gebhart/patrepeval huggingface dataset:
Evidence for two distinct tumor‐suppressor gene loci on the long arm of chromosome 11 in human oral cancer (1996)

Loss of heterozygosity (LOH) on human chromosome 11 has been reported in a variety of human cancers. To search for the existence of tumor-suppressor gene(s) associated with oral squamous cell carcinoma (SCC) on chromosome 11, we have performed high-resolution deletion mapping in 31 patients with oral SCC using 22 microsatellite markers for this chromosomal region. LOH was observed in 14 of 25 cases (56.0%) that were informative with at least one locus. Most allelic deletions detected in our study were specific to the long arm of the chromosome. Furthermore, the data presented here show 2 distinct, commonly deleted regions. The first region, with frequent LOH, was restricted between markers D11S939 and D11S924 separated by 3 centimorgans (cM) on chromosome 11q23. The second region of common deletion was identified between markers D115912 and D11S910, separated by 7 cM at 11q25. Our results suggest that at least 2 tumor-suppressor genes involved in the development of oral SCC are present on the long arm of chromosome II. © 1996 Wiley-Liss, Inc.
Differentiating effects of murine nerve growth factor in the peripheral and central nervous systems of Xenopus laevis tadpoles. (1985)

The present investigation was directed toward exploration of the spectrum of action of murine nerve growth factor (m-NGF) in peripheral cells and neurons in the central nervous system (CNS) of Xenopus laevis tadpoles. It was found that systemic m-NGF injections elicit growth and differentiative effects not only on sensory and sympathetic nerve cells but also on several populations in the CNS. The finding that aminergic and peptidergic neurons in brain centers are highly receptive to m-NGF activity provides evidence for the broad spectrum of action of this molecule in lower vertebrates and calls for a systematic search for these and other putative target cells in the CNS of higher vertebrates.
Mechanism of Auxiliary Subunit Modulation of Neuronal α1E Calcium Channels (1998)

Voltage-gated calcium channels are composed of a main pore-forming alpha1 moiety, and one or more auxiliary subunits (beta, alpha2 delta) that modulate channel properties. Because modulatory properties may vary greatly with different channels, expression systems, and protocols, it is advantageous to study subunit regulation with a uniform experimental strategy. Here, in HEK 293 cells, we examine the expression and activation gating of alpha1E calcium channels in combination with a beta (beta1-beta4) and/or the alpha2 delta subunit, exploiting both ionic- and gating-current measurements. Furthermore, to explore whether more than one auxiliary subunit can concomitantly specify gating properties, we investigate the effects of cotransfecting alpha2delta with beta subunits, of transfecting two different beta subunits simultaneously, and of COOH-terminal truncation of alpha1E to remove a second beta binding site. The main results are as follows. (a) The alpha2delta and beta subunits modulate alpha1E in fundamentally different ways. The sole effect of alpha2 delta is to increase current density by elevating channel density. By contrast, though beta subunits also increase functional channel number, they also enhance maximum open probability (Gmax/Qmax) and hyperpolarize the voltage dependence of ionic-current activation and gating-charge movement, all without discernible effect on activation kinetics. Different beta isoforms produce nearly indistinguishable effects on activation. However, beta subunits produced clear, isoform-specific effects on inactivation properties. (b) All the beta subunit effects can be explained by a gating model in which subunits act only on weakly voltage-dependent steps near the open state. (c) We find no clear evidence for simultaneous modulation by two different beta subunits. (d) The modulatory features found here for alpha1E do not generalize uniformly to other alpha1 channel types, as alpha1C activation gating shows marked beta isoform dependence that is absent for alpha1E. Together, these results help to establish a more comprehensive picture of auxiliary-subunit regulation of alpha1E calcium channels.
Magnetic properties of Fe-base amorphous ultrafine particles (1985)

Sputter-etching an appropriate polymer substrate produces a densely-packed array of needlelike projections on the polymer surface. Rf sputter deposition of Fe <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">80</inf> B <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">20</inf> onto this surface produces an array of elongated finger-like projections of amorphous magnetic material, with diameters well under 1 μm and aspect ratios of 5 or more. These finger-like projections meet the definition of ultra-fine particles(UFP). Planar samples prepared in this way have a magnetic easy axis perpendicular to the sample surface with K <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">u</inf> /2πM <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">s</inf> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> =0.1-0.2, and have coercive fields up to 400 Oe. The dependence of magnetic properties on the sample morphology is described and discussed. Possible applications are briefly mentioned.
American Chemical Society-239th national meeting--Investigating new therapeutic candidates: part 2. 21-25 March 2010, San Francisco, CA, USA. (2010)

