gebhart/patrepeval huggingface dataset:
A systematic method to identify genomic islands and its applications in analyzing the genomes of Corynebacterium glutamicum and Vibrio vulnificus CMCP6 chromosome I (2004)

Programs used in this work and numerical results are available upon request.
In Quest of Audience: Sir Garfield Todd's Sermons and Political and Prophetic Addresses (2008)

Casey, M.W. (2007). The rhetoric of Sir Garfield Todd: Christian imagination and the dream of an African democracy. Waco, TX: Baylor University Press. 436 pp. ISBN: 978-1-932792-86-7. $34.95 (cloth...
Nematic liquid-crystal alignment on stripe-patterned substrates (2010)

Here, we use molecular simulation to consider the behavior of a thin nematic film confined between two identical nanopatterned substrates. Using patterns involving alternating stripes of homeotropic-favoring and homogeneous-favoring substrates, we investigate the influence of the relative stripe width and the film thickness. From this, we show that the polar anchoring angle can be varied continuously from planar to homeotropic by appropriate tuning of these parameters. For very thin films with equal stripe widths, we observe orientational bridging, the surface patterning being written in domains which traverse the nematic film. This dual-bridging-domain arrangement breaks down with increase in film thickness, however, being replaced by a single tilted monodomain. Strong azimuthal anchoring in the plane of the stripe boundaries is observed for all systems.
Immunotherapy in cancer (1996)

The History of Immunotherapy (M. Gore & P. Riches). Interferons (S. Fosse). Interferon-Beta and Interferon-Gamma in Cancer Therapy (S. Malik). Interleukin-2 (J. Atzpodien, et al.). Tumour Necrosis Factor (C. Boshoff & A. Jones). Recently Available Cytokines in Early Clinical Trials (IL1, IL3, IL4, IL6, IL12) (T. Eisen). Haemopoietic Growth Factors (H. Wagner, et al.). Tumour Vaccines (R. Vile, et al.). The Role of Monoclonal Antibodies in the Management of Cancer (H. Linardou & A. Epenetos). Gene Therapy (P. Patel & M. Collins). Adoptive Immunotherapy (J. Bridgewater). Practical Aspects of Delivering Cytokines (J. Moore). Index.
Protein kinase Cϵ interacts with cytochrome <i>c</i> oxidase subunit IV and enhances cytochrome <i>c</i> oxidase activity in neonatal cardiac myocyte preconditioning (2005)

We have previously identified a phorbol ester-induced PKCepsilon (protein kinase Cepsilon) interaction with the ( approximately 18 kDa) COIV [CO (cytochrome c oxidase) subunit IV] in NCMs (neonatal cardiac myocytes). Since PKCepsilon has been implicated as a key mediator of cardiac PC (preconditioning), we examined whether hypoxic PC could induce PKCepsilon-COIV interactions. Similar to our recent study with phorbol esters [Ogbi, Chew, Pohl, Stuchlik, Ogbi and Johnson (2004) Biochem. J. 382, 923-932], we observed a time-dependent increase in the in vitro phosphorylation of an approx. 18 kDa protein in particulate cell fractions isolated from NCMs subjected to 1-60 min of hypoxia. Introduction of a PKCepsilon-selective translocation inhibitor into cells attenuated this in vitro phosphorylation. Furthermore, when mitochondria isolated from NCMs exposed to 30 min of hypoxia were subjected to immunoprecipitation analyses using PKCepsilon-selective antisera, we observed an 11.1-fold increase in PKCepsilon-COIV co-precipitation. In addition, we observed up to 4-fold increases in CO activity after brief NCM hypoxia exposures that were also attenuated by introducing a PKCepsilon-selective translocation inhibitor into the cells. Finally, in Western-blot analyses, we observed a >2-fold PC-induced protection of COIV levels after 9 h index hypoxia. Our studies suggest that a PKCepsilon-COIV interaction and an enhancement of CO activity occur in NCM hypoxic PC. We therefore propose novel mechanisms of PKCepsilon-mediated PC involving enhanced energetics, decreased mitochondrial reactive oxygen species production and the preservation of COIV levels.
Discovery and early development of squaraine rotaxanes (2009)

