gebhart/patrepeval huggingface dataset:
PFunkel: Efficient, Expansive, User-Defined Mutagenesis (2012)

We introduce PFunkel, a versatile method for extensive, researcher-defined DNA mutagenesis using a ssDNA or dsDNA template. Once the template DNA is prepared, the method can be completed in a single day in a single tube, and requires no intermediate DNA purification or sub-cloning. PFunkel can be used for site-directed mutagenesis at an efficiency approaching 100%. More importantly, PFunkel allows researchers the unparalleled ability to efficiently construct user-defined libraries. We demonstrate the creation of a library with site-saturation at four distal sites simultaneously at 70% efficiency. We also employ PFunkel to create a comprehensive codon mutagenesis library of the TEM-1 ß-lactamase gene. We designed this library to contain 18,081 members, one for each possible codon substitution in the gene (287 positions in TEM-1 x 63 possible codon substitutions). Deep sequencing revealed that ∼97% of the designed single codon substitutions are present in the library. From such a library we identified 18 previously unreported adaptive mutations that each confer resistance to the ß-lactamase inhibitor tazobactam. Three of these mutations confer resistance equal to or higher than that of the most resistant reported TEM-1 allele and have the potential to emerge clinically.
Expression of intermediate-sized filaments in developing and adult human kidney and in renal cell carcinoma. (1990)

We studied the distribution of intermediate-sized filaments in developing and adult kidneys and renal cell carcinoma (RCC) by indirect immunohistochemistry, using a pan-cytokeratin mouse monoclonal antibody (MAb), chain-specific anti-cytokeratin MAb, and anti-vimentin and anti-desmin MAb, to resolve controversy concerning intermediate-sized filament expression in the kidney. With the pan-cytokeratin MAb, cytokeratin expression was detectable in all stages of nephron development, starting with expression in the renal vesicles, the progenitors of the glomeruli, proximal tubules, Henle's loop, and part of the distal tubules. Using chain-specific anti-cytokeratin MAb, cytokeratin 8 and 18 expression was demonstrated in all developmental structures of the nephron, whereas cytokeratin 19 expression was more complex. None of the nephrogenic blastema cells from which the renal vesicles arise expressed cytokeratins. Transient expression of vimentin and cytokeratin 19 was observed in differentiating collecting ducts and proximal tubule cells at the S-shaped stage of nephron development, respectively. In RCC, cytokeratin expression closely resembled that of the mature proximal tubule, i.e., RCC cells expressed cytokeratins 8 and 18. However, in a subset of RCC additional cytokeratin 19 expression was noted. In addition, all except one RCC showed co-expression of cytokeratins and vimentin.
Human MSC Suppression Correlates With Cytokine Induction of Indoleamine 2,3-Dioxygenase and Bystander M2 Macrophage Differentiation (2011)

Clinical trials testing the use of either autologous or allogeneic human bone marrow-derived mesenchymal stromal cells (MSC) as a cell-based pharmaceutical for suppression of autoimmune and alloimmune ailments are underway. Reported results from completed trials vary in effectiveness within and between studies without any clear mechanistic explanation. We propose that these discrepancies may arise from intrinsic variability in the immunosuppressive potential of each MSC donor source. Here, we demonstrate that tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated MSC derived from normal adult volunteers suppress T cell proliferation in vitro in a variegated manner, an observation linked to IFN-mediated indoleamine 2,3-dioxygenase (IDO) upregulation. We also demonstrate that MSC IDO activity is implicated in the differentiation of monocytes into interleukin (IL)-10-secreting M2 immunosuppressive macrophages (CD14(+)/CD206(+)). Those monocyte-derived M2 are in turn implicated in the suppression of T cell proliferation in an IL-10-independent manner, thus amplifying the immunosuppressive effect generated by MSC. In summary, the immune plasticity of IFN-γ and TNF-α licensed veto function of MSC vary among donors and defines a central role to inducible IDO activity and its bystander effect on lymphomyeloid immune effectors.
Enoyl Coenzyme A Hydratase (Crotonase) (1972)

