gebhart/patrepeval huggingface dataset:
WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia (1994)

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
Soluble Robo4 receptor inhibits in vivo angiogenesis and endothelial cell migration (2004)

Roundabout receptors are molecular guidance molecules that function by interaction with Slit proteins to regulate axon guidance, neuronal migration, and leukocyte chemotaxis. We recently isolated a novel roundabout gene, called Robo4, which is restricted in expression to the endothelium, notably in areas of angiogenesis. The aim of this study was to use the soluble extracellular domain of Robo4 as a probe of function in angiogenesis and endothelial biology. Thus, the soluble extracellular domain of the receptor (Robo4Fc) showed diverse in vivo and in vitro activities including 1) inhibition of angiogenesis in vivo in the rodent subcutaneous sponge model, 2) inhibition of tube formation in the rat aortic ring assay, 3) inhibition of VEGF- and bFGF-stimulated endothelial cell migration, and 4) inhibition of endothelial proliferation. To assess whether Robo4Fc was inhibiting Slit-mediated effects, we determined whether Robo4 and Slit interact. Recombinant Slits-1, -2, and -3 were shown by immunoprecipitation and BiaCore analysis to bind to Robo1 but not Robo4. Further study of the role of Robo4 in angiogenesis appears justified.
Immunity of cholera in man: Relative role of antibacterial versus antitoxic immunity (1979)

Purified cholera toxoid is antigenic when given enterally and orally. Purified toxoid fails to provide protection against experimental challenge. Clinical cholera confers formidable protection against homologous or heterologous rechallenge. Failure to culture vibrios from intestinal fluid or stool of re-challenge volunteers suggests that the predominant immune mechanism is antibacterial rather than antitoxic.
FGF23 Elevation and Hypophosphatemia after Intravenous Iron Polymaltose: A Prospective Study (2009)

Parenteral iron suppresses renal tubular phosphate reabsorption and 1alpha-hydroxylation of vitamin D resulting in hypophosphatemia. Our data suggest that this is mediated by an increase in FGF23.
The technology, formulation and application of powder coatings (2000)

PREFACE INTRODUCTION Early developments Powder types and usage The advantages and disadvantages of powder coatings The economics of powder usage Markets for powder coatings The powder manufacturing process The VAMP process Agglomeration Aqueous powder slurry REFERENCES RESINS FOR THERMOSETTING POWDER COATINGS Resin parameters Epoxy Resins Polyester resins Acrylic resins FURTHER READING REFERENCES CURING AGENTS AND CURING REACTIONS Curing agents for epoxy resins Curing agents for polyester resins Curing agents for acrylic resins FURTHER READING REFERENCES RAW MATERIALS Resins and curing agents Pigments Fillers and extenders Additives FURTHER READING REFERENCES THE FORMULATION OF POWDER COATINGS Epoxy Polyester-epoxy Polyester Acrylics REFERENCES FORMULATING FOR SPECIFIC APPLICATIONS AND FINISHES Exterior durability Speciality finishes Special applications REFERENCES UV-CURING POWDER COATINGS Film formation and curing UV-curing powder coating chemistry Markets for UV-cured powders The future for UV-cured powder coatings REFERENCES FILM FORMATION AND CURE Factors controlling film formation Viscometry and thermo-viscoelastic measurements Review of some published TVA results Differential scanning calorimetry Other measurement techniques REFERENCES TEST METHODS AND PROCEDURES Background Terminology Test methods for powders Raw materials-resins Coating properties REFERENCES COLOUR MEASUREMENT AND MATCHING The concept of colour The trichromatic and CIE colour measurement system Metamerism Colour space and colour difference Instruments Colour matching FURTHER READING REFERENCES THE FUTURE FOR POWDER COATINGS New markets Resin and curing agent systems Cure Manufacture Conclusions REFERENCES INDEX
Abstract 2827: Activity of the proprietary Hsp90 inhibitor IPI-493 in models of colorectal cancer correlates with RAS pathway activation (2011)

