gebhart/patrepeval huggingface dataset:
EGFR blockade by tyrosine kinase inhibitor or monoclonal antibody inhibits growth, directs terminal differentiation and induces apoptosis in the human squamous cell carcinoma HN5. (1998)

Human squamous cell carcinomas frequently overexpress the epidermal growth factor receptor (EGFR) and this is often associated with poor prognosis in patients with these cancers. The high level of expression of the EGFR provides an important target for therapy and we and others have shown that monoclonal antibodies (mAbs) which block the activation of the receptor by the EGF family of ligands inhibit the growth of EGFR overexpressing tumours in vitro and induce the regression of established tumours grown as xenografts in athymic mice. Inhibitors of the tyrosine kinase associated with the EGFR have also been shown to block receptor activation and prevent tumour cell proliferation. Using the EGFR-overexpressing head and neck carcinoma cell line HN5, we have compared the biological consequences of treatment with an inhibitor of EGFR tyrosine kinase (PD153035) with anti-EGFR monoclonal antibodies (mAbs) ICR63 or ICR80. We found that both the anti-EGFR mAbs and the TK inhibitor produce similar biological changes namely, they inhibit the EGF and TGFá-induced tyrosine phosphorylation of the receptor and the growth in culture of HN5 cells. At concentrations above 100 nM, the TK inhibitor prevented the growth in culture of HN5 cells completely with an IC50 of 40 nM. With the anti-EGFR mAbs, growth of HN5 cells was inhibited completely at concentrations above 4 nM with an IC50 of 1 nM. More importantly we found that, like the anti-EGFR mAbs, treatment with the TK inhibitor directs HN5 cells to undergo terminal differentiation as monitored by the expression of cytokeratin 10. In addition, our results indicate that the growth inhibitory effects of the anti-EGFR agents also lead to induction of apoptosis as determined by 7-amino actinomycin D staining (7-AAD). We conclude that EGFR blockade by anti-EGFR mAbs or TK inhibitor influences the growth in culture of EGFR overexpressing tumours by directing terminal differentiation and inducing apoptosis.
Identification of macrophage migration inhibitory factor (MIF) in human skin and its immunohistochemical localization (1996)

The presence and tissue localization of macrophage migration inhibitory factor (MIF) in human skin were examined. Reverse transcription‐polymerase chain reaction analysis revealed that MIF mRNA was expressed in both surgically obtained normal human epidermis and primary cultured human keratinocytes. The expression of MIF was further confirmed by Western blot analysis, which demonstrated a single band at about 12.5 kDa using a polyclonal antibody against human recombinant MIF. Immunohistochemical studies showed that MIF existed in human epidermis, especially in the basal layer. The pathophysiological role of MIF in human skin remains undefined; however, the present results indicate that MIF may play an important role in immunity, inflammation and cellular differentiation of epidermal cells.
Insecticidal Activity and Lectin Homology of Arcelin Seed Protein (1988)

Arcelin, a major seed protein discovered in wild beans (Phaseolus vulgaris), has toxic effects on an important bean bruchid pest, Zabrotes subfasciatus. Transfer of the arcelin-1 allele to bean cultivars and addition of purified arcelin to artificial seeds results in high levels of insect resistance. The nucleotide and derived amino acid sequences of the arcelin-1 complementary DNA are very similar to those of genes encoding the bean seed lectin, phytohemagglutinin. The gene or genes encoding arcelin may have evolved from a phytohemagglutinin gene or genes resulting in an effective mechanism for resistance to bean bruchids.
Cytochrome P450 in rat astrocytes in vivo and in vitro: Intracellular localization and induction by phenytoin (1994)

Cytochrome P450IIB1,2 (nomenclature according to Nelson et al., DNA Cell Biol 12:1-51, 1993 and Volk et al., Neuroscience 42:215-235, 1991) immunoreactivity (P450-IR) is associated with astrocytes both in vivo and in vitro. Although they are unevenly distributed throughout the brain with a preference for phylogenetically elder parts, no significant differences between astrocytes prepared from different brain regions were observed in astrocyte cultures. The percentage of strongly immunoreactive astrocytes decreased from 40% after 7 days in culture to 15% after 21 days. Essentially all astrocytes have a low but significant P450-IR within this interval. Preembedding immunoelectron microscopy revealed peroxidase reaction products on the endoplasmic reticulum and on the outer membranes of mitochondrial and nuclear envelopes. Phenytoin (1 microM) added to the medium for 7 days significantly (1.22-fold) increased the amount of total P450 in astrocyte homogenates as measured by spectrophotometry. Considerably more immunoreactive cells (1.5-fold) were found in treated cultures than in controls.
Lack of Expression of Thy-1 (CD90) on Acute Myeloid Leukemia Cells With Long-Term Proliferative Ability In Vitro and In Vivo (1997)