The American Chemical Society 239th National Meeting, held in San Francisco, included topics covering developments related to the chemical optimization of therapeutics. This conference report highlights selected presentations on second-generation cholesterol absorption inhibitors (CAIs), CCK2 receptor antagonists to prevent acid rebound, HIF-PH inhibitors for anemia, the neonatal Fc receptor (FcRn) as a target for autoimmune disease, and GPR119 agonists and GLP-1 receptor agonists for the treatment of diabetes. Investigational drugs discussed include LPD-608 (Lipideon Biotechnology AG), a second-generation CAI series from Merck & Co Inc, JNJ-26070109 and JNJ-42041935 (both Johnson & Johnson), SYN-1436 (Syntonix Pharmaceuticals Inc), a series of GPR119 agonists from Roche Holding AG and Schering-Plough Research Institute, and a series of GLP-1 receptor agonists from Bristol-Myers Squibb Co.
An Incomplete Program of Cellular Tyrosine Phosphorylations Induced by Kinase-defective Epidermal Growth Factor Receptors (1995)

Although signaling by the epidermal growth factor (EGF) receptor is thought to be dependent on receptor tyrosine kinase activity, it is clear that mitogen-activated protein (MAP) kinase can be activated by receptors lacking kinase activity. Since analysis of the signaling pathways used by kinase-defective receptors could reveal otherwise masked capabilities, we examined in detail the tyrosine phosphorylations and enzymes of the MAP kinase pathway induced by kinase-defective EGF receptors. Following EGF stimulation of B82L cells expressing a kinase-defective EGF receptor mutant (K721M), we found that ERK2 and ERK1 MAP kinases, as well as MEK1 and MEK2 were all activated, and SHC became prominently tyrosine-phosphorylated. By contrast, kinase-defective receptors failed to induce detectable phosphorylations of GAP (GTPase-activating protein), p62, JAK1, or p91STAT1, all of which were robustly phosphorylated by wild-type receptors. These data demonstrate that kinase-defective receptors induce several protein tyrosine phosphorylations, but that these represent only a subset of those seen with wild-type receptors. This suggests that kinase-defective receptors activate a heterologous tyrosine kinase with a specificity different from the EGF receptor. We found that kinase-defective receptors induced ErbB2/c-Neu enzymatic activation and ErbB2/c-Neu binding to SHC at a level even greater than that induced by wild-type receptors. Thus, heterodimerization with and activation of endogenous ErbB2/c-Neu is a possible mechanism by which kinase-defective receptors stimulate the MAP kinase pathway.
3D–2D image registration for target localization in spine surgery: investigation of similarity metrics providing robustness to content mismatch (2016)

In image-guided spine surgery, robust three-dimensional to two-dimensional (3D-2D) registration of preoperative computed tomography (CT) and intraoperative radiographs can be challenged by the image content mismatch associated with the presence of surgical instrumentation and implants as well as soft-tissue resection or deformation. This work investigates image similarity metrics in 3D-2D registration offering improved robustness against mismatch, thereby improving performance and reducing or eliminating the need for manual masking. The performance of four gradient-based image similarity metrics (gradient information (GI), gradient correlation (GC), gradient information with linear scaling (GS), and gradient orientation (GO)) with a multi-start optimization strategy was evaluated in an institutional review board-approved retrospective clinical study using 51 preoperative CT images and 115 intraoperative mobile radiographs. Registrations were tested with and without polygonal masks as a function of the number of multistarts employed during optimization. Registration accuracy was evaluated in terms of the projection distance error (PDE) and assessment of failure modes (PDE > 30 mm) that could impede reliable vertebral level localization. With manual polygonal masking and 200 multistarts, the GC and GO metrics exhibited robust performance with 0% gross failures and median PDE < 6.4 mm (±4.4 mm interquartile range (IQR)) and a median runtime of 84 s (plus upwards of 1-2 min for manual masking). Excluding manual polygonal masks and decreasing the number of multistarts to 50 caused the GC-based registration to fail at a rate of >14%; however, GO maintained robustness with a 0% gross failure rate. Overall, the GI, GC, and GS metrics were susceptible to registration errors associated with content mismatch, but GO provided robust registration (median PDE = 5.5 mm, 2.6 mm IQR) without manual masking and with an improved runtime (29.3 s). The GO metric improved the registration accuracy and robustness in the presence of strong image content mismatch. This capability could offer valuable assistance and decision support in spine level localization in a manner consistent with clinical workflow.
Inhibition of p185neu kinase activity and cellular transformation by co-expression of a truncated neu protein. (1996)

