gebhart/patrepeval huggingface dataset:
Liver X receptor activation induces apoptosis of melanoma cell through caspase pathway (2014)

Liver X receptors (LXRs) are nuclear receptors that function as ligand-activated transcription factors regulating lipid metabolism and inflammation. Recent discoveries found LXRs could regulate tumor growth in a variety of cancer cell lines. In this study, we investigated the effect of LXR activation on melanoma cell proliferation and apoptosis both in vitro and in vivo. Treatment of B16F10 and A-375 melanoma cells with synthetic LXR agonist T0901317 significantly inhibited the proliferation of melanoma cells in vitro. Meanwhile, T0901317 induced the apoptosis of B16F10 melanoma cells in a dose-dependent manner. Furthermore, western blot assay showed that the pro-apoptotic effect of T0901317 on B16F10 melanoma cells was mediated through caspase-3 pathway. Oral administration of T0901317 inhibited the growth of B16F10 melanoma in C56BL/6 mice. Altogether, this study demonstrates the critical role of LXRs in the regulation of melanoma growth and presents the LXR agonist T0901317 as a potential anti-melanoma agent.
Induction of Cell Cycle Progression and Acceleration of Apoptosis Are Two Separable Functions of c-Myc: Transrepression Correlates with Acceleration of Apoptosis (2000)

Analysis of amino-terminus mutants of c-Myc has allowed a systematic study of the interrelationship between Myc's ability to regulate transcription and its apoptotic, proliferative, and transforming functions. First, we have found that c-Myc-accelerated apoptosis does not directly correlate with its ability to transactivate transcription using the endogenous ornithine decarboxylase (ODC) gene as readout for transactivation. Furthermore, deletion of the conserved c-Myc box I domain implicated in transactivation does not inhibit apoptosis. Second, the ability of c-Myc to repress transcription, using the gadd45 gene as a readout, correlates with its ability to accelerate apoptosis. A conserved region of c-Myc implicated in mediating transrepression is absolutely required for c-Myc-accelerated apoptosis. Third, a lymphoma-derived Thr58Ala mutation diminishes c-Myc-accelerated apoptosis through a decreased ability to induce the release of cytochrome c from mitochondria. This mutation in a potential phosphorylation site does not affect cell cycle progression, providing genetic evidence that induction of cell cycle progression and acceleration of apoptosis are two separable functions of c-Myc. Finally, we show that the increased ability of Thr58Ala mutant to elicit cellular transformation correlates with its diminished ability to accelerate apoptosis. Bcl-2 overexpression blocked and the lymphoma-associated Thr58Ala mutation decreased c-Myc-accelerated apoptosis, and both led to a significant increase in the ability of Rat1a cells to form colonies in soft agar. This enhanced transformation was greater in soft agar containing a low concentration of serum, suggesting that protection from apoptosis is a mechanism contributing to the increased ability of these cells to proliferate in suspension. Thus, we show here for the first time that, in addition to mutations in complementary antiapoptotic genes, c-Myc itself can acquire mutations that potentiate neoplastic transformation by affecting apoptosis independently of cell cycle progression.
Transformation of Balb 3T3 cells by the BNLF-1 gene of Epstein-Barr virus. (1988)

The BNLF-1 protein is the only non-nuclear Epstein-Barr virus (EBV) encoded protein that has been detected in B-lymphocytes immortalized by EBV. We demonstrate that the BNLF-1 gene induces anchorage-independent growth and tumorigenic transformation of the murine cell-line, Balb/3T3. This demonstration extends the earlier observation that the BNLF-1 gene can transform Rat-1 cells. In addition we find that the BNLF-1 protein is located in the particulate fraction of cells, is phosphorylated, and is turned over with a half-life of 2.0 to 3.5 h in the BNLF-1 transformed Balb/3T3 cells, just as it is in EBV-genome-positive B-cell-lines.
Rat monoclonal antibodies to the external domain of the product of the C‐erbB‐2 proto‐oncogene (1990)

