gebhart/patrepeval huggingface dataset:
A sugar-quinoline fluorescent chemosensor for selective detection of Hg2+ ion in natural water (2006)

A selective and sensitive fluorescent sensor for detection of Hg2+ in natural water was achieved by incorporating the well-known fluorophore quinoline group and a water-soluble D-glucosamine group within one molecule.
Detection of Methicillin-ResistantStaphylococcus aureusand Simultaneous Confirmation by Automated Nucleic Acid Extraction and Real-Time PCR (2002)

A molecular assay for the simultaneous detection of a Staphylococcus aureus-specific gene and the mecA gene, responsible for the resistance to methicillin in staphylococci, was evaluated. The assay included an automated DNA extraction protocol conducted with a MagNA Pure instrument and real-time PCR conducted with a LightCycler instrument. The performance and robustness of the assay were evaluated for a suspension of methicillin-resistant S. aureus (MRSA) strain with a turbidity equivalent to a McFarland standard of 0.5, which was found to be the ideal working concentration. The specificity of the new molecular assay was tested with a panel of 30 gram-negative and gram-positive bacterial strains other than MRSA. No cross-reactivity was observed. In a clinical study, 109 isolates of MRSA were investigated. All clinical MRSA isolates gave positive results for the S. aureus-specific genomic target, and all but one were positive for the mecA gene. In conclusion, the new molecular assay was found to be quick, robust, and laborsaving, and it proved to be suitable for a routine molecular diagnostic laboratory.
Codon usage in yeast: cluster analysis clearly differentiates highly and lowly expressed genes (1986)

Codon usage data has been compiled for 110 yeast genes. Cluster analysis on relative synonymous codon usage revealed two distinct groups of genes. One group corresponds to highly expressed genes, and has much more extreme synonymous codon preference. The pattern of codon usage observed is consistent with that expected if a need to match abundant tRNAs, and intermediacy of tRNA-mRNA interaction energies are important selective constraints. Thus codon usage in the highly expressed group shows a higher correlation with tRNA abundance, a greater degree of third base pyrimidine bias, and a lesser tendency to the A+T richness which is characteristic of the yeast genome. The cluster analysis can be used to predict the likely level of gene expression of any gene, and identifies the pattern of codon usage likely to yield optimal gene expression in yeast.
Hypoxic up-regulation of erythroid 5-aminolevulinate synthase (2002)

The erythroid-specific isoform of 5-aminolevulinate synthase (ALAS2) catalyzes the rate-limiting step in heme biosynthesis. The hypoxia-inducible factor-1 (HIF-1) transcriptionally up-regulates erythropoietin, transferrin, and transferrin receptor, leading to increased erythropoiesis and hematopoietic iron supply. To test the hypothesis that ALAS2 expression might be regulated by a similar mechanism, we exposed murine erythroleukemia cells to hypoxia (1% O(2)) and found an up to 3-fold up-regulation of ALAS2 mRNA levels and an increase in cellular heme content. A fragment of the ALAS2 promoter ranging from -716 to +1 conveyed hypoxia responsiveness to a heterologous luciferase reporter gene construct in transiently transfected HeLa cells. In contrast, iron depletion, known to induce HIF-1 activity but inhibit ALAS2 translation, did not increase ALAS2 promoter activity. Mutation of a previously predicted HIF-1-binding site (-323/-318) within this promoter fragment and DNA-binding assays revealed that hypoxic up-regulation is independent of this putative HIF-1 DNA-binding site.
Dinucleotide repeat polymorphism in human GLUT2/liver facilitative glucose transporter gene on chromosome 3 (1991)

Journal Article Dinucleotide repeat polymorphism in human GLUT2/liver facilitative glucose transporter gene on chromosome 3 Get access M. Granqvist, M. Granqvist Howard Hughes Medical Institute, University of Chicago5841 S. Maryland Avenue, Box 391, Chicago, IL 60637, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Xiang, K. Xiang Howard Hughes Medical Institute, University of Chicago5841 S. Maryland Avenue, Box 391, Chicago, IL 60637, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Seino, M. Seino Howard Hughes Medical Institute, University of Chicago5841 S. Maryland Avenue, Box 391, Chicago, IL 60637, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Fukumoto, H. Fukumoto Howard Hughes Medical Institute, University of Chicago5841 S. Maryland Avenue, Box 391, Chicago, IL 60637, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar G.I. Bell G.I. Bell * Howard Hughes Medical Institute, University of Chicago5841 S. Maryland Avenue, Box 391, Chicago, IL 60637, USA * To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 17, 11 September 1991, Page 4791, https://doi.org/10.1093/nar/19.17.4791 Published: 11 September 1991
Characterization of isocitrate dehydrogenase from the green sulfur bacterium Chlorobium limicola (2002)

