gebhart/patrepeval huggingface dataset:
Transcription of the β-galactoside α2,6-sialyltransferase gene in B lymphocytes is directed by a separate and distinct promoter† (1996)

A single human gene, SIAT1, encodes the beta-galactoside alpha 2,6-sialyltransferase from which multiple mRNA isoforms are generated. In rat, expression of the hepatic mRNA isoform (Form 1) has been defined with respect to the transcriptional initiation site and promoter region. We show here that a similar hepatic SIAT1 mRNA isoform exists in human. Another human mRNA isoform, a mature B-cell-specific mRNA isoform (Form 2), was previously reported. Here, we used 5'-RACE and S1 nuclease protection analysis to define the 5'-untranslated region of Form 2 human SIAT1 mRNA. We demonstrate conclusively that Form 2 mRNA is initiated from a point completely distinct from that of Form 1 mRNA. A number of cis-acting regulatory elements residing immediately 5'of the Form 2 initiation site includes AP-1, AP-2, NF-kappa B, NF-IL6, C/EBP, and CREB. A TATAA box is also present 29 bp 5' of the transcriptional initiation site. CAT reporter gene expression from serially-truncated segments of the 5'-flanking region of the Form 2 initiation site indicates that the segment between -784 and +125 was sufficient to promote high level CAT expression in Louckes, a mature B-cell line. The 5'-flanking region to the human Form 1 initiation site is competent in expression of CAT upon transfection of the fusion construct into HepG2, a human hepatoma cell line. Cellular specificity of expression is apparently retained. Louckes cells expressed CAT efficiently from Form 2 promoter but only marginally from the Form 1 promoter. In contrast, CAT expression from Form 1 promoter is more efficient than from the Form 2 promoter in HepG2 cells.
A stop codon mutation in SCN9A causes lack of pain sensation (2007)

The general lack of pain experience is a rare occurrence in humans, and the molecular causes for this phenotype are not well understood. Here we have studied a Canadian family from Newfoundland with members who exhibit a congenital inability to experience pain. We have mapped the locus to a 13.7 Mb region on chromosome 2q (2q24.3-2q31.1). Screening of candidate genes in this region identified a protein-truncating mutation in SCN9A, which encodes for the voltage-gated sodium channel Na(v)1.7. The mutation is a C-A transversion at nucleotide 984 transforming the codon for tyrosine 328 to a stop codon. The predicted product lacks all pore-forming regions of Na(v)1.7. Indeed, expression of this altered gene in a cell line did not produce functional responses, nor did it cause compensatory effects on endogenous voltage-gated sodium currents when expressed in ND7/23 cells. Because a homozygous knockout of Na(v)1.7 in mice has been shown to be lethal, we explored why a deficiency of Na(v)1.7 is non-lethal in humans. Expression studies in monkey, human, mouse and rat tissue indicated species-differences in the Na(v)1.7 expression profile. Whereas in rodents the channel was strongly expressed in hypothalamic nuclei, only weak mRNA levels were detected in this area in primates. Furthermore, primate pituitary and adrenal glands were devoid of signal, whereas these two glands were mRNA-positive in rodents. This species difference may explain the non-lethality of the observed mutation in humans. Our data further establish Na(v)1.7 as a critical element of peripheral nociception in humans.
Intact cell adhesion to glycan microarrays (2003)

A rapid and reproducible method was developed to detect and quantify carbohydrate-mediated cell adhesion to glycans arrayed on glass slides. Monosaccharides and oligosaccharides were covalently attached to glass slides in 1.7-mm-diameter spots (200 spots/slide) separated by a Teflon gasket. Primary chicken hepatocytes, which constitutively express a C-type lectin that binds to nonreducing terminal N-acetylglucosamine residues, were labeled with a fluorescent dye and incubated in 1.3-microL aliquots on the glycosylated spots. After incubating to allow cell adhesion, nonadherent cells were removed by immersing the slide in phosphate buffered saline, inverting, and centrifuging in a sealed custom acrylic chamber so that cells on the derivatized spots were subjected to a uniform and controlled centrifugal detachment force while avoiding an air-liquid interface. After centrifugation, adherent cells were fixed in place and detected by fluorescent imaging. Chicken hepatocytes bound to nonreducing terminal GlcNAc residues in different linkages and orientations but not to nonreducing terminal galactose or N-acetylgalactosamine residues. Addition of soluble GlcNAc (but not Gal) prior to incubation reduced cell adhesion to background levels. Extension of the method to CD4+ human T-cells on a 45-glycan diversity array revealed specific adhesion to the sialyl Lewis x structure. The described method is a robust approach to quantify selective cell adhesion using a wide variety of glycans and may contribute to the repertoire of tools for the study of glycomics.
Carcinoembryonic Antigen in Histopathology: Immunoperoxidase Staining of Conventional Tissue Sections2 (1976)

