gebhart/patrepeval huggingface dataset:
Specific binding of erythropoietin to spleen cells infected with the anemia strain of Friend virus. (1984)

Tritiated erythropoietin with full biological activity has been prepared, and a relatively homogeneous population of enriched progenitor cells that respond to the hormone has been generated by infection of mice with the Friend virus that produces anemia. These cells, obtained from the spleens of infected mice, develop into mature erythroblasts and erythrocytes in the presence of erythropoietin. We have measured the binding of erythropoietin to these target cells; 62% of the binding was inhibited by excess unlabeled erythropoietin, but no inhibition occurred with albumin, serum, or a variety of growth factors and glycoproteins. Apparent equilibrium was reached by 2 hr at 37 degrees C and by 3.5-4 hr at 10 degrees C. The extent of specific binding increased linearly with cell concentration. In binding experiments at 10 degrees C, apparent saturation of specific binding occurred at approximately equal to 8.7 nM. Scatchard analysis showed a single class of binding sites. The dissociation constant is 5.2 nM with an average of 660 binding sites per cell. At 0.06 nM, where most of the cells are induced to terminally differentiate in vitro, an average of only 8 erythropoietin molecules bound per cell. These studies indicate that erythropoietin attaches to specific binding sites, which are most likely receptors since they manifest high affinity and specificity, and that the biologic effect of the hormone may be produced by attachment of a very small number of erythropoietin molecules.
Modulation of synovial cell products by a factor from a human cell line: T lymphocyte induction of a mononuclear cell factor. (1982)

A human cell line (U937) can be stimulated to produce a soluble factor (MCF) by either lectin-activated T lymphocytes or their soluble products. In prior studies, we showed that MCF produced by peripheral blood mononuclear cells can increase production of collagenase and prostaglandin E2 by adherent synovial cells obtained from enzymatically dispersed rheumatoid synovium. We show here that peripheral blood T lymphocytes or cloned human T lymphocyte lines are capable of inducing MCF production by the monocyte-like U937 cells. MCF can be demonstrated in the supernatant fluid from cocultures of U937 cells and T lymphocytes that have been stimulated with phytohemagglutinin or concanavalin A for 24-48 hr. In addition, the supernatant fluid from 24-hr lectin-stimulated T lymphocytes can be transferred onto the U937 cells and subsequently, MCF activity can be recovered from the U937 culture medium. The activity of the soluble T cell product on the U937 cells is both time- and dose-dependent. A human cell line capable of MCF production in continuous culture has not been previously available. The use of a monocyte-like cell line (U937) and cloned T lymphocytes now makes it possible to demonstrate the role of discrete cell populations in the production of MCF and other mediators.
Targeting SYK kinase‐dependent anti‐apoptotic resistance pathway in B‐lineage acute lymphoblastic leukaemia (ALL) cells with a potent SYK inhibitory pentapeptide mimic (2010)

The present study found that the pentapeptide mimic C-61, targeting the substrate binding P-site of SYK tyrosine kinase acted as a potent inducer of apoptosis in chemotherapy-resistant SYK-expressing primary leukemic B-cell precursors taken directly from relapsed B-precursor leukaemia (BPL) patients (but not SYK-deficient infant pro-B leukaemia cells), exhibited favourable pharmacokinetics in mice and non-human primates, and eradicated in vivo clonogenic leukaemia cells in severe combined immunodeficient mouse xenograft models of chemotherapy-resistant human BPL at dose levels non-toxic to mice and non-human primates. These in vitro and in vivo findings provide proof of principle for effective treatment of chemotherapy-resistant BPL by targeting SYK-dependent anti-apoptotic blast cell survival machinery with a SYK P-Site inhibitor. Further development of C-61 may provide the foundation for therapeutic innovation against chemotherapy-resistant BPL.
Isolation and characterization of human DNA fragments with nucleotide sequence homologies with the simian virus 40 regulatory region. (1982)