Abstract The substrate specificity of bovine liver crotonase has been examined with seven Δ2, 3-trans-enoyl-CoA substrates, containing an even number of carbon atoms. The Vmax for this series decreases progressively from a value of about 340,000 moles per min per mole of enzyme for crotonyl-CoA, the C4 derivative, to 2,300 for the C16 derivative. The action of several CoA derivatives on crotonase has been tested. None were found to stimulate the enzyme and only one derivative, acetoacetyl-CoA, was found to be markedly inhibitory. Evidence was obtained that the enolate form of acetoacetyl CoA was the inhibitory species and acted as a competitive inhibitor with a Ki of 1.6 x 10-6 m, a value about ten times lower than the Km for the best substrate, crotonyl-CoA. The interaction of acetoacetyl-CoA with crotonase was studied by ultraviolet difference spectroscopy and it was found that 6 molecules of inhibitor were bound per molecule of enzyme, or an average of one per subunit. This suggests that there are six active sites per molecule of native enzyme. The binding constant for the inhibitor was about equal to the kinetically determined value for Ki. The catalytic properties of crotonase have been compared with the turnover numbers and substrate specificities of the other enzymes acting in β oxidation of fatty acyl-CoA derivatives. This comparison suggests that crotonase, by virtue of its substrate specificity and its sensitivity to feedback inhibition by acetoacetyl-CoA, may play a regulatory role in fatty acid oxidation. The effects of acetoacetyl-CoA on the rate of oxidation of butyric, octanoic, and palmitic acids by heart muscle or liver mitochondria were those expected if crotonase is acting, at least in part, to regulate fatty acid oxidation.
Hierarchical model-based reinforcement learning (2008)

Hierarchical decomposition promises to help scale reinforcement learning algorithms naturally to real-world problems by exploiting their underlying structure. Model-based algorithms, which provided the first finite-time convergence guarantees for reinforcement learning, may also play an important role in coping with the relative scarcity of data in large environments. In this paper, we introduce an algorithm that fully integrates modern hierarchical and model-learning methods in the standard reinforcement learning setting. Our algorithm, R-maxq, inherits the efficient model-based exploration of the R-max algorithm and the opportunities for abstraction provided by the MAXQ framework. We analyze the sample complexity of our algorithm, and our experiments in a standard simulation environment illustrate the advantages of combining hierarchies and models.
Determination of measles, mumps, and rubella immunization status using oral fluid samples (1994)

<h3>Objective.</h3> —To determine if oral fluid samples can be used to reliably assess protective blood levels of antibodies to measles, mumps, and rubella. <h3>Design.</h3> —A comparison of matched serum and oral fluid samples from asymptomatic subjects in enzyme-linked immunosorbent assays for measles, mumps, and rubella antibodies. A longitudinal study compared matched serum and oral fluid samples from 11 subjects after measles-mumps-rubella vaccination. <h3>Setting.</h3> —Five US clinical sites with samples tested at the reporting laboratory. <h3>Participants.</h3> —A total of 157 asymptomatic subjects including 55 subjects younger than 18 years. <h3>Main Outcome Measures and Results.</h3> —The presence of antibodies in oral fluid specimens correlated with that in serum with the following levels of sensitivity and specificity: measles, 97% and 100%, respectively; mumps, 94% and 94%, respectively; rubella, 98% and 98%, respectively. Longitudinal studies of subjects after vac cination showed similar seroconversion profiles in oral fluid and serum samples. <h3>Conclusion.</h3> —Protective blood levels of antibodies to measles, mumps, and rubella can be assessed by means of an oral fluid sample with good reliability. (<i>JAMA</i>. 1994;272:219-221)
A deductive method of haplotype analysis in pedigrees. (1987)

Derivation of haplotypes from pedigree data by means of likelihood techniques requires large computational resources and is thus highly limited in terms of the complexity of problems that can be analyzed. The present paper presents 20 rules of logic that are both necessary and sufficient for deriving haplotypes by means of nonstatistical techniques. As a result, automated haplotype analysis that uses these rules is fast and efficient, requiring computer memory that increases only linearly (rather than exponentially) with family size and the number of factors under analysis. Some error analysis is also possible. The rules are completely general with regard to any system of completely linked, discrete genetic markers that are autosomally inherited. There are no limitations on pedigree structure or the amount of missing data, although the existence of incomplete data usually reduces the fraction of haplotypes that can be completely determined.
Tumor-Penetrating iRGD Peptide Inhibits Metastasis (2014)