A triple-bridge, indirect peroxidase-antiperoxidase method for demonstrating carcinoembryonic antigen (CEA) in frozen, ethanol-fixed or formalin-fixed, paraffin-embedded specimens was evaluated. Examination of 359 tissue specimens--234 malignant tumors, 37 benign neoplasms, 41 nonneoplastic diseased tissues, and 47 normal specimens--showed that CEA could usually be demonstrated in a group of cancers. We could detect CEA in carcinomas of the stomach, colon, rectum, pancreas, lung, and cervix. However, malignant tumors of the breast, prostate, kidney, larynx, brain, lymphoreticular system, soft tissues, and skin proved negative for CEA by the immunoperoxidase test. CEA could be detected in ethanol- or formalin-fixed sections. The only nonmalignant specimens showing CEA staining were a few benign tumors, the mucosae of some cases of colitis, and the resection margins of 2 cases of colon cancer; however, these were commonly very weak reactions. Measurement of tumor CEA content by radioimmunoassay revealed two causes for this relative specificity of the immunoperoxidase test for CEA:1) a quantitative difference existed in tissue CEA among the various specimens, and 2) the threshold for CEA staining in malignant specimens was usually above that in nonmalignant specimens. An analysis of the formalin-paraffin-treated sections showed that immunoperoxidase-tested CEA positivity reflected CEA levels in tissue of at least 3.0-5.0 mug/g; this permitted retrospective estimates of minimal tissue CEA concentrations in older histopathologic specimens by the immunoperoxidase reaction method. Formalin-paraffin-treated sections as old as 10 years still had demonstrable CEA. Although tumor CEA concentration correlated well with immunoperoxidase staining for CEA, plasma CEA titer did not necessarily reflect tumor CEA content. CEA positivity in primary and secondary tumors was strongly correlated; it was less strongly correlated with level of tumor differentiation.
Reducing complexity in computational imaging systems (2003)

Traditional methods of optical design trade optical system complexity for image quality. High quality imagers often require high system complexity. A new imaging methodology called Wavefront Coding uses aspheric optics and signal processing in order to reduce system complexity and deliver high quality imagery. An example in terms of a conformal IR imaging system is given.
An efficient frequency offset estimator for OFDM systems and its performance characteristics (2001)

In this paper, we propose a new frequency synchronization algorithm for orthogonal frequency division multiplexing (OFDM) systems requiring only one training symbol, based on a conventional method which requires two training symbols. While the timing synchronization is obtained by using the conventional method, the carrier frequency offset is efficiently estimated by the proposed method. It is shown that the proposed method not only reduces the number of the training symbols but also possesses better performance than the conventional method without increase in complexity.
2-D Terahertz Metallic Photonic Crystals in Parallel-Plate Waveguides (2007)

2-D metallic photonic crystals without defects, with point defects, and with a Fabry-Perot (F-P) defect are characterized by terahertz time-domain spectroscopy. The metal parallel-plate waveguide (PPWG) with single TEM-mode propagation is used as a tool to simulate 2-D photonic crystals in free space. The 2-D metallic photonic-crystal structures were fabricated by coating Au on an SU-8 polymer cylinder array. Wide terahertz bandgaps were observed in the photonic crystals within the PPWG. The experimental measurements have excellent agreement to 2-D photonic-crystal theory without defects. Defect modes are observed in the samples with defects and show the F-P defect has a strong localization effect
Methionine residues as endogenous antioxidants in proteins (1996)