Isocitrate dehydrogenase (IDH) catalyzes the reversible conversion between isocitrate and 2-oxoglutarate accompanied by decarboxylation/carboxylation and oxidoreduction of NAD(P)+ cofactor. While this enzyme has been well studied as a catabolic enzyme in the tricarboxylic acid (TCA) cycle, here we have characterized NADP-dependent IDH from Chlorobium limicola, a green sulfur bacterium that fixes CO2 through the reductive tricarboxylic acid (RTCA) cycle, focusing on the CO2-fixation ability of the enzyme. The gene encoding Cl-IDH consisted of 2226 bp, corresponding to a polypeptide of 742 amino acid residues. The primary structure and the size of the recombinant protein indicated that Cl-IDH was a monomeric enzyme of 80 kDa distinct from the dimeric NADP-dependent IDHs predominantly found in bacteria or eukaryotic mitochondria. Apparent Michaelis constants for isocitrate (45 +/- 13 microm) and NADP+ (27 +/- 10 microm) were much smaller than those for 2-oxoglutarate (1.1 +/- 0.5 mm) and CO2 (1.3 +/- 0.3 mm). No significant differences in kinetic properties were observed between Cl-IDH and the dimeric, NADP-dependent IDH from Saccharomyces cerevisiae (Sc-IDH) at the optimum pH of each enzyme. However, in contrast to the 20% activity of Sc-IDH toward carboxylation as compared with that toward decarboxylation at pH 7.0, the activities of Cl-IDH for both directions were almost equivalent at this pH, suggesting a more favorable property of Cl-IDH than Sc-IDH as a CO2-fixation enzyme under physiological pH. Furthermore, we found that among various intermediates, oxaloacetate was a competitive inhibitor (K(i) = 0.35 +/- 0.04 mm) for 2-oxoglutarate in the carboxylation reaction by Cl-IDH, a feature not found in Sc-IDH.
Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor Fails to Interact with G-proteins (1995)

The binding of insulin-like growth factor II (IGF II) to the mannose 6-phosphate (M6P)/IGF II receptor has previously been reported to induce the activation of trimeric G(i)2 proteins by functional coupling to a 14-amino acid region within the cytoplasmic receptor domain (Nishimoto, I., Murayama, Y., Katada, T., Ui, M., and Ogata, E. (1989) J. Biol. Chem. 264, 14029-14038). In the present study, we examined further the potential functional coupling of G-proteins with the human M6P/IGF II receptor and mutant receptors lacking the proposed G-protein activator sequence. IGF II treatment of mouse L-cells expressing either wild type or mutant M6P/IGF II receptors failed to attenuate the pertussis toxin-catalyzed modification of a 40-kDa protein or enhance GTPase activity. In broken L-cell membranes expressing wild type or mutant M6P/IGF II receptors, 30 nM IGF II also failed to affect the pertussis toxin substrate activity. By using phospholipid vesicles reconstituted with human wild type or mutant M6P/IGF II receptors and pertussis toxin-sensitive G-proteins, no stimulation of GTP gamma S binding to or GTPase activity of G(i)2, G(o)1, or G(i)/G(o) mixtures were observed in response to 1 microM IGF II. Furthermore, in vesicles containing purified wild type M6P/IGF II receptors and monomeric G alpha o1 or G alpha i2 and beta gamma dimers no effects of IGF II on GTP gamma S binding could be detected. However, when vesicles reconstituted with M6P/IGF II receptors and G(i)2 proteins were incubated with 100 microM mastoparan GTP gamma S binding was stimulated and GTPase activity was increased significantly. These results indicate that the human M6P/IGF II receptor neither interacts with G-proteins in mouse L-cell membranes nor is coupled to G(i)2 proteins in phospholipid vesicles. This study suggests strongly that the M6P/IGF II receptor does not function in transmembrane signaling in response to IGF II.
Online Measurement of Urea Concentration in Spent Dialysate during Hemodialysis (2004)