With the breast carcinoma cell line BT 474 used as a source of antigen, four rat monoclonal antibodies (MAbs) (3 IgG2a and I IgA) have been prepared against the external domain of the product of the c-erbB-2 proto-oncogene. All 4 antibodies stain frozen sections of tissues that over-express the product of the c-erbB-2 proto-oncogene, and competitive binding assays showed that the antibodies recognized 2 non-overlapping epitopes. Representative antibodies from the two groups (ICR12 and 13) were shown to specifically immunoprecipitate a 190 kDa protein from 35S-methionine-labelled breast carcinoma cells where the c-erbB-2 is amplified (BT 474 and MDA-MB 361). Two of the antibodies (ICR12 and ICR17) bind to the denatured antigen in Western blots and ICR12 stains formolsaline-fixed sections of breast carcinoma tissue that over-expresses the product of the c-erbB-2 proto-oncogene. These antibodies should be useful not only for immunocytochemical diagnoses but also for radio-immunoscintigraphic and therapeutic applications.
Transforming Growth Factor β–Activated Kinase 1 Signaling Pathway Critically Regulates Myocardial Survival and Remodeling (2014)

These results indicate that TAK1 functions as a key survival factor in the heart by directly antagonizing necroptosis, which is critical for the maintenance of myocardial homeostasis and the prevention of adverse myocardial remodeling.
The Perception of Speech and Its Relation to Telephony (1950)

The intelligibility of the speech received over a communication system is usually expressed in terms of one or another measure such as the vowel or the consonant articulation, the average speech sound articulation, the syllable articulation, the word articulation, or the sentence intelligibility. The present paper establishes relationships among several of these measures and the articulation index. Relationships based upon statistical considerations are compared with the results of observations. Functions are developed which permit the calculation of articulation index and hence of articulation for communication systems which include a wide variety of response versus frequency characteristics and of noise conditions, as well as several special types of distortion. Although the treatment is predominantly empirical, the functions and processes are closely related to various fundamental properties of speech and hearing. Four principal series of articulation tests are cited in detail, some of which have been described in published articles by various persons. The response and the noise, if any, are given for each of these cases and the observed articulations are compared with values calculated by the method here presented. The application of the computational method to the perception of speech by deafened persons is reserved for a subsequent paper. A “Foreword” to the present paper describes the historical importance of articulation tests in the Bell Telephone System.
Touch and force reflection for telepresence surgery (2002)

This paper describes our on-going work on the development of an advanced telepresence glove, capable of providing touch and force reflection to the human operator. Such a glove will be essential in a telepresence surgery environment. The development of the glove currently constitutes three steps. First, an algorithm is being developed to map human finger motions on to the generally dissimilar robot hands, using the human grasp posture as the reference criteria. Second, a touch reflection system is being built where a set of touch sensors, placed on the robot finger tips, detect touch and activate a set of shape memory alloy based actuators attached to the human finger tips. Third, a force reflection system is being developed where a set of flexible pneumatic tubes, attached to the human fingers, reflect the grasping forces of the remote robot fingers.
The Use of Audits in Purchasing (1988)

Purchasing audits have received too little attention; an improved methodology is described here with increased emphasis on the technicalities of procurement.
Salivary Cortisol in Psychobiological Research: An Overview (1989)

The measurement of cortisol in saliva provides the basic scientist as well as the clinician with a reliable tool for investigations of hypothalamus-pituitary-adrenal axis activity. Since saliva samples can be obtained stress-free and independent from medically trained personnel this method may be well suited for use in psychobiological studies. This overview intends to give a comprehensive introduction to the method of salivary cortisol assessment and to briefly discuss its application in different scientific disciplines.
Intracellular interaction of human immunodeficiency virus type 1 (ARV-2) envelope glycoprotein gp160 with CD4 blocks the movement and maturation of CD4 to the plasma membrane (1990)

The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) plays a major role in the down-regulation of its receptor, CD4. Using a transient-expression system, we investigated the interaction of the HIV-1 envelope glycoprotein with CD4 during their movement through the intracellular membrane traffic. In singly transfected cells, the envelope glyprotein gp160 was synthesized, glycosylated, and localized predominantly in the endoplasmic reticulum. Only a minor fraction of gp160 was proteolytically cleaved, producing gp120 and gp41, and gp120 was secreted into the medium. On the other hand, the CD4 molecule, when expressed alone, was properly glycosylated and transported efficiently to the cell surface. However, when gp160 and CD4 were coexpressed in the same cell, the cell surface delivery of CD4 was greatly reduced. In coexpressing cells, CD4 formed a specific intracellular complex with gp160 as both proteins could be immunoprecipitated by antibodies against either the gp160 or CD4 (OKT4) but not by OKT4A, a blocking antibody against CD4. The specific gp160-CD4 complex was localized predominantly in the endoplasmic reticulum, and the CD4 in the complex did not acquire endoglycosidase H resistance. The present studies demonstrated that a specific intracellular interaction between gp160 and CD4 was responsible for the cell surface down-regulation of CD4 in cells expressing both the envelope glycoprotein of HIV-1 and its receptor, CD4.
Inhibition of the production and maintenance of long-term potentiation in rat hippocampal slices by a monoclonal antibody. (1987)

