gebhart/patrepeval huggingface dataset:
Immunomagnetic recovery of Chlamydia trachomatis from urine with subsequent colorimetric DNA detection. (1992)

There is need for integrated systems that provide rapid and sensitive diagnosis of Chlamydia trachomatis. Here we describe for the first time that specific antibodies to a C. trachomatis surface protein can be used for magnetic recovery of bacteria directly from crude urine samples. The combination of immunomagnetic separation (IMS), where the bacterial cells are both purified and concentrated, with a colorimetric PCR assay makes the method sensitive and suitable for routine clinical screening in microtiter format. No filtrations, centrifugations, extractions, or electrophoretic techniques are required throughout the whole procedure. Using magnetic beads as the solid phase, the colorimetric detection of immobilized amplified nucleic acids (DIANA) also allow direct DNA sequencing of positive samples for more detailed analysis. Of the 27 urine samples analyzed, eight were found to be positive using this method. Only five out of these eight were determined to be positive by cell culture.
γ-Phosphate-substituted 2′-Deoxynucleoside 5′-Triphosphates as Substrates for DNA Polymerases (1996)

Several 2'-deoxythymidine 5'-triphosphate and 3'-azido-2', 3'-dideoxythymidine 5'-triphosphate analogs containing a hydrophobic phosphonate group instead of the gamma-phosphate were synthesized and evaluated as substrates for human immunodeficiency virus (HIV) and avian myeloblastosis virus reverse transcriptases, human placental DNA polymerases alpha and beta, and calf thymus terminal deoxynucleotidyl transferase. They were efficiently incorporated into the DNA chain by the retroviral enzymes but were not utilized by the mammalian ones. Also, some gamma-ester and gamma-amide derivatives of dTTP and 3'-azido-2',3'-dideoxythymidine 5'-triphosphate (AZTTP) were synthesized and studied. They proved to be substrates for both the retroviral and mammalian enzymes under study. The Km values for incorporation of the dTTP derivatives into the DNA chain were close to those for dTTP and AZTTP. The Km for the AZTTP derivatives were one order of magnitude greater than those for dTTP and AZTTP. The results obtained indicate that HIV and avian myeloblastosis virus reverse transcriptases have no sterical obstacles for binding the triphosphate fragment bearing a bulky substituent at the gamma-position. Modification of the gamma-phosphate in AZTTP increased the selectivity of HIV reverse transcriptase inhibition versus DNA polymerase alpha. gamma-Methylphosphonate and gamma-phenylphosphonate were dephosphorylated in human serum much less rapidly than AZTTP. Besides, they were shown to be markedly more hydrophobic than AZTTP. Thus, replacement of the gamma-phosphate in AZTTP with gamma-phosphonate markedly alters its substrate properties toward some cellular DNA polymerases and blood dephosphorylating enzymes but does not change its substrate activity with respect to HIV reverse transcriptase.
Kinetic Characterization of Protein Arginine Deiminase 4:  A Transcriptional Corepressor Implicated in the Onset and Progression of Rheumatoid Arthritis (2005)