Urea concentrations can be continuously monitored during hemodialysis by near-infrared spectroscopy. Calibrations based on the net analyte signal of urea are particularly appealing because they do not require a training step, as do statistical multivariate calibration procedures such as partial least-squares regression.
Cold nerve injury is enhanced by intermittent cooling (1999)

Clinically nonfreezing cold nerve injury (NFCNI) is often preceded by fluctuating ambient temperatures. To simulate this we exposed the sciatic nerve of Wistar rats to intermittent cooling and rewarming. This paradigm was contrasted with one in which the sciatic nerve was continuously cooled. Despite an identical duration and degree of sciatic nerve cooling in both experiments, the pathology, as assessed neurophysiologically and morphologically, was much more severe when the nerve was intermittently cooled. It is likely that this exaggerated pathology is a result of repeated reperfusion injury. These experimental results suggest the need for a trial of free radical scavengers or antioxidants in models of NFCNI.
Antimicrobial Peptides (AMPs): Peptide Structure and Mode of Action (2005)

Antimicrobial peptides (AMPs) have been isolated and characterized from tissues and organisms representing virtually every kingdom and phylum. Their amino acid composition, amphipathicity, cationic charge, and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of AMP activity, their relevance to resolving how peptides damage and kill microorganisms still needs to be clarified. Moreover, many AMPs employ sophisticated and dynamic mechanisms of action to carry out their likely roles in antimicrobial host defense. Recently, it has been speculated that transmembrane pore formation is not the only mechanism of microbial killing by AMPs. In fact, several observations suggest that translocated AMPs can alter cytoplasmic membrane septum formation, reduce cell-wall, nucleic acid, and protein synthesis, and inhibit enzymatic activity. In this review, we present the structures of several AMPs as well as models of how AMPs induce pore formation. AMPs have received special attention as a possible alternative way to combat antibiotic-resistant bacterial strains. It may be possible to design synthetic AMPs with enhanced activity for microbial cells, especially those with antibiotic resistance, as well as synergistic effects with conventional antibiotic agents that lack cytotoxic or hemolytic activity.
Toward an AIDS Vaccine (2008)

A quarter century of scientific discovery has been applied to developing an AIDS vaccine, yet this goal remains elusive. Specific characteristics of the virus, including the extreme genetic variability in circulating viral isolates worldwide, biological properties of HIV that impede immune attack, and a high mutation rate that allows for rapid escape from adaptive immune responses, render this a huge challenge. However, evidence of protection against AIDS viruses in animal models and control of HIV in humans under certain circumstances, together with scientific advances in understanding disease pathogenesis, provide a strong rationale and objective paths to continue the pursuit of an effective AIDS vaccine to stem the global epidemic.
Dicrotic notch detection using wavelet transform analysis (2002)

The objective of this research was to devise a method of accurately and consistently extracting the dicrotic notch from the aortic blood pressure signal for various heart rates and arrhythmias. The aortic blood pressure signal has been analyzed by calculating the wavelet transform at several scales to consistently detect the temporal location of the dicrotic notch. The simultaneous locations of the peaks in the wavelet transforms of the first derivative of the aortic pressure waveform across 2 consecutive scales corresponds to the location of the dicrotic notch. A final algorithm analyzes the transform results and labels the notch point. Locating the dicrotic notch is critical for analyzing systolic time interval.
Attomole-Sensitivity Electrospray Source for Large-Molecule Mass Spectrometry (1995)

Full mass spectra of high resolving power are obtained from 0.2 nL sample volumes of large (> 10 kDa) nucleotides and proteins using a new electrospray ionization (ESI) system combined with Fourier transform mass spectrometry. The ESI needles are fabricated by laser-heated pulling of fused-silica tubing (5-20 microns i.d.), followed by chemical etching and surface metalization. Total analyte loaded at the instrument of 8.6 fmol and 216 amol produces signal-to-noise ratios of 400:1 and 60:1, respectively, and resolving power of > 10(5) for full mass spectra, while the total amount of material consumed is approximately 150 and 10 amol, respectively.
New developments in therapeutic ultrasound (1996)