Abstract Heat shock protein 90 (Hsp90) plays a role in regulating the stability of key cancer-causing proteins through its role as a protein chaperone. Proteins chaperoned by Hsp90, known as client proteins, include cancer-causing forms of ALK, BCR-ABL, EGFR, FLT3, and HER2. Infinity is developing two drug candidates in its Hsp90 chaperone inhibitor program: IPI-504 (retaspimycin hydrochloride), an intravenously-administered small molecule, and IPI-493, which is administered orally. To investigate the activity of IPI-493 in colorectal cancer (CRC), we performed in vitro growth inhibition (GI) studies on a CRC cell line panel. IPI-493 demonstrated GI50s in the range of 10-100nM in cell lines harboring either kRAS or bRAF mutations. To explore the in vivo potency of IPI-493, several mutant bRAF, mutant kRAS, as well as a wild-type kRAS/bRAF xenograft models were developed. Administration of IPI-493 at 100 mg/kg three times weekly demonstrated dramatic effects in all of the mutant models tested, with tumor growth inhibition (TGI) values between 70 and 90% and regression in one mutant bRAF model. Importantly, when IPI-493 was evaluated in combination with irinotecan, the combination resulted in greater tumor regression than seen with either agent alone with complete regressions observed in 4 of 10 animals. Interestingly, in the wild-type kRAS/bRAF models, IPI-493 administration did not lead to tumor growth inhibition. These results suggest that activation of the MAPK pathway may predispose these cells to sensitivity to Hsp90 inhibition. To investigate the effect of IPI-493 on MAPK pathway activity, we performed pharmacodynamic analysis after a single dose of IPI-493 in multiple xenograft models differing in their RAF/RAS mutation status. In mutant bRAF models, pathway activity was high, and IPI-493 administration resulted in downregulation of the activity of both bRAF and MEK. In models containing no mutations in kRAS or bRAF, we detect low baseline levels of both p-bRAF and p-MEK and little effect of IPI-493 administration. When Ras pathway activity in all CRC xenografts was compared with IPI-493 efficacy, there was a clear correlation between pathway activation and tumor growth inhibition by IPI-493. Our finding that Ras pathway activation predisposes CRC cells to sensitivity to IPI-493 and our combination data with irinotecan provide a clear rationale for the evaluation of Hsp90 inhibitors in colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2827. doi:10.1158/1538-7445.AM2011-2827
Cyclic siloxanes and silsesquioxanes as cores and frameworks for the construction of ferrocenyl dendrimers and polymers (1999)

Starting from 1,3,5,7-tetramethylcyclotetrasiloxane as core, novel ferrocenyl silicon-containing dendrimers have been constructed up to the third generation, which contains 16 peripheral ferrocene moieties. As precursors of these ferrocenyl dendritic molecules, SiCl- and Siallyl-terminated cyclotetrasiloxane-based dendrimers were also built step by step, by the repetition of hydrosilylation and alkenylation reactions as growing steps. The dendritic structures have been confirmed by 1H, 13C and 29Si NMR, infrared spectroscopy, elemental analysis, mass spectrometry and vapor-pressure osmometry. Solution electrochemical studies showed that all the ferrocenyl redox centers attached to the dendritic surface behave as independent, electronically isolated units, so that the dendrimers exchange all the electrons simultaneously at the same potential. We also describe the application of the first redox-active ferrocenyl polymer containing an octakis(dimethylsiloxy)octasilsesquioxane framework, as a mediator in the electrocatalytic oxidation of ascorbic acid. Copyright © 1999 John Wiley & Sons, Ltd.
Bone bonding behavior of MgOCaOSiO2P2O5CaF2 glass (mother glass of A · W‐glass‐ceramics) (1989)