Acute myeloid leukaemia (AML) is thought to be maintained by a small population of leukemic progenitor cells. To define the phenotype of such cells with long-term proliferative capacity in vitro and in vivo, we have used the production of leukemic clonogenic cells (CFU) after 2 to 8 weeks in suspension culture as a measure of these cells in vitro and compared their phenotype with that of cells capable of engrafting nonobese diabetic severe combined immune deficient (NOD/SCID) mice. Leukemic blast peripheral blood cells were evaluated for expression of CD34 and Thy-1 (CD90) antigens. The majority of AML blast cells at diagnosis lacked expression of Thy-1. Most primary CFU-blast and the CFU detected at up to 8 weeks from suspension cultures were CD34+/Thy-1-. AML cells that were capable of engrafting NOD/SCID mice were also found to have the CD34+/Thy-1- phenotype. However, significant engraftment was achieved using both CD34+/Thy-1- and CD34- subfractions from one AML M5 patient. These results suggest that while heterogeneity exists between individual patients, the leukemic progenitor cells that are capable of maintaining the disease in vitro and in vivo differ from normal hematopoietic progenitor cells in their lack of expression of Thy-1.
Trapping Silicon Surface-Based Radicals (2006)

The spontaneous one-electron reduction of diazonium salts on hydride-terminated porous silicon (pSi) and flat silicon produces surface radicals that can be trapped chemically. These silicon radicals react with reagents such as alkyl/arylselenoethers, alkenes, alkynes, and alkylbromide groups to generate covalently bound functionalities in a manner analogous to the chemistry of molecular-based silicon radical species, prepared via different methods. When pSi is exposed to an acetonitrile solution of any of the three diazonium salts examined in this study, aryl groups from the diazonium precursor become covalently bound and significant oxidation is noted; if, however, a reactive trapping agent is added, such as an alkyl/arylselenoether or a carbon-carbon unsaturated bond, no aryl group attachment is observed and oxidation is circumvented due to the efficiency of the trapping chemistry. The reactions proceed rapidly, in less than 3 h to maximum coverage, at room temperature. The diazonium salt-initiated radical reaction with alpha,omega-alkenes and alkynes tolerates various functional groups including aryl, diene, diyne, carboxylic acid, and hydroxyl, reacting exclusively via the carbon-carbon unsaturated bond; alpha,omega-bromoalkenes are not, however, compatible with this chemistry. A silicon-based molecule, tris(trimethylsilyl)silane, in the presence of a diazonium salt initiator and a primary alkyne does not lead to the hydrosilylation product but to tris(trimethylsilyl)silylbromide and the hydrogenated arene, derived from the diazonium. The difference in reactivity between the molecule and the surface is due to the fact that the silicon surface is a source of electrons to reduce the diazonium salts to aryl radicals, whereas a heterolytic pathway is followed in the molecular silane case.
KRAFT AND MODIFIED KRAFT PULPING OF BAMBOO (PHYLLOSTACHYS BAMBUSOIDES) (2017)

Delignification of bamboo (Phyllostachys bambusoides) grown in the Eastern Black Sea region of Turkey was carried out by kraft, kraft-anthraquinone (AQ) and kraft-sodium borohydride (NaBH4) pulping under a variety of conditions to determine the effect of AQ, NaBH4 and cooking parameters on pulp and paper properties such as yield, kappa number, viscosity, and strength properties. The chemical composition and fibre dimensions of the cell wall of Phyllostachys bambusoides culm fibres were also investigated. The analysed data revealed the following optimum krafi pulping conditions: Active alkali, 16% (as Na2O); NaBH4, 0.3%; AQ, 0.1%; and cooking time, 90 min. The modified kraft method with 0.1% AQ was found to provide better pulp properties than those with 0.3% NaBH4. Increasing the thickness of chip used in cooking from 2.0 mm to 4.0 mm increase the yield. The optimum cooking conditions of Phyllostachys bambusoides modified krafi pulps were found to be: screened yield, 48.1%; reject ratio, 0.53%; kappa number; 24.1; viscosity, 1210 ml/g; breaking length, 6.05 kin; burst index, 5.08 kPa m(2)/g; tearing index, 4.99 mNm(2)/g; brightness 20.35%.
Regulation of the c-jun Gene in p210 BCR-ABL Transformed Cells Corresponds With Activity of JNK, the c-jun N-Terminal Kinase (1998)