The main purpose of this article is to review selective research and developments during the last decade in the field. There has been tremendous progress in engineering and science coupled with ultrasound transducer technology and imaging modalities during the last 10 years. These new R and D efforts have enhanced the capabilities of ultrasound therapy, and it now appears that the ultrasound therapy base will be expanded for clinical applications, particularly as noninvasive surgery becomes a more acceptable method of treatment. This article limits its review to novel developments in ultrasound hyperthermia and noninvasive ultrasound surgery. Along with descriptions of ultrasound devices and new accompanying techniques such as magnetic resonance image (MRI) guided noninvasive surgery, some relevant clinical results are summarized as a measure of progress.
Interaction of androgen-induced autocrine heparin-binding growth factor with fibroblast growth factor receptor on androgen-dependent Shionogi carcinoma 115 cells. (1990)

Stimulation of a Shionogi carcinoma 115-derived cultured cell line (SC-3) with androgen resulted in secretion of heparin-binding growth factor. In this study, we analyzed cell-surfaced receptors for growth factors. Binding data of growth factors on intact SC-3 cells revealed the presence of low and high affinity receptors for epidermal growth factor (EGF), insulin, and fibroblast growth factor (FGF). The dissociation constant values were 50 pM and 1.0 nM for EGF, 1.2 nM and 30 nM for insulin, and 34 pM and 7.5 nM for FGF. The numbers of maximal binding sites were 300 and 900/cell for EGF, 2,000 and 14,000/cell for insulin, and 13,000 and 810,000/cell for FGF. To examine the association of androgen-induced growth factor with one of these receptors, the conditioned medium prepared from androgen-stimulated SC-3 cells was fractionated through a heparin-Sepharose column. Growth factor activity adsorbed and eluted by 1 M NaCl from the column was comigrated with the activity inhibiting FGF-receptor association. In addition, basic 125I-FGF was cross-linked, using disuccinimidyl suberate, to the receptor with an apparent molecular weight of 130,000, whose labeling was inhibited when basic FGF, acidic FGF, or highly purified androgen-induced growth factor was present in excess. Furthermore, the highly purified growth factor-, basic FGF- or androgen-induced growth of SC-3 cells was significantly and similarly inhibited by anti-basic FGF antibody IgG. These results indicate that androgen-induced FGF-like factor acts as an autocrine growth factor via the FGF receptor in a process of SC-3 cell proliferation.
Dystrophin and Utrophin Bind Actin through Distinct Modes of Contact (2006)

This study was designed to define the molecular epitopes of dystrophin-actin interaction and to directly compare the actin binding properties of dystrophin and utrophin. According to our data, dystrophin and utrophin both bound alongside actin filaments with submicromolar affinities. However, the molecular epitopes involved in actin binding differed between the two proteins. In utrophin, the amino-terminal domain and an adjacent string of the first 10 spectrin-like repeats more fully recapitulated the activities measured for full-length protein. The homologous region of dystrophin bound actin with low affinity and near 1:1 stoichiometry as previously measured for the isolated amino-terminal, tandem (CH) domain. In contrast, a dystrophin construct including a cluster of basic spectrin-like repeats and spanning from the amino terminus through repeat 17, bound actin with properties most similar to full-length dystrophin. Dystrophin and utrophin both stabilized preformed actin filaments from forced depolymerization with similar efficacies but did not appear to compete for binding sites on actin. We also found that dystrophin binding to F-actin was markedly sensitive to increasing ionic strength, although utrophin binding was unaffected. Although dystrophin and utrophin are functionally homologous actin-binding proteins, these results indicate that their respective modes of contact with actin filaments are markedly different. Finally, we reassessed the abundance of dystrophin in striated muscle using full-length protein as the standard and measured greater than 10-fold higher values than previously reported.
CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear cell TNF-α and MMP-3 production in patients with inflammatory bowel disease (2009)

These results provides a mechanistic rationale for both the failure of lenalidomide (CC-5013) in a recent randomised controlled trial in Crohn's disease, and for the evaluation of CC-10004 as a novel oral therapy in the treatment of CD and UC.
Carcinoembryonic Antigen (1986)