A recombinant library of human DNA sequences was screened with a segment of simian virus 40 (SV40) DNA that spans the viral origin of replication. One hundred and fifty phage were isolated that hybridized to this probe. Restriction enzyme and hybridization analyses indicated that these sequences were partially homologous to one another. Direct DNA sequencing of two such SV40-hybridizing segments indicated that this was not a highly conserved family of sequences, but rather a set of DNA fragments that contained repetitive regions of high guanine plus cytosine content. These sequences were not members of the previously described Alu family of repeats and hybridized to SV40 DNA more strongly than do Alu family members. Computer analyses showed that the human DNA segments contained multiple homologies with sequences throughout the SV40 origin region, although sequences on the late side of the viral origin contained the strongest cross-hybridizing sequences. Because of the number and complexity of the matches detected, we could not determine unambiguously which of the many possible heteroduplexes between these DNAs was thermodynamically most favored. No hybridization of these human DNA sequences to any other segment of the SV40 genome was detected. In contrast, the human DNA segments isolated cross-hybridized with many sequences within the human genome. We tested for the presence of several functional domains on two of these human DNA fragments. One SV40-hybridizing fragment, SVCR29, contained a sequence which enhanced the efficiency of thymidine kinase transformation in human cells by approximately 20-fold. This effect was seen in an orientation-independent manner when the sequence was present at the 3' end of the chicken thymidine kinase gene. We propose that this segment of DNA contains a sequence analogous to the 72-base-pair repeats of SV40. The existence of such an "activator" element in cellular DNA raises the possibility that families of these sequences may exist in the mammalian genome.
The Role of EGFR Inhibition in the Treatment of Non-Small Cell Lung Cancer (2009)

The identification of certain molecular mechanisms underlying lung carcinogenesis and progression has led to the development of targeted agents against different families of growth factors and receptors. The epidermal growth factor receptor (EGFR) is one such target for therapeutic exploitation. Inhibition of EGFR downstream signaling can be accomplished through two primary mechanisms: (a) the direct blocking of intracellular kinase activity with small-molecule tyrosine kinase inhibitors (TKIs) (e.g., gefitinib, erlotinib) and (b) the blocking of EGFR ligand binding using antibodies directed against the extracellular domain of the receptor (e.g., cetuximab). Resistance to available EGFR-targeted treatments has emerged as a substantial clinical issue in non-small cell lung cancer (NSCLC). Several novel agents with the potential to overcome such resistance are currently in clinical development, including irreversible EGFR TKIs, monoclonal antibodies, and TKIs directed against multiple signaling pathways. Here we discuss the clinical application of the currently available EGFR-targeted agents in NSCLC, the underlying mechanisms of resistance, and the novel agents in clinical development that may overcome resistance.
New hexahydroxybiphenyl derivatives as inhibitors of protein kinase C (1994)

We have previously shown that some ellagitannins are potent inhibitors of protein kinase C (PKC). On the basis of this finding, several series of hexahydroxybiphenyl derivatives of ellagic acid were synthesized as simple analogs of these ellagitannins and were evaluated for their inhibitory effect against PKC. Compounds 23 and 26 were found to be potent inhibitors of PKC, while hexakis-(benzyloxy)biphenyl derivatives exhibited weak anti-PKC activity.
JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease (2004)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopamine-containing neurons, but the molecular pathways underlying its pathogenesis remain uncertain. Here, we show that by eliminating c-Jun N-terminal kinases (JNKs) we can prevent neurodegeneration and improve motor function in an animal model of PD. First, we found that c-Jun is activated in dopaminergic neurons from PD patients and in the 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP) mouse model of PD. Examination of various JNK-deficient mice shows that both JNK2 and JNK3, but not JNK1, are required for MPTP-induced c-Jun activation and dopaminergic cell demise. Furthermore, we have identified cyclooxygenase (COX) 2 as a molecular target of JNK activation and demonstrated that COX-2 is indispensable for MPTP-induced dopaminergic cell death. Our data revealed that JNK2- and JNK3-induced COX-2 may be a principle pathway responsible for neurodegeneration in PD.
Expression of Dp260 in muscle tethers the actin cytoskeleton to the dystrophin-glycoprotein complex and partially prevents dystrophy (2002)

Dystrophin forms a mechanical link between the actin cytoskeleton and the extracellular matrix in muscle that helps maintain sarcolemmal integrity. Two regions of dystrophin have been shown to bind actin: the N-terminal domain and rod domain repeats 11-17. To better understand the roles of these two domains and whether the rod domain actin-binding domain alone can support a mechanically functional link with actin, we constructed transgenic mice expressing Dp260 in skeletal muscle. Dp260, the retinal isoform of dystrophin, lacks the N-terminal domain and a significant portion of the rod domain, but retains the rod domain actin-binding domain. Our results indicate that Dp260 expression restores a stable association between costameric actin and the sarcolemma, assembles the dystrophin-glycoprotein complex, and significantly slows the progression of the dystrophy in the dystrophin-deficient mdx mouse. We assessed the functional integrity of the mechanical link in Dp260 transgenic mdx mice and found that Dp260 muscles showed normal resistance to contraction-induced injury, but dramatic reductions in force generation similar to those found with mdx muscles. Morphologically, Dp260 muscles displayed reduced amounts of inflammation and fibrosis, but still showed a significant, albeit reduced, amount of degeneration/regeneration. These data demonstrate that protection from contraction-induced injury can dramatically ameliorate, but not completely halt, the dystrophic process. We suggest that a non-mechanical defect, attributed to the loss of the N terminus of dystrophin, is likely responsible for the residual dystrophy observed.
Design Criteria for Near-Field-Focused Planar Arrays (2012)

