gebhart/patrepeval huggingface dataset:
A Transient Product of DNA Alkylation Can Be Stabilized by Binding Localization (2003)

A 9-aminoacridine conjugate of a silyl-protected bis(acetoxymethyl)phenol (bisQMP) was synthesized and evaluated as an inducible cross-linking agent of DNA to test our ability to harness the chemistry of reactive quinone methide intermediates (QM). The acridine component was chosen for its ability to delivery an appendage to the major groove of DNA, and the silyl-protected component was chosen for its ability to generate two quinone methide equivalents in tandem upon addition of fluoride. This design created competition between reaction of (1) the 2-amino group of guanine that reacts irreversibly to form a stable QM adduct and (2) the more nucleophilic N7 group of guanine that reacts more efficiently but reversibly to form a labile QM adduct. This lability was apparently compensated by co-localization of the N7 group and QM in the major groove since the N7 adduct appeared to dominate the profile of products formed by duplex DNA. The controlling influence of acridine was also expressed in the sensitivity of the conjugate to ionic strength. High salt concentration inhibited covalent reaction just as it inhibits intercalation of the cationic acridine. As expected for QM formation, the presence of fluoride was indeed necessary for initiating reaction, and no direct benzylic substitution was observed. The conjugate also cross-linked DNA with high efficiency, forming one cross-link for every four alkylation events. Both alkylation and cross-linking products formed by duplex DNA were labile to hot piperidine treatment which led to approximately 40% strand scission and approximately 50% reversion to a material with an electrophoretic mobility equivalent to the parent DNA. All guanines exhibited at least some reactivity including those which were recalcitrant to cross-linking by an oligonucleotide-bisQMP conjugate designed for triplex formation [Zhou, G.; Pande, P.; Johnson, A. E.; Rokita, S. E. Bioorg. Med. Chem. 2001, 9, 2347-2354].
Inhibition of two copper-containing enzymes, tyrosinase and dopamine beta-hydroxylase, by L-mimosine. (1977)

Because of the structural similarity of L-mimosine to L-tyrosine and L-dopa and its tendency to chelate cupric ion, the influence of this compound on mammalian tyrosinase from mouse melanoma and dopamine β-hydroxylase extracted from bovine adrenal medulla was investigated in vitro. L-Mimosine inhibited tyrosinase competitively and reversibly, and the inhibitory effect was decreased by ferric, aluminum, or cupric ion. Dopamine β-hydroxylase was inhibited by L-mimosine, mimosinamine, and mimosinic acid, but the inhibition was uncompetitive. The results suggest that these enzymes are inhibited by different mechanisms: L-mimosine inhibits tyrosinase because of its structural similarity to the substrate, L-dopa. Dopamine β-hydroxylase is inhibited by L-mimosine, mimosinamine, and mimosinic acid because of their chelate-forming ability.
Nasogastric Administration of Omeprazole (1998)

A section for the publication of questions and responses of current interest from drug information centres.
FlgM is a primary regulator of sigmaD activity, and its absence restores motility to a sinR mutant (1996)

We have used mini-Tn1O mutagenesis to identify negative regulators of sigmaD activity. Nine independent insertions were mapped to five genes: flgM, flgK, fliD, fliS, and fliT, suggesting that FlgM export is regulated similarly in Bacillus subtilis and Salmonella typhimurium. We show that a deletion of flgM can restore sigmaD activity to a sinR null mutant of B. subtilis, although fla/che operon expression is affected by neither SinR nor FlgM.
OLAP and statistical databases (1997)

Article Free Access Share on OLAP and statistical databases: similarities and differences Author: Arie Shoshani Lawrence Berkeley National Lahoratory, Berkeley, California Lawrence Berkeley National Lahoratory, Berkeley, CaliforniaView Profile Authors Info & Claims PODS '97: Proceedings of the sixteenth ACM SIGACT-SIGMOD-SIGART symposium on Principles of database systemsMay 1997 Pages 185–196https://doi.org/10.1145/263661.263682Published:01 May 1997Publication History 109citation2,001DownloadsMetricsTotal Citations109Total Downloads2,001Last 12 Months142Last 6 weeks27 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
A career dedicated to translational research in colorectal cancer (2015)