The chemical and photophysical properties of a fluorescent squaraine dye are greatly enhanced when it is mechanically encapsulated inside a tetralactam macrocycle. This feature article describes the synthesis, structure, and photophysical performance of first-generation squaraine rotaxanes, and shows how they can be used as fluorescent imaging probes and chemosensors.
A novel design-process optimization technique based on self-consistent electrical performance evaluation (2005)

Accurate manufacturing of devices at sub-wavelength nodes is becoming increasingly difficult. Lithography and lithographic process effects are quickly becoming a major concern for physical designers working at sub-wavelength process nodes. Beyond the rapidly expanding design rule deck, physical designers must have deeper access to and understanding of the process in order to grasp the full impact of layout changes on electrical performance. Process aberrations, such as misalignment, are manifested as CD variation resulting in parametric shifts and systematic yield problems. These yield issues must be addressed by designers, but designers do not have adequate tools nor information to fully comprehend these issues. To correct this situation, a new approach is needed to bring information from the manufacturing process upstream into the design creation process. This work extends and generalizes concepts presented in [1-3] and presents an integrated implementation of the methodology in a complete, self-consistent flow. This methodology integrates calibrated process simulation, electrical circuit performance analysis and optionally, automatic Optical Proximity Correction (OPC) into a comprehensive Design-for-Manufacturing (DFM) flow. Process window simulations uncover design-process interactions across multiple process variables (misalignment, bias, etc.). To characterize the process, a design of experiments qualifies the impact of design variation on electrical performance. Data from these experiments is used to refine and calibrate process simulation models, ensuring accurate simulation. As a result, this procedure identifies critical performance and systematic yield issues prior to tapeout, eliminating costly design respins and preserving design intent.
DRUG-ELUTING BIORESORBABLE STENTS FOR VARIOUS APPLICATIONS (2006)

A stent is a medical device designed to serve as a temporary or permanent internal scaffold to maintain or increase the lumen of a body conduit. Metallic coronary stents were first introduced to prevent arterial dissections and to eliminate vessel recoil and intimal hyperplasia associated with percutaneous transluminal coronary angioplasty. The stent application range has expanded as more experience was gained, and encouraging results have been obtained in the treatment of vascular diseases. Stents are currently used for support of additional body conduits, including the urethra, trachea, and esophagus. The rationale for bioresorbable stents is the support of a body conduit only during its healing process. The stent mass and strength decrease with time, and the mechanical load is gradually transferred to the surrounding tissue. Bioresorbable stents also enable longer term delivery of drugs to the conduit wall from an internal reservoir and abolish the need for a second surgery to remove the device. The present review describes recent advances in bioresorbable stents, focusing on drug-eluting bioresorbable stents for various applications. Controlled release of an active agent from a stent can be used to enhance healing of the surrounding tissues, to increase the implant's biocompatibility, as well as to help cure certain diseases. Because a lot of research in this field has been done by us, examples for these functions are described based mainly on developments in our laboratories.
Oxidation of substituted phenols by Pseudomonas putida F1 and Pseudomonas sp. strain JS6 (1988)

The biodegradation of benzene, toluene, and chlorobenzenes by Pseudomonas putida involves the initial conversion of the parent molecules to cis-dihydrodiols by dioxygenase enzyme systems. The cis-dihydrodiols are then converted to the corresponding catechols by dihydrodiol dehydrogenase enzymes. Pseudomonas sp. strain JS6 uses a similar system for growth on toluene or dichlorobenzenes. We tested the wild-type organisms and a series of mutants for their ability to transform substituted phenols after induction with toluene. When grown on toluene, both wild-type organisms converted methyl-, chloro-, and nitro-substituted phenols to the corresponding catechols. Mutant strains deficient in dihydrodiol dehydrogenase or catechol oxygenase activities also transformed the phenols. Oxidation of phenols was closely correlated with the induction and activity of the toluene dioxygenase enzyme system.
2‐Aminopurine selectively blocks the transcriptional activation of cellular genes by virus, double‐stranded RNA and interferons in human cells (1989)