A detailed performance analysis of near-field-focused planar arrays is addressed. Design curves and performance data are shown for planar square arrays as a function of the array size, the inter-element distance, and the focal distance. The performance curves are compared with results presented in earlier studies relevant to continuous-aperture antennas, as well as with numerical results obtained from a full-wave analysis of planar microstrip arrays.
Cancer chemopreventive activity of Xanthohumol, a natural product derived from hop. (2002)

Characterization and use of effective cancer chemopreventive agents have become important issues in public health-related research. Aiming to identify novel potential chemopreventive agents, we have established an interrelated series of bioassay systems targeting molecular mechanisms relevant for the prevention of tumor development. We report anticarcinogenic properties of Xanthohumol (XN), a prenylated chalcone from hop (Humulus Iupulus L.) with an exceptional broad spectrum of inhibitory mechanisms at the initiation, promotion, and progression stage of carcinogenesis. Consistent with anti-initiating potential, XN potently modulates the activity of enzymes involved in carcinogen metabolism and detoxification. Moreover, XN is able to scavenge reactive oxygen species, including hydroxyl- and peroxyl radicals, and to inhibit superoxide anion radical and nitric oxide production. As potential antitumor-promoting mechanisms, it demonstrates anti-inflammatory properties by inhibition of cyclooxygenase-1 and cyclooxygenase-2 activity and is antiestrogenic without possessing intrinsic estrogenic potential. Antiproliferative mechanisms of XN to prevent carcinogenesis in the progression phase include inhibition of DNA synthesis and induction of cell cycle arrest in S phase, apoptosis, and cell differentiation. Importantly, XN at nanomolar concentrations prevents carcinogen-induced preneoplastic lesions in mouse mammary gland organ culture. Because XN is easily cyclized to the flavanone isoxanthohumol, activities of both compounds were compared throughout the study. Together, our data provide evidence for the potential application of XN as a novel, readily available chemopreventive agent, and clinical investigations are warranted once efficacy and safety in animal models have been established.
Traumatic spinal cord injury in rats causes increases in tissue thromboxane but not peptidoleukotrienes (1988)

Spinal cord samples from rats subjected to three different levels of impact trauma (25, 50, 100 g-cm) were examined for immunoreactive thromboxane B2 and 6-sulfidopeptide-containing leukotrienes, using specific radioimmunoassays. Trauma resulted in pronounced increases in thromboxane levels as early as 5 min after injury, with maximum values at 1 hr. Although thromboxane values then slowly declined, they remained significantly above control values for up to 7 days. Significantly smaller thromboxane values were found in rats subjected to mild injury (25 g-cm) than in those that received more severe, irreversible impact injury (50 and 100 g-cm). No statistically significant changes were observed in leukotriene levels in any of the experimental groups. These findings are consistent with the hypothesis that cyclooxygenase products of arachidonic acid metabolism may contribute to secondary injury after spinal cord trauma and provides the rationale for the use of cyclooxygenase inhibitors in the treatment of such injury.
Capturing the Diversity in Lexical Diversity (2013)

The range, variety, or diversity of words found in learners’ language use is believed to reflect the complexity of their vocabulary knowledge as well as the level of their language proficiency. Many indices of lexical diversity have been proposed, most of which involve statistical relationships between types and tokens, and which ultimately reflect the rate of word repetition. These indices have generally been validated in accordance with how well they overcome sample‐size effects and/or how well they predict language knowledge or behavior, rather than in accordance with how well they actually measure the construct of lexical diversity. In this article, I review developments that have taken place in lexical diversity research, and also describe obstacles that have prevented it from advancing further. I compare these developments with parallel research on biodiversity in the field of ecology, and show what language researchers can learn from ecology regarding the modeling and measurement of diversity as a multidimensional construct of compositional complexity.
Isolation and Molecular Cloning of Insulin-Like Growth Factor-Binding Protein-6 (1991)

