gebhart/patrepeval huggingface dataset:
Resident Enteric Bacteria Are Necessary for Development of Spontaneous Colitis and Immune System Activation in Interleukin-10-Deficient Mice (1998)

Mice with targeted deletion of the gene for interleukin-10 (IL-10) spontaneously develop enterocolitis when maintained in conventional conditions but develop only colitis when kept in specific-pathogen-free (SPF) environments. This study tested the hypothesis that enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice. IL-10-deficient mice were maintained in either SPF conditions or germfree conditions or were populated with bacteria known to cause colitis in other rodent models. IL-10-deficient mice kept in SPF conditions developed colitis in all segments of the colon (cecum and proximal and distal colon). These mice exhibited immune system activation as evidenced by increased expression of CD44 on CD4(+) T cells; increased mesenteric lymph node cell numbers; and increased production of immunoglobulin A (IgA), IgG1, and IL-12 p40 from colon fragment cultures. Mice populated with bacterial strains, including Bacteroides vulgatus, known to induce colitis in other rodent models had minimal colitis. Germfree IL-10-deficient mice had no evidence of colitis or immune system activation. We conclude therefore that resident enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice.
Inhibition of Lysyl Oxidases Improves Drug Diffusion and Increases Efficacy of Cytotoxic Treatment in 3D Tumor Models (2015)

Tumors are characterized by a rigid, highly cross-linked extracellular matrix (ECM), which impedes homogeneous drug distribution and potentially protects malignant cells from exposure to therapeutics. Lysyl oxidases are major contributors to tissue stiffness and the elevated expression of these enzymes observed in most cancers might influence drug distribution and efficacy. We examined the effect of lysyl oxidases on drug distribution and efficacy in 3D in vitro assay systems. In our experiments elevated lysyl oxidase activity was responsible for reduced drug diffusion under hypoxic conditions and consequently impaired cytotoxicity of various chemotherapeutics. This effect was only observed in 3D settings but not in 2D-cell culture, confirming that lysyl oxidases affect drug efficacy by modification of the ECM and do not confer a direct desensitizing effect. Both drug diffusion and efficacy were strongly enhanced by inhibition of lysyl oxidases. The results from the in vitro experiments correlated with tumor drug distribution in vivo, and predicted response to therapeutics in murine tumor models. Our results demonstrate that lysyl oxidase activity modulates the physical barrier function of ECM for small molecule drugs influencing their therapeutic efficacy. Targeting this process has the potential to significantly enhance therapeutic efficacy in the treatment of malignant diseases.
cis-analysis of the wound-inducible promoter wun1 in transgenic tobacco plants and histochemical localization of its expression. (1989)

The 5' region of the wound-inducible gene wun1, derived from potato, has been sequenced and analyzed for cis-acting elements important in controlling gene expression in transgenic tobacco plants. Different 5' deletion fragments were linked to the reporter gene beta-glucuronidase (GUS) as transcriptional fusions, and the expression of these chimeric genes was analyzed in leaf tissue. Sequences 111 base pairs upstream of the transcriptional start site were not able to drive the GUS expression over background levels, whereas sequences between -111 and -571 showed a slightly higher activity with equal levels of transcription in wounded and nonwounded tissue. The addition of further upstream sequences (-571 to -1022) enhanced the level of expression by a factor between 13 and 370. The expression driven by this fragment was inducible by a factor of twofold to ninefold by wounding. Histochemical analysis of different tissue from transgenic plants that contain wun1-GUS fusions demonstrates wound-inducible and cell-specific wun1 promoter activity in plants containing the -1022-base pair fragment. The location of GUS activity appears to be cell-specific, being highest in epidermal cells of leaves and stems and lower in vascular cells. Activity was reduced to levels that could not be detected by histochemical staining in leaves, stems, and roots of plants containing the deleted promoter fragments. Plants that contain the different deletion constructs and plants that carry the -1022-base pair fragment show high expression in anthers and pollen grains that could not be stimulated by wounding.
Paths to peace in Northern Ireland (I): Civil society and consociational approaches (1997)