Cysteine and methionine are the two sulfur-containing residues normally found in proteins. Cysteine residues function in the catalytic cycle of many enzymes, and they can form disulfide bonds that contribute to protein structure. In contrast, the specific functions of methionine residues are not known. We propose that methionine residues constitute an important antioxidant defense mechanism. A variety of oxidants react readily with methionine to form methionine sulfoxide, and surface exposed methionine residues create an extremely high concentration of reactant, available as an efficient oxidant scavenger. Reduction back to methionine by methionine sulfoxide reductases would allow the antioxidant system to function catalytically. The effect of hydrogen peroxide exposure upon glutamine synthetase from Escherichia coli was studied as an in vitro model system. Eight of the 16 methionine residues could be oxidized with little effect on catalytic activity of the enzyme. The oxidizable methionine residues were found to be relatively surface exposed, whereas the intact residues were generally buried within the core of the protein. Furthermore, the susceptible residues were physically arranged in an array that guarded the entrance to the active site.
Modification of tumor cell exosome content by transfection with wt-p53 and microRNA-125b expressing plasmid DNA and its effect on macrophage polarization (2016)

Exosomes are responsible for intercellular communication between tumor cells and others in the tumor microenvironment. These microvesicles promote oncogensis and can support towards metastasis by promoting a pro-tumorogenic environment. Modifying the exosomal content and exosome delivery are emerging novel cancer therapies. However, the clinical translation is limited due to feasibility of isolating and delivery of treated exosomes as well as an associated immune response in patients. In this study, we provide proof-of-concept for a novel treatment approach for manipulating exosomal content by genetic transfection of tumor cells using dual-targeted hyaluronic acid-based nanoparticles. Following transfection with plasmid DNA encoding for wild-type p53 (wt-p53) and microRNA-125b (miR-125b), we evaluate the transgene expression in the SK-LU-1 cells and in the secreted exosomes. Furthermore, along with modulation of wt-p53 and miR-125b expression, we also show that the exosomes (i.e., wt-p53/exo, miR-125b/exo and combination/exo) have a reprogramed global miRNA profile. The miRNAs in the exosomes were mainly related to the activation of genes associated with apoptosis as well as p53 signaling. More importantly, these altered miRNA levels in the exosomes could mediate macrophage repolarization towards a more pro-inflammatory/antitumor M1 phenotype. However, further studies, especially in vivo studies, are warranted to assess the direct influence of such macrophage reprogramming on cancer cells and oncogenesis post-treatment. The current study provides a novel platform enabling the development of therapeutic strategies affecting not only the cancer cells but also the tumor microenvironment by utilizing the 'bystander effect' through genetic transfer with secreted exosomes. Such modification could also support antitumor environment leading to decreased oncogenesis.
Molecular Properties of Corticosteroid Binding Globulin and the Sex-Steroid Binding Proteins* (1990)

AVARIETY of extracellular binding proteins enhance the solubility of steroid hormones in biological fluids and facilitate their transport from steroidogenic tissues to target cells (1). In mammals, albumin is quantitatively the most important of these proteins and provides a large reservoir of loosely bound hormone that may be released within some target tissues (2). Two albumin-related proteins, vitamin D binding protein and α-fetoprotein, also appear to have arisen by duplication of a common ancestral gene (3) and are characterized by higher affinities and specificities for steroid ligands. The molecular composition and structure of the vitamin D binding protein have already been described in detail (4), and this review will concentrate on the molecular properties of two other biologically important classes of extracellular steroid binding proteins: corticosteroid binding globulin (CBG) and the sex-steroid binding proteins; sex hormone binding globulin (SHBG) and androgen binding protein (ABP). These proteins are far less abundant than those of the albumin superfamily, but they bind biologically active steroid hormones with remarkably high affinity and specificity. As a result, they not only transport steroid hormones but also modulate steroid bioavailability (5), and may participate directly in the delivery of steroids to certain cells by interaction with plasma membrane receptors (6). Indeed, it is becoming increasingly obvious that their activities may be attributed to unique structural properties; a greater understanding of which may help define their physiological importance.
Synthesis of cholera toxin is positively regulated at the transcriptional level by toxR. (1984)