In this study, it was found that a Ca-P layer and a Si layer were formed on the interface of the mother glass of apatite-wollastonite containing glass-ceramics (designated AW) and bone tissue. The dissolution of Si, Ca, and P from glass (MgO-CaO-SiO2-P2O5-CaF2) is necessary to form a chemical film (a Si layer and a Ca-P layer). The three kinds of glasses used were 1) a mirror surface of the mother glass (MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, CaF 0.5 weight ratio) of AW (designated G-AW (mirror], 2) an abraded surface of G-AW (designated G-AW (#2000)), 3) a mirror surface SiO2 glass (designated G-Si, 100% SiO2). The glass plates (15 mm x 10 mm x 2 mm) were implanted into the metaphysis of tibia of mature male rabbits for 10 and 25 weeks. The failure load, when an implant detached from the bone or when the bone itself broke, was measured by a detaching test and the interface of glass/bone was observed by SEM-EPMA. Failure loads in G-Si, G-AW (mirror), and G-AW (#2000) 10 weeks after implantation were 0.18 +/- 0.24, 3.06 +/- 1.29, and 2.94 +/- 1.77 kg, respectively. Those in G-Si, G-AW (mirror), and G-AW (#2000) 25 weeks after implantation were 1.30 +/- 1.18, 3.88 +/- 1.06, and 3.55 +/- 1.51, respectively. The failure loads in G-Si vs. G-AW (mirror) and those in G-Si vs. G-AW (#2000) differed significantly (P less than 0.01). There were no significant differences in the failure load according to the surface roughness of G-AW. As shown by SEM-EPMA observation, a Si layer next to G was adjacent to a Ca-P layer next to the bone. The chemical film showed no increase in thickness as time passed. A Ca-P layer did not form on the interface of Si-G and bone.
Characterization of a corrinoid protein involved in the C1 metabolism of strict anaerobic bacterium Moorella thermoacetica (2007)

The strict anaerobic, thermophilic bacterium Moorella thermoacetica metabolizes C1 compounds for example CO(2)/H(2), CO, formate, and methanol into acetate via the Wood/Ljungdahl pathway. Some of the key steps in this pathway include the metabolism of the C1 compounds into the methyl group of methylenetetrahydrofolate (MTHF) and the transfer of the methyl group from MTHF to the methyl group of acetyl-CoA catalyzed by methyltransferase, corrinoid protein and CO dehydrogenase/acetyl CoA synthase. Recently, we reported the crystallization of a 25 kDa methanol-induced corrinoid protein from M. thermoacetica (Zhou et al., Acta Crystallogr F 2005; 61:537-540). In this study we analyzed the crystal structure of the 25 kDa protein and provide genetic and biochemical evidences supporting its role in the methanol metabolism of M. thermoacetia. The 25 kDa protein was encoded by orf1948 of contig 303 in the M. thermoacetica genome. It resembles similarity to MtaC the corrinoid protein of the methanol:CoM methyltransferase system of methane producing archaea. The latter enzyme system also contains two additional enzymes MtaA and MtaB. Homologs of MtaA and MtaB were found to be encoded by orf2632 of contig 303 and orf1949 of contig 309, respectively, in the M. thermoacetica genome. The orf1948 and orf1949 were co-transcribed from a single polycistronic operon. Metal analysis and spectroscopic data confirmed the presence of cobalt and the corrinoid in the purified 25 kDa protein. High resolution X-ray crystal structure of the purified 25 kDa protein revealed corrinoid as methylcobalamin with the imidazole of histidine as the alpha-axial ligand replacing benziimidazole, suggesting base-off configuration for the corrinoid. Methanol significantly activated the expression of the 25 kDa protein. Cyanide and nitrate inhibited methanol metabolism and suppressed the level of the 25 kDa protein. The results suggest a role of the 25 kDa protein in the methanol metabolism of M. thermoacetica.
Use of a zinc-finger consensus sequence framework and specificity rules to design specific DNA binding proteins. (1993)

