gebhart/patrepeval huggingface dataset:
Drug-induced hERG Block and Long QT Syndrome (2010)

Drug-induced long QT syndrome is a cardiac safety issue that all drugs seeking approval must currently address, in part via in vitro electrophysiological testing of the drug's effects on the function of the human Ether-à-go-go Related Gene (hERG) potassium channel. This regulatory strategy has also been scientifically successful, in that these in vitro assays are cheaper and faster than are many other surrogates for arrhythmogenic risk, including QT prolongation in humans and action potential prolongation in cardiomyocytes. In some ways hERG assays are also more sensitive to the underlying repolarization anomalies that lead to the risk of the Torsades de pointes arrhythmia. In addition, the higher throughput of hERG assays combined with advances in our understanding of the molecular structures underlying this pathophysiology have led to new approaches in the medicinal chemistry of "designing out" hERG liability from lead compounds. While generally effectual, hERG screening produces some false positives: drugs with an apparent liability that are known not to be clinically arrhythmogenic. New technologies continue to be developed to improve hERG screening, while further insights into the molecular pharmacology of hERG and cardiac repolarization are providing avenues to mitigate and make sense of the lack of torsadogenic specificity in extant hERG assays.
Shrink-Induced Superhydrophobic and Antibacterial Surfaces in Consumer Plastics (2012)

Structurally modified superhydrophobic surfaces have become particularly desirable as stable antibacterial surfaces. Because their self-cleaning and water resistant properties prohibit bacteria growth, structurally modified superhydrophobic surfaces obviate bacterial resistance common with chemical agents, and therefore a robust and stable means to prevent bacteria growth is possible. In this study, we present a rapid fabrication method for creating such superhydrophobic surfaces in consumer hard plastic materials with resulting antibacterial effects. To replace complex fabrication materials and techniques, the initial mold is made with commodity shrink-wrap film and is compatible with large plastic roll-to-roll manufacturing and scale-up techniques. This method involves a purely structural modification free of chemical additives leading to its inherent consistency over time and successive recasting from the same molds. Finally, antibacterial properties are demonstrated in polystyrene (PS), polycarbonate (PC), and polyethylene (PE) by demonstrating the prevention of gram-negative Escherichia coli (E. coli) bacteria growth on our structured plastic surfaces.
Targeting of cytotoxic peptides to haematological malignancies (2005)

Amphipathic peptides with an a-helical structure disrupt membranes rich in negatively charged phospholipids and have antibiotic properties. They are toxic to eukaryotic cells if internalised by a suitable targeting mechanism. We have targeted one such peptide D(KLAKLAK)2 to haemopoetic cells by conjugating it to monoclonal antibodies which recognise lineage-specific cell-surface molecules. An anti-CD33: peptide conjugate was cytotoxic to one of three CD33-positive myeloid leukaemia lines, whereas an anti- CD 19: peptide conjugate efficiently killed three out of three B lymphoid lines with IC50 in the low nanomolar range. Cell lines which did not express the relevant antigen were resistant to the conjugates at the concentrations used. Peptide conjugated to anti-CD 19 and anti-CD33 antibodies had cytotoxic activity towards cells isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML) respectively. CLL cells isolated from heavily pre-treated patients or from poor risk category individuals, as determined by elevated expression of the ZAP-70 protein tyrosine kinase, were as sensitive to the conjugate as were untreated or good risk category patients. Cell death was shown to be by an apoptotic mechanism and independent of the level of expression of anti-apoptotic proteins Bcl-2, Mcl-1 and XIAP. In addition the conjugate acted synergistically with chlorambucil. The data here suggest that anti-CD 19 D(KLAKLAK)2 displays a highly selective and potent cytotoxic activity against CLL cells and may be of therapeutic value in the treatment of this incurable leukaemia. We also panned a phage display library in an attempt to isolate a peptide that would bind to CD33 and thereby create a peptide with both targeting and cytotoxic activity towards malignant myeloid cells.
Superoxide Dismutases in Polymorphonuclear Leukocytes (1974)