Interferons, double-stranded RNA and viruses induce the transcription of partly overlapping sets of cellular genes. We have studied the regulation of 11 interferon-inducible genes by these agents and found that four of them were also directly inducible by virus and double-stranded RNA, and two by virus only. We have investigated whether an inhibitor of interferon-beta gene activation, 2-aminopurine, would block this induction process. Induction of these genes by virus and double-stranded RNA was indeed blocked by 2-aminopurine. Since a single cis-acting element can confer inducibility both to interferons, and to virus and double-stranded RNA, we tested the effect of 2-aminopurine on gene activation by interferon-alpha and interferon-gamma. Remarkably, in all the cell lines tested, these induction processes and the establishment of an antiviral state were blocked by the drug. These observations contrast with previous reports. The inhibitory effect of this drug on gene induction was exerted in a selective fashion and at the transcriptional level. This indicate that for the virus-, double-stranded-RNA-, and interferons-mediated gene induction, an early and similar step in signal transduction was affected by 2-aminopurine.
Prodigiosin Rescues Deficient p53 Signaling and Antitumor Effects via Upregulating p73 and Disrupting Its Interaction with Mutant p53 (2013)

p53 reactivation offers a broad-based strategy for cancer therapy. In this study, we report the identification of prodigiosin that can reactivate p53 family-dependent transcriptional activity in p53-deficient human colon cancer cells. Prodigiosin and its structural analogue (compound R) induced the expression of p53 target genes accompanied by cell-cycle arrest and apoptosis in p53-deficient cancer cells. Prodigiosin restored p53 signaling in cancer cells harboring hotspot TP53 mutations, with little to no detectable cytotoxicity in normal human fibroblasts and with no genotoxicity. Prodigiosin induced the expression of p73 and disrupted its interaction with mutant p53, thereby rescuing p53 pathway deficiency and promoting antitumor effects. The disruption of mutant p53/p73 interaction was specific to prodigiosin and not related to mTOR inhibition. Our findings suggest that mutant p53 needs to be targeted in the context of p73 stimulation to allow efficient restoration of the p53 pathway. In exhibiting this capability, prodigiosin and its analogue provide lead compounds to rescue deficiencies in the p53 pathway in cancer cells by upregulating p73 and targeting mutant p53/p73 interaction there.
DEGRADATION OF AROMATIC AMINO ACIDS BY FUNGI: II. PURIFICATION AND PROPERTIES OF PHENYLALANINE AMMONIA-LYASE FROM USTILAGO HORDEI (1967)

Phenylalanine ammonia-lyase (EC 4.3.1.5) isolated from the cells of Ustilago hordei was purified 128-fold. The purified enzyme catalyzed the stoichiometric deamination of L-phenylalanine to trans-cinnamic acid. The optimum pH was about 8.8 and the Michaelis constant for L-phenylalanine was 0.45 mM. The enzyme preparations also catalyzed the deamination of DL-m-fluorophenylalanine, DL-p-fluorophenylalanine, and DL-m-hydroxyphenylalanine, although there was greater affinity of L-phenylalanine. The enzymic product from m-hydroxyphenylalanine was isolated and characterized as m-coumaric acid. No deamination of tyrosine could be demonstrated either with crude or purified preparations. Apparently there was no cofactor or metal ion requirement for the reaction. Sulfhydryl inhibitors like p-chloromercuribenzoate and N-ethylmaleimide partially inhibited the reaction in the presence of ethylenediaminetetracetate. The high susceptibility of the enzyme to inactivation by heavy metal ions like Ag + , Hg + , and Cd ++ also suggest the involvement of sulfhydryl groups in the reaction. Several compounds structurally related to phenylalanine were inhibitory, trans-Cinnamic acid exerted strong product inhibition. Reversibility of the reaction was demonstrated.
A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin. (1996)

All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution.
Distorted Distribution of Nicotinamide-Adenine Dinucleotide Phosphate—Diaphorase Neurons in Temporal Lobe of Schizophrenics Implies Anomalous Cortical Development (1993)

The distribution of neurons expressing the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) in the lateral and medial temporal lobes of schizophrenic and matched control brains was investigated in a systematic blind analysis. Schizophrenics had significantly lower numbers of NADPH-d neurons in the hippocampal formation and in the neocortex of the lateral temporal lobe but significantly greater numbers of NADPH-d neurons in the white matter of the lateral temporal lobe and a tendency toward greater numbers in parts of the parahippocampal white matter. The distorted distribution of NADPH-d neurons in the lateral temporal lobe, which may be explained by developmental disturbances, such as impaired neuronal migration or an alteration in the death cycle of transitory subcortical neurons, is similar to that found in the prefrontal cortex of schizophrenics. Alterations of cortical ontogenesis, as reflected in the distribution of NADPH-d neurons, appear to be widespread among neocortical association fields in schizophrenics and may provide a clue to the cause of the disease.
Use of Cfengine for Automated, Multi-Platform Software and Patch Distribution (2000)

The use of salting-out effect for the off-line preconcentration of charged analytes in capillary electrophoresis is demonstrated for the first time. Using benzalkonium chloride (BAK) as model compound, a mixture of cationic surfactants consisting of even-numbered alkylbenzyl quaternary ammonium homologues (C8-C18), the addition of appropriate amounts of sodium chloride and acetonitrile in the sample solution (2 mL sample volume) was found to be capable of providing ca. 40-fold enhancement in detection sensitivity. In addition to affording a preconcentrating effect due to the extraction of BAK in the smaller volume water-miscible organic solvent phase (acetonitrile), the organic solvent also serves to improve the peak area and shape of the longer chain surfactants. Optimal experimental conditions, such as volume of acetonitrile and concentration of sodium chloride, for the preconcentration of BAK with good preconcentration factors and reproducibility were investigated. The usefulness of the present method was demonstrated for the improved determination of BAK present in commercially available industrial and pharmaceutical products.
First shipborne GNSS-R campaign for receiving low elevation angle sea surface reflected signals (2016)

Global Navigation Satellite System Reflectometry (GNSS-R) was regarded as a promising way to observe atmospheric duct by utilizing low elevation angle ocean surface reflected signals. To invest the Delay maps' feature of low elevation angle reflected signals in the atmospheric duct, a shipborne GNSS-R campaign was conducted in July, 2015 by the scientific investigation ship called Shiyan 3 on the South China Sea. During the campaign, the atmospheric temperature, pressure, and relative humidity which were used to detect atmospheric duct were recorded by GPS radiosondes and meteorological recorder. The GNSS-R payload developed by National Space Science Center (NSSC) and fixed on the rail of Shiyan3 was used to generate Delay maps. Preliminary results showed that atmospheric duct, especially evaporation duct, existed almost all the time in the experimental ocean region. Ocean surface reflected signals with elevation angle less than 10° were received and formed delay maps successfully. Affected by the direct signal and specular reflected signal's strong interference, apparent code correlation peaks appeared on Delay maps' tail. The experimental values of correlation peaks and simulated code autocorrelation were synthetically used to fit the curve of direct signal and specular reflected signal's strong interference utilizing the least square method. After removing the interference, cleaner reflected signals without direct and specular reflection signals were obtained.
Clinical experience with antithrombotic drugs acting on purine receptor pathways (2001)