Protein arginine deiminase 4 (PAD4) is a Ca(2+)-dependent enzyme that catalyzes the posttranslational conversion of arginine to citrulline (Arg --> Cit) in a number of proteins, including histones. While the gene encoding this enzyme has been implicated in the pathophysiology of rheumatoid arthritis (RA), little is known about its mechanism of catalysis, its in vivo role, or its role in the pathophysiology of RA; however, recent reports suggest that this enzyme can act as a transcriptional corepressor for the estrogen receptor. Herein, we report our initial kinetic and mechanistic characterization of human PAD4. Specifically, these studies confirm that PAD4 catalyzes the hydrolytic deimination of Arg residues to produce Cit and ammonia. The metal dependence of PAD4 has also been evaluated, and the results indicate that PAD4 activity is highly specific for calcium. Calcium activation of PAD4 catalysis exhibits positive cooperativity with K(0.5) values in the mid to high micromolar range. Evidence indicating that calcium binding causes a conformational change is also presented. Additionally, the steady-state kinetic parameters for a number of histone H4-based peptide substrates and benzoylated Arg derivatives have been determined. K(m) values for these compounds are in the high micromolar to the low millimolar range with k(cat) values ranging from 2.8 to 6.6 s(-)(1). The ability of PAD4 to catalyze the deimination of methylated Arg residues has also been evaluated, and the results indicate that these compounds are poor PAD4 substrates (V/K <or= 31.3 M(-)(1) s(-)(1)) in comparison to other substrates. These findings suggest that the full-length enzyme does not catalyze this reaction in vitro and possibly in vivo either. Collectively, the studies described herein will provide a firm foundation for the future development of PAD4 selective inhibitors.
Characterization of the Bystander Effect of Somatostatin Receptor sst2 After In Vivo Gene Transfer into Human Pancreatic Cancer Cells (2005)

Pancreatic cancer is one of the most aggressive and devastating human malignancies. The present study was conducted to determine whether in vivo sst2 gene transfer into human pancreatic tumors would impair tumor progression, and to characterize sst2 antitumoral bystander mechanisms. sst2 administration, using the synthetic vector PEI, strongly inhibited tumor progression of human pancreatic adenocarcinoma, in vivo. sst2 gene transfer induced intratumoral production of its ligand somatostatin. Disruption of this autocrine loop by RNA interference completely reversed sst2 antitumoral activity. Mice depleted of natural killer (NK) cells did not hamper sst2 tumor growth inhibition. However, microvessel density and vascular endothelial growth factor (VEGF) expression were markedly reduced in sst2-transfected tumors, whereas sst3 somatostatin receptor was upregulated. Depleting somatostatin by RNA interference completely abolished the sst2 inhibitory effect on VEGF expression and tumor angiogenesis, and sst2-induced sst3 expression in peripheral tumor vessels. We conclude that in vivo sst2 gene transfer elicited intratumoral somatostatin production and strongly impaired human pancreatic tumor growth. NK cells were not involved in this antitumoral bystander effect. VEGF and tumor vascularization were identified as novel targets for sst2-mediated antitumoral bystander effect. sst3 somatostatin receptor was upregulated in sst2-transfected tumors. Therefore, in vivo gene delivery of sst2 receptor to target the angiogenic process in pancreatic ductal adenocarcinoma might be a new therapeutic approach for treatment of pancreatic cancer in patients with unresectable disease.
Validation of a competitive ELISA and a virus neutralization test for the detection and confirmation of antibodies to Senecavirus A in swine sera (2017)

Senecavirus A (SVA; family Picornaviridae) is a nonenveloped, single-stranded RNA virus associated with idiopathic vesicular disease (IVD) in swine. SVA was detected in pigs with IVD in Brazil, United States, Canada, and China in 2015, triggering the need to develop and/or validate serologic assays for SVA. Our objective was to fully validate a previously developed competitive enzyme-linked immunosorbent assay (cELISA) as a screening test for antibodies to SVA. Additional objectives included the development and validation of a virus neutralization test (VNT) as a confirmatory test for SVA antibody detection, and the comparison of the cELISA, VNT, and an existing immunofluorescent antibody test (IFAT) for the detection of SVA antibodies in serial bleeds from SVA outbreaks. The diagnostic specificity and sensitivity were 98.2% (97.2-98.9%) and 96.9% (94.5-98.4%) for the cELISA, and 99.6% (99.0-99.9%) and 98.2% (95.8-99.4%) for the VNT, respectively. There was strong agreement among cELISA, VNT, and IFAT when compared based on kappa coefficient. Based on these performance characteristics, these tests are considered suitable for serologic detection of SVA in pigs.
The neu-oncogene: signal transduction pathways, transformation mechanisms and evolving therapies. (1994)