We have cloned a positive regulatory gene ( toxR ) from Vibrio cholerae that controls cholera toxin transcription. This was done by first constructing a genetic fusion consisting of the lacZ gene fused to the promoter of the cholera toxin operon ctxAB . This operon fusion was used to screen a V. cholerae genomic library for genes that could activate the ctx promoter in Escherichia coli. This method allowed the identification of a gene, toxR , that increases ctx expression by more than 100-fold. Complementation analysis indicated that certain hypotoxinogenic mutants of V. cholerae 569B probably have mutations in the toxR gene. Southern blot analysis suggests that all V. cholerae, including nontoxinogenic strains, have the toxR gene. Moreover, nontoxinogenic strains not only lack the structural genes for cholera toxin but also sequences associated with the larger 7-kilobase ctx genetic element.
Satisfiability modulo theories (2011)

Checking the satisfiability of logical formulas, SMT solvers scale orders of magnitude beyond custom ad hoc solvers.
Ultra high resolution pinhole SPECT (2002)

The aim of the study is to develop an ultra high-resolution pinhole SPECT system and analyze the performance by simulations. The pinhole SPECT was conducted with a Toshiba GCA-7200A gamma camera. The diameter of the pinhole was 1 mm. Data were acquired with a 128/spl times/128 matrix, and the distance from the center of rotation to the pinhole was 20 mm. The data were collected at 4 degree increments over 360 degrees. The Feldkamp method was used for image reconstruction. Before the image reconstruction, the authors corrected the center of rotation of the pinhole collimator. The imaging voxel was 0.27/spl times/0.27/spl times/0.27 mm/sup 3/. From the experiments with a resolution phantom the spatial resolution was 1.05 mm (FWHM). The pinhole SPECT was also examined for in vivo imaging for studies of the heart in mice which were injected with Tc-99m-Tetrofosmin intravenously. In the reconstructed image the heart muscle of the mouse was clearly visualized. The authors also investigated the spatial resolution of the reconstructed image by means of simulations. The spatial resolution obtained from the simulation was 0.86 mm (FWHM).
Birth size and subsequent risk for prostate cancer: A prospective population-based study in Norway (2004)

Studies on birth size characteristics and adult risk for prostate cancer have been few and inconclusive. We prospectively examined the association between birth size and risk for prostate cancer with particular emphasis on metastatic disease. A total of 19,681 singleton males born between 1920 and 1958, whose birth records were kept at St. Olav's University Hospital (Trondheim, Norway), were followed up for prostate cancer by linkage to the Norwegian Cancer Registry. A total of 159 cases of prostate cancer were diagnosed during follow-up; 33 had metastases at diagnosis. Overall, there was little evidence for any association between birth size and prostate cancer risk; however, there was a positive association for birth size and metastatic disease. Men in the highest quartile of birth length (> or =53 cm) had a relative risk of 2.5 (95% CI 1.0-6.3) compared to men in the lowest quartile (<51 cm). Further, men in the highest quartile of both birth weight and birth length had a relative risk of 3.8 (95% CI 1.2-12.0) for metastatic prostate cancer compared to men in the lowest category of both factors. These results support the hypothesis that factors that determine intrauterine growth could be important for aggressive forms of prostate cancer in adulthood.
Effect of E‐64, Thiol Protease Inhibitor, on the Secondary Anti‐SRBC Response In Vitro (1984)

E-64, L-trans-epoxysuccinyl- leucylamido (4-guanidino) butane, a specific inhibitor of thiol proteases originally isolated from the culture of a fungus, was examined in connection with the immune responses to the splenocytes of mice. In cultures of C3H/He mouse splenocytes, E-64 and its analogues showed mitogenic activity, and some of them enhanced the lymphocyte blast transformation induced by a suboptimal concentration of concanavalin A. E-64 caused a significant suppressive effect on the secondary anti-SRBC responses when 7- or 14-day-primed BDF1 mouse splenocytes were cultured with SRBC, while it induced no effect on cultured splenocytes either from mice treated with cyclophosphamide, from mice sensitized with dinitrophenyl-Ficoll. The results with E-64 and its close analogues revealed that their effects on the immune response roughly correlated with their inhibitory activity against thiol protease. These results suggest that a thiol protease might be involved in the process of secondary immune response in mouse splenocytes.
Signal transduction in chemotaxis to oxygen in Escherichia coli and Salmonella typhimurium (1988)