Tumor-specific tissue-penetrating peptides deliver drugs into extravascular tumor tissue by increasing tumor vascular permeability through interaction with neuropilin (NRP). Here, we report that a prototypic tumor-penetrating peptide iRGD (amino acid sequence: CRGDKGPDC) potently inhibits spontaneous metastasis in mice. The antimetastatic effect was mediated by the NRP-binding RXXK peptide motif (CendR motif), and not by the integrin-binding RGD motif. iRGD inhibited migration of tumor cells and caused chemorepulsion in vitro in a CendR- and NRP-1-dependent manner. The peptide induced dramatic collapse of cellular processes and partial cell detachment, resulting in the repellent activity. These effects were prominently displayed when the cells were seeded on fibronectin, suggesting a role of CendR in functional regulation of integrins. The antimetastatic activity of iRGD may provide a significant additional benefit when this peptide is used for drug delivery to tumors.
Prostaglandin H2 (PGH2) accelerates formation of amyloid β1−42 oligomers (2002)

Epidemiologic evidence implicates cyclooxygenase activity in the pathogenesis of Alzheimer's disease, in which amyloid plaques have been found to contain increased levels of dimers and higher multimers of the amyloid beta peptide. The product of the oxygenation of arachidonic acid by the cyclooxygenases, prostaglandin H2 (PGH2), rearranges non-enzymatically to several prostaglandins, including the highly reactive gamma-keto aldehydes, levuglandins E2 and D2. We demonstrate that PGH2 markedly accelerates the formation of dimers and higher oligomers of amyloid beta1-42. This is associated with the formation of levuglandin adducts of the peptide. These findings provide the molecular basis for a hypothesis linking cyclooxygenase activity to the formation of oligomers of amyloid beta.
Synthesis of N‐[3‐OXO‐(4,5‐3H2)‐hexanoyl] homoserine lactone: Biologically active tritium‐labelled vibrio fischeri autinducer (1985)

Abstract N‐(3‐oxo‐4‐hexenoyl) homoserine lactone was synthesized and then reduced with Wilkinson's catalyst in the presence of tritium gas to form N‐[3‐oxo‐(4,5‐ 3 H 2 )‐hexanoyl] homoserine locatone (45–55 Ci/mmol). The labelled compound was indistinguishable from the autoinducer for Vibrio fischeri luciferase [N‐(3‐oxohexanoyl) homosernine lactone] by high‐performance liquid chromatography and it was biologically active.
Preparation of Achiral and of Enantiopure Geminally Disubstituted β-Amino Acids for β-Peptide Synthesis (2000)

While geminally disubstituted α-amino acids are helix-inducing residues in α-peptides, gem-disubstituted β-amino acids are predicted not to fit into any of the three major secondary structures of β-peptides recognized to date [the 314 helix, the 12/10/12 helix, and the pleated sheet (Figure 1)]. In order to be able to synthesize and structurally identify β-peptides containing such building blocks, or consisting entirely of them, and in order to establish the chirality of secondary structures they may form, achiral and chiral gem-disubstituted β-amino acids must be readily available. The methods of preparation of 3-amino carboxylic acids with two carbon substituents at the 2- or 3-position (β2,2-/β3,3-amino acids, Figure 2) are reviewed. While there are numerous essentially classical routes to achiral and rac-β-amino acids of this type (Schemes 1-4), their EPC synthesis is currently the subject of investigations. These include the nucleophilic addition to (R)- or (S)-N-sulfinimines (Schemes 6-10) and other Mannich-type transformations (Schemes 19-22), stereoselective alkylations of various chiral hydropyrimidines (Schemes 11, 12, 18), of esters or amides of 2-cyano-alkanoic acids (Schemes 13, 14, 16), and of Li2 derivatives of non-racemic N-protected 3-amino-alkanoates (Scheme 17), as well as sequences of reactions involving enantiopure gem-disubstituted succinic acid derivatives and a Curtius degradation (Schemes 23-26). Oligomers of the achiral gem-disubstituted compounds 1-(aminomethyl)-cyclopropane and -cyclohexane carboxylic acid have already been shown to form 8- and 10-membered hydrogen-bonded rings, respectively (Figure 5), which provide novel motifs for the possible construction of turns, links, or steps in β-peptidic chains.
Idiopathic subconjunctival abscess. (2004)

