify selective inhibitors of the Abl tyrosine protein kinase. Herein we describe an inhibitor (CGP 57148) of the Abl and platelet-derived growth factor (PDGF) receptor protein-tyrosine kinases from the 2-phenylaminopyrimidine class, which is highly active in vitro and in vivo. Submicromolar concentrations of the compound inhibited both v-Abl and PDGF receptor autophosphorylation and PDGF-induced c-fos mRNA expression selectively in intact cells. In contrast, ligand-induced growth factor receptor autophosphorylation in response to epidermal growth factor (EGF), insulin-like growth factor-I, and insulin showed no or weak inhibition by high concentrations of CGP 57148. c-fos mRNA expression induced by EGF, fibroblast growth factor, or phorbol ester was also insensitive to inhibition by CGP 57148. In antiproliferative assays, the compound was more than 30-100-fold more potent in inhibiting growth of v-abl-transformed PB-3c cells and v-sis-transformed BALB/c 3T3 cells relative to inhibition of EGF-dependent BALB/MK cells, interleukin-3-dependent FDC-P1 cells, and the T24 bladder carcinoma line. Furthermore, anchorage-independent growth of v-abl- and v-sis-transformed BALB/c 3T3 cells was inhibited potently by CGP 57148. When tested in vivo, CGP 57148 showed antitumor activity at tolerated doses against tumorigenic v-abl- and v-sis-transformed BALB/c 3T3 cells. In contrast, CGP 57148 had no antitumor activity when tested using src-transformed BALB/c 3T3 cells. These findings suggest that CGP 57148 may have therapeutic potential for the treatment of diseases that involve abnormal cellular proliferation induced by Abl protein-tyrosine kinase deregulation or PDGF receptor activation.
Yogurt — An Autodigesting Source of Lactose (1984)

Large quantities of yogurt are consumed by some lactase-deficient population groups. We used breath hydrogen measurements to determine whether lactase-deficient subjects absorbed lactose in yogurt better than lactose in milk. Ingestion of 18 g of lactose in yogurt resulted in only about one third as much hydrogen excretion as a similar load of lactose in milk or water, indicating a much better absorption of lactose in yogurt. Ingestion of yogurt also resulted in fewer reports of diarrhea or flatulence than did a similar quantity of lactose ingested in milk or a water solution. The enhanced absorption of lactose in yogurt appeared to result from the intraintestinal digestion of lactose by lactase released from the yogurt organisms. This autodigesting feature makes yogurt a well-tolerated source of milk for lactase-deficient persons and may explain the widespread consumption of yogurt by lactase-deficient population groups.
Synthesis of All the Stereoisomers of 13,17-Dimethyl-1-tritriacontene and 13,17-Dimethyl-1-pentatriacontene, the Contact Sex Pheromone Components of the Female Tsetse Fly, Glossina austeni (2001)

All of the stereoisomers of 13,17-dimethyl-1-tritriacontene (1) and 13,17-dimethyl-1-pentatriacontene (2), the contact sex pheromone components of the female tsetse fly (Glossina austeni), were synthesized starting from the enantiomers of the protected syn- and anti-2,6-dimethylheptane-1,7-diol (3), which were prepared from the enantiomers of methyl 3-hydroxy-2-methylpropanoate (4) and methyl phenyl sulfone (5).
Three-dimensional atom probe investigation of boron distribution in CoFeB∕MgO∕CoFeB magnetic tunnel junctions (2008)

Significant lateral compositional variations have been revealed in a three-dimensional atom probe (3DAP) study of the MgO barriers of magnetic tunnel junctions. High resolution electron microscopy of the CoFeB∕MgO∕CoFeB∕Ru∕CoFe∕PtMn multilayer indicates that the MgO barrier is smooth, uniform, and with good crystallinity. Nevertheless, the 3DAP data show lateral variations in the MgO composition over length scales on the order of tens of nanometers. Boron is not uniformly distributed within the CoFeB layers, but has tended to segregate to the interfaces. Annealing has no significant effect on the distribution of B, indicating that the segregation occurring during growth is relatively stable.
Assembly of the Prothrombinase Complex on Lipid Vesicles Depends on the Stereochemical Configuration of the Polar Headgroup of Phosphatidylserine (1994)