This article comes in two parts. Part I describes the consociational and civil society approaches to conflict resolution. Consociationalism is a ‘top‐down’ form of power‐sharing which is elite‐oriented and sceptical of democracy. It is also distinctive in its preference for ethnic autonomy or segregation as a means for producing a more conducive environment for conflict resolution. By contrast the civil society or ‘bottom‐up’ model favours the extension of democracy and greater interethnic contact. By extending democracy moderate civil society is able to put pressure on the political elite to accommodate. Part II of the article will consider the assumptions of the two models against the experience of the peace processes 1973–74 and 1994–96.
Chemistry, Pharmacology, Pharmacokinetics, and Clinical Applications of Mesalamine for the Treatment of Inflammatory Bowel Disease (1994)

Mesalamine is the therapeutically active moiety of sulfasalazine used to treat inflammatory bowel disease. A controlled-release mesalamine capsule (Pentasa) is designed to release the agent continuously, and largely unaffected by intestinal pH, throughout the small and large bowel due to a diffusion-dependent, semipermeable ethylcellulose coating. It is a safe and efficacious single agent for inducing remission and producing therapeutic benefit in patients with mild to moderately active ulcerative colitis (UC) (2 or 4 g/day) or Crohn's disease (4 g/day), as well as for significantly enhancing quality of life for patients with mild to moderately active UC (2 or 4 g/day). It is also effective for maintaining remission in patients with quiescent UC and Crohn's disease (4 g/day). Disease location (left-sided UC or pancolitis) did not affect the agent's effect in active disease or maintaining remission. Fewer treatment-related adverse events were reported with mesalamine than with placebo in treating UC. In the treatment of active Crohn's disease, data showed no statistically significant differences in response for patients with ileitis, ileocolitis, or Crohn's colitis. This formulation of mesalamine may also be a possible steroid-sparing agent for patients with either active or quiescent Crohn's disease.
Studies on the combined action of phosphonomycin with streptomycin, penicillin G and ampicillin. (1976)

Using the serial dilution method in solid media, sensitivity of isolated strains of S. aureus and E. coli to phosphonomycin, streptomycin, penicillin G and ampicillin, and the effect of combined action of phosphonomycin with these antibiotics were studied. Against S. aureus strains, phosphonomycin in combination with penicillin G showed synergistic action more often than in combination with streptomycin. On the other hand, against E. coli strains the combination of phosphonomycin with streptomycin and ampicillin was similarly synergistic. The findings suggest the possibility of clinical applications of combined therapy with phosphonomycin and antibiotics of the beta-lactam and aminoglycoside groups.
A novel CMP method for cost-effective bonded SOI wafer fabrication (2002)

The BOnded Silicon On Insulator (BOSOI) has been considered as a promising substitute for bulk silicon technology because of its structural flexibility. However,there are considerable drawbacks if epitaxial etch stopping or localized plasma etching technique is used in the fabrication process because of low throughput and high cost. In order to obtain the ultrathin SOI layer with uniform thickness, this paper describes the cost-effective fabrication method of bonded SOI wafer using the double step CMP method in which the abrasive concentration of slurry is controlled to enhance the polish throughput. In this technique, a low total thickness variation (TTV) wafer is used as a handle wafer and the thickness variation of SOI layer can be easily reduced within a reasonable polishing time if the abrasive concentration of slurry is properly adjusted.
Mitotic Synchrony in Mammalian Cells Treated with Nitrous Oxide at High Pressure (1968)

Mammalian cells grown in suspension or monolayer cultures were synchronized for cell division by the application of nitrous oxide under pressure. The metaphase block induced by nitrous oxide was dependent on pressure and was reversible. Exposure of HeLa cells to nitrous oxide had no significant effect on the synthesis of DNA, RNA, or protein. The progress of cells through the mitotic cycle was also unaffected. A high degree of mitotic synchrony was obtained in suspension cultures of HeLa cells treated with thymidine during exponential growth, resuspended in fresh medium, and then exposed to nitrous oxide.
In Vivo Stimulation of Vascular Plasminogen Activator Inhibitor-1 Production by very Low-Density Lipoprotein Involves Transcription Factor Binding to a VLDL-Responsive Element (2000)

High plasma levels of plasminogen activator inhibitor-1 (PAI-1) are associated with an increased risk of cardiovascular disease. There is also a close relation between high plasma levels of PAI-1 and hypertriglyceridemia. Cell culture studies have shown that very low density lipoprotein (VLDL) increases the production and secretion of PAI-1 in endothelial cells and hepatocytes, suggesting a possible mechanism for this association. To determine whether VLDL stimulates PAI-1 production in vascular cells also in vivo, Sprague-Dawley rats were injected intravenously with 6 mg/kg of VLDL (derived from human subjects with type IV hyperlipidemia). Previous studies have demonstrated that this results in an accumulation of human VLDL in the aorta and other arteries followed by increased nuclear factor-kappa B (NF-kappaB) activation. Endothelial, but not smooth muscle cells, showed a basal PAI-1 mRNA and protein expression as assessed by in situ hybridization and immunohistochemistry, respectively. Six to twenty-four hours after the VLDL injection, lipoprotein particle accumulation was seen in the aortic wall, which was accompanied by increasing PAI-1 mRNA and protein expression in endothelial and smooth muscle cells. Within the rat PAI-1 promoter we identified a sequence located at -589 to -571 with 74% homology with the recently described VLDL responsive element in the human PAI-1 promoter and located adjacent to a 4-guanosine motif presumably corresponding to the human 4G/5G polymorphism. Transient transfection studies showed that VLDL exerts its stimulatory effects on rat PAI-1 gene expression in vascular cells by interaction with promoter sequences located within bp -656 and -505. Electrophoretic mobility shift assays showed that VLDL increases the binding of as yet incompletely characterized factors to this response element. Taken together these observations support a direct influence of VLDL on vascular PAI-1 gene expression ill vivo. This stimulation is exerted on the level of PAI-1 gene transcription, and involves transcription factor binding to a VLDL responsive element adjacent to a 4G motif within the PAI-1 promoter.
ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis (2009)

Bone metastasis is mediated by complex interactions between tumor cells and resident stromal cells in the bone microenvironment. The functions of metalloproteinases in organ-specific metastasis remain poorly defined despite their well-appreciated role in matrix degradation and tumor invasion. Here, we show a mechanism whereby two distinct metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1) and matrix metalloproteinase-1 (MMP1), orchestrate a paracrine signaling cascade to modulate the bone microenvironment in favor of osteoclastogenesis and bone metastasis. Proteolytic release of membrane-bound epidermal growth factor (EGF)-like growth factors, including Amphiregulin (AREG), heparin-binding EGF (HB-EGF), and transforming growth factor alpha (TGFalpha) from tumor cells suppress the expression of osteoprotegerin (OPG) in osteoblasts and subsequently potentiate osteoclast differentiation. EGF receptor (EGFR) inhibitors block osteolytic bone metastasis by targeting EGFR signaling in bone stromal cells. Furthermore, elevated MMP1 and ADAMTS1 expression is associated with increased risk of bone metastasis in breast cancer patients. This study established MMP1 and ADAMTS1 in tumor cells, as well as EGFR signaling in osteoblasts, as promising therapeutic targets for inhibiting bone metastasis of breast cancer.
Simple production and purification of monoclonal antibodies in serum-free medium. (2000)

Although serum is a main source of essential nutrients and growth factors, its use creates highly complex and poorly defined media. The use of serum-free media is more efficient than the use of media containing serum especially when the purification and characterization of antibodies are considered. In this study, we developed a serum-free medium system for cultivation of hybrid cells producing monoclonal antibodies specific for Tobacco Mosaic Virus (1F5) and 17b-estradiol (10F4) (15D4). Cells were cultivated in a medium with 10 % FCS for three days, and subsequently in serum-free medium for two days. The procedure was repeated once again providing monoclonal antibody in the serum-free supernatants comparable in amounts and activity with that in serum containing media. The method enabled purification of antibodies by a single step in high purity.
Induction of cytotoxic T cells to a cross-reactive epitope in the hepatitis C virus nonstructural RNA polymerase-like protein (1992)