Activity of the c-jun N-terminal kinase (JNK) has been shown in hematopoietic cells transformed by p210 BCR-ABL. However, analysis has not been reported for hematopoietic cells on the consequences of this activity for c-jun promoter regulation within its distinctive proximal 8-base consensus CRE-like element, an element linked to JNK-mediated increase in c-jun transcription. In the present study, regulation of the proximal c-jun promoter was studied in murine myeloid cells transformed by p210 BCR-ABL. Promoter regulation in p210 BCR-ABL transformed cells was compared with regulation of the promoter in nontransformed interleukin-3 (IL-3)–dependent parental cells. The composition of nuclear AP-1 proteins contained within cells with p210 BCR-ABL, and their binding to the c-jun promoter proximal CRE-like element, was compared with the composition and binding of AP-1 proteins in IL-3–treated parental cells without p210 BCR-ABL. The present analysis found fivefold increased c-jun transcription occurring in p210 BCR-ABL transformed murine myeloid cells possessing a corresponding magnitude of increased kinase activity of JNK, compared with IL-3–stimulated parental cells. Augmented JNK activity was accompanied by increased nuclear abundance of c-jun and c-fos proteins that bound specifically to the proximal c-jun promoter CRE element. Also, representative human leukemic cell lines expressing p210 BCR-ABL and possessing abundant kinase activity of JNK, when compared with parental cells that were deficient in JNK activity, had increased c-jun and c-fosproteins. Finally, to show the relevance of these observations in model systems, we studied blast cells from patients with Philadelphia chromosome–positive acute leukemic transformation, and observed comparable activities of JNK catalysis and c-jun/AP-1 protein relative to the cell lines that possessed p210 BCR-ABL and JNK activity. These studies provide a basis for investigating the set of downstream genes which augmented c-jun/AP-1 activity enlists in the process of transformation by p210 BCR-ABL.
Progress in fluoroalkylation of organic compounds via sulfinatodehalogenation initiation system (2012)

The sulfinatodehalogenation reaction represents one of the most important methodologies to incorporate fluorine into organic molecules. Using inexpensive sulfur-containing reactants such as Na(2)S(2)O(4) under mild conditions, per- and polyfluoroalkyl halides (R(F)X, X = Br, I, CCl(3)) can be transformed smoothly into the corresponding sulfinate salts. This method is also used for the perfluoroalkylation of alkenes, dienes, alkynes and aromatics. Notably, after 1998, the sulfinatodehalogenation of perfluoroalkyl chlorides (R(F)Cl) has been realized by using dimethylsulfoxide (DMSO) as a solvent instead of CH(3)CN/H(2)O in the Na(2)S(2)O(4)/NaHCO(3) initiation system. Perfluoroalkyl chlorides, ethyl chlorofluoroacetates and chlorodifluoroacetates, and even nonfluorinated compounds, such as ethyl chloro- or dichloroacetates and chloroform, were either converted into the corresponding sulfinate salts or alkylated alkenes, alkynes and aromatics (including porphyrins). The sulfinatodehalogenation reaction has remarkable advantages. With the increasing demands to utilize the unique properties of fluorine and fluorinated functional groups in medicinal, agricultural and material sciences, we believe that there will continue to be useful developments in sulfinatodehalogenation chemistry and it will be applied more widely in the future.
Inhibition of Corneal Neovascularization by Genetic Ablation of CCR2 (2003)

Development of corneal neovascularization is inhibited in CCR2-deficient mice.
Glucolipsin A and B, Two New Glucokinase Activators Produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii. (1999)

During the screening of the natural products for their ability to increase the activity of glucokinase by relieving inhibition by long chain fatty acyl CoA esters (FAC), two novel compounds, glucolipsin A (1) and B (2) were isolated from the butanol extracts of Streptomyces purpurogeniscleroticus WC71634 and Nocardia vaccinii WC65712, respectively. The structures of these two compounds were established by spectroscopic methods and chemical degradation. Glucolipsin A (1) and B (2) relieved the inhibition of glucokinase by FAC with RC50 values of 5.4 and 4.6 microM.
A Prospective Study of the Accuracy of the Surgeonʼs Diagnosis and Significance of Positive Margins in Nonmelanoma Skin Cancers (2001)

