gebhart/patrepeval huggingface dataset:
Adeno-associated virus P5 promoter contains an adenovirus E1A-inducible element and a binding site for the major late transcription factor (1989)

Activity of the adeno-associated virus P5 transcriptional control region was found to be induced by adenovirus E1A gene products. A pair of adjacent sequence elements was found to mediate both basal and E1A-induced P5 activity. The first element is a binding site for the major late transcription factor (MLTF), a factor first identified on the basis of its binding to a specific sequence within the adenovirus major late promoter. The second element is a tandemly repeated 10-base-pair sequence whose relationship to previously described binding sites is unclear. Each element individually conferred E1A responsiveness on a heterologous promoter, and deletion analysis demonstrated that each contributed to the level of P5 activity in the presence of E1A products both in transfection- and infection-based assays. Although deletion of the MLTF binding site led to reduced P5 transcriptional activity in the presence of E1A proteins, the deletion generated enhanced P5 basal activity in the absence of the transcriptional activator. The negative effect of the MLTF binding site in the absence of activator and its positive effect in the presence of activator combine to enhance the magnitude of the response by the P5 control region to E1A gene products.
Sterically Stabilized Anti-HER2 Immunoliposomes:  Design and Targeting to Human Breast Cancer Cells in Vitro (1997)

Liposomes (70-100 nm) of 1-palmitoyl-2-oleoylphosphatidylcholine, cholesterol, and poly(ethylene glycol) (PEG)-modified phosphatidylethanolamine (PEG-DSPE) were conjugated to Fab' fragments of a humanized recombinant MAb against the extracellular domain of HER2/neu to create sterically stabilized immunoliposomes (anti-HER2 SL) as a drug carrier targeting HER2-overexpressing cancers. Conjugation employed maleimide-terminated membrane-anchored spacers of two kinds: a short spacer, providing attachment of Fab' close to the liposome bilayer, or a long spacer, with Fab' attachment at the distal terminus of the PEG chain. Confocal microscopy and spectrofluorometry of HER2-overexpressing breast cancer cells incubated with fluorescently labeled anti-HER2 SL prepared with either spacer showed binding of liposomes (8000-23000 vesicles/cell) followed by endocytosis (rate constant ke = 0.012-0.033 min-1) via the coated-pit pathway, evidenced by intracellular acidification and colocalization with transferrin. Uptake of anti-HER2 immunoliposomes by breast cancer cells with low HER2 expression, or after preincubation of cells with free anti-HER2 Fab', was less than 0.2% and 4.3%, respectively, of the uptake by HER2-overexpressing cells. Increasing PEG-DSPE content (up to 5.7 mol %) in anti-HER2-SL prepared with the short spacer decreased liposome-cell binding affinity 60-100-fold, while ke decreased only 2-fold; however, when Fab' fragments were conjugated via a PEG spacer, both binding affinity and ke were unaffected by PEG-DSPE content. Cell binding and internalization of anti-HER2 immunoliposomes increased at higher surface density of conjugated Fab' fragments, reaching plateaus at approximately 40 Fab'/liposome for binding and approximately 10-15 Fab'/liposome for internalization. Uptake of anti-HER2 immunoliposomes correlated with the cell surface density of HER2 and significantly (p < 0.005) correlated with the antiproliferative effect of the targeting antibody but not with the total level of cellular HER2 expression. The results obtained were used to optimize in vivo preclinical studies of anti-HER2 SL loaded with antineoplastic drugs.
Regulation of beta-adrenergic receptors by "permissive" hormones: glucocorticoids increase steady-state levels of receptor mRNA. (1988)