Subconjunctival abscess is a relatively rare cause of ocular infection. It is usually associated with predisposing factors such as previous trauma or surgery. We report a case of subconjunctival abscess in a 61-year-old woman with no known risk factors. The subconjunctival abscess resolved completely after surgical excision and treatment with topical ciprofloxacin. The final vision preserved 20/20.
Thrombin Modulates the Expression of a Set of Genes Including Thrombospondin-1 in Human Microvascular Endothelial Cells (2005)

Thrombospondin-1 (THBS1) is a large extracellular matrix glycoprotein that affects vasculature systems such as platelet activation, angiogenesis, and wound healing. Increases in THBS1 expression have been liked to disease states including tumor progression, atherosclerosis, and arthritis. The present study focuses on the effects of thrombin activation of the G-protein-coupled, protease-activated receptor-1 (PAR-1) on THBS1 gene expression in the microvascular endothelium. Thrombin-induced changes in gene expression were characterized by microarray analysis of approximately 11,000 different human genes in human microvascular endothelial cells (HMEC-1). Thrombin induced the expression of a set of at least 65 genes including THBS1. Changes in THBS1 mRNA correlated with an increase in the extracellular THBS1 protein concentration. The PAR-1-specific agonist peptide (TFLLRNK-PDK) mimicked thrombin stimulation of THBS1 expression, suggesting that thrombin signaling is through PAR-1. Further studies showed THBS1 expression was sensitive to pertussis toxin and protein kinase C inhibition indicating G(i/o)- and G(q)-mediated pathways. THBS1 up-regulation was also confirmed in human umbilical vein endothelial cells stimulated with thrombin. Analysis of the promoter region of THBS1 and other genes of similar expression profile identified from the microarray predicted an EBOX/EGRF transcription model. Expression of members of each family, MYC and EGR1, respectively, correlated with THBS1 expression. These results suggest thrombin formed at sites of vascular injury increases THBS1 expression into the extracellular matrix via activation of a PAR-1, G(i/o), G(q), EBOX/EGRF-signaling cascade, elucidating regulatory points that may play a role in increased THBS1 expression in disease states.
Treatment of Septic Shock with the Tumor Necrosis Factor Receptor:Fc Fusion Protein (1996)

In patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.
Novel association approach for determining the genetic predisposition to schizophrenia: Case‐control resource and testing of a candidate gene (1993)

We have developed a two-tiered approach to elucidating the genetic predisposition to schizophrenia. The approach first involves the examination of candidate genes in a subset of schizophrenic individuals to identify DNA sequence variations of likely functional significance, i.e., that produce either structural alterations in the protein or affect the level of gene expression. Once identified, the prevalence of the aberrant allele is examined in a large group of unrelated schizophrenic cases and controls to assess whether a true disease association exists. Herein, we describe the establishment of a DNA bank on nearly 200 unrelated schizophrenic cases defined by DSM-III-R criteria and on over 300 unrelated, ethnically similar controls. Characteristics of the study sample are described. The study approach then is illustrated by testing known mutations in the phenylalanine hydroxylase gene, responsible for the autosomal recessive disease of phenylketonuria, in the case-control sample to determine if carriership of a mutant allele is associated with an increased risk of schizophrenia. Using PCR amplification of specific alleles (PASA), we screened 190 schizophrenic cases and 336 controls for two common point mutations in the phenylalanine hydroxylase gene. Two carriers were found among the controls, while none of the cases was shown to carry a mutant allele. Thus, carriership of either of two common mutations in the phenylalanine hydroxylase gene does not appear to be associated with an increased risk of schizophrenia. As additional candidate genes are tested in this case-control resource, adjustment for multiple comparisons will become crucial in order to reduce the chance of false positive findings.(ABSTRACT TRUNCATED AT 250 WORDS)
Liquid-crystal adaptive lenses with modal control (1998)

We report on a novel approach to the realization of nematic liquid-crystal (LC) phase correctors to form spherical and cylindrical wave fronts. A LC cell with a distributed reactive electrical impedance was driven by an ac voltage applied to the cell boundary to yield the desired spatial distribution of the refractive index. The two-dimensional function of the phase delay introduced into the light beam depends on the frequency of the ac control voltage, the geometry of the boundary electrode surrounding the LC cell, and the electrical parameters of the cell. We realized a cylindrical adaptive lens with a clear aperture of 15 mm x 4mm and a spherical adaptive lens with circular aperture of 6.5 mm. Both devices are capable of focusing collimated light in the range infinity...0.5 m.
Immunologic effects of interleukin 2 in primary immunodeficiency diseases (1983)