Even with a precise preoperative diagnosis, complete excision of nonmelanoma skin cancer is not always achieved. The conundrum remains the decision for appropriate secondary treatment. Many surgeons, regardless of the nature of the lesion, consider re-excision to be the only option. In a prior 4-year prospective study that ascertained the accuracy of our clinical diagnosis of skin lesions removed in an office setting, one-fifth were found to be malignant and 98 percent (n = 415) of the lesions were nonmelanoma skin cancer. Unfortunately, 65 (15.7 percent) of the malignant nonmelanoma skin cancer lesions had positive margins. The outcome of our management for these specific lesions was followed prospectively over the 7.5 years of this study to determine whether aggressive surgical intervention was justified in every case. Of 65 patients with lesions, early and complete re-excision of margin-positive nonmelanoma skin cancer was performed for 34 (52.3 percent), with residual tumor found in 11 (32.4 percent), followed by a later recurrence in one (2.9 percent). The remaining 31 patients agreed to semiannual office visits, with one (3.2 percent) recurrence in this group. Thus, the overall rate of recurrence for margin-positive nonmelanoma skin cancer was 3.1 percent, with a mean follow-up of 3.6 years (range, 0 to 7.5 years). There were no recurrences for basal cell carcinoma in either treatment group, suggesting that, at least for "simple" primary lesions without confounding risk factors, there is some validity to a "wait and see" attitude, in which treatment of a potential recurrence would be straightforward. Despite our observed infrequent local recurrences of squamous cell cancers (13.3 percent), the small risk of metastases still suggests the appropriateness of complete surgical eradication for these tumors whenever feasible.
Isocitrate Dehydrogenase 1 and 2 Mutations in Cancer: Alterations at a Crossroads of Cellular Metabolism (2010)

Dysregulation of metabolism is a common phenomenon in cancer cells. The NADP+-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) function at a crossroads of cellular metabolism in lipid synthesis, cellular defense against oxidative stress, oxidative respiration, and oxygen-sensing signal transduction. We review the normal functions of the encoded enzymes, frequent mutations of &lt;it&gt;IDH1&lt;/it&gt; and &lt;it&gt;IDH2&lt;/it&gt; recently found in human cancers, and possible roles for the mutated enzymes in human disease. &lt;it&gt;IDH1&lt;/it&gt; and &lt;it&gt;IDH2&lt;/it&gt; mutations occur frequently in some types of World Health Organization grades 2–4 gliomas and in acute myeloid leukemias with normal karyotype. &lt;it&gt;IDH1&lt;/it&gt; and &lt;it&gt;IDH2&lt;/it&gt; mutations are remarkably specific to codons that encode conserved functionally important arginines in the active site of each enzyme. To date, all &lt;it&gt;IDH1&lt;/it&gt; mutations have been identified at the Arg132 codon. Mutations in &lt;it&gt;IDH2&lt;/it&gt; have been identified at the Arg140 codon, as well as at Arg172, which is aligned with &lt;it&gt;IDH1&lt;/it&gt; Arg132. &lt;it&gt;IDH1&lt;/it&gt; and &lt;it&gt;IDH2&lt;/it&gt; mutations are usually heterozygous in cancer, and they appear to confer a neomorphic enzyme activity for the enzymes to catalyze the production of &lt;scp&gt;d&lt;/scp&gt;-2-hydroxyglutarate. Study of alterations in these metabolic enzymes may provide insights into the metabolism of cancer cells and uncover novel avenues for development of anticancer therapeutics.
Improving Twitter Sentiment Analysis with Topic-Based Mixture Modeling and Semi-Supervised Training (2014)

In this paper, we present multiple approaches to improve sentiment analysis on Twitter data. We first establish a state-of-the-art baseline with a rich feature set. Then we build a topic-based sentiment mixture model with topic-specific data in a semi-supervised training framework. The topic information is generated through topic modeling based on an efficient implementation of Latent Dirichlet Allocation (LDA). The proposed sentiment model outperforms the top system in the task of Sentiment Analysis in Twitter in SemEval-2013 in terms of averaged F scores.
Structurally intact (78-kDa) forms of maternal lactoferrin purified from urine of preterm infants fed human milk: identification of a trypsin-like proteolytic cleavage event in vivo that does not result in fragment dissociation. (1991)