Cytotoxic T lymphocytes (CTL) have been found to mediate protection in vivo against certain virus infections. CTL also may play an important role in control of infection by hepatitis C virus (HCV), but no CTL epitopes have yet been defined in any HCV protein. The nonstructural protein with homology to RNA polymerase should be a relatively conserved target protein for CTL. To investigate the epitope specificity of CTL specific for this protein, we used 28 peptides from this sequence to study murine CTL. Mice were immunized with a recombinant vaccinia virus expressing the HCV nonstructural region corresponding to the flavivirus NS5 gene (RNA polymerase), and the primed spleen cells were restimulated in vitro with peptides. CTL from H-2d mice responded to a single 16-residue synthetic peptide (HCV 2422 to 2437). This relatively conserved epitope was presented by H-2d class I major histocompatibility complex (MHC) molecules to conventional CD4- CD8+ CTL but was not recognized by CTL restricted by H-2b. Moreover, exon shuffle experiments using several transfectants expressing recombinant Dd/Ld and Kd demonstrated that this peptide is seen in association with alpha 1 and alpha 2 domains of the Dd class I MHC molecule. This peptide differs from the homologous segments of this nonstructural region from three other HCV isolates by one residue each. Variant peptides with single amino acid substitutions were made to test the effect of each residue on the ability to sensitize targets. Neither substitution affected recognition. Therefore, these conservative mutations affected peptide interaction neither with the Dd class I MHC molecule nor with the T-cell receptor. Because these CTL cross-react with all four sequenced isolates of HCV in the United States and Japan, if human CTL display similar cross-reactivity, this peptide may be valuable for studies of HCV diagnosis and vaccine development. Our study provides the first evidence that CD8+ CTL can recognize an epitope from the HCV sequence in association with a class I MHC molecule.
A Broad-Host-Range, Generalized Transducing Phage (SN-T) Acquires 16S rRNA Genes from Different Genera of Bacteria (2005)

Genomic analysis has revealed heterogeneity among bacterial 16S rRNA gene sequences within a single species; yet the cause(s) remains uncertain. Generalized transducing bacteriophages have recently gained recognition for their abundance as well as their ability to affect lateral gene transfer and to harbor bacterial 16S rRNA gene sequences. Here, we demonstrate the ability of broad-host-range, generalized transducing phages to acquire 16S rRNA genes and gene sequences. Using PCR and primers specific to conserved regions of the 16S rRNA gene, we have found that generalized transducing phages (D3112, UT1, and SN-T), but not specialized transducing phages (D3), acquired entire bacterial 16S rRNA genes. Furthermore, we show that the broad-host-range, generalized transducing phage SN-T is capable of acquiring the 16S rRNA gene from two different genera: Sphaerotilus natans, the host from which SN-T was originally isolated, and Pseudomonas aeruginosa. In sequential infections, SN-T harbored only 16S rRNA gene sequences of the final host as determined by restriction fragment length polymorphism analysis. The frequency of 16S rRNA gene sequences in SN-T populations was determined to be 1 x 10(-9) transductants/PFU. Our findings further implicate transduction in the horizontal transfer of 16S rRNA genes between different species or genera of bacteria.
Linear‐Hyperbranched Amphiphilic AB Diblock Copolymers Based on Polystyrene and Hyperbranched Polyglycerol (2005)

