gebhart/patrepeval huggingface dataset:
Phase Ia/Ib Trial of Anti-GD2 Chimeric Monoclonal Antibody 14.18 (ch l4.18) and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) in Metastatic Melanoma (1996)

We performed a phase Ia/Ib trial of chimeric anti-GD2 monoclonal antibody 14.18 (ch14.18) in combination with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to determine the maximum tolerated dose as well as immunologic and biologic responses to the regimen. Sixteen patients with metastatic malignant melanoma received escalating doses of ch14.18 (15-60 mg/m2) administered intravenously for 4 h on day 1. Twenty-four hours later, subcutaneous injections of rhGM-CSF were administered daily for a total of 14 days. Significant side effects were related to ch14.18 infusion and consisted of moderate to severe abdominal and/or extremity pain, blood pressure changes, headache, nausea, diarrhea, peripheral nerve dysesthesias, myalgias, and weakness. Dose-limiting toxicity was observed at 60 mg/m2 and consisted of severe hypertension, hypotension, and atrial fibrillation in one patient each, respectively. Significant increases in white blood cell count, granulocyte count, eosinophil count, and monocyte count occurred after rhGM-CSF treatment. Significant enhancement of in vitro and in vivo monocyte and neutrophil tumoricidal activity and antibody-dependent cellular cytotoxicity along with significant elevations in C-reactive protein and neopterin were observed. Despite these immunological and biological changes, no antitumor activity was seen. In short, the combination of ch14.18 and rhGM-CSF resulted in toxicity similar to that observed with ch14.18 alone without improvement in tumor response.
Multilayer Assembly and Patterning of Poly(p-phenylenevinylene)s via Covalent Coupling Reactions (2004)

Poly(p-phenylenevinylene)s with amines and pentafluorophenyl esters on side chains were synthesized and assembled on solid substrates by sequential layer-by-layer (LBL) deposition. This approach enables the creation of robust multilayer thin films via in-situ covalent coupling reactions between successive layers. The buildup of the multilayers was followed by UV/vis absorption spectroscopy and ellipsometry. The observed complex assembly behavior suggests that both covalent and hydrogen-bonding interactions are involved in the formation of multilayer films. The organized structure and surface morphology of resultant multilayers were investigated by reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. This covalent LBL method was further applied to generate conjugated polymer micropatterns using microstamped self-assembled monolayers as templates.
Induction of Glyoxylate Cycle Expression in Caenorhabditis elegans:  A Fasting Response throughout Larval Development (1997)

The mRNA and the bifunctional protein for the two glyoxylate cycle (GC) enzymes, isocitrate lyase and malate synthase, are expressed in a tissue- and stage-specific pattern in Caenorhabditis elegans. Since expression of the two enzymes for the carbon-conserving glyoxylate cycle is regulated by the availability of carbon sources in microorganisms, we have studied the bifunctional GCP gene expression under fasting conditions and in certain mutants of C. elegans in order to understand possible mechanisms regulating its expression during nematode development. The GCP mRNA and protein levels were elevated in early larvae which were never fed, a result consistent with previous enzyme activity measurements (Khan, F.R., & McFadden, B.A. (1982) Exp. Parasitol. 54, 48-54]. However, larvae of later stages also expressed higher levels of GCP mRNA and protein when they were shifted from normal to fasting growing conditions. The GCP expression appeared to be regulated primarily at the transcriptional level throughout development. Although the expression of both the GCP gene and lin-14 peaks at about the same time during development and are induced by fasting, the regulation of the GCP gene is independent of the heterochronic lin-14 control mechanism of postembryonic lineages, as demonstrated by the fact that there was no significant change of the GCP at both mRNA and protein levels in the heterochronic lin-4 (lf) and lin-14 (gf) mutants compared to the wild type.
Absence of detectable hepatitis B virus DNA in sera and liver of chimpanzees with non‐A, non‐B hepatitis (1985)