Monoclonal antibodies generated to 5-day-old postnatal rat dentate gyri were tested for their effects on long-term potentiation (LTP) in rat hippocampal slices. One antibody, B6E11, was found to block the production of LTP and to suppress established LTP in both area CA1 of the hippocampus and the dentate gyrus. In CA1, B6E11 was effective only when applied to the apical dendrites synapsing with the potentiating input. The production of LTP could not be blocked if B6E11 was applied to the cell bodies or to the basal dendrites of CA1. In field CA1, B6E11 had no effect on the production of short-term potentiation. Another monoclonal antibody from the same panel as B6E11, of the same immunoglobulin class, which also binds to hippocampal neurons similarly to B6E11, had no effect on LTP production. These results supply evidence that B6E11 modulates LTP by an interaction with a specific cell-surface protein associated with the dendrites of neurons in both dentate gyrus and CA1 regions.
Interleukin-13 Signal Transduction in Lymphohemopoietic Cells (1995)

Interleukin-13 (IL-13) and interleukin-4 (IL-4) are related in structure and function and are thought to share a common receptor component. We have investigated the signal transduction pathways activated by these two growth factors, as well as insulin, in cell-lines and primary cells of lymphohemopoietic origin. All three factors induced the tyrosine phosphorylation of a protein of 170 kDa (p170), which coimmunoprecipitated with the p85 subunit of P13'-kinase, via high affinity interactions mediated by the SH2 domains of p85. Antibodies raised against the entire insulin-receptor substrate-1 (IRS-1) protein immunoprecipitated p170 much less efficiently than they did IRS-1 from 3T3 cells. However, antibodies directed against the conserved pleckstrin homology domain of IRS-1 immunoprecipitated both p170 and IRS-1 with similar efficiency, suggesting they share structural similarities in this region. In lymphohemopoietic cells, IL-13, IL-4, and insulin failed to induce increased tyrosine phosphorylation of Shc, or its association with grb2, modification of Sos1, or activation of erk-1 and erk-2 mitogen-activated protein kinases, suggesting that p170 mediates downstream pathways distinct from those mediated by IRS-1. Both IL-13 and IL-4 induced low levels of tyrosine phosphorylation of Tyk-2 and Jak-1. IL-4 also activated the Jak-3-kinase, but, despite other similarities, IL-13 did not. Insulin failed to activate any of the known members of the Janus family of kinases. In that Jak-3 is reported to associate with the IL-2 gamma c chain, these data suggest that the IL-13 receptor does not utilize this subunit. However, both IL-13 and IL-4 induced tyrosine phosphorylation of the IL-4-140 kDa receptor chain, suggesting that this is a component of both receptors in these cells and accounts for the similarities in signaling pathways shared by IL-13 and IL-4.
Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption (1999)

Osteopontin is one of the major noncollagenous bone matrix proteins produced by osteoblasts and osteoclasts, bone cells that are uniquely responsible for the remodeling of mineralized tissues. Osteoclasts express the alphavbeta3 integrin, which is one of the receptors for osteopontin. Recent knockout studies revealed that noncollagenous bone matrix proteins are functionally important in regulation of bone metabolism. However, the significance of the presence of osteopontin in in vivo has not been known. We report here that osteopontin knockout mice are resistant to ovariectomy-induced bone resorption compared with wild-type mice. Microcomputed tomography analysis indicated about 60% reduction in bone volume by ovariectomy in wild-type mice, whereas the osteopontin-deficient mice exhibited only about 10% reduction in trabecular bone volume after ovariectomy. Reduction in uterine weight was observed similarly in both wild-type and osteopontin-deficient mice, indicating the specificity of the effect of osteopontin deficiency on bone metabolism. We propose that osteopontin is essential for postmenopausal osteoporosis in women. Strategies to counteract osteopontin's action may prove effective in suppressing osteoporosis.
Prostate Specific Antigen in the Diagnosis and Treatment of Adenocarcinoma of the Prostate. II. Radical Prostatectomy Treated Patients (1989)