Abstract Summary: A convenient three‐step strategy has been developed for the preparation of well‐defined amphiphilic, linear‐hyperbranched block copolymers by hypergrafting. The synthetic procedure is based on a combination of carbanionic polymerization with the alkoxide‐based, controlled ring‐opening multibranching polymerization of glycidol. A linear AB diblock copolymer polystyrene‐ block ‐polybutadiene (PS‐ b ‐PB) with narrow polydispersity was obtained by anionic copolymerization. Subsequent hydroxylation by hydroboration led to PS 508 ‐ b ‐(PB‐OH) 56 , used as macroinitiator for the polymerization of glycidol under slow monomer addition conditions. Structure of the linear‐hyperbranched amphiphilic AB diblock copolymer PS 508 ‐ b ‐(PB 56 ‐ hg ‐PG x ) and an AFM micrograph of its micellar core–shell structure observed after solution casting. magnified image Structure of the linear‐hyperbranched amphiphilic AB diblock copolymer PS 508 ‐ b ‐(PB 56 ‐ hg ‐PG x ) and an AFM micrograph of its micellar core–shell structure observed after solution casting.
Shunt fluid examination: risks and benefits in the evaluation of shunt malfunction and infection (1984)

A combined retrospective and prospective study was designed to assess the efficacy of shunt fluid examination in the evaluation of shunt malfunction and/or infection, and to ascertain the complication rate associated with this procedure. Ninety-one patients with shunts for the treatment of hydrocephalus underwent a total of 209 diagnostic shunt "taps." Of 72 instances of mechanical obstruction documented at surgery, 70 were correctly identified by abnormal shunt fluid dynamics, either an opening cerebrospinal fluid (CSF) pressure in excess of the expected valve pressure or absent flow of fluid. The organisms responsible for 12 of 13 shunt-related infections were correctly isolated on initial and all subsequent shunt fluid cultures obtained prior to the institution of appropriate antibiotics. With one infection, a bacterial pathogen was not identified until the third tap. In all instances in which lumbar or ventricular CSF, blood, or wound cultures disclosed an organism, shunt fluid cultures also identified the agent. In addition, these procedures were less reliable. No complications occurred during or immediately following any of the shunt taps. Long-term consequences were assessed in 53 patients with an average follow-up period of 26 months. Some shunt systems subsequently required revision and two infections were documented. The uniformly long interval between the shunt fluid examination and these complications makes it unlikely that the taps contributed to the development of malfunction or infection. Shunt fluid examination appears to be a simple, benign, and yet accurate means of diagnosing shunt malfunction and/or shunt-related infection.
Effects of Calcium and Calcium Chelators on Growth and Morphology of Escherichia coli L-Form NC-7 (2000)

Growth of a wall-less, L-form of Escherichia coli specifically requires calcium, and in its absence, cells ceased dividing, became spherical, swelled, developed large vacuoles, and eventually lysed. The key cell division protein, FtsZ, was present in the L-form at a concentration five times less than that in the parental strain. One interpretation of these results is that the L-form possesses an enzoskeleton partly regulated by calcium.
Real-time programmable shading (1995)

One of the main techniques used by software renderers to produce stunningly realistic images is programmable shading—executing an arbitrarily complex program to compute the color at each pixel. Thus far, programmable shading has only been available on software rendering systems that run on general-purpose computers. Rendering each image can take from minutes to hours.
Ocrelizumab, a humanized anti‐CD20 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I/II randomized, blinded, placebo‐controlled, dose‐ranging study (2008)

Ocrelizumab therapy in combination with MTX was well tolerated. Doses of 200 mg (2 infusions) and higher showed better clinical responses, better reduction of C-reactive protein levels, and very low immunogenicity.
Sensitivity limits to ferrimagnetic Faraday effect magnetic field sensors (1991)

In general, the sensitivity of ferrimagnetic Faraday effect magnetic field sensors is a function of both the crystal geometry and composition. The geometrical dependence of the sensitivity in nonellipsoidal crystals, such as cylinders, is complicated by their spatially nonuniform demagnetizing factors. We compare sensitivity data obtained from a variety of cylindrical iron garnet samples with models which predict the effective demagnetizing factor Neff as a function of the length-to-diameter ratio. With respect to composition, we present experimental results of sensitivity vs diamagnetic substitution (x) in the iron garnet series Y3Fe5−xGaxO12. As expected, the sensitivity rises sharply as x approaches the compositional compensation point.
Twin-Twin Transfusion Syndrome (2003)

Vascular programming is evident in monozygotic twins with intertwin transfusion and is altered but not abolished by intrauterine therapy to resemble that seen in dichorionic twins.