Incubation of DDT1 MF-2 hamster vas deferens cells with glucocorticoids results in a marked increase in beta-adrenergic receptor (beta AR) number. The increase in receptor number was visualized by indirect immunofluorescence with antiserum specific for the beta AR and was verified by radioligand binding. The steady-state levels of beta AR mRNA were quantified in untreated (control) and glucocorticoid-treated cells by DNA-excess solution hybridization using a single-stranded probe corresponding to nucleotides +12 to 182 of the hamster beta 2AR cDNA coding region. The steady-state level increased from 0.37 pg of beta AR mRNA per microgram of total cellular RNA in untreated cells to 1.05 pg of beta AR mRNA per microgram of RNA in cells treated with dexamethasone (500 nM) for 2-4 hr. After this sharp transient peak, the steady-state level of receptor mRNA declined by 6 hr to a level approximately twice that of the untreated cells. Half-maximal effects were achieved at 20-40 nM dexamethasone. Testosterone (500 nM) and 17 beta-estradiol (500 nM), in contrast, did not alter the steady-state levels of beta AR mRNA. Actinomycin D, a potent inhibitor of transcription, abolished the dexamethasone-induced increase in beta AR mRNA, suggesting that the permissive hormone effect was exerted on gene transcription. The half-life of the receptor mRNA measured in the presence of actinomycin D was found to be 12 hr in both the untreated and the dexamethasone-treated cells. These studies provide a molecular explanation for the well-known regulation of GTP-binding protein (G-protein)-linked cell-surface receptors by permissive hormones.
Control of Blood Pressure: Does It Matter Which Agent You Use? (2007)

A panel was convened to discuss the question, "Is blood pressure lowering the sole determinant of outcome, or do specific drugs make a difference?" The panel was moderated by Marvin Moser, MD, Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT. Panelists included Norman Kaplan, MD, Clinical Professor of Medicine at the University of Texas Southwestern Medical Center at Dallas, TX, and William Cushman, MD, Professor of Medicine at the University of Tennessee in Memphis, TN. The discussion was supported by Boehringer Ingelheim, and each author received an honorarium from Boehringer Ingelheim for time and effort spent participating in the discussion or reviewing the transcript for intellectual content before publication. The authors maintained full control of the discussion and the resulting content of this article.
Combinatorial autoantibodies to dihydrolipoamide acetyltransferase, the major autoantigen of primary biliary cirrhosis. (1993)

mRNA from a regional lymph node of a patient with primary biliary cirrhosis (PBC) was used to construct a combinatorial immunoglobulin library in the lambda phage vector system. Six human monoclonal IgG Fab clones (LC1-LC6) specific for the major autoantigen of PBC--dihydrolipoamide acetyltransferase, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2)--were isolated, appearing at a frequency of 0.01% in the combinatorial immunoglobulin library. These Fab clones recognize human PDC-E2 with high affinity (Ka = 10(-7)-10(-9) M-1). Using both immunoblotting and ELISA, LC1-LC6 showed little cross-reactivity to any of the other autoantigens commonly recognized by PBC sera or to other antigens commonly recognized by PBC sera or to other antigens such as histone, calf thymus DNA, and bovine serum albumin. The Fab monoclonal antibodies show a typical anti-mitochondrial staining pattern in HEp-2 cells but react strongly with the luminal aspect of biliary epithelial cells of patients with PBC. Our results demonstrate that a recombinant combinatorial immunoglobulin library can be used to isolate high-affinity Fabs against a specific autoantigen. Such reagents will facilitate the analysis of immunoglobulin gene structure, idiotype, and antigen-antibody interactions in autoimmune disease.
Connective Tissue Growth Factor-(CTGF, CCN2) – A Marker, Mediator and Therapeutic Target for Renal Fibrosis (2009)

Connective tissue growth factor (CTGF, CCN2) is a key mediator of tissue fibrosis. CCN2 plays an important role in the development of glomerular and tubulointerstitial fibrosis in progressive kidney diseases. In this review, we discuss the biology of CCN2 with a focus on the regulation of CCN2 gene, cellular mechanisms of profibrotic CCN2 effects and the current in vivo and in vitro evidence for the role of CCN2 in the development of renal fibrosis. We also discuss the therapeutic potential of targeting CCN2 for the treatment of renal fibrosis.
Hypercholesterolemia promotes bone marrow cell mobilization by perturbing the SDF-1:CXCR4 axis (2009)