Serum prostate specific antigen was determined (Yang polyclonal radioimmunoassay) in 102 men before hospitalization for radical prostatectomy. Prostate specimens were subjected to detailed histological and morphometric analysis. Levels of prostate specific antigen were significantly different between patients with and without a Gleason score of 7 or greater (p less than 0.001), capsular penetration greater than 1 cm. in linear extent (p less than 0.001), seminal vesicle invasion (p less than 0.001) and pelvic lymph node metastasis (p less than 0.005). Prostate specific antigen was strongly correlated with volume of prostate cancer (r equals 0.70). Bivariate and multivariate analyses indicate that cancer volume is the primary determinant of serum prostate specific antigen levels. Prostate specific antigen was elevated 3.5 ng. per ml. for every cc of cancer, a level at least 10 times that observed for benign prostatic hyperplasia. Prostate specific antigen is useful as a preoperative marker because no patient with lymph node metastasis had serum levels of less than 10 ng. per ml. (4 times the upper limit of normal range). Of the patients with greater than 50 ng. per ml. two-thirds had microscopic lymph node metastasis and 90 per cent had seminal vesicle invasion. Serum prostatic acid phosphatase levels showed a significantly weaker correlation with cancer volume (r equals 0.51) and every other pathological parameter. Of the patients 73 per cent had serum prostatic acid phosphatase levels in the normal range (0 to 2.1 ng. per ml.), including 7 per cent who had pelvic lymph node metastasis. Postoperative prostate specific antigen values were available in 97 of 102 patients, with a mean and maximum followup of 12 and 38 months. No patient with pelvic lymph node metastasis achieved an undetectable prostate specific antigen level without adjunctive therapy (hormonal or radiation). No difference in preoperative or postoperative prostate specific antigen levels, cancer volume, seminal vesicle invasion or incidence of pelvic lymph node metastasis was seen between patients with no capsular penetration and those with minimal capsular penetration (1 cm. or less total linear extent of full thickness penetration), providing the first quantitative evidence that small amounts of capsular penetration may not be of biological or prognostic significance.
Selection and Screening of Polymers for Enhanced-Oil Recovery (2008)

Abstract A number of commercially available polymers have been tested for enhanced oil recovery based upon viscosity, filterability, and surfactant compatibility, and chemical and thermal stability testing has been carried out with some of these as well. Several high molecular weight polymers exhibited high viscosities at salinities up to 170,000 ppm NaCl and with greater than 17,000 ppm CaCl2 present. Polyacrylamide polymers hydrolyze at high temperatures and beyond a certain point are subject to precipitation by calcium. If calcium concentrations can be kept below about 200 ppm, the use of polyacrylamide polymers is feasible up to reservoir temperatures of at least 100°C. For higher concentrations of calcium, copolymers including AMPS moieties should be considered. Calcium tolerance can be improved with sodium metaborate or by using copolymers of acrylamide and sodium 2-acrylamido-2-methylpropane sulfonate (AMPS). The stability problems at elevated temperatures in the presence of iron can be mitigated by the use of chemicals such as sodium dithionite and sodium carbonate. The polymers tested did not lose viscosity after 220 days of aging at 100°C with dithionite present.
Species differences in the renal toxicity of the antiarthritic drug, gold sodium thiomalate (1996)

Two gold compounds, gold sodium thiomalate (AuTM) and auranofin, are presently in clinical use in therapy of rheumatoid arthritis. In these studies, AuTM administered to Sprague-Dawley rats and three strains of mice, Swiss-Webster, C3H/HeJ, and DBA/2J, were studied with regard to its effect on liver and renal monooxygenases, metallothionein contents, and serum levels of alanine aminotransferase and urea nitrogen. These effects of AuTM were compared to those of cadmium, since the latter metal has exhibited tissue and species differences in the induction of metallothionein. Benzo(a)pyrene hydroxylase and benzphetamine N-demethylase activities were not altered by AuTM in livers of rats and the three strains of mice. Benzo(a)pyrene hydroxylase activity was significantly decreased in rat kidney, whereas this enzyme activity was not affected in the kidneys of mice. In rats, AuTM caused a sevenfold induction in liver metallothionein, while in mice, liver metallothionein was induced twofold in Swiss-Webster mice and about fivefold in the inbred strains. AuTM caused minimal changes in renal metallothionein contents in the three strains of mice studied. Serum alanine amino-transferase, an indicator of hepatotoxicity, was not altered by AuTM in rats and mice studied. Blood urea nitrogen, an indicator of kidney dysfunction, was increased threefold in rats, but not in AuTM-treated mice. These data demonstrate that AuTM, a nephrotoxic agent in rats and humans, showed no nephrotoxic effects in the mouse strains studied here.
Heparin-stimulated inhibition of factor IXa generation and factor IXa neutralization in plasma (1990)