Abstract The risk of hepatitis B infections has been reduced by screening of blood donors for hepatitis B surface antigen (HBsAg). However, recipients remain at significant risk of developing post‐transfusion hepatitis. Studies have shown that non‐A, non‐B hepatitis virus(es) are responsible for the majority of post‐transfusion hepatitis infections. In spite of many efforts, these non‐A, non‐B hepatitis viruses have not yet been identified. Epidemiological studies, however, suggest that non‐A, non‐B hepatitis shares many features with hepatitis B. Recently, Wands et al [1982] showed, in chimpanzees infected with non‐A, non‐B hepatitis agents, the presence of antigenemia or viremia by radioimmunoassay with monoclonal antibodies directed toward distinct determinants of HBsAg and by molecular hybridization analysis. They suggested that non‐A, non‐B hepatitis agents may be related, but distinct variant(s) of hepatitis B virus (HBV). In this study, five chimpanzees were inoculated with three different agents that have been shown to transmit non‐A, non‐B hepatitis. The following inocula were used (I) a factor VIII preparation kindly provided by D.W. Bradley, (II) acute phase serum from a chimpanzee infected with the F strain kindly provided by A.J. Zuckerman, and (III) a DS‐antigen serum previously shown by us to transmit non‐A, non‐B hepatitis [Duermeyer et al, 1983]. All chimpanzees developed a rise in transaminase levels between 8 and 10 weeks after inoculation. None of the chimpanzees was positive for any markers of HBV infection. No evidence was obtained of infection with hepatitis A, cytomegalovirus, or Epstein‐Barr virus. One chimpanzee developed chronic liver disease. The presence of HBV DNA in sera and in liver biopsies was studied. HBV DNA hybridizable sequences were not detected in any of the samples collected at different stages of the disease. These findings suggest that the non‐A, non‐B hepatitis agents in our study are not related to HBV.
The influence of 3TC-resistance mutations E89G and M184V in the human immunodeficiency virus reverse transcriptase on mispair extension efficiency (1998)

Two nucleoside analog resistance mutations in HIV-1 reverse transcriptase (RT), E89G and M184V, were previously shown to increase the dNTP insertion fidelity of HIV-1 RT. However, forward mutation assays using a lacZ alpha reporter gene have revealed a lack of impact on the overall error rate of these variants. In an effort to investigate the basis for this discrepancy, we have examined whether the increases in misinsertion fidelity observed for E89G and M184V RTs are accompanied by an increase in mispair extension fidelity. The relative efficiencies with which the wild type, E89G, M184V and M184V/E89G HIV-1 RTs extend model template-primer duplexes containing 3'-OH terminal mismatches were measured. The calculated efficiencies of mispair extension ( f ext) were, in general, not significantly decreased from the wild type HIV-1 RT. In fact, the efficiency of extension from one of the mispaired primer-template duplexes was significantly increased for two of the mutants tested. These results suggest that amino acid substitutions that increase the fidelity of dNTP insertion do not necessarily increase misextension fidelity, and that the decreased misextension fidelity may counterbalance the increases in misinsertion fidelity observed for E89G and M184V RTs.
Enzymatic incorporation of a third nucleobase pair (2007)

DNA polymerases are identified that copy a non-standard nucleotide pair joined by a hydrogen bonding pattern different from the patterns joining the dA:T and dG:dC pairs. 6-Amino-5-nitro-3-(1'-beta-D-2'-deoxyribofuranosyl)-2(1H)-pyridone (dZ) implements the non-standard 'small' donor-donor-acceptor (pyDDA) hydrogen bonding pattern. 2-Amino-8-(1'-beta-D-2'-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)-one (dP) implements the 'large' acceptor-acceptor-donor (puAAD) pattern. These nucleobases were designed to present electron density to the minor groove, density hypothesized to help determine specificity for polymerases. Consistent with this hypothesis, both dZTP and dPTP are accepted by many polymerases from both Families A and B. Further, the dZ:dP pair participates in PCR reactions catalyzed by Taq, Vent (exo-) and Deep Vent (exo-) polymerases, with 94.4%, 97.5% and 97.5%, respectively, retention per round. The dZ:dP pair appears to be lost principally via transition to a dC:dG pair. This is consistent with a mechanistic hypothesis that deprotonated dZ (presenting a pyDAA pattern) complements dG (presenting a puADD pattern), while protonated dC (presenting a pyDDA pattern) complements dP (presenting a puAAD pattern). This hypothesis, grounded in the Watson-Crick model for nucleobase pairing, was confirmed by studies of the pH-dependence of mismatching. The dZ:dP pair and these polymerases, should be useful in dynamic architectures for sequencing, molecular-, systems- and synthetic-biology.
Large-scale synthesis of the bifunctional chelating agent 2-(p-nitrobenzyl)-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid, and the determination of its enantiomeric purity by chiral chromatography (1992)