Hypercholesterolemia is associated with elevated peripheral blood leukocytes and increased platelet levels, generally attributed to cholesterol-induced proinflammatory cytokines. Bone marrow (BM) cell mobilization and platelet production is achieved by disrupting the SDF-1:CXCR4 axis, namely with granulocyte colony-stimulating factor and/or CXCR4 antagonists. Here we show that high cholesterol disrupts the BM SDF-1:CXCR4 axis; promotes the mobilization of B cells, neutrophils, and progenitor cells (HPCs); and creates thrombocytosis. Hypercholesterolemia was achieved after a 30-day high-cholesterol feeding trial, resulting in elevated low-density lipoprotein (LDL) cholesterol levels and inversion of the LDL to high-density lipoprotein cholesterol ratio. Hypercholesterolemic mice displayed lymphocytosis, increased neutrophils, HPCs, and thrombocytosis with a lineage-specific decrease in the BM. Histologic analysis revealed that megakaryocyte numbers remained unaltered but, in high-cholesterol mice, they formed large clusters in contact with BM vessels. In vitro, LDL induced stromal cell-derived factor-1 (SDF-1) production, suggesting that megakaryocyte delocalization resulted from an altered SDF-1 gradient. LDL also stimulated B cells and HPC migration toward SDF-1, which was blocked by scavenger receptor class B type I (cholesterol receptor) inhibition. Accordingly, hypercholesterolemic mice had increased peripheral blood SDF-1 levels, increased platelets, CXCR4-positive B lymphocytes, neutrophils, and HPCs. High cholesterol interferes with the BM SDF-1:CXCR4 axis, resulting in lymphocytosis, thrombocytosis, and HPC mobilization.
Specificity of T‐cell protein tyrosine phosphatase toward phosphorylated synthetic peptides (1993)

The local specificity determinants for a T-cell protein tyrosine phosphatase (TC-PTP) have been inspected with the aid of a series of synthetic peptides, either enzymically or chemically phosphorylated, derived from the phosphoacceptor sites of phosphotyrosyl proteins. The truncated form of T-cell PTP, deprived of its C-terminal down-regulatory domain, readily dephosphorylates submicromolar concentrations of eptapeptides to eicosapeptides, reproducing the C-terminal down-regulatory site of pp60c-src (Tyr527), the phosphorylated loop IV of calmodulin and the main autophosphorylation site of two protein tyrosine kinases of the src family (Tyr416 of pp60c-src and Tyr412 of p51fgr). However, phosphopeptides of similar size, derived from phosphoacceptor tyrosyl sites of the abl and epidermal-growth-factor receptor protein tyrosine kinases, the phosphorylated loop III of calmodulin, and phosphoangiotensin II undergo either very slow or undetectable dephosphorylation, even if tested up to 1 microM concentration. The replacement of either Ser-P or O-methylated phosphotyrosine for phosphotyrosine within suitable peptide substrates gives rise to totally inert derivatives. Moreover, amino acid substitutions around phosphotyrosine in the peptides src(412-418), src(414-418) and abl-(390-397) deeply influence the dephosphorylation efficiency. From these data and from a comparative analysis of efficient versus poor phosphopeptide substrates, it can be concluded that acidic residues located on the N-terminal side of phosphotyrosine, with special reference to position -3, play a crucial role in substrate recognition, while basic residues in the same positions act as negative determinants. In any event, the presence of at least two aminoacyl residues upstream of phosphotyrosine represents a necessary, albeit not sufficient, condition for detectable dephosphorylation to occur. By replacing the truncated form of TC-PTP with the full length TC-PTP, the dephosphorylation efficiencies of all peptides tested are dramatically impaired. Such an effect is invariably accounted for by a substantial increase in Km values, accompanied by a more or less pronounced decrease in Vmax values. These data support the concept that the C-terminal regulatory domain of TC-PTP exerts its function primarily by altering the affinity of the enzyme toward its phosphotyrosyl targets.
A tale of two Paks (2008)