Five children with primary deficiencies of T cell function were studied to assess the effects of highly purified exogenous Interleukin 2 (IL 2) on their in vitro T cell responses. The lymphocytes from one child with Nezelof's T cell deficiency demonstrated absence of endogenous IL 2 production and improved proliferative responses to mitogen or alloantigen in the presence of exogenous IL 2. Moreover, during in vitro mixed lymphocyte culture in the presence of exogenous IL 2, his lymphocytes were able to develop into cytotoxic effector cells. A second child with Nezelof's syndrome demonstrated a different type of defect. The lymphocytes from this child had less impairment of endogenous IL 2 production. Although IL 2 increased the proliferation of his cells in response to PHA, similar augmentation was not seen after stimulation with OKT3 or alloantigen. In cell-mediated cytotoxicity assays, after mixed lymphocyte culture, natural killer-like activity was strongly boosted in the cultures that contained IL 2, but T cell-mediated cytotoxicity was not. The lymphocytes from three patients with severe combined immunodeficiency did not show improved proliferative responses in the presence of IL 2. Thus, only one of the five patients demonstrated the combination of defective endogenous IL 2 production, but preservation of the ability to respond appropriately to exogenous IL 2. This child may therefore have suffered from a T cell defect pathophysiologically similar to that seen in nude or aged mice.
TNM classification (2001)

The TNM guidelines for the number of regional lymph nodes examined for pN0 has been misinterpreted as a requirement.
Adherence of Salmonella typhimurium to Caco-2 cells: identification of a glycoconjugate receptor (1996)

The mechanism by which Salmonella species adhere to the epithelium of the intestine is not well understood. To identify components on intestinal epithelial cells that may be involved in the initial adherence of Salmonella typhimurium, we correlated patterns of adherence to well-differentiated Caco-2BBe cell monolayers with expression of brush border membrane components and lectin binding sites. This cloned cell line shows heterogeneous expression of sucrase-isomaltase and most lectin receptors. S. typhimurium adhered to a subpopulation of living or formaldehyde-fixed cells with a high multiplicity (up to 150 bacteria per cell). Bacterial binding to selected cells was not correlated with expression of the brush border hydrolases dipeptidyl-peptidase IV and sucrase-isomaltase or with binding of 10 of the 12 lectins tested. However, binding was correlated with the presence of binding sites for peanut agglutinin (PNA) [specific for Gal beta (1-3) GalNAc] and soybean agglutinin (specific for terminal GalNAc). Preincubation of live and fixed Caco-2BBe monolayers with PNA inhibited bacterial binding, while preincubation with soybean agglutinin did not. Electron microscopic analysis demonstrated that the initial adherence of S. typhimurium to Caco-2 cells in vitro involved peripheral components of the glycocalyx on apical microvilli. These results suggest that a Gal beta (1-3)GalNAc epitope recognized by PNA and located in the glycocalyx is involved in the early recognition events between S. typhimurium and Caco-2 cells and that differences in glycosylation patterns among individual epithelial cells may be a determinant in cell-selective adherence of S. typhimurium.
Studies Towards Synthesis of Dinucleoside Arylphosphonates with Metal Complexing Properties (2003)

An efficient and stereospecific synthesis of dinucleoside 4'-(2,2':6',2''-terpyridyl)phosphonate 2 and 5-(2,2'-bipyridyl)phosphonate 3 via a palladium(0) cross coupling strategy has been developed.
Feeling and seeing: issues in force display (1990)

article Free Access Share on Feeling and seeing: issues in force display Authors: Margaret Minsky View Profile , Ouh-young Ming View Profile , Oliver Steele View Profile , Frederick P. Brooks View Profile , Max Behensky View Profile Authors Info & Claims ACM SIGGRAPH Computer GraphicsVolume 24Issue 2Mar. 1990pp 235–241https://doi.org/10.1145/91394.91451Published:01 February 1990Publication History 347citation2,443DownloadsMetricsTotal Citations347Total Downloads2,443Last 12 Months151Last 6 weeks19 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF