gebhart/patrepeval huggingface dataset:
Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage (2010)

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.
Tuning inflammation with anti-inflammatory neuropeptides (2007)

The immune system is confronted with the daunting task of defending the organism against invading pathogens while at the same time remaining self-tolerant to the body's own constituents and preserving its integrity. The loss of immune tolerance stemming from an unbalance in pro-inflammatory factors versus anti-inflammatory cytokines, or of autoreactive/inflammatory T helper 1 cells versus regulatory/suppressive T cells, results in the breakdown of immune homeostasis and the subsidiary appearance of exacerbated inflammatory and autoimmune diseases. Some neuropeptides have been shown to have anti-inflammatory properties and to participate in maintaining immune tolerance. Here the authors examine the most recent developments in this field and highlight the effectiveness of using neuropeptides in treating several inflammatory and autoimmune disorders.
Glycomic Analysis: An Array of Technologies (2009)

Carbohydrates encode biological information necessary for cellular function. The structural diversity and complexity of these sugar residues have necessitated the creation of novel methodologies for their study. This review highlights recent technological advancements that are starting to unravel the intricate web of carbohydrate biology. New methods for the analysis of both glycoconjugates and glycan structures are discussed. With the use of these innovative tools, the field of glycobiology is poised to take center-stage in the postgenomic era of modern biology and medicine.
Synthesis of functionally tethered oligodeoxynucleotides by the convertible nucleoside approach (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of functionally tethered oligodeoxynucleotides by the convertible nucleoside approachAndrew M. MacMillan and Gregory L. VerdineCite this: J. Org. Chem. 1990, 55, 24, 5931–5933Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/jo00311a005https://doi.org/10.1021/jo00311a005research-articleACS PublicationsRequest reuse permissionsArticle Views556Altmetric-Citations107LEARN 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 Get e-Alerts
2D Equation-of-State Model for Corona Phase Molecular Recognition on Single-Walled Carbon Nanotube and Graphene Surfaces (2014)

Corona phase molecular recognition (CoPhMoRe) has been recently introduced as a means of generating synthetic molecular recognition sites on nanoparticle surfaces. A synthetic heteropolymer is adsorbed and confined to the surface of a nanoparticle, forming a corona phase capable of highly selective molecular recognition due to the conformational imposition of the particle surface on the polymer. In this work, we develop a computationally predictive model for analytes adsorbing onto one type of polymer corona phase composed of hydrophobic anchors on hydrophilic loops around a single-walled carbon nanotube (SWCNT) surface using a 2D equation of state that takes into consideration the analyte-polymer, analyte-nanoparticle, and polymer-nanoparticle interactions using parameters determined independently from molecular simulation. The SWCNT curvature is found to contribute weakly to the overall interaction energy, exhibiting no correlation for three of the corona phases considered, and differences of less than 5% and 20% over a larger curvature range for two other corona phases, respectively. Overall, the resulting model for this anchor-loop CoPhMoRe is able to correctly predict 83% of an experimental 374 analyte-polymer library, generating experimental fluorescence responses within 20% error of the experimental values. The modeling framework presented here represents an important step forward in the design of suitable polymers to target specific analytes.
Endothelial Leukocyte Adhesion Molecule 1: an Inducible Receptor for Neutrophils Related to Complement Regulatory Proteins and Lectins (1989)

Focal adhesion of leukocytes to the blood vessel lining is a key step in inflammation and certain vascular disease processes. Endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell surface glycoprotein expressed by cytokine-activated endothelium, mediates the adhesion of blood neutrophils. A full-length complementary DNA (cDNA) for ELAM-1 has now been isolated by transient expression in COS cells. Cells transfected with the ELAM-1 clone express a surface structure recognized by two ELAM-1 specific monoclonal antibodies (H4/18 and H18/7) and support the adhesion of isolated human neutrophils and the promyelocytic cell line HL-60. Expression of ELAM-1 transcripts in cultured human endothelial cells is induced by cytokines, reaching a maximum at 2 to 4 hours and decaying by 24 hours; cell surface expression of ELAM-1 protein parallels that of the mRNA. The primary sequence of ELAM-1 predicts an amino-terminal lectin-like domain, an EGF domain, and six tandem repetitive motifs (about 60 amino acids each) related to those found in complement regulatory proteins. A similar domain structure is also found in the MEL-14 lymphocyte cell surface homing receptor, and in granule-membrane protein 140, a membrane glycoprotein of platelet and endothelial secretory granules that can be rapidly mobilized (less than 5 minutes) to the cell surface by thrombin and other stimuli. Thus, ELAM-1 may be a member of a nascent gene family of cell surface molecules involved in the regulation of inflammatory and immunological events at the interface of vessel wall and blood.
Nitric Oxide Modulates Dopamine Release During Global Temporary Cerebral Ischemia (1995)

Dopamine (DA) is released in large quantities from the striatum during cerebral ischemia. Along with excitatory neurotransmitters, DA plays a role in cellular neuronal ischemic injury. In this study we examined the role of nitric oxide (NO) in the ischemia-induced release of DA. A microdialysis probe was stereotactically placed into the corpus striatum of 16 Sprague-Dawley rats for DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) level determinations. After probe stabilization, the animals received either NG-nitro-L-arginine-methyl ester (L-NAME), a NO synthase inhibitor, or vehicle through the microdialysis probe. Temporary global forebrain ischemia was induced using bilateral carotid artery ligature tightening and controlled hemorrhagic hypotension for 15 min. L-NAME administration caused a reduction in ischemic estimated extraneuronal DA concentration by 60% (P < 0.005) compared with control. There was an increase in both DOPAC and HVA concentrations during the recovery period compared to baseline values in the control group (P < 0.05). L-NAME also caused a reduction in HVA concentration compared to vehicle administration during the latter part of recovery (P < 0.05). These data support the concept that ischemic dopamine release may be mediated by NO. This NO-modulated DA release may contribute to the previously reported deleterious neurotoxic effects of NO during ischemia.
Potent Inhibitors of Subgenomic Hepatitis C Virus RNA Replication through Optimization of Indole-N-Acetamide Allosteric Inhibitors of the Viral NS5B Polymerase (2005)

Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. Compounds that block replication of subgenomic HCV RNA in liver cells are of interest because of their demonstrated antiviral effect in the clinic. In followup to our recent report that indole-N-acetamides (e.g., 1) are potent allosteric inhibitors of the HCV NS5B polymerase enzyme, we describe here their optimization as cell-based inhibitors. The crystal structure of 1 bound to NS5B was a guide in the design of a two-dimensional compound array that highlighted that formally zwitterionic inhibitors have strong intracellular potency and that pregnane X receptor (PXR) activation (an undesired off-target activity) is linked to a structural feature of the inhibitor. Optimized analogues devoid of PXR activation (e.g., 55, EC(50) = 127 nM) retain strong cell-based efficacy under high serum conditions and show acceptable pharmacokinetics parameters in rat and dog.
Single-tooth implants and their role in preserving remaining teeth: a 10-year survival study. (1999)

The use of teeth as abutments for fixed and removable partial dentures can result in biologically destructive consequences. Teeth adjacent to edentulous spaces should exhibit improved prognoses if restorative trauma is to be avoided or minimized. Implants offer a method of tooth replacement without relying upon the surrounding dentition for support. This investigation evaluates implant survival and prosthetic complications of implants that replaced single missing teeth and were placed in clinical practice during a 10-year period. It further examines preoperative status and survival of teeth adjacent to these implant restorations during the same 10-year time span. Ninety-nine patients treated with 116 implants and 112 single-tooth implant prostheses in a prosthodontic practice were examined between 1988 and 1998. The purpose of this study was to evaluate the role of implants in preventing the use of intact teeth for initial support of prostheses and in avoiding the use of additional teeth as abutments upon the replacement of existing restorations. Three implants failed over a 10-year period, for a survival rate of 97.4%. Complications included the loss of 2 implant crowns, screw loosening, broken screws, cement washout, margin exposure, and porcelain fracture. Of 196 teeth adjacent to edentulous spaces, 156 (79.6%) were intact or minimally restored. Only 3 of these teeth were restored as part of initial prosthodontic therapy. Over the ensuing 10 years, only 1 tooth required a replacement restoration, and 1 tooth was extracted. Results of this patient evaluation demonstrated that implant survival over a 10-year period was favorable, with minimal prosthetic complications. Furthermore, teeth adjacent to single-tooth implants exhibited an extremely low complication rate. This report indicates that implants can be effective in preserving intact teeth in patients undergoing initial prosthodontic therapy and in preventing the use of additional teeth as abutments in patients whose existing prostheses must be replaced.
Electrochemical Potential-Step Investigations of the Aerobic Interconversions of [NiFe]-Hydrogenase fromAllochromatiumvinosum:  Insights into the Puzzling Difference between Unready and Ready Oxidized Inactive States (2004)