Isolated human polymorphonuclear leukocytes were found to contain two distinct superoxide dismutases, electrophoretically identical to the superoxide dismutases found in other human tissues. One is inhibited by cyanide and is located in the cytosol. The other is not inhibited by cyanide and is mitochondrial. These findings disagree with reports by other laboratories, which did not find the cyanide-sensitive cytoplasmic enzyme. The superoxide dismutase-containing preparation of leukocytes released large amounts of superoxide into the medium when the cells were phagocytizing, suggesting that, if the cell population is homogeneous, superoxide production probably takes place on the outer surface of the cell membrane, in addition to inside the phagocytic vacuole.
Purification and partial characterization of a hepatocyte antiproliferative glycopeptide (1989)

A low molecular weight compound, which inhibits the G1-S transition in rat hepatocytes, was obtained by tryptic hydrolysis of human alpha 2-macroglobulin followed by ultrafiltration at pH 10. It was purified by high-performance liquid chromatography on mu Bondapak C18 and mu Bondapak NH2 with a practically quantitative yield; from 5.1 g of alpha 2-macroglobulin, 2.8 micrograms of purified compound were recovered. Inactivation by specific enzymes and chemical analyses showed that the inhibitor is a sialylated glycopeptide whose peptide moiety contains a pyroglutamyl residue. Its molecular mass, estimated by gel permeation chromatography, would be in the interval 3,500-4,600. However, amino acid analyses indicated that it is not yet pure. All these data suggest that alpha 2-macroglobulin could be the carrier of the precursor form of the glycopeptide.
Human liver alcohol dehydrogenase: purification, composition, and catalytic features (1976)

Alcohol dehydrogenase has been purified from human liver by affinity chromatography. Ultracentrifugation, Sephadex G-200 chromatography, and amino acid analyses of multiple preparations demonstrate homogeneity of molecular weight. Sodium dodecyl sulfate disc gel electrophoresis reveals a single species of molecular weight 42 000. Based on a molecular weight of 85 000 for the dimer obtained from the amino acid composition and a molar absorptivity of A280nm0.1% = 0.58, the enzyme contains 3.6-4.2 g-atoms of zinc, as determined by emission spectrography, microwave-induced emission, and atomic absorption spectrometry. Inhibition by o-phenanthroline, (ethylenedinitrilo)tetraacetic acid, and alpha,alpha'-bipyridine demonstrates that zinc is essential to enzymatic function. Detailed kinetic analyses using primary alcohols of the homologous series CH3(CH2)nOH, n = 0-5, and the corresponding aldehydes as substrates show that KM values become smaller as n increases. This suggest that hydrophobic interactions play a role in substrate binding. The availability of well-defined preparations of human liver alcohol dehydrogenase now allows definitive genetic and functional studies of this enzyme to elucidate human ethanol metabolism.
Herpes Zoster in an Adult Recipient of Live Attenuated Varicella Vaccine (1989)

A healthy 30-y-old female physician who was immunized with two doses of live attenuated varicella vaccine developed a localized case of zoster involving the right T8-10 dermatomes 36 mo after vaccination. The virus isolated from her rash was an unusual wild-type of varicella-zoster virus. After immunization she developed detectable antibodies to varicella-zoster virus, but antibodies were no longer detectable after 20 mo. Six months before development of zoster, she was exposed to a patient with varicella; however, she did not develop a clinical illness although she again became seropositive. To date, this is the only reported case of zoster among 187 healthy adult vaccinees.
PCR Bias in Ecological Analysis: a Case Study for Quantitative Taq Nuclease Assays in Analyses of Microbial Communities (2000)

Succession of ecotypes, physiologically diverse strains with negligible rRNA sequence divergence, may explain the dominance of small, red-pigmented (phycoerythrin-rich) cyanobacteria in the autotrophic picoplankton of deep lakes (C. Postius and A. Ernst, Arch. Microbiol. 172:69-75, 1999). In order to test this hypothesis, it is necessary to determine the abundance of specific ecotypes or genotypes in a mixed background of phylogenetically similar organisms. In this study, we examined the performance of Taq nuclease assays (TNAs), PCR-based assays in which the amount of an amplicon is monitored by hydrolysis of a labeled oligonucleotide (TaqMan probe) when hybridized to the amplicon. High accuracy and a 7-order detection range made the real-time TNA superior to the corresponding end point technique. However, in samples containing mixtures of homologous target sequences, quantification can be biased due to limited specificity of PCR primers and probe oligonucleotides and due to accumulation of amplicons that are not detected by the TaqMan probe. A decrease in reaction efficiency, which can be recognized by direct monitoring of amplification, provides experimental evidence for the presence of such a problem and emphasizes the need for real-time technology in quantitative PCR. Use of specific primers and probes and control of amplification efficiency allow correct quantification of target DNA in the presence of an up to 10(4)-fold excess of phylogenetically similar DNA and of an up to 10(7)-fold excess of dissimilar DNA.
Mitogenic Activities of Water-Soluble and -Insoluble Insulin Conjugates (1997)