Insulin-like growth factors (IGFs) together with their binding proteins (BPs) are potential regulators of folliculogenesis in mammalian ovary. To identify the various species of IGFBPs present in the ovary, we have undertaken a comprehensive purification scheme using gel filtration, ligand-affinity chromatography, and several steps of reverse phase HPLC to isolate all of the BPs in pig ovarian follicular fluid. Our effort yielded five distinct IGFBPs, and upon analysis, they were found to correspond to the previously identified human and rat IGFBP-2, -3, -4, -5, and -6. IGFBP-1 was not found in the pig ovarian follicular fluid under our experimental procedure. Of the six known classes of IGFBPs, the complete primary structures of the first five have been determined, but not IGFBP-6. Using amino acid sequence information from a tryptic fragment of pig IGFBP-6 to prepare a probe, cDNA clones encoding rat and human IGFBP-6 have been isolated and characterized. The deduced amino acid sequence revealed that rat IGFBP-6 contains 201 amino acids with a calculated mol wt of 21,461, while the human homolog contains 216 amino acids with a calculated mol wt of 22,847. In addition, a distinctive feature of human and rat IGFBP-6 is that they lack, respectively, two and four of the 18 homologous cysteines that are present in all other five IGFBPs. The missing cysteines in IGFBP-6 resulted in the absence of the invariant Gly-Cys-Gly-Cys-Cys sequence in the amino-terminal region of the molecule. Human IGFBP-6 possesses a single Asn-linked glycosylation site near the carboxyl-terminal, whereas no potential Asn-linked glycosylation sites are present in the rat sequence. A single 1.3-kilobase IGFBP-6 mRNA was detected by Northern analysis in all rat tissues examined, including testis, intestine, adrenal, kidney, stomach, spleen, heart, lung, brain, and liver, indicating that this BP is a ubiquitous protein. The chromosome location of the IGFBP-6 gene in human has been determined using polymerase chain reaction on somatic cell hybrid DNAs of human and hamster, and the results showed that it is located on chromosome 12.
A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. (1996)

The serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessively of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.
The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age‐dependent manner (2010)

Levels of autoantibodies, cytokines/chemokines, and CRP are elevated in the preclinical period of RA development. In preclinical autoantibody-positive cases, the number of elevated cytokines/chemokines is predictive of the time of diagnosis of future RA in an age-dependent manner.
Trench capacitor design issues in VLSI DRAM cells (1986)

Major issues involved in the optimization of trench capacitors for VLSI DRAMs are considered, using the previously described 4Mb DRAM cross-point Trench-Transistor Cell (TTC) as a vehicle. The effects of capacitor plate doping, trench etch angle and depth on the capacitance of the trench capacitor are studied. Pisces-II simulations show that there is adequate electrical isolation between adjacent cells, with a grounded substrate. Any tendencies for intercell leakage are further minimized, by reverse-biasing the substrate at-2.0V. High-resolution TEM and lattice imaging techniques are utilized to study the quality of oxide dielectric in the trench capacitor. In addition, a simple way of enlarging the capacitor area, in order to increase the storage capacitance, is presented.
A COMPARISON OF THE PROTEIN CONTENT OF URINE SAMPLES IN DIFFERENT INTERVALS (2003)

Objective To make a comparison of the content of protein among different interval urine samples. Methods 2 , 8 , 12 , and 24 hour urine samples were collected and detected from 94 patients with proteinuria. The protein content was measured by using Ponceau S method and analyzed by one way ANOVA. Results The 2 hour urine protein content was significantly lower than those of 8 , 12 , and 24 hour urine samples( F=73.53, q=3.63-4.40, P 0.01). The differences among 8 , 12 , and 24 hour urine contents were not significant. Conclusion The contents of protein of 8 or 12 hour urine samples may replace 24 hour urine protein detection in patients with proteinuria, which can be carried out clinically.
Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk (2011)

IDLVs provide an attractive platform for the tolerogenic expression of intracellular or secreted proteins in the liver with a substantially reduced risk of insertional mutagenesis.
Structural and functional relationships among the RTX toxin determinants of Gram-negative bacteria (1992)

The RTX (repeats in toxin) cytolytic toxins r represent a family of important virulence factors that have disseminated widely among Gram-negative bacteria. They are characterised by a series of glycine-rich repeat units at the C-terminal end of each protein. They also have other features in common. Secretion from the cell occurs without a periplasmic intermediate by a novel mechanism which involves recognition of a signal sequence at the C-terminus of the toxin by membrane-associated proteins that export the toxin directly to the outside of the cell. The structural gene for each protein encodes an inactive toxin which is modified post-translationally to an active cytotoxic form by another gene product before secretion. The genes for toxin synthesis, activation and secretion are for the most part grouped together on the chromosome and form an operon. The toxins all create pores in the cell membrane of target cells leading to eventual cell lysis and they appear to require Ca2+ for cytotoxic activity. Although the toxins have a similar mode of action, they vary in target cell specificity. Some are cytotoxic for a wide variety of eukaryotic cell types while others exhibit precise target cell specificity and are only active against leukocytes from certain host species. The characteristic glycine-rich repeat units have been identified in other exoproteins besides those with cytotoxic activity and it is likely that the novel secretory mechanism has been harnessed by a variety of pathogens to release important virulence-associated factors from the cell or to locate them on the cell surface.