Senior Editor of Colorectal Cancer, Professor Heinz-Josef Lenz* speaks to Roshaine Gunawardana, Managing Commissioning Editor: Heinz-Josef Lenz is Professor of Medicine and Professor of Preventive Medicine, holds the Kathryn Balakrishnan Chair for Cancer Research, is Associate Director, Clinical Research, Co-Chair of GI Oncology, Co-Director USC Center for Molecular Pathways and Drug Discovery at the University of Southern California Keck School of Medicine and USC/Norris Comprehensive Cancer Center, Los Angeles, CA, USA. Dr Lenz received his medical degree from Johannes-Gutenberg Universität in Mainz, Germany, and went on to complete a residency in hematology and oncology at the Eberhard-Karls Universität Tübingen, Germany before completing clerkships in oncology and hematology at George Washington University and the Beth Israel Hospital of Harvard Medical School, respectively. He completed a postdoctoral Fellowship in the Department of Biochemistry and Molecular Biology at the USC Keck School of Medicine. Dr Lenz's research focus is in the identification of predictive and prognostice biomarkers in gastrointestinal (GI) cancers, early drug development and novel clinical trials. He is Co-Chair of SWOG GI Committee, Chair SWOG GI Translational Medicine and member of the NCI GI Steering Committee, NCI Investigational Drug Steering Committee and the NCI Gastroesophageal Task Force. He is the Principal Investigator for R01, U01, U10 and USC PI for N01. He has been awarded a number of prestigious awards including ASCO Young Investigator Award, ASCO Career Development Award, NCI Career Development Award, STOP Cancer Career Development Award and Research Recognition Award. He has published over 270 peer reviewed papers including Nature Medicine, Nature Genetics, JCO and Lancet.
Evaluation of a Single-Tube Multiplex Real-Time PCR for Differentiation of Members of the Mycobacterium tuberculosis Complex in Clinical Specimens (2011)

Members of the Mycobacterium tuberculosis complex (MTBC) differ in virulence attributes, drug resistance patterns, and host preferences. The rapid differentiation of these species to determine zoonotic or human sources of tuberculosis disease or to direct treatment can benefit both public health and patient management. Commercially available assays cannot differentiate these species, and published assays have not been evaluated directly on clinical specimens. A real-time PCR assay for the differentiation of M. tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. microti, and M. canettii was developed. The presence or absence of regions of difference (RD) between the genomes of members of the MTBC allowed for the design of a single-tube five-plex real-time PCR assay to differentiate these species. This assay assesses the presence of RD1, RD4, RD9, RD12, and a region exterior to RD9 which is present in all MTBC members. To evaluate the performance of this assay, 192 clinical specimens positive for MTBC by real-time PCR were tested, resulting in a 94% correlation of the real-time PCR with the identification results obtained with cultured material. Additionally, 727 Bactec MGIT 960-positive cultures were tested, resulting in a 97% concordance between the methods. This real-time PCR is an inexpensive and rapid (2.5-h) method performed in a closed-format system and requiring minimal hands-on time that can be implemented in a clinical laboratory and used directly on clinical specimens.
CSF biomarkers for Alzheimer’s disease: use in early diagnosis and evaluation of drug treatment (2005)

Early diagnosis of Alzheimer's disease is important in initiating symptomatic treatment with acetylcholine esterase inhibitors, and will be of even greater significance if drugs with a potential to slow down the degenerative process, such as beta-secretase inhibitors and beta-amyloid vaccination, prove to have a clinical effect. During the last decade, research efforts have focused on developing cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. In this review, the background and principles for, and the diagnostic performance of, the CSF biomarkers total tau, phosphorylated tau and the 42-amino acid form of beta-amyloid, are reviewed. New candidate CSF biomarkers and new strategies, including multiparameter immunoassays and CSF proteomics techniques, in the search of additional CSF biomarkers are also reviewed. Finally, the rationale for the use of CSF biomarkers to identify and monitor the biochemical effect of new drug candidates is reviewed.
Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies (2013)

Substantial advances have been made in understanding critical molecular and cellular mechanisms driving tumor initiation, maintenance, and progression in non-small-cell lung cancer (NSCLC). Over the last decade, these findings have led to the discovery of a variety of novel drug targets and the development of new treatment strategies. Already, the standard of care for patients with advanced-stage NSCLC is shifting from selecting therapy empirically based on a patient's clinicopathologic features to using biomarker-driven treatment algorithms based on the molecular profile of a patient's tumor. This approach is currently best exemplified by treating patients with NSCLC with first-line tyrosine kinase inhibitors when their cancers harbor gain-of-function hotspot mutations in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. These genotype-based targeted therapies represent the first step toward personalizing NSCLC therapy. Recent technology advances in multiplex genotyping and high-throughput genomic profiling by next-generation sequencing technologies now offer the possibility of rapidly and comprehensively interrogating the cancer genome of individual patients from small tumor biopsies. This advance provides the basis for categorizing molecular-defined subsets of patients with NSCLC in whom a growing list of novel molecularly targeted therapeutics are clinically evaluable and additional novel drug targets can be discovered. Increasingly, practicing oncologists are facing the challenge of determining how to select, interpret, and apply these new genetic and genomic assays. This review summarizes the evolution, early success, current status, challenges, and opportunities for clinical application of genotyping and genomic tests in therapeutic decision making for NSCLC.
Review of Reported Clinical Information System Adverse Events in US Food and Drug Administration Databases (2011)

BACKGROUND: The US FDA has been collecting information on medical devices involved in significant adverse advents since 1984. These reports have been used by researchers to advise clinicians on potential risks and complications of using these devices. OBJECTIVE: Research adverse events related to the use of Clinical Information Systems (CIS) as reported in FDA databases. METHODS: Three large, national, adverse event medical device databases were examined for reports pertaining to CIS. RESULTS: One hundred and twenty unique reports (from over 1.4 million reports) were found, representing 32 manufacturers. The manifestations of these adverse events included: missing or incorrect data, data displayed for the wrong patient, chaos during system downtime and system unavailable for use. Analysis of these reports illustrated events associated with system design, implementation, use, and support. CONCLUSION: The identified causes can be used by manufacturers to improve their products and by clinical facilities and providers to adjust their workflow and implementation processes appropriately. The small number of reports found indicates a need to raise awareness regarding publicly available tools for documenting problems with CIS and for additional reporting and dialog between manufacturers, organizations, and users.
Transparent, highly conductive graphene electrodes from acetylene-assisted thermolysis of graphite oxide sheets and nanographene molecules (2009)

Transparent and highly conductive graphene electrodes have been fabricated through acetylene-assisted thermolysis of graphite oxide (GO) sheets. This novel procedure uses acetylene as a supplemental carbon source to repair substantial defects within GO sheets, leading to the enhancement of graphitization of synthesized graphene electrodes. The as-prepared graphene on quartz substrates exhibits an electrical conductivity of 1425 S cm−1 with an optical transmittance of more than 70% at a wavelength of 500 nm. Such an acetylene-assisted thermal treatment approach is also adopted to fabricate graphene electrodes from synthetic nanographene molecules, with an almost five times increase in conductivity compared to samples prepared by the common thermal reduction.
Polyamine-like actions of peptides derived from conantokin-G, an N-methyl-D-aspartate (NMDA) antagonist (1993)

Conantokins-T and -G are highly conserved polypeptides derived from Conus venoms. The N-methyl-D-aspartate (NMDA) antagonist properties of these compounds have been attributed to a potent noncompetitive inhibition of polyamine responses. Substitution of the highly conserved gamma-carboxyglutamate residues as well as modification of the N and C termini of conantokin-G abolished the inhibition of polyamine responses at the NMDA receptor complex. However, several of these modified polypeptides closely mimicked the neurochemical profile of polyamines at the NMDA receptor complex. One of these derivatives, Tyr0-conantokin-G, was found to be the most potent compound exhibiting polyamine-like actions at the NMDA receptor complex described to date, approximately 7-fold more potent than spermine. Circular dichroism studies demonstrate a significant alpha-helical content in conantokin-G (27% in aqueous medium). However, this alpha-helicity is not sufficient for the NMDA antagonist action of the parent peptide and is neither necessary nor sufficient for the polyamine-like behavior of several conantokin-G analogs. The modified conantokin-G derivatives described in this report should be useful probes for examining the role of both polyamines and the polyamine recognition site in the operation of the NMDA receptor complex.
Donor and acceptor strengths in C–H···O hydrogen bonds quantified from crystallographic data of small solvent molecules (1998)

The influence of donor and acceptor strengths on mean distances in C–H···O hydrogen bonds is quantified in a crystallographic database study. Small solvent molecules are used as donors, which are cocrystallized in organic and organometallic crystals. This system provides chemically homogeneous sets of C–H groups, allowing better defined statistical analysis compared to studies based on molecular fragments. Eight kinds of O-atom acceptors are considered, ranging from the very strong acceptor PO to the weak acceptor M–CO (M=transition metal atom). For the strongest donor considered, chloroform, mean hydrogen bond distances vary by ca. 0.5 Å as the acceptor strength is varied from PO to M–CO. For the weak donor acetone, this variation is only ca. 0.1 Å. It is confirmed that even weakly polar C–H groups can donate, and that the O-atoms of M–CO groups can accept C–H···O hydrogen bonds.
Algorithmic and Combinatorial Analysis of Trapping Sets in Structured LDPC Codes (2005)

Several combinatorial properties of low-density parity-check (LDPC) codes, such as minimum distance, diameter, stopping number, girth and cycle-length distribution of the corresponding Tanner graph, are known to influence their performance under iterative decoding. Recently, a new class of combinatorial configurations, termed trapping sets, was shown to be of significant importance in determining the properties of LDPC codes in the error-floor region. Very little is known both about the existence/parameters of trapping sets in structured LDPC codes and about possible techniques for reducing their negative influence on the code's performance. In this paper, we address both these problems from an algorithmic and combinatorial perspective. We first provide a numerical study of the trapping phenomena for the Margulis code, which exhibits a fairly high error-floor. Based on this analysis, conducted for two different implementations of iterative belief propagation, we propose a novel decoding process, termed averaged decoding. Averaged decoding provides for a significant reduction in the number of incorrectly decoded frames in the error-floor region of the Margulis code. Furthermore, based on the results of the algorithmic approach, we suggest a novel combinatorial characterizations of trapping sets in the class of LDPC codes based on finite geometries. Projective geometry LDPC codes are suspected to have extremely low error-floors, which is a property that we may attribute to the non-existence of certain small trapping sets in the code graph.
Transcriptional Repression Mediated by Polycomb Group Proteins and Other Chromatin-associated Repressors Is Selectively Blocked by Insulators (2000)

Polycomb group (PcG) proteins repress gene activity over a considerable distance, possibly by spreading along the chromatin fiber. Insulators or boundary elements, genetic elements within the chromatin, may serve to terminate the repressing action of PcG proteins. We studied the ability of insulators to block the action of chromatin-associated repressors such as PcG proteins, HP1, and MeCP2. We found that the Drosophila special chromatin structure insulator completely blocks transcriptional repression mediated by all of the repressors we tested. The Drosophila gypsy insulator was able to block the repression mediated by the PcG proteins Su(z)2 and RING1, as well as mHP1, but not the repression mediated by MeCP2 and the PcG protein HPC2. The 5'-located DNase I-hypersensitive site in the chicken beta-globin locus displayed a limited ability to block repression, and a matrix or scaffold attachment region element was entirely unable to block repression mediated by any repressor tested. Our results indicate that insulators can block repression mediated by PcG proteins and other chromatin-associated repressors, but with a high level of selectivity. This high degree of specificity may provide a useful assay to define and characterize distinct classes of insulators.
Mariner Sails into Leishmania (1997)

[ Daniel L. Hartl ][1] Transposons are bits of DNA that can move from place to place in the genomes of plants and animals. The wide-ranging transposon mariner is found in many different animals, and in this issue [Gueiros-Filho and Beverley][2] show that, given the right circumstances, it can also move into the genome of Leishmania , the cause of a deadly disease in the tropics. In his Perspective, Hartl explains the features of this transposable element and how the ability to move it into the Leishmania genome will increase the tools available in the search for a treatment for this pathogen. 


[][3]

 [1]: http://www.sciencemag.org#affiliation
 [2]: http://www.sciencemag.org/cgi/content/short/276/5319/1716
 [3]: http://
On The Palmitoylation Of Surfactant-associated Protein C (1995)

Surfactant-associated protein C (SP-C) contributes to the surface active properties of pulmonary surfactant. Processed from a 21 kDa precursor, the mature form of SP-C is 34-35 amino acids in length. Both the precursor and the mature protein are modified by palmitoylation. Due to its small size and extreme hydrophobicity, SP-C has been difficult to isolate, detect and study. Using molecular exclusion chromatography, SP-C was isolated from calf lung surfactant extract, characterized by partial sequencing, amino acid analysis, tricine polyacrylamide gel electrophoresis, and absence of immune-reactivity with antibodies raised against surfactant-associated protein B (SP-B). A method was developed to label, detect and quantify SP-C based on the reaction of iodoacetamide with sulfhydryl groups released upon the treatment of the protein with mild alkali to cleave the thioester bond through which the palmitates are bound to the protein. The surface active properties of lipid mixtures of dipalmitoylphosphatidylcholine (DPPC): phosphatidylglycerol (PG) with SP-C were studied using the pulsating bubble surfactometer. The presence of SP-C enhanced lipid adsorption onto the air-liquid interface. Upon compression, the mixture exhibited low surface tension, but the surface tension did not approach zero values except at moderately acidic pH values (2.5-3.5) or after prolonged pulsation. This partially clarified the inconsistency in the literature regarding the role of SP-C in lowering the surface tension as a pH effect. The function of palmitoylation was studied using both the pulsating bubble and the captive bubble surfactometers. Palmitoylation was found to contribute to enhancing lipid adsorption but to be absolutely essential for the stability of DPPC:PG:SP-C monolayers and for lipid re-spreading to form surface active layers after depletion of surfactant from the subphase. SP-C palmitoylation was carried out in vitro in the presence of palmitoyl CoA as the lipid donor. No other factors were needed for the re-palmitoylation of chemically depalmitoylated SP-C, indicating that the process is likely to be non-enzymatic. In addition to donating palmitate for covalent incorporation, palmitoyl CoA associated with SP-C in a highly specific but non-covalent manner. Palmitic acid, CoA, and surfactant lipids did not compete with palmitoyl CoA in its interaction with SP-C. This specificity suggests the possibility that the palmitoylation of SP-C may be a self-catalyzed process.