A variety of pathways exist to transmit biological signals. One mechanism used for the regulated control of cell growth and differentiation is through the transduction of signals resulting from the binding of soluble polypeptide growth factors to their cognate receptors. The specificity of growth factor action is mediated by the interaction of ligand with cognate receptors which can lead to exquisite control in a tissue- and developmental-specific manner. In addition, individual receptors on the cell surface can form complex assemblies with other receptor/signal transduction molecules that potentially lead to additional levels of signal transmissions. Biological signaling by peptide ligands can be mediated through the enzymatic activation of the receptor resulting in the triggering of a defined biochemical pathway. Ultimately, a mitogenic or differentiation signal is delivered to the nucleus, completing the biological action of the growth factor. The biochemical mechanisms of signal transduction by the p185 neu/c-erbB-2 growth factor receptor and the subsequent physiological responses are the topics of this review. Study of the p185 growth factor receptor has helped to illustrate the functional role of receptor homo- (and hetero-) dimerization in enzyme activation and, in malignant cells, the detrimental results of structural mutations or aberrant gene expression which may effect this dimerization. The ability of one type of growth factor receptor to affect the activity of another (as illustrated by the p185/epidermal growth factor receptor heterodimeric complex) is likely to be a common regulatory feature of growth factor receptor action. The nomenclature to be used in this review will refer to the oncogenic mutated form of the rat protein as 'p185neu', the proto-oncogenic rat protein as 'p185c-neu' and the human form as 'p185c-erbB-2'. The term 'p185' will be used to refer to any type of protein, regardless of the source.
Effects of Iron Nitrosylation on Sickle Cell Hemoglobin Solubility (2002)

One mechanism by which nitric oxide (NO) has been proposed to benefit patients with sickle cell disease is by reducing intracellular polymerization of sickle hemoglobin (HbS). In this study we have examined the ability of nitric oxide to inhibit polymerization by measuring the solubilizing effect of iron nitrosyl sickle hemoglobin (HbS-NO). Electron paramagnetic resonance spectroscopy was used to confirm that, as found in vivo, the primary type of NO ligation produced in our partially saturated NO samples is pentacoordinate alpha-nitrosyl. Linear dichroism spectroscopy and delay time measurements were used to confirm polymerization. Based on sedimentation studies we found that, although fully ligated (100% tetranitrosyl) HbS is very soluble, the physiologically relevant, partially ligated species do not provide a significant solubilizing effect. The average solubilizing effect of 26% NO saturation was 0.045; much less than the 0.15 calculated for the effect of 26% oxygen saturation. Given the small amounts of NO-ligated hemoglobin achievable through any kind of NO therapy, we conclude that NO therapy does not benefit patients through any direct solubilizing effect.
Human Defensins: Synthesis and Structural Properties (2007)

Defensins are small, beta-sheet-rich, cationic peptides found in many organisms. All defensins have amphiphilic properties, which are central for antimicrobial activities of the proteins. The human genome encodes many defensin-line molecules, of which 10 have been characterized. Molecules of all known human defensins are stabilized by three intramolecular disulfide bonds arranged in a conserved pattern. To date, studies of human defensins indicate that these proteins are involved in various biological processes associated primarily with defensive and regulatory responses to infections by pathological agents. A comprehensive understanding of the multiple roles played by defensins within the immune system is greatly increased by reviewing the results of detailed structural studies. Emerging structural data, derived by the X-ray crystallography and the NMR spectroscopy in solution combined with functional studies; allow a rational understanding of the different activities of defensins and the mechanisms controlling these activities. Due to their well-established antimicrobial properties, defensins are also being investigated for their potential as therapeutics agents. Recently, increased effort has been focused on studies of the immunoregulatory properties of defensins, associated with their ability to bind and activate the G(i)-protein-coupled seven-transmembrane receptors. Comprehensive studies of defensins require development of simple, efficient, and inexpensive methods to generate these proteins and their derivatives in correctly folded form. This review highlights the current status of the sample generation methods, structural studies, and the structure-function relationships for human defensins.
Coligand Modulated Six-, Eight-, and Ten-Connected Zn/Cd-1,2,4-Triazolate Frameworks Based on Mono-, Bi-, Tri-, Penta-, and Heptanuclear Cluster Units (2007)