We have designed three zinc-finger proteins with different DNA binding specificities. The design strategy combines a consensus zinc-finger framework sequence with previously characterized recognition regions such that the specificity of each protein is predictable. The first protein consists of three identical zinc fingers, each of which was expected to recognize the subsite GCG. This protein binds specifically to the sequence 5'-GCG-GCG-GCG-3' with a dissociation constant of approximately 11 microM. The second protein has three zinc fingers with different predicted preferred subsites. This protein binds to the predicted recognition site 5'-GGG-GCG-GCT-3' with a dissociation constant of 2 nM. Furthermore, selection experiments indicate that this is the optimal binding site. A permuted version of the second protein was also constructed and shown to preferentially recognize the corresponding permuted site 5'-GGG-GCT-GCG-3' over the non-permuted site. These results indicate that earlier observations on the specificity of zinc fingers can be extended to generalized zinc-finger structures and realize the use of zinc fingers for the design of site-specific DNA binding proteins. This consensus-based design system provides a useful model system with which to study details of zinc-finger-DNA specificity.
Hierarchical B-spline refinement (1988)

Refinement is usually advocated as a means of gaining finer control over a spline curve or surface during editing. For curves, refinement is a local process. It permits the change of control vertices and subsequent editing of the detail in one region of the curve while leaving control vertices in other regions unaffected. For tensor-product surfaces, however, refinement is not local in the sense that it causes control vertices far from a region of interest to change as well as changing the control vertices that influence the region. However, with some care and understanding it is possible to restrict the influence of refinement to the locality at which an editing effect is desired. We present a method of localizing the effect of refinement through the use of overlays , which are hierarchically controlled subdivisions. We also introduce two editing techniques that are effective when using overlays: one is direct surface manipulation through the use of edit points and the other is offset referencing of control vertices.
Fitness Alters the Associations of BMI and Waist Circumference with Total and Abdominal Fat (2004)

These findings suggest that a reduction in total adiposity and abdominal fat may be a means by which CRF attenuates the health risk attributable to obesity as determined by BMI and WC.
The desk area network (1991)

A novel architecture for use within an end computing system is described. This attempts to extend the concepts used in modern high speed networks into computer system design. A multimedia workstation is being built based on this concept to evaluate the approach.
Priming to heat shock proteins in infants vaccinated against pertussis (1993)

To investigate whether and in which proportion normal individuals experience a priming to microbial heat shock proteins (hsp), the presence of antibodies to two mycobacterial hsp was tested in serum sample from 2- to 4-mo-old children before and at different times after vaccination with the trivalent vaccine against tetanus, diphtheria, and pertussis (DTP). We show that 88.9% of infants vaccinated with DTP developed antibody responses to mycobacterial hsp. Such a response was due to the whole-cell pertussis component of the vaccine, because it was not observed in infants receiving an acellular pertussis vaccine. Antibodies and cells reactive to the mycobacterial 65-kDa hsp were also found in mice immunized with DTP. Interestingly, whole-cell pertussis vaccine-induced anti-hsp antibodies cross-reacted with the Escherichia coli GroEL hsp, and at a some extent with the human 60-kDa hsp, belonging to the same hsp family. These data suggest that priming of the immune system to hsp is a common phenomenon occurring very early in life.
Efficient functioning of plant promoters and poly(A) sites inXenopusoocytes (1989)

Mature Xenopus oocytes were challenged with DNA constructs including plant regulatory elements, namely, the Cauliflower mosaic virus (CaMV) 35S promoter as well as the nopaline synthase (NOS) promoter and polyadenylation signal. The bacterial chloramphenicol acetyl transferase (CAT) was used as a reporter gene. When microinjected into these cells, the plant-derived DNA constructs effectively promoted CAT synthesis in a manner dependent on the presence of the plant promoters and probably also on the polyadenylation signals. Structural studies revealed that the supercoiled structures of the above DNA plasmids were much more active in supporting CAT synthesis in microinjected oocytes than their linear forms, with clear correlation between efficient gene expression and DNA topology. In contrast, the linear forms of these plasmids were considerably more active than the supercoiled ones in transfected plant protoplasts. These findings demonstrate, for the first time, the activity of regulatory elements from plant genes in Xenopus oocytes and shed new light on the specific rules applicable for gene expression in plant and animal cells.
Sequence diversity in the major fimbrial subunit gene (flp‐1) of Actinobacillus actinomycetemcomitans (2002)