The attachment of radiometals to monoclonal antibodies for medical applications requires extreme stability under physiological conditions, with no significant release of metal. Chelators that can hold radiometals like 111In, 67Ga, and 90Y with high stability under these conditions are essential for radiotherapy or immunoscintigraphy. 2-(p-Nitrobenzyl)-1,4,7,10-tetraazacyclododecane- N,N',N'',N'''-tetraacetic acid (nitrobenzyl-DOTA) is one of the most promising bifunctional chelating agents. A large-scale synthesis of nitrobenzyl-DOTA is described. The overall yield for the nine-step synthesis sequence starting from nitrophenylalanine is 5.6%. Synthesis of nitrobenzyl-DOTA according to the new procedure yields up to approximately 10 g without special apparatus. Both enantiomers of the chiral chelate nitrobenzyl-DOTA have been prepared, and their enantiomeric purity has been checked by chiral chromatography.
Characterization of cytosolic and nuclear glucocorticoid-binding components in human leukemic lymphocytes. (1979)

Abstract Nuclear binding and the physicochemical characteristics of a glucocorticoid-binding component were studied in glucocorticoid-responsive lymphocytes from patients with chronic lymphatic leukemia (CLL). As previously reported from this laboratory for corticoid-sensitive mouse P1798 tumor lymphocytes, 4 mm MgCl2 and 1 mm spermidine released about 60% of [3H]triamcinolone acetonide ([3H]TA) from nuclei isolated from CLL cells that had been incubated with the radioactive steroid at 37°. Ten mm spermidine extracted 90% of [3H]TA from CLL nuclei and in this respect were as effective as was 0.6 m KCl. Agarose gel filtration and glycerol density gradient centrifugation of 0.6 m KCl, 10 mm spermidine, or 4.5 mm MgCl2 extracts of [3H]TA-labeled CLL nuclei revealed that most of the radioactivity in the extract was in the form of a large, asymmetrical macromolecule complex when the protease inhibitors, carbobenzoxy-l-phenylalanine or leupeptin, were included in the extraction buffer. Leupeptin was usually more effective than carbobenzoxy-l-phenylalanine and was therefore the protease inhibitor of choice. The [3H]TA complex had an apparent molecular weight of 90,000 to 96,000, a sedimentation coefficient of 3.7S, and a Stokes radius of 56 to 60 A, corresponding to a frictional ratio of 1.8 and an axial ratio (prolate ellipsoid) of 15. When protection against cleavage was inadequate, a variable amount of 35 A material was detected by agarose gel filtration, associated with decreased recovery of the 56 to 60 A complex. Cytosolic [3H]TA binding components isolated from CLL lymphocytes incubated with [3H]TA at 4° were indistinguishable by agarose gel filtration and glycerol density gradient centrifugation from nuclear-associated [3H]TA macromolecule complexes in cells that were labeled at 37°. The Stokes radius and sedimentation coefficient of nuclear glucocorticoid-binding components from cells labeled with [3H]dexamethasone were identical to the values characteristic of nuclear-associated [3H]TA-macromolecule complexes. This observation, together with the results of Scatchard analysis of nuclear binding data and of competition experiments, suggested that [3H]TA and [3H]dexamethasone interacted with the same class(es) of binding sites in CLL lymphocytes. However, [3H]dexamethasone complexes appeared to be less stable than [3H]TA complexes, as indicated by the considerable dissociation of [3H]dexamethasone but not of [3H]TA during agarose gel filtration and glycerol density gradient centrifugation. Our results raise the possibility that a large, asymmetrical glucocorticoid-binding component that can be readily extracted from nuclei with millimolar concentrations of divalent or polyvalent cations may be required for steroid action on human malignant lymphocytes.
Materialized Sample Views for Database Approximation (2008)