Two forms of lactoferrin, an intact lactoferrin and a "nicked" but apparently intact (i.e., 78-kDa) form, have been isolated from the urine of preterm infants fed human milk. These two forms of lactoferrin, demonstrated to be entirely of maternal origin, were copurified using affinity columns of immobilized single-stranded DNA-agarose. The relative concentrations of the intact lactoferrin and the "nicked" lactoferrin were determined after denaturation and separation by reverse-phase HPLC. N-terminal sequence analyses showed that the intact 78-kDa form had lost two residues from its N terminus. The nicked 78-kDa form was composed of only two fragments; one fragment was identified as the N terminus of the N-lobe (residues 3-283). The other fragment started with Ser-284 and included the alpha-helical structures at the C terminus of the N-lobe, as well as the entire C-lobe. Although no disulfide bonds connect these two fragments, they were tightly associated in vivo and were not separated in vitro except under denaturing conditions. Limited in vitro digestion of human milk lactoferrin with trypsin produced a nicked, but stable (78-kDa), form of DNA-binding lactoferrin nearly indistinguishable from the isolated urinary lactoferrin, except for the absence of one additional arginine residue at the N terminus of the N-lobe. Residues involved in the stable molecular interaction between fragments were evaluated using data obtained from the high-resolution crystal structure of hololactoferrin. Two features, entirely within the N-lobe, account for the lack of fragment dissociation after cleavage at residue 283 in vivo: an extensive interface at the hinge region behind the iron-binding cleft and an "anchor" sequence traversing the remainder of the N-lobe at 90 degrees relative to the fragment interface. These results document the remarkably limited degradation of absorbed lactoferrin in vivo and suggest that iron-binding activity, receptor-binding properties, and postulated immune cell regulatory functions remain intact.
Competitive RNA templates for detection and quantitation of growth factors, cytokines, extracellular matrix components and matrix metalloproteinases by RT-PCR. (1996)

Detection of low-abundance mRNAs by reverse transcription-polymerase chain reaction (RT-PCR) has become a standard technique to determine gene expression by tissues and cells in culture. The ability to determine relative or absolute copy number of specific mRNAs has been difficult due to inadequate internal standards to control for sample-to-sample variation. The use of a synthetic RNA standard with identical sequences to the PCR primers allows reproducible quantitation between samples and assays. By designing multi-sequence templates, several specific mRNAs can be quantitated using a single template. Addition of multiple templates to a single RT reaction allows the quantitation of a large number of targets from as little as 4 micrograms of total RNA. In this report, we present a series of seven primer/template systems to detect and quantitate 52 specific messages, including 26 growth factors and receptors, 8 extracellular matrix components, 10 matrix-modifying enzymes and their inhibitors and 8 cytokines.
A second major class of Alu family repeated DNA sequences in a primate genome (1983)

We have analyzed repetitive DNA sequences in a prosimian, Galago crassicaudatus, and found that there are two distinct, highly repetitive families of sequences related to the human Alu family. The Type I family is closely analogous to the human Alu Family. The Type II family of repeats, which appears to be present in higher copy number, has a right half that is almost identical to the Type I family. However, the left half of the Type II sequence shows only limited homology to the galago Type I or human Alu families. A comparison of homologous sequences in the left half indicated that they are centered in regions of the Alu family which function as RNA polymerase III promoters. We have also observed at least one example of a Type II left half that was integrated into the genome independent of the Alu family right half sequence. The Type II family appears to be of much more recent evolutionary origin than the Type I and may have arisen by the independent integration of a RNA polymerase III promoter adjacent to the right half of a Type I Alu family sequence.
A Novel Binding Site in Collagen Type III for Integrins α1β1 and α2β1 (2005)

Previously identified high affinity integrin-binding motifs in collagens, GFOGER and GLOGER, are not present in type III collagen. Here, we first characterized the binding of recombinant I domains from integrins alpha(1) and alpha(2) (alpha(1)I and alpha(2)I) to fibrillar collagen types I-III and showed that each I domain bound to the three types of collagens with similar affinities. Using rotary shadowing followed by electron microscopy, we identified a high affinity binding region in human type III collagen recognized by alpha(1)I and alpha(2)I. Examination of the region revealed the presence of two sequences that contain the critical GER motif, GROGER and GAOGER. Collagen-like peptides containing these two motifs were synthesized, and their triple helical nature was confirmed by circular dichroism spectroscopy. Experiments show that the GROGER-containing peptide was able to bind both alpha(1)I and alpha(2)I with high affinity and effectively inhibit the binding of alpha(1)I and alpha(2)I to type III and I collagens, whereas the GAOGER-containing peptide was considerably less effective. Furthermore, the GROGER-containing peptide supported adhesion of human lung fibroblast cells when coated on a culture dish. Thus, we have identified a novel high affinity binding sequence for the collagen-binding integrin I domains.