The conversion of prothrombin into thrombin is an imperative step in the sequence of reactions leading to the formation of a hemostatic plug. This reaction is catalyzed by the prothrombinase complex, composed of factors Xa and Va, which is assembled on a phospholipid surface through Ca-mediated interactions with the lipid polar headgroups. In this paper we describe experiments indicative for a major role of the stereochemical configuration of phosphatidylserine in the binding of the prothrombinase complex to a phospholipid surface. Using two stereoisomers of phosphatidylserine, i.e., L-alpha-glycerophosphoryl-L-serine (PLS) and L-alpha-glycerophosphoryl-D-serine (PDS), we demonstrate that membranes containing PLS are appreciably more favorable than membranes containing PDS in promoting assembly of the prothrombinase complex and catalysis of prothrombin conversion. Ellipsometric analysis of the binding of factor Va and factor Xa to a surface composed of phosphatidylcholine and 10 mol % of either PLS or PDS reveals that the apparent Kd for factor Va increases about 25-fold when substituting PDS for PLS. For factor Xa a 5-fold increase in Kd was observed on replacing PDS for PLS. When PLS is replaced by phosphatidyl-beta-lactate (PLac), a phospholipid resembling PS but lacking the amino group, a similar decrease in prothrombinase activity is found as observed with PDS, implicating the importance of both the amino group and the stereoconfiguration of the serine moiety for the assembly of the prothrombinase complex.(ABSTRACT TRUNCATED AT 250 WORDS)
[Heat resistance of "Bacillus subtilis" and "Bacillus stearothermophilus" spores in ethylene glycol, propylene glycol and butylene glycol solutions. Criticism of the use of thermodynamic parameters (author's transl)]. (1975)

Increasing concentrations of ethylene glycol (EG), 1,2-propylene glycol (PG) or 2,3-butylene glycol (BG) lower the heat resistance of B. subtilis SJ2 and B. stearothermophilus 1518 spores, and there is a linear relationship between logarithm of decimal reduction time (D) and glycol concentration. D120 degreesc values of B. subtilis spores in 0.02M, pH 7.0 phosphate buffer containing 20 per cent (w/w) EG, PG and BG are respectively 1, 0.7 and 1.1 min compared to 1.5 min in buffer alone. Corresponding values for B. stearothermophilus spores are 2, 2.4 and 3 min compared to 3.2 min. The type of glycol has little effect upon temperature coefficient z for destruction of the B. subtilis spores (average 6.9 degrees C). On the contrary, in the case of B. stearothermophilus, z increases when the number of carbons increases in the glycol molecule (from 7 to 15 degrees). The thermodynamic parameters which characterize the activation of the spore destruction reaction cannot lead to a general conclusion about a possible mechanism of destruction in the presence of chemical compounds belonging to an homologous series: the two behave diversely, and there is no "isokinetic temperature".
Potential role of MCP-1 in endothelial cell tight junction `opening': signaling via Rho and Rho kinase (2003)

The expression of the monocyte chemoattractant protein-1 (MCP-1) receptor CCR2 by brain endothelial cells suggests that MCP-1 may have other functions than purely driving leukocyte migration into brain parenchyma during inflammation. This study examines one of these potential novel roles of MCP-1 regulation of endothelial permeability using primary cultures of mouse brain endothelial cells. MCP-1 induces reorganization of actin cytoskeleton (stress fiber formation) and redistribution of tight junction proteins, ZO-1, ZO-2 occludin and claudin-5, from the Triton X-100-soluble to the Triton X-100-insoluble fractions. These morphological changes are associated with a decrease in transendothelial electrical membrane resistance and an increase in [14C]inulin permeability. MCP-1 did not induce these events in brain endothelial cells prepared from mice genotype CCR2-/-. The Rho kinase inhibitor Y27632 and inhibition of Rho (C3 exoenzyme, and dominant negative mutant of Rho, RhoT19N) prevented MCP-1-induced stress fiber assembly, reorganization of tight junction proteins and alterations in endothelial permeability. In all, this suggests that a small GTPase Rho and Rho kinase have a pivotal role in MCP-1-induced junction disarrangement. These data are the first to strongly suggest that MCP-1, via CCR2 present on brain endothelial cells, contributes to increased brain endothelial permeability.
Isolation and characterization of polyoma virus mutants able to develop in embryonal carcinoma cells. (1980)