We consider the problem of creating a sample view of a database table. A sample view is an indexed materialized view that permits efficient sampling from an arbitrary range query over the view. Such "sample views" are very useful in applications that require random samples from a database: approximate query processing, online aggregation, data mining, and randomized algorithms are a few examples. Our core technical contribution is a new file organization called the appendability, combinability, and exponentiality (ACE) tree that is suitable for organizing and indexing a sample view. One of the most important aspects of the ACE tree is that it supports online random sampling from the view. That is, at all times, the set of records returned by the ACE tree constitutes a statistically random sample of the database records satisfying the relational selection predicate over the view. Our paper presents experimental results that demonstrate the utility of the ACE tree.
Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells (2003)

CD4+CD25+ regulatory T (TR) cells have been described in both humans and mice. In mice, TR are thymically derived, and lack of TR leads to organ-specific autoimmunity. Recently, the forkhead/winged helix transcription factor, FoxP3, has been shown to be important for the function of TR cells in mice. In this study, human TR cells were examined and, in results similar to those of studies done in mice, expression of FoxP3 was found exclusively in CD4+CD25+ T cells and correlated with the suppressive activity of these cells. In contrast to the mouse studies, activation of human CD4+CD25- T cells led to expression of FoxP3. Expression of FoxP3 in activated human CD4+CD25+ cells also correlated with suppression of proliferation by these cells in freshly isolated CD4+CD25- T cells from the same donor. This suppression was cell-contact dependent and cytokine independent. Thus, in humans, during activation of CD4+CD25- T cells in an immune response, two populations of cells may arise, effector CD4+CD25+ and regulatory CD4+CD25+ T cells, with expression of FoxP3 correlated with regulatory activity. These data also raise the possibility that a failure to generate peripheral TR cells properly may contribute to autoimmune disease and suggest a possible therapeutic role for FoxP3 in the treatment of such diseases.
The Determination of the Membrane Potential of Chlorella vulgaris. Evidence for Electrogenic Sugar Transport (1976)

From data on the accumulation of tetraphenylphosphonium within Chlorella vulgaris cells, it can be estimated that these cells possess a membrane potential of −120 to −I50 mV (inside negative). Under anaerobic conditions as well as in the presence of uncoupling agents the membrane potential drops to about −60 to −80 mV. Nystatin (50 μg/ml) abolishes it almost completely. Since it took more than 1 h before the tetraphenylphosphonium equilibrium was reached, this method could not be used to measure relatively fast transient changes in membrane potential. However, the rate of influx of tetraphenylphosphonium is also directly dependent on membrane potential and can be followed within minutes. Using this phenomenon as an indicator for membrane potential a brief transient depolarisation was detected after the addition of sugars taken up by Chlorella via the proton cotransport system. The depolarisation was absent from cells not induced for sugar uptake and induced cells did not show it with substances not transported, like mannitol. The maximal depolarisation observed amounted to about 70 mV; after 1 min, however, the membrane potential returned to a value about 25 mV less negative than the one before sugar was added. The results demonstrate that sugar uptake in Chlorella is electrogenie. The ΔpH plus membrane potential measured for Chlorella completely cover the energy required to explain the 1600-fold accumulation of' 6-deoxyglucose experimentally observed.
Origins of conjugated triene fatty acids. The biosynthesis of calendic acid by Calendula officinalis (1984)

Results from isotopic and incorporation experiments are consistent with formation of calendic acid form linoleic acid via a rearranged allyl radical, with loss of a hydrogen atom; since appropriate 9-hydroxy- and 9-hydroperoxy-diene acids were not converted into calendic acid by marigold seed homogenate, an elimination mechanism for formation of the 8(E)-double bond is not supported.
IQ-TREE: A Fast and Effective Stochastic Algorithm for Estimating Maximum-Likelihood Phylogenies (2014)