The rat neu oncogene product encodes a 185 kDa receptor tyrosine kinase which is constitutively activated as a result of a single amino acid substitution (Val664-->Glu) within the transmembrane region. In this study, we show that the transforming activity of oncogenic p185neu (also termed Tneu) can be inhibited by co-expression of a truncated neu protein with a large cytoplasmic deletion (termed T691stop) which includes the tyrosine kinase domain. In cell lines co-expressing full-length and truncated neu proteins, we observed co-dimerization between full-length p185neu and truncated T691 stop, resulting in the formation of a kinase-inactive heteromeric complex. Phenotypic analysis of several different clones showed that the degree of inhibition of transformation in vitro and tumorigenicity in vivo was related to the ratio of full-length and truncated p185 proteins co-expressed in cells. These results provide evidence that expression of kinase-deficient neu proteins leads to co-dimerization that results in suppression of kinase activation and oncogenicity of associated p185neu-activated receptors. The mutant neu protein mediates inhibition in both transfected fibroblasts expressing oncogenic p185neu and mammalian cancer cells derived from a rat primary neuroglioblastoma expressing oncogenic p185neu. This truncated peptide may be important for the design of future therapies directed against erbB family oncoproteins.
Direct determination of inorganic phosphorus in serum with a single reagent. (1983)

Estimation of inorganic phosphate in serum based on the formation of "molybdenum blue" may be simplified by eliminating the reduction stage. The yellow complex formed by the reaction of phosphate with molybdate in an acid medium is measured at 390 nm. The yellow complex behaves in accordance with Beer's law over a wide concentration range (to at least 80 mg of P per liter in the initial sample); its molar absorptivity at 390 nm is 2.51 X 10(3) L mol-1 cm-1. Sensitivity is increased in the presence of a detergent (triethanolamine lauryl sulfate), which is also used to dissolve the proteins. Because only one reagent is used (a stable combination of, per liter, 20 mmol of sodium molybdate, 82 mmol of nitric acid, and 100 mg of the detergent), the method is simple and rapid. We describe a manual procedure and an automated one. Within-run precision was 1.9%, and day-to-day precision less than 7%. Results by the automated method compare favorably (r = 0.96) with those obtained by Drewes's method (Clin Chim Acta 39: 81-88, 1972).
Direct detection of double-stranded DNA: molecular methods and applications for DNA diagnostics (2006)

Methodologies to detect DNA sequences with high sensitivity and specificity have tremendous potential as molecular diagnostic agents. Most current methods exploit the ability of single-stranded DNA (ssDNA) to base pair with high specificity to a complementary molecule. However, recent advances in robust techniques for recognition of DNA in the major and minor groove have made possible the direct detection of double-stranded DNA (dsDNA), without the need for denaturation, renaturation, or hybridization. This review will describe the progress in adapting polyamides, triplex DNA, and engineered zinc finger DNA-binding proteins as dsDNA diagnostic systems. In particular, the sequence-enabled reassembly (SEER) method, involving the use of custom zinc finger proteins, offers the potential for direct detection of dsDNA in cells, with implications for cell-based diagnostics and therapeutics.
Chromosome-Mediated Gene Transfer of Multidrug Resistance (1986)

Multidrug resistance can be transferred from drug-resistant LZ Chinese hamster cells to drug-susceptible mouse LTA cells by chromosome-mediated gene transfer. Analysis of genomic DNA demonstrated the transfer of multiple copies of a DNA domain which is amplified in the donor multidrug-resistant cells. The transfer of 10 to 15 copies of the Chinese hamster gene was sufficient to produce a multidrug-resistant phenotype. Chromosome transferents exhibited overexpression of an mRNA of approximately 5 kilobases which has previously been demonstrated to be encoded by the amplified DNA domain of the donor LZ cells. Phenotypic analysis of individual clones selected in adriamycin showed the resistance to be pleiotropic. All clones tested demonstrated similar levels of cross-resistance to the drugs daunorubicin and colchicine. These results indicate that the DNA sequences transferred confer the complete multidrug-resistant phenotype on recipient cells and suggest that multidrug resistance is due to overexpression of the protein encoded by the 5-kilobase mRNA.
Characterization of the proteins purified with monoclonal antibodies to glutamic acid decarboxylase (1988)