Paks (p21-activated kinases) are effectors for the small GTPases Cdc42 (cell division cycle 42) and Rac that play fundamental roles in a wide range of cellular processes, including cell morphology, motility, survival, gene transcription, apoptosis and hormone signalling. These enzymes are widely expressed in numerous tissues and are activated by extracellular signals through GTPase-dependent and -independent mechanisms. On the basis of structural and biochemical features, the Pak family members have been classified into two groups, comprising three members each. The two Pak groups have generally been considered as two halves of a single entity, but accumulating evidence indicates that this is not so. In this review, we discuss recent advances in our understanding of the structure, regulation and function of these kinases, emphasizing the many differences between these two groups of signalling proteins.
THERMAL DECARBONYLATION OF CATECHOL, HYDROQUINONE AND RESOLSINOL (1976)

Abstract Decarbonylation proceeded as the main primary process in thermal reactions of catechol, hydroquinone, and resorcinol at 500–600°C under H2 or He dilution. An accompanying minor process was dehydration to form phenol. The rate of decarbonylation of hydroquinone pyrolysis was smaller than that of p-benzoquinone pyrolysis under H2 dilution.
Net effect of an acute phase response—Partial alleviation with probiotic supplementation (2009)

The acute phase response (APR) is characterized by inflammation, fever, and altered organ metabolism resulting in muscle catabolism and anorexia. Lipopolysaccharide (LPS)-induced APR may reflect depressed growth and appetite loss. Therefore, a 1-wk growth experiment was conducted to examine whether dietary supplementation of a multispecies probiotic (PoultryStar) would alleviate growth suppression and anorexia caused by LPS-induced APR. The experiment was designed with 4 treatments (n = 8 cages/treatment; 6 birds/cage) starting at 14 d of age. Before (0 to 14 d of age) and for the experiment (14 to 21 d of age), male broiler chicks were fed diets devoid of probiotic or were supplemented with 1.7 x 10(8) cfu/kg of probiotic. At 14 d of age, birds fed the diet devoid of probiotic were further divided into 3 treatments: an unchallenged positive control, LPS-challenged negative control (LPS-NC), and a treatment that was pair-fed to LPS-NC. The probiotic-fed birds were also then challenged with LPS. The LPS (Escherichia coli 055:B5) was injected intraperitoneally 4 times at 48-h intervals at 1 mg/kg of BW. The LPS challenge dramatically depressed BW gain from 14 to 21 d of age by 22% (P < 0.001). However, 41% of growth depression was attributable to factors other than feed intake reduction when compared with the pair-fed treatment. Probiotic supplementation recovered 17% of depressed growth (vs. LPS-NC; P = 0.068), but this improved growth was not due to improvements in feed intake (P = 0.47). However, recovery of feed intake of the probiotic + LPS birds occurred 48-h earlier than the LPS-NC birds. Growth depression induced by LPS administration resulted in an overall relative feed intake (vs. positive control) of 0.83 and also decreased net energy and protein accretion. Probiotic supplementation did not alleviate the reduction in net energy or protein accretion induced by LPS. In conclusion, APR (induced by LPS administration) diverted a large portion of consumed nutrients from tissue accretion. Probiotic supplementation lessened the anorexic effects of LPS resulting in a trend toward BW gain improvement versus the LPS-NC.
Pretreatment with the ciclosporin derivative NIM811 reduces delayed neuronal death in the hippocampus after transient forebrain ischaemia (2010)

These findings strongly suggest that NIM811 inhibits mPT and ameliorates delayed neuronal death in mice subjected to transient forebrain ischaemia.
Differences in Off-Road Glances: Effects on Young Drivers’ Performance (2010)

Young drivers display more risk-taking behavior than other age groups. Performing distracting tasks is one such risky behavior that is observed among young drivers. However, due to inexperience, young drivers may not be able to appropriately compensate for the effects of distractions. A driving simulator study with 53 young drivers (aged 18–21) was conducted to assess the level of engagement with an in-vehicle secondary task. A cluster analysis revealed three groups of drivers that differed based on eye glance behavior and driving performance: drivers with low-risk, moderate-risk, and high-risk behavior. A subset of these drivers was provided with feedback to help modulate their distracting activities with the riskiest group benefitting most from feedback as indicated by enhanced glance behavior and driving performance. The findings have implications for developing better crash countermeasures to mitigate the effects of distraction.
Combined dynamic voltage scaling and adaptive body biasing for lower power microprocessors under dynamic workloads (2002)