Insulin was covalently bound to water-soluble polymers such as poly(oxyethylene) and poly(acrylic acid). The former and the latter product are water-soluble monovalent and multivalent conjugates, respectively. Insulin was also bound to a poly(acrylic acid)-grafted polystyrene film, to form a water-insoluble multivalent conjugate. The matrix polymer was prepared by graft polymerization of acrylic acid initiated by glow-discharged polystyrene film. Insulin coupled with poly(oxyethylene) reduced the mitogenic activity, but the poly(acrylic acid)-insulin conjugate stimulated cell growth more than native insulin. A concentration of immobilized insulin much lower than that of native insulin and the water-soluble insulin conjugates accelerated cell growth. The maximal mitogenic effect of the immobilized insulin was greater than that of native insulin or the water-soluble insulin conjugates. The findings suggest that the mitogenic effect of the water-insoluble, multivalent insulin conjugate lasts longer than that of the water-soluble conjugates, owing to the absence of internalization into the cell.
ChemInform Abstract: Sequence‐Selective Peptide Binding with a Synthetic Receptor. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Electro-Optical Performances of p-on-n and n-on-p Silicon Photomultipliers (2012)

Silicon photomultipliers (SiPMs) are fabricated in two different configurations: p-on-n and n-on-p junctions. p-on-n SiPMs turn out to be more suitable for application in positron emission tomography (PET), due to their higher sensitivity in blue wavelength range where common PET scintillators have their emission spectrum. In this paper, we report on the electro-optical performances of the first p-on-n SiPMs manufactured at STMicroelectronics, Catania. The results obtained on these devices are compared with those measured on the standard n-on-p technology.
In search of models for hepatic and placental pharmacokinetics (2003)

Several in vitro methods using both human and animal tissues have been developed to study hepatic metabolism and placental transfer. The pressure to minimize animal studies has increased during the past few decades due to the public opinion and ethical considerations. However, these methods need further evaluation of their predictive power when applied in vivo. The aim of this work was to produce new information of the metabolism and transplacental passage of several anticonvulsants as well as to evaluate the usefulness of the placental perfusion method and several in vitro methods for analyzing metabolism in the prediction of clinical pharmacokinetics. Carbamazepine (CBZ) metabolism was studied using human and mouse liver microsomes, human hepatocytes, human liver slices and yeast cells expressing recombinant enzymes. All test systems predicted well the major metabolite carbamazepine-10,11-epoxide (CBZ-E). Also, minor metabolites were produced in slightly variable amounts in all systems except cells with recombinant enzymes. All human liver systems demonstrated that CYP3A4 is the principal CBZ metabolising enzyme. However, our results on CBZ-treated mice suggested that the metabolism of CBZ to CBZ-E is mainly mediated by CYP1A1 in C57/BL6 mice. Autoinduction of CBZ metabolism was seen in hepatocytes and in incubations using microsomes from CBZ-treated mice. Human liver and mouse liver microsomes metabolized oxcarbazepine (OCBZ) mainly to its active metabolite, 10-hydroxy-10,11dihydro-carbamazepine (10-OH-CBZ). Also, 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine (10,11-D) and an unknown metabolite were detected. Placental transfer of lamotrigine (LTG) and diazepam (DZP) was considerable in the human placental perfusion system, indicating marked fetal exposure in vivo. The OCBZ, 10-OH-CBZ and 10,11-D analyzed from maternal venous and cord blood also suggested significant fetal exposure. The placental perfusion system predicts well the transplacental passage of LTG and OCBZ and its major metabolite. However, in vivo cord blood concentrations of DZP are higher than maternal concentrations. Placental perfusion studies did not predict this. Still, even with its limitations, the human placental perfusion method provides information that can be used to evaluate the risk factors associated with drug use during pregnancy because understanding of specific transport characteristics is a good basis