Abstract Rupture of atherosclerotic plaques and subsequent thrombus formation in coronary arteries are key events in the progression of coronary artery disease and the pathogenesis of acute coronary syndromes. Platelets play a crucial role in this thrombus formation and the success of aspirin in reducing cardiovascular morbidity and mortality has spurred on the search for antiplatelet agents that have an alternative mechanism of action and may, therefore, add to the therapeutic effects of aspirin. The thienopyridines, ticlopidine and clopidogrel, act via metabolites on the platelet ADP receptor subtype designated P 2T , and these agents have proven clinical efficacy, either as alternatives to aspirin or, in prevention of coronary stent thrombosis, in combination with aspirin. Potent P 2T receptor antagonists have been developed that act directly on the receptor and have a rapid onset of action. One such antagonist, AR‐C69931MX, is being developed for clinical use. AR‐C69931MX is a potent antagonist of ADP‐induced platelet activation, aggregation, and secretion and also antagonises platelet responses to all other agonists in view of the central role of the P 2T receptor in amplifying platelet responses. Phase II studies of intravenous AR‐C69931MX in patients with acute coronary syndromes show that this agent has a rapid onset of action, rapidly achieving steady‐state inhibition of platelet aggregation, with a half‐life of only a few minutes. AR‐C69931MX appears to be safe and well tolerated as adjunctive therapy in these patients, and more effective inhibition of platelet function is achieved than with the thienopyridine clopidogrel. Orally active antagonists are also being developed that may be more effective than the thienopyridines. Drug Dev. Res. 52:202–212, 2001. © 2001 Wiley‐Liss, Inc.
Introduction to the Immunology of Tuberculosis (1989)

This paper serves to introduce some concepts of modern immunobiology that are relevant to the understanding of the complex interactions between mycobacteria and the infected host. Six topics are discussed: (1) the phenotypic markers and functions of human T lymphocyte subsets; (2) the nature of antigen receptors on T cells; (3) antigen processing and presentation; (4) adhesion molecules that facilitate cellular interactions; (5) surface molecules on phagocytes that promote the entry of pathogens into cells; and (6) compartmentalization of the immune system in vivo.
Imaging photosensitizer distribution and pharmacology using multiphoton microscopy (2002)

Multiphoton microscopy is a powerful tool for imaging sub- cellular distribution of luminescent compounds present in living cells. We have used this tool to study the distribution and pharmacology of photosensitizers in tissue and tissue culture. Murine hepatoma tumor cells dosed with a photosensitizer were briefly photoactivated, then imaged for periods up to several hours. Using the photosensitizer Rose Bengal with green light activation, nearly immediate photolytic release of lysosomal enzymes resulted in catastrophic cell destruction within 5 - 30 minutes. The magnitude and rapidity of this response is markedly different than that observed with other photosensitizer agents, and is consistent with in vivo studies illustrating that Rose Bengal is capable of causing extremely rapid destruction of treated tumors.
Identification of a cDNA encoding a second putative prohormone convertase related to PC2 in AtT20 cells and islets of Langerhans. (1991)

PC2 and furin are two recently identified members of a class of mammalian proteins homologous to the yeast precursor processing protease kex2 and the bacterial subtillisins. We have used the polymerase chain reaction to identify and clone a cDNA (PC3) from the mouse AtT20 anterior pituitary cell line that represents an additional member of this growing family of mammalian proteases. PC3 encodes a 753-residue protein that begins with a signal peptide and contains a 292-residue domain closely related to the catalytic modules of PC2, furin, and kex2. Within this region 58%, 65%, and 50% of the amino acids of PC3 are identical to those of the aligned PC2, furin, and kex2 sequences, respectively, and the catalytically important Asp, His, and Ser residues are all conserved. On Northern blots, PC3 hybridizes to two transcripts of 3 and 5 kilobases. Tissue distribution studies indicate that both PC2 and PC3 are expressed in a variety of neuroendocrine tissues, including pancreatic islets and brain, but are not expressed in liver, kidney, skeletal muscle, and spleen. The high degree of similarity of PC3, PC2, and furin suggests that they are all members of a superfamily of mammalian proteases that are involved in the processing of prohormones and/or other protein precursors. In contrast to furin, PC3, like PC2, lacks a hydrophobic transmembrane anchor, but it has a potential C-terminal amphipathic helical segment similar to the putative membrane anchor of carboxypeptidase H. These and other differences suggest that these proteins carry out compartmentalized proteolysis within cells, such as processing within regulated versus constitutive secretory pathways.