Dynamic voltage scaling (DVS) reduces the power consumption of processors when peak performance is unnecessary. However, the achievable power savings by DVS alone is becoming limited as leakage power increases. In this paper, we show how the simultaneous use of adaptive body biasing (ABB) and DVS can be used to reduce power in high-performance processors. Analytical models of the leakage current, dynamic power, and frequency as functions of supply voltage and body bias are derived and verified with SPICE simulation. We then show how to determine the correct trade-off between supply voltage and body bias for a given clock frequency and duration of operation. The usefulness of our approach is evaluated on real workloads obtained using real-time monitoring of processor utilization for four applications. The results demonstrate that application of simultaneous DVS and ABB results in an average energy reduction of 48% over DVS alone.
Identification of NTRK fusions in pediatric mesenchymal tumors (2017)

NTRK fusions occur in a subset of young patients with mesenchymal or sarcoma-like tumors at a low frequency, and are eminently druggable targets via either investigational agents or approved drugs.
Multiple-scattering calculations of x-ray-absorption spectra (1995)

A high-order multiple-scattering (MS) approach to the calculation of polarized x-ray-absorption spectra, which includes both x-ray-absorption fine structure and x-ray-absorption near-edge structure, is presented. Efficient calculations in arbitrary systems are carried out by using a curved-wave MS path formalism that ignores negligible paths, and has an energy-dependent self-energy and MS Debye-Waller factors. Embedded-atom background absorption calculations on an absolute energy scale are included. The theory is illustrated for metallic Cu, Cd, and Pt. For these cases the MS expansion is found to converge to within typical experimental accuracy, both to experiment and to full MS theories (e.g., band structure), by using only a few dozen important paths, which are primarily single-scattering, focusing, linear, and triangular.
Telomeric Repeat–Containing RNA and RNA Surveillance Factors at Mammalian Chromosome Ends (2007)

Telomeres, the DNA-protein complexes located at the end of linear eukaryotic chromosomes, are essential for chromosome stability. Until now, telomeres have been considered to be transcriptionally silent. We demonstrate that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA molecules are heterogeneous in length, are transcribed from several subtelomeric loci toward chromosome ends, and localize to telomeres. We also show that suppressors with morphogenetic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated messenger RNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss. Thus, telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.
A simple and highly stereoselective route to E-.alpha.,.beta.-unsaturated aldehydes (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA simple and highly stereoselective route to E-.alpha.,.beta.-unsaturated aldehydesMoncef Bellassoued and Assieh MajidiCite this: J. Org. Chem. 1993, 58, 9, 2517–2522Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/jo00061a027https://doi.org/10.1021/jo00061a027research-articleACS PublicationsRequest reuse permissionsArticle Views1409Altmetric-Citations66LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Nuclear scaffolds and scaffold-attachment regions in higher plants. (1991)

DNA in the nuclei of eukaryotic organisms undergoes a hierarchy of folding to be packaged into interphase and metaphase chromosomes. The first level of packaging is the 11-nm nucleosome fiber, which is further coiled into a 30-nm fiber. Evidence from fungal and animal systems reveals the existence of higher order packaging consisting of loops of the 30-nm fibers attached to a proteinaceous nuclear scaffold by an interaction between the scaffold and specific DNA sequences called scaffold-attachment regions (SARs). Support for the ubiquitous nature of such higher order packaging of DNA is presented here by our work with plants. We have isolated scaffolds from tobacco nuclei using buffers containing lithium diiodosalicylate to remove histones and then using restriction enzymes to remove the DNA not closely associated with the scaffold. We have used Southern hybridization to show that the DNA remaining bound to the scaffolds after nuclease digestion includes SARs flanking three root-specific tobacco genes. This assay for SARs is termed the endogenous assay because it identifies genomic sequences as SARs by their endogenous association with the scaffold. Another assay, the exogenous assay, depends upon the ability of scaffolds to specifically bind exogenously added DNA fragments containing SARs. The tobacco scaffolds specifically bind a well-characterized yeast SAR, and cloned DNA fragments derived from the 3'-flanking regions of the root-specific genes are confirmed to contain SARs by this exogenous assay.