Embryonal carcinoma (EC) mouse cells have been shown to be resistant to infection by retroviruses and small oncogenic DNA viruses, including simian virus 40 and polyoma. When allowed to differentiate, in vitro or in vivo, EC cells become as susceptible to these viruses as differentiated mouse cell lines are. In order to study the relationships between differentiation of EC cells and viral expression, we have isolated and characterized several polyoma mutants that can express early and late functions in undifferentiated EC cells. These mutants, which arose spontaneously during high-multiplicity infection of PCD3 cells (a differentiated fibroblast-like cell line derived from PCC3 EC cells), were selected on PCC4 cells (undifferentiated EC cells) and twice plaque purified. Restriction enzyme analysis of the DNA from several mutants has shown that they all exhibit an additional sequence located in the Pvu II endonuclease fragment 4, close to the junction between Hpa II endonuclease fragments 3 and 5. The size of the insertion varies from 10 to 50 base pairs. The biological properties, including oncogenicity, transforming ability, host range, and burst size of the mutants so far analyzed are similar to those of wild-type virus.
Market-based resource control for mobile agents (1998)

Article Market-based resource control for mobile agents Share on Authors: Jonathan Bredin Department of Computer Science, Dartmouth College, Hanover, NH Department of Computer Science, Dartmouth College, Hanover, NHView Profile , David Kotz Department of Computer Science, Dartmouth College, Hanover, NH Department of Computer Science, Dartmouth College, Hanover, NHView Profile , Daniela Rus Department of Computer Science, Dartmouth College, Hanover, NH Department of Computer Science, Dartmouth College, Hanover, NHView Profile Authors Info & Claims AGENTS '98: Proceedings of the second international conference on Autonomous agentsMay 1998 Pages 197–204https://doi.org/10.1145/280765.280801Online:01 May 1998Publication History 37citation644DownloadsMetricsTotal Citations37Total Downloads644Last 12 Months2Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Aspirin, Ibuprofen, and Other Non-Steroidal Anti-Inflammatory Drugs in Cancer Prevention: A Critical Review of Non-Selective COX-2 Blockade (Review) (2005)

No AccessJournal of UrologyUrological Survey: Uro-Science1 Aug 2005Aspirin, Ibuprofen, and Other Non-Steroidal Anti-Inflammatory Drugs in Cancer Prevention: A Critical Review of Non-Selective COX-2 Blockade (Review) Timothy L. RatliffPh.D. Timothy L. RatliffTimothy L. Ratliff View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)68393-9AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Aspirin, Ibuprofen, and Other Non-Steroidal Anti-Inflammatory Drugs in Cancer Prevention: A Critical Review of Non-Selective COX-2 Blockade (Review)." The Journal of Urology, 174(2), pp. 787–788 © 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 174Issue 2August 2005Page: 787-788 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.MetricsAuthor Information Timothy L. Ratliff More articles by this author Expand All Advertisement PDF DownloadLoading ...
Laser Welding of Synthetic Epikeratoplasty Lenticules to the Cornea (1990)

We used a milliwatt continuous wave CO2 laser mounted on an operating microscope to study the feasibility of welding synthetic collagen epikeratoplasty lenticules to the cornea. In vitro studies and experimentation in rabbits and monkeys showed no welding effects using direct laser radiation with powers ranging from 17 mW to 1 W. Only tissue shrinkage was observed. Experiments using various adjunctive solders produced a temporary welding effect using 30% bovine serum albumin welded with a power of 35-45 mW, 325 microns spot size, moving the beam 5 mm/sec. The lenticules remained in place until the 4th postoperative day when epithelium grew underneath the lenticule, dislodging it. Histopathologic examination demonstrated epithelial migration over the solder displacing the epikeratoplasty lenticule and anterior stromal denaturization and disruption.