The level of carcinoembryonic antigen (CEA) is often elevated in the serum of patients with cancer. This article reviews the clinical usefulness of this observation. Carcinoembryonic antigen is not useful for detecting asymptomatic cancer; its sensitivity and specificity are not high, particularly for early stages of disease, so in populations with low prevalence of disease there are many false-positive and false-negative results. Similarly, the antigen level cannot, by itself, provide enough diagnostic certainty to confirm or rule out suspected cancer. For some cancers, antigen levels at the time of diagnosis provide more precise prognosis than staging alone, but this information does not lead to more effective treatment. Serial measurement of CEA levels after surgery in patients with colorectal cancer can detect recurrences early, but few lives can be saved by this approach. Thus, CEA assays provide accurate information about some aspects of cancer but rarely lead to better outcomes for patients.
Abstract 13189: Cardiovascular Evaluation of the Selective BET Inhibitor, Apabetalone, in ACS Patients With Diabetes: Baseline Characteristics of the BETonMACE CV Outcomes Study (2018)

Introduction: Vascular perturbation in acute coronary syndrome (ACS) is linked to inflammation. Bromodomain and extraterminal (BET) proteins coordinate gene transcription following inflammatory ins...
Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury. (1989)

Cyclic variations in coronary blood flow (CFVs) in dogs with experimental coronary artery stenosis and endothelial injury appear to result primarily from the aggregation of platelets at the site of stenosis followed by dislodgement and distal embolization. Using this canine model, we tested the hypotheses: (a) that thrombin is an important mediator of CFVs in dogs with coronary stenoses and endothelial injury; (b) that inhibition of thrombin with heparin, or MCI-9038, a selective thrombin inhibitor, abolishes CFVs in this model; and (c) that abolition of CFVs by thrombin inhibition is time dependent. CFVs, produced in open-chest dogs by placing a flow-reducing plastic constrictor around the left anterior coronary artery, were monitored for either 30 min (group I) or 3 h (group II) before treatment with either heparin or 4-methyl-1-(N2-[(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl (MCI-9038). In group I, cyclic flow variations were abolished by heparin in 12 of 18 dogs and by MCI-9038 in 5 of 7 dogs. In group II, cyclic flow variations were not abolished by heparin in any of seven dogs and were abolished by MCI-9038 in only one of seven dogs. Thus, (a) thrombin appears to be an important mediator of cyclic flow variations in dogs with coronary artery stenosis and endothelial injury and (b) inhibition of thrombin abolishes CFVs after short but not prolonged periods of CFVs.
AEETES: A solar reflux receiver thermal performance numerical model (1991)

Reflux solar receivers for dish-Stirling electric power generation systems are currently being investigated by several companies and laboratories. In support of these efforts, the AEETES thermal performance numerical model has been developed to predict thermal performance of pool-boiler and heat-pipe reflux receivers. The formulation of the AEETES numerical model, which is applicable to axisymmetric geometries with asymmetric incident fluxes, is presented in detail. Thermal efficiency predictions agree to within 4.1% with test data from on-sun tests of a pool-boiler reflux receiver. Predicted absorber and sidewall temperatures agree with thermocouple data to within 3.3 and 7.3%, respectively. The importance of accounting for the asymmetric incident fluxes is demonstrated in comparisons with predictions using azimuthally averaged variables. The predicted receiver heat losses are characterized in terms of convective, solar radiative, and infrared radiative, and conductive heat transfer mechanisms.
Pralatrexate Pharmacology and Clinical Development (2013)

Folates are well known to be essential for many cellular processes, including cellular proliferation. As a consequence, antifolates, the fraudulent mimics of folic acid, have been shown to be potent therapeutic agents in many cancers. Over the past several decades, efforts to improve on this class of drugs have met with little success. Recently, one analog specifically designed to have high affinity for the reduced folate carrier, which efficiently internalizes natural folates and antifolates, has been shown to be very active in T-cell lymphoma. Pralatrexate, approved by the U.S. Food and Drug Administration in 2009, is highly active across many lymphoid malignancies, including chemotherapy-resistant T-cell lymphoma. Emerging combination studies have now shown that pralatrexate is highly synergistic with gemcitabine, histone deacetylase inhibitors like romidepsin and bortezomib. These insights are leading to a number of novel phase I and II combination studies which could challenge existing regimens like CHOP, and improve the outcome of patients with T-cell lymphoma.