Using nonsubstituted 1,2,4-triazole and the second bridging ligands as coligands, a series of three-dimensional metal–organic frameworks based on different secondary building units (SBUs), namely, Zn2(trz)3(SCN) (1), Zn2(trz)2(ox) (2), Cd3(trz)2(suc)Cl2(3), [Cd5(trz)6(OAc)2Cl2(H2O)2]·2H2O (4), and [Zn7(trz)6(1,2,4,5-BTC)2(H2O)6]·8H2O (5) (trz = 1,2,4-triazole, ox = oxalate, suc = succinic acid, 1,2,4,5-BTC = 1,2,4,5-benzenetetracarboxylate), have been synthesized and structurally characterized with the aid of single-crystal X-ray diffraction. The SBUs in 1–5 vary from mononuclear, binuclear, linear trinuclear, linear pentanuclear to heptanuclear d10-1,2,4-triazolate polynuclear clusters. Compound 1 presents a complicated 3,6-connected topology based on three nonequivalent nodes. Compound 2 adopts a 6-connected 3D network of distorted α-Po topology that is built from dizinc units. The structure of 3 consists of two intersecting (4,4) grids which generate a novel self-penetrating 4,8-connected net with (456)(412616) topology when the tricadmium cores and succinic acid ligands are regarded as eight-connected and four-connected nodes, respectively. Compound 4 can be described as an 8-connected CsCl-type net utilizing unprecedented linear pentacadmium cores as eight-connected nodes and trz ligands as linkers. The microporous structure of 5 exhibits a novel 4,10-connected net constructed from ten-connected heptanuclear [Zn7(trz)6]8+ cluster and four-connected 1,2,4,5-BTC ligand. Detailed structural comparison of these complexes indicated that the increase in the length of the second bridging ligands induces the progressive increase in the metal nuclearity and the increase in the connectivities of the ultimate nets: that is, the length of the second bridging ligand plays a significant role in tuning the nuclearity of metal-1,2,4-triazolate clusters and the connectivity of a specific network. All the complexes exhibit high thermal stability and strong fluorescence properties.
Preliminary Studies of GaAs Deposition on Au(100), (110), and (111) Surfaces by Electrochemical Atomic Layer Epitaxy (1992)

The development of a new method for epitaxial growth of compound semiconductors is briefly described: electrochemical atomic layer epitaxy (ECALE). ECALE is based on the successive underpotential deposition (UPD) of atomic layers of different elements to form a compound. Preliminary studies of the ECALE deposition of were performed in a thin‐layer electrochemical cell with a polycrystalline Au electrode. Potentials required for oxidative UPD of As and reductive UPD of Ga were evaluated with different solution concentrations and pH's. Subsequent studies were performed in an ultrahigh vacuum surface analysis instrument interfaced to an electrochemical cell. A gold single crystal supporting the three low‐index planes was used in these studies. Auger electron spectroscopy (AES) and coulometry were used for surface composition analysis, while low energy electron diffraction (LEED) was used for structural analysis. Arsenic electrodeposition from solutions resulted in a succession of LEED patterns as the coverage increased on each face. Low coverage structures, corresponding to less than one monolayer of As, were observed only on the (100) and (110) faces: a at coverage and a at coverage. Oxidative UPD of As from was observed only on the (100) and (110) faces, resulting in low coverage ordered structures analogous to those formed during deposition from at low As coverages. Ga UPD from solutions was observed on all three faces, although it resulted in disordered layers of Ga oxide upon removal of the substrate from solution, due to partial oxidation of the Ga in contact with water in the absence of potential control. UPD of Ga on As‐covered surfaces ( and ) resulted in stoichiometric coverages of Ga and As on both. Structures displaying and LEED patterns were formed on the (100) and (110) faces, respectively. The stability of in aqueous solutions was evaluated. Potentials vs.pH plots were calculated for several concentrations of dissolved Ga and As species.
Expression of Brca1 is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice. (1995)