Cells of the periodontal pathogen Actinobacillus actinomycetemcomitans exhibit tight adherence to surfaces such as glass, plastic and hydroxyapatite, a property that probably plays an important role in the ability of this bacterium to colonize teeth and other surfaces. Tight adherence is mediated by long fibrils of bundled pili (fimbriae) that form on the surface of the cell. The flp-1 gene encodes the major pilin protein component of A. actinomycetemcomitans fimbriae. In this study we compared flp-1 DNA sequences from 43 strains of A. actinomycetemcomitans isolated in Europe, Japan and the United States and identified seven distinct flp-1 allelic classes. DNA and predicted protein sequences were almost completely conserved within each flp-1 class but were highly divergent between classes. Most amino acid substitutions occurred in the C-terminus of the pilin protein, a region that has been shown to be important for the bundling and adhesive properties of the pili. flp-1 classes correlated with serotypes and 16S rRNA genotypes in most strains. At least five strains showed evidence of horizontal transfer of flp-1 between strains of different serotypes and 16S rRNA genotypes. Four of the seven flp-1 classes were present in geographically diverse isolates. Strains representing all seven flp-1 classes, but not a strain carrying a transposon insertion in flp-1, bound avidly to polystyrene in an in vitro adherence assay. Strains representing six of the seven flp-1 classes were isolated from localized juvenile periodontitis patients, suggesting that phylogenetically diverse strains carry pathogenic potential. Our findings provide a framework for future biochemical, immunological and genetic studies of A. actinomycetemcomitans fimbriae.
Mechanism of action of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases. Direct evidence for carbanion formation as an intermediate step using enzyme-catalyzed C-2 proton/deuteron exchange in the absence of C-3 exchange. (1985)

The mechanisms of the initial interactions of three rat liver acyl-CoA dehydrogenases (short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases) and their fatty acyl-CoA substrate were studied using enzyme-catalyzed deuterium exchange. The reaction products were identified and quantitated using mass spectroscopy and 1H-NMR. When fatty acyl-CoA substrates were incubated with catalytic amounts of acyl-CoA dehydrogenase in D2O in the absence of an electron acceptor, a rapid monodeuteration of the substrate occurred to replace one of the prochiral C-2 hydrogens, while no C-3 hydrogens were exchanged with deuterium. The C-2 monodeuteration proceeded to the extent of 80% of the total amount of substrate added at 90 min and almost to completion at 120 min. The pKa values and optimum pD values for the C-2 proton/deuteron exchange reactions were 6.0 and 7.5, respectively, for each of the three acyl-CoA dehydrogenases. The apparent turnover numbers were 3.0, 3.3, and 0.5 s-1 for short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases, respectively. These results provide the first direct evidence for carbanion formation via abstraction of a C-2 hydrogen by a base in the enzyme, as the first step of the catalytic pathway of acyl-CoA dehydrogenation. When the acyl-CoA dehydrogenases were reacted with moderate excesses of acyl-CoA substrates in D2O in the absence of an electron acceptor, maximum bleaching of the FAD absorbance and the appearance of the long wavelength absorbance, attributed to a charge transfer complex, were observed. However, the dehydrogenation products, 2-enoyl-CoAs, were produced either not at all or in an amount which represented only a minor fraction of the amount of the enzyme added, while the substrates in the enzyme-substrate complexes rapidly turned over as indicated by the extensive monodeuteration which concomitantly occurred. Unlike previous hypothesis, these results indicate that the hydride ion transfer from C-3 of the substrate to the enzyme-FAD is not yet complete in the charge-transfer complex. The transfer of the hydride ion to alloxazine N-5 and the release of products are completed only in the presence of electron-transfer flavoprotein or another suitable electron acceptor.