Pathways previously proposed for sensory transduction in chemotaxis to oxygen (aerotaxis) involved either (i) cytochrome o, the electron transport system, and proton motive force or (ii) enzyme IIGlucose and the phosphoenolpyruvate:carbohydrate phosphotransferase system for active transport. This investigation distinguished between these possibilities. Aerotaxis was absent in a cyo cyd strain of Escherichia coli that lacked both cytochrome o and cytochrome d, which are the terminal oxidases for the branched electron transport system in E. coli. Aerotaxis, measured by either a spatial or temporal assay, was normal in E. coli strains that had a cyo+ or cyd+ gene or both. The membrane potential of all oxidase-positive strains was approximately -170 mV in aerated medium at pH 7.5. Behavioral responses to changes in oxygen concentration correlated with changes in proton motive force. Aerotaxis was normal in ptsG and ptsI strains that lack enzyme IIGlucose and enzyme I, respectively, and are deficient in the phosphotransferase system. A cya strain that is deficient in adenylate cyclase also had normal aerotaxis. We concluded that aerotaxis was mediated by the electron transport system and that either the cytochrome d or the cytochrome o branch of the pathway could mediate aerotaxis.
Determination of the Absolute P-Configuration of a Phthalidyl-Phosphonate Thymidine-Thymidine Dimer (2003)

Phthalidyl modified oligonucleotide thymidine-thymidine dimer building blocks were synthesized via the H-phosphonate-method. The compounds which are diastereomeric at the phosphorus atom were separated by chromatography and the absolute configuration at the phosphorus atoms was determined using ROE-experiments using the corresponding methyl-phosphonates.
Design and Evaluation of a Real-World Virtual Environment for Architecture and Urban Planning (2007)

In this paper we present a user-centered design approach to the development of a Virtual Environment (VE), by utilizing an iterative, user-informed process throughout the entire design and development cycle. A preliminary survey was first undertaken with end users, that is, architects, chief engineers, and decision makers of a real-world architectural and urban planning project, followed by a study of the traditional workflow employed. We then determined the elements required to make the VE useful in the real-world setting, choosing appropriate graphical and auditory techniques to develop audiovisual VEs with a high level of realism. Our user-centered design approach guided the development of an appropriate interface and an evaluation methodology to test the overall usability of the system. The VE was evaluated both in the laboratory and, most importantly, in the users' natural work environments. In this study we present the choices we made as part of the design and evaluation methodologies employed, which successfully combined research goals with those of a real-world project. Among other results, this evaluation suggests that involving users and designers from the beginning improves the effectiveness of the VE in the context of the real world urban planning project. Furthermore, it demonstrates that appropriate levels of realism, in particular spatialized 3D sound, high-detail vegetation, and shadows, as well as the presence of rendered crowds, are significant for the design process and for communicating about designs; they enable better appreciation of overall ambience of the VE, perception of space and physical objects, as well as the sense of scale. We believe this study is of interest to VE researchers, designers, and practitioners, as well as professionals interested in using VR in their workplace.
Solvent effects in the hydrodechlorination of 2,4‐dichlorophenol over Pd/Al2O3 (2009)

Abstract Solvent effects in the liquid phase (0.1 MPa; 303 K) hydrodechlorination (HDC) of 2,4‐dichlorophenol have been established over Pd/Al 2 O 3 . In the absence of secondary reactions, catalyst deactivation, and transport limitations, a stepwise HDC yields 2‐chlorophenol and phenol, where product selectivity was insensitive to the nature of the solvent. In contrast, the initial HDC rates exhibited a marked dependence on the reaction medium and increased in the order: benzene &lt; THF &lt; n ‐hexane &lt; cyclohexane &lt; alcohols &lt; water. Higher rates result from the concomitant effect of an increase in the dielectric constant (ε) and a decrease in the molar volume ( $\overline {\nu}$ ) of the solvent, where the major (ca. 80%) contribution is due to ε. We attribute this response to the increased solvent capacity to stabilize the arenium intermediate at higher/lower ε/ $\overline {\nu}$ , an effect that extends to reaction in water + organic combinations. We provide, for the first time, a reliable quantification of solvent effects that can be potentially applied to other catalytic hydrogenolysis systems. © 2009 American Institute of Chemical Engineers AIChE J, 2010