Generation and inhibition of activated factor IXa was studied in factor XIa-activated plasma containing 4 mmol/L free calcium ions and 20 mumol/L phospholipid (25 mol% phosphatidylserine/75 mol% phosphatidylcholine). Interference of other (activated) clotting factors with the factor IXa activity measurements could be avoided by using a highly specific and sensitive bioassay. Factor IXa generation curves were analyzed according to a model that assumed Michaelis-Menten kinetics of factor XIa-catalyzed factor IXa formation and pseudo first order kinetics of inhibition of factor XIa and factor IXa. In the absence of heparin, factor IXa activity in plasma reached final levels that were found to increase with increasing amounts of factor XIa used to activate the plasma. When the model was fitted to this set of factor IXa generation curves, the analysis yielded a rate constant of inhibition of factor XIa of 0.7 +/- 0.1 min-1 and a kcat/Km ratio of 0.29 +/- 0.01 (nmol/L)-1 min-1. No neutralization of factor IXa activity was observed (the estimated rate constant of inhibition of factor IXa was 0). Thus, in the absence of heparin, the final level of factor IXa in plasma is only dependent on the initial factor XIa concentration. While neutralization of in situ generated factor IXa in normal plasma was negligible, unfractionated heparin dramatically enhanced the rate of inactivation of factor IXa (apparent second order rate constant of inhibition of 5.2 min-1/per microgram heparin/mL). The synthetic pentasaccharide heparin, the smallest heparin chain capable of binding antithrombin III, stimulated the inhibition of in situ generated factor IXa, but sevenfold less than unfractionated heparin (k = 0.76 min-1 per microgram pentasaccharide/mL). We found that free calcium ions were absolutely required to observe an unfractionated heparin and pentasaccharide-stimulated neutralization of factor IXa activity. Factor XIa inhibition (psuedo first order rate constant of 0.7 min-1) was not affected by unfractionated heparin or pentasaccharide in the range of heparin concentrations studied.
CTCF Regulates Allelic Expression of Igf2 by Orchestrating a Promoter-Polycomb Repressive Complex 2 Intrachromosomal Loop (2008)

CTCF is a zinc finger DNA-binding protein that regulates the epigenetic states of numerous target genes. Using allelic regulation of mouse insulin-like growth factor II (Igf2) as a model, we demonstrate that CTCF binds to the unmethylated maternal allele of the imprinting control region (ICR) in the Igf2/H19 imprinting domain and forms a long-range intrachromosomal loop to interact with the three clustered Igf2 promoters. Polycomb repressive complex 2 is recruited through the interaction of CTCF with Suz12, leading to allele-specific methylation at lysine 27 of histone H3 (H3-K27) and to suppression of the maternal Igf2 promoters. Targeted mutation or deletion of the maternal ICR abolishes this chromatin loop, decreases allelic H3-K27 methylation, and causes loss of Igf2 imprinting. RNA interference knockdown of Suz12 also leads to reactivation of the maternal Igf2 allele and biallelic Igf2 expression. CTCF and Suz12 are coprecipitated from nuclear extracts with antibodies specific for either protein, and they interact with each other in a two-hybrid system. These findings offer insight into general epigenetic mechanisms by which CTCF governs gene expression by orchestrating chromatin loop structures and by serving as a DNA-binding protein scaffold to recruit and bind polycomb repressive complexes.
Comprehensive Survey of Combinatorial Library Synthesis:  2002 (2003)

The sixth annual review provides an accounting of 388 chemical libraries reported in the year 2002. Libraries are segregated into 10 tables, providing a convenient reference to libraries published with and without accompanying biological data. Three tables inventory solid-phase reagents and scavengers, linkers, and polymer-supported chiral ligands.