Large phylogenomics data sets require fast tree inference methods, especially for maximum-likelihood (ML) phylogenies. Fast programs exist, but due to inherent heuristics to find optimal trees, it is not clear whether the best tree is found. Thus, there is need for additional approaches that employ different search strategies to find ML trees and that are at the same time as fast as currently available ML programs. We show that a combination of hill-climbing approaches and a stochastic perturbation method can be time-efficiently implemented. If we allow the same CPU time as RAxML and PhyML, then our software IQ-TREE found higher likelihoods between 62.2% and 87.1% of the studied alignments, thus efficiently exploring the tree-space. If we use the IQ-TREE stopping rule, RAxML and PhyML are faster in 75.7% and 47.1% of the DNA alignments and 42.2% and 100% of the protein alignments, respectively. However, the range of obtaining higher likelihoods with IQ-TREE improves to 73.3-97.1%. IQ-TREE is freely available at http://www.cibiv.at/software/iqtree.
Activation of the MAPK Signal Cascade by the Neural Cell Adhesion Molecule L1 Requires L1 Internalization (1999)

L1-mediated axon growth involves intracellular signaling, but the precise mechanisms involved are not yet clear. We report a role for the mitogen-activated protein kinase (MAPK) cascade in L1 signaling. L1 physically associates with the MAPK cascade components Raf-1, ERK2, and the previously identified p90(rsk) in brain. In vitro, ERK2 can phosphorylate L1 at Ser(1204) and Ser(1248) of the L1 cytoplasmic domain. These two serines are conserved in the L1 family of cell adhesion molecules, also being found in neurofascin and NrCAM. The ability of ERK2 to phosphorylate L1 suggests that L1 signaling could directly regulate L1 function by phosphorylation of the L1 cytoplasmic domain. In L1-expressing 3T3 cells, L1 cross-linking can activate ERK2. Remarkably, the activated ERK localizes with endocytosed vesicular L1 rather than cell surface L1, indicating that L1 internalization and signaling are coupled. Inhibition of L1 internalization with dominant-negative dynamin prevents activation of ERK. These results show that L1-generated signals activate the MAPK cascade in a manner most likely to be important in regulating L1 intracellular trafficking.
Effects of Age on Testicular Function and Consequences of Testosterone Treatment1 (2001)

Testosterone and gonadotropins. Several studies demonstrate that the serum testosterone concentration declines with increasing age. In one cross-sectional study of 83 healthy men, the free testosterone concentration declined by age 80 to approximately 40% of that at age 20, but because the serum concentration of sex hormone binding globulin (SHBG) increased during this age span, the serum concentration of total testosterone declined only to approximately 80% of that at age 20 (1). In another cross-sectional study of 71 healthy men, aged 26–90 yr, living in similar circumstances, the 33 younger men had a mean free testosterone concentration of 10.7 6 3.4 ng/dL (sd) and the 38 older men had a mean free testosterone concentration of 5.8 ng/dL (P , 0.01) (2). Total serum testosterone concentrations in the two groups were 659 6 201 ng/dL and 490 6 160 ng/dL, respectively (P , 0.01). In a third cross-sectional study in 810 healthy men mostly between 50 and 84 yr old, the serum bioavailable testosterone concentration declined by approximately 55– 60%, but the serum total testosterone concentration did not decline at all (3). In one longitudinal study, 39 healthy men whose mean serum total testosterone concentration was 633 6 22 ng/dL (se) when they enrolled in a study of aging in 1980 had a mean value of 464 6 33 ng/dL in 1994 (4). In another longitudinal study of 890 men, both total testosterone and the ratio of testosterone to SHBG decreased with age (Fig. 1) (5). The decline in testicular function appears to involve a combination of primary and secondary hypogonadism. A gradual increase in the serum concentration of LH indicates a degree of primary hypogonadism. In a cross-sectional study, the mean serum LH concentration in 33 men of an average age of 37 yr was 1.9 6 0.6 ng/mL and in 38 men of an average age of 71 yr was 2.2 6 0.6 ng/mL (2). In a longitudinal study, 39 men whose mean LH was 9.4 6 0.4 (se) mIU/mL when they enrolled in 1980 had a mean value of 13.7 6 1.3 mIU/mL in 1994 (4). However, the findings that LH secretory burst amplitude decreases with increasing age and that this decrease was the most prominent determinant of decreased testosterone secretion indicates a degree of secondary hypogonadism (6). This conclusion is supported by the failure of LH secretion to respond to drug-induced reduction of the serum testosterone concentration in old men as well as in young men (7).