Dynamic electrochemical studies, incorporating catalytic voltammetry and detailed potential-step manipulations, provide compelling evidence that the oxidized inactive state of [NiFe]-hydrogenases termed Unready (or Ni-A) contains a product of partial reduction of O(2) that is trapped in the active site.
Monocyte chemotactic and activating factor/monocyte chemoattractant protein (MCAF/MCP-1) in bronchoalveolar lavage fluid from patients with atopic asthma and chronic bronchitis. (1997)

Monocyte chemotactic and activating factor/monocyte chemoattractant protein (MCAF/MCP-1) is a member of the beta (C-C) subfamily of chemokines. The biological roles played by MCAF/MCP-1 in a number of inflammatory and noninflammatory diseases states is not well known. Several studies have confirmed that inflammation is present in the airways of subjects with atopic asthma and with chronic bronchitis. Analysis of bronchoalveolar lavage fluid (BALF) is an effective method of sampling lower respiratory tract inflammation. The aim of this study was to examine associations among MCAF/MCP-1, BALF cells and spirometry parameters and bronchial hyperresponsiveness in patients with atopic asthma and chronic bronchitis. Twenty patients with atopic asthma, 10 patients with chronic bronchitis and 10 patients of the control group, took part in this study. An ELISA test was used to assess MCAF/MCP-1 in BALF. The levels of MCAF/ MCP-1 (mean +/- SEM) were 150 +/- 18.6 pg/ml in patients with atopic asthma, 320 +/- 39.7 pg/ml in chronic bronchitis and 74.9 +/- 3.3 pg/ml in the control group (p < 0.05). When all patients with disease were considered, there was negative correlation with FEF50 (Kendall's correlation coefficient = - 0.4; p < 0.01). Regression analysis has shown that a level of MCAF/MCP-1 over 100 pg/ml was correlated with duration of illness (Pearson's correlation coefficient = 0.7; p < 0.02). In conclusion, MCAF/MCP-1 probably possesses proinflammatory properties in atopic asthma and chronic bronchitis. The elevated level of this chemokine may support the clinical suspicion of specific diagnosis.
CaMKII?-cre transgene expression and recombination patterns in the mouse brain (2000)

An 8.5 kb 5flanking genomic fragment of the alpha subunit of the calcium/calmodulin-dependent protein kinase II gene (CaMKII) has been shown to confer brain specific expression on a variety of transgenes in the mouse, including Cre recombinase (Mansuy et al.,
Expression of Drosophila glass protein and evidence for negative regulation of its activity in non-neuronal cells by another DNA-binding protein (1993)

The glass gene encodes a DNA-binding zinc-finger protein required for the development of Drosophila photoreceptor cells and which appears to regulate a number of genes specifically expressed in photoreceptors. We have generated monoclonal antibodies to Glass and used them to examine Glass distribution during development. Glass is expressed in all cell types of the developing eye and in all other organs that contain photoreceptor cells in Drosophila, including a small number of cells in the brain. We altered the normal pattern of glass expression by placing the gene under the control of the hsp70 promoter. Our results suggest that nonphotoreceptor cells are restricted in their response to Glass expression. In an effort to discover the mechanism of this restriction, we examined the expression of a number of reporter gene constructs. Our results suggest that nonsensory cells are unable to express certain reporter constructs in response to Glass expression because another DNA-binding factor represses Glass activity in nonsensory cells.
Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta. (1999)

The ability of chemokines to bind to glycosaminoglycans (GAGs) on cell surfaces and in the extracellular matrix is thought to play a crucial role in chemokine function. We investigated the structural basis for chemokine binding to GAGs by using in vitro mutagenesis to identify amino acids of chemokine macrophage-inflammatory protein-1 beta (MIP-1 beta) that contribute to its interaction with the model GAG heparin. Among six basic residues that are organized into a single basic domain in the folded MIP-1 beta monomer, three (R18, K45, and R46) were found to contribute significantly to heparin binding. Of these, R46 was found to play a dominant role, and proved essential for the interaction of MIP-1 beta with both heparin and heparan sulfate in physiological salt. The results of this mutational analysis have implications for the structure of the MIP-1 beta-heparin complex, and a comparison of these results with those obtained by mutational analysis of the MIP-1 alpha-heparin interaction suggests a possible structural difference between the MIP-1 beta-heparin and MIP-1 alpha-heparin complexes. To determine whether GAG binding plays an important role in receptor binding and cellular activation by MIP-1 beta, the activities of wild-type MIP-1 beta and R46-substituted MIP-1 beta were compared in assays of T lymphocyte chemotaxis. The two proteins proved equipotent in this assay, arguing that interaction of MIP-1 beta with GAGs is not intrinsically required for functional interaction of MIP-1 beta with its receptor.
Reduction of the Major Swine Xenoantigen, the α-Galactosyl Epitope by Transfection of the α2,3-Sialyltransferase Gene (1998)