Immunoaffinity columns are prepared from the monoclonal antibody (MAb) GAD-1. These columns are used to enrich glutamic acid decarboxylase (GAD) from the cytosolic fraction of rat brain homogenates and from Triton X-100 extracts of the brain membrane fraction. In each case enzyme activity is enriched over 400-fold. The immunopurified fractions were analyzed by SDS-PAGE. Fractions purified from the cytosol consisted of a quantitatively major band of 59 kDa, and one band of 63 kDa, as well as a group centered around 55 kDa. Fractions purified from membranes consisted primarily of the 59 and 63 kDa components; only traces of the lower-molecular-weight components were present. The entire set of proteins purified on GAD-1 immunoaffinity columns is strongly recognized by 2 widely used antisera to GAD, those described in Saito et al. (1974) and Oertel et al. (1981). The 59 kDa protein from the cytosolic fraction was purified to homogeneity by preparative SDS-PAGE; a partial amino acid sequence of this protein was obtained. The 59 kDa protein has a high degree of sequence homology with the deduced amino acid sequence of the protein that was coded for by a cDNA for feline GAD (Kaufman et al., 1986; Kobayashi et al., 1987). Thus, these proteins are either products of a single gene that diverged during the evolution of rat and cat from a common ancestor, or are members of a closely related set of genes found in both species. The MAb GAD-6 recognizes the 59 kDa band and the group of bands centered around 55 kDa on Western blots. Therefore, these proteins are immunochemically related. GAD-6 does not recognize the 63 kDa band. In Western blots of unfractionated homogenates of the whole brain, the only band recognized by GAD-6 is a 59 kDa band.(ABSTRACT TRUNCATED AT 250 WORDS)
Further complexities of the Rh antigen D disclosed by testing category DII cells with monoclonal anti‐D (1993)

The reaction pattern of monoclonal anti-D with category DII cells differed from those of other category D cells. DII cells express epD1, epD2, epD3, epD5, epD6/7 and epD8 but lack epD4 and a new epitope epD9. The new epitope, epD9, is proposed to explain the failure of some monoclonal anti-D (previously considered to be anti-epD3) to react with DII cells.
Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer (2012)

Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion. However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available. In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells. In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic activities of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1. However, it did not exhibit any apparent correlation with MMP-14 expression levels. Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results indicate that ppGalNAc‑T2 may be used as a novel therapeutic target for human gastric cancer treatment.
Genetically Engineered Viral Insecticides (1988)

Baculoviruses play a central role in the natural control of insect pest populations, chiefly Lepidoptera. This has sustained an interest in the commercial potential of these as larvicides in several pest control situations; however, performance drawbacks have limited their general usefulness. Modification of the viruses through genetic engineering is anticipated to greatly increase their effectiveness. How this may be accomplished will be discussed. The effect modifications may have on the well-established safety of these agents as well as their perceived safety will also be covered. Pertinent examples from our work and that of others are discussed.
Effects of platelet-modifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition. (1985)

To resolve questions of drug actions, efficacy, and interactions for platelet-modifying agents used clinically, we have compared the relative capacities and mechanisms of aspirin, dipyridamole, sulfinpyrazone, and dazoxiben to prevent arterial thromboembolism in a baboon model. In 136 studies the agents were given twice daily by oral administration both singly and in combination. The antithrombotic efficacy of a given therapy was determined by its capacity to interrupt steady-state platelet utilization induced by thrombogenic arteriovenous cannulae. When given alone, dipyridamole and sulfinpyrazone reduced the rate at which platelets were utilized by thrombus formation in a dose-dependent manner with essentially complete interruption by dipyridamole at 10 mg/kg per d. In contrast, neither aspirin (2-100 mg/kg per d) nor dazoxiben (20-100 mg/kg per d) decreased cannula platelet consumption detectably despite the striking reduction in the capacity of platelets to produce thromboxane B2. However, aspirin, but not dazoxiben, potentiated the antithrombotic effects of dipyridamole and sulfinpyrazone in a dose-dependent fashion without changing the pharmacokinetics for any of the agents. Complete potentiation required aspirin at 20 mg/kg per d to be given with each dose of dipyridamole. Because dazoxiben's blockade of platelet thromboxane A2 production was not associated with antithrombotic potentiation, and because complete potentiation by aspirin required a dose that fully inhibited vascular production of prostaglandin I2 (PGI2), we conclude that aspirin's potentiating effect on dipyridamole is independent of PGI2 production or inhibition of thromboxane A2 formation. In addition, because frequent repeated and synchronous dosing of aspirin was necessary, aspirin's potentiating effects appear to be produced by mechanism(s) unrelated to its potent, irreversible inhibition of platelet cyclooxygenase.
Electroosmotic Flow Control of Fluids on a Capillary Electrophoresis Microdevice Using an Applied External Voltage (2000)

Independent control of electroosmosis is important for separation science techniques such as capillary zone electrophoresis and for the movement of fluids on microdevices. A capillary electrophoresis microdevice is demonstrated which provides more efficient control of electroosmosis with an applied external voltage field. The device is fabricated in a glass substrate where a 5.0 cm separation channel (30 microm wide) is paralleled with two embedded electrodes positioned 50 microm away in the substrate. With this structure, greatly reduced applied external potentials (< or = 120 V compared to tens of kilovolts) still effectively altered electroosmosis. The efficiency for the control of electroosmosis by the applied external field is improved by approximately 40 times over published values.