We have isolated genomic and cDNA clones of Brca1, a mouse homolog of the recently cloned breast cancer-associated gene, BRCA1. Brca1 encodes an 1812-amino-acid protein with a conserved zinc finger domain and significant homology to the human protein. Brca1 maps to Chromosome 11 within a region of conserved synteny with human chromosome 17, consistent with the mapping of the human gene to 17q21. Brca1 transcripts are expressed in a variety of cultured cells but reveal a specific and dynamic expression pattern during embryonic development. For example, expression is observed first in the otic vesicle of embryonic day 9.5 (E9.5) embryos. This expression diminishes and is replaced by expression in the neuroectoderm at E10.5. By E11-12.5, higher levels are observed in differentiating keratinocytes and in whisker pad primordia. Transcripts also become evident in epithelial cells of the E14-17 kidney. Brca1 expression occurs in differentiating epithelial cells of several adult organs as well, suggesting a general role in the functional maturation of these tissues. Consistent with this, Brca1 transcripts are expressed in both alveolar and ductal epithelial cells of the mammary gland. During pregnancy, there is a large increase in Brca1 mRNA in mammary epithelial cells, an increase that parallels their functional differentiation. Because high rates of breast cancer are associated with loss of BRCA1 in humans, it is possible that this gene provides an important growth regulatory function in mammary epithelial cells. In addition, increased transcription of mammary Brca1 during pregnancy might contribute, in part, to the reduced cancer risk associated with exposure to pregnancy and lactation.
A comparative study of methods of photoreceptor morphometry. (1991)

A comparative study was performed to compare methods of quantitative evaluation of damage to photoreceptor cells in rat eyes exposed to light. Using a manual count of individual photoreceptor nuclei as the standard, the following measurements were compared: (1) outer nuclear layer column count, (2) area, (3) thickness, and (4) the number of nuclei of the outer nuclear layer of the retina using a newly developed computer program that counts a digitized image. Linear-regression analysis of the data showed that the computer method was the most accurate with a Pearson correlation coefficient of 0.9911. The other methods tested also correlated well with the manual count, with coefficients ranging from 0.9367-0.9532. All these methods were reasonably accurate measurements of photoreceptor layer integrity, with the computer count most closely approximating the values obtained by a manual count. However, the outer nuclear layer thickness measurement appeared to be the fastest and most convenient method to evaluate photoreceptor cell damage quantitatively. Computer counting could be reserved for situations in which a high degree of accuracy is required.
20 Å Cd4In16S3514- Supertetrahedral T4 Clusters as Building Units in Decorated Cristobalite Frameworks (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXT20 Å Cd4In16S3514- Supertetrahedral T4 Clusters as Building Units in Decorated Cristobalite FrameworksHailian Li, Jaheon Kim, T. L. Groy, M. O'Keeffe, and O. M. YaghiView Author Information Materials Design and Discovery Group Department of Chemistry, University of Michigan Ann Arbor, Michigan 48109-1055 Department of Chemistry, Arizona State University Tempe, Arizona 85287-1604 Cite this: J. Am. Chem. Soc. 2001, 123, 20, 4867–4868Publication Date (Web):April 28, 2001Publication History Received16 February 2001Published online28 April 2001Published inissue 1 May 2001https://pubs.acs.org/doi/10.1021/ja010413fhttps://doi.org/10.1021/ja010413frapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1363Altmetric-Citations159LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Cations,Chemical structure,Cluster chemistry,Cluster structure,Crystal structure Get e-Alerts