alpha2,3-Sialyltransferase represents a putative enzyme that reduces the Galalpha1-3Gal beta1-4GlcNAc-R (the alpha-galactosyl epitope) by intracellular competition with alpha1,3-galactosyltransferase for a common acceptor substrate. This study demonstrates that the overexpression of the alpha2,3-sialyltransferase gene suppresses the antigenicity of swine endothelial cells to human natural antibodies by 77% relative to control cells and by 30% relative to cells transfected with alpha1,2-fucosyltransferase, and in addition, it reduces the complement-mediated cell lysis by 75% compared with control cells and by 22% compared with cells transfected with alpha1, 2-fucosyltransferase. The mechanism by which the alpha-galactosyl epitope was reduced was also studied. Suppression of alpha1, 3-galactosyltransferase activity by 30-63% was observed in the transfectants with alpha2,3-sialyltransferase, and mRNA expression of the alpha1,3-galactosyltransferase gene was reduced as well. The data suggest that the alpha2,3-sialyltransferase effectively reduced the alpha-galactosyl epitope as well as or better than the alpha1, 2-fucosyltransferase did and that the reduction of the alpha-galactosyl epitope is due not only to substrate competition but also to an overall reduction of endogenous alpha1, 3-galactosyltransferase enzyme activity.
An Introduction to PCR Primer Design and Optimization of Amplification Reactions (2003)

PCR optimization is usually performed in order to obtain maximum specificity and yield. In some applications for which the amount of template may be limiting, or when there is a large amount of nontarget sequences, the sensitivity is maximized. Nonoptimized conditions promote artifactual bands resulting from primer dimerization and mispriming, broad bands containing a mixture of correct and incomplete products, and, generally speaking, a poor signal-to-noise ratio. Poorly designed PCR protocols also lack robustness. Such situations can occur in which the PCR is challenged with less than pristine DNAs or when the ingredients of the reaction are not added in the exact amounts as described by the authors of the protocol. Thus, a well-optimized PCR should be reliable in the hands of a coworker or in the laboratory of another institute.
Extracellular Matrix of Ovarian Tumors (2006)

Tumor cells interfere with the normal programming of extracellular matrix (ECM) biosynthesis and can extensively modify the structure and composition of the matrix. The role of ECM components is becoming increasingly recognized as an important determinant for the growth and progression of solid tumors. The extensive remodeling of the normal ECM in tumors can proceed through the degradation of pre-existing ECM molecules and/or by the neosynthesis of ECM components, which in many cases are not present in the ECM of normal tissues. In the ovary the ECM comprises a variety of molecules including the collagen superfamily and noncollagenous proteins such as glycoproteins, proteoglycans, and hyaluronan. Elevated levels of laminin-gamma2, collagen types I and III, fibronectin, syndecan-1, glypican-1, versican, and hyaluronan and its receptors CD44 have all been associated with a poor prognosis of ovarian cancers. Generally, there is a differential expression of laminin chains alpha1, alpha4, and beta2 among serous (alpha1, beta2), mucinous (alpha4), and endometrioid (alpha1) tumors. This review focuses on these and other ECM molecules in ovarian tumors.
Molecular Basis of Downregulation of G-Protein–Coupled Inward Rectifying K+Current (IK,ACh) in Chronic Human Atrial Fibrillation (2001)

Chronic human AF induces transcriptionally mediated upregulation of I(K1) but downregulation of I(K,ACh) and attenuates the muscarinic receptor-mediated shortening of atrial action potentials. This suggests that atrial myocytes adapt to a chronically high rate by downregulating I(K,ACh) to counteract the shortening of the atrial effective refractory period due to electrical remodeling.
Personal communication on residential power lines-assessment of channel parameters (2002)

A possible concept of voice communication using a residential distribution power line for the access network is investigated with special reference to its application in the underprovided regions of developing countries. Usually such a distribution grid connects up to 100 houses served by one transformer unit and spreads out up to 1 km. Acceptable grade of service (GOS) requires a capacity of 10 channels and reliable random access scheme. The survey of literature shows that precise channel parameters are not known, as noise, attenuation and impedance change with frequency, distance, time and location (network topology and point of connection). The efforts to date have mostly concentrated on systems or modems design for data rather than voice communication. Aided by statistical processing of the measurement data one should be able to create a "more stable", usable analytical model of the channel, on which the authors are currently working. Meanwhile several channel refinements (noise filtering, impedance stabilization and line coupling) introduced to overcome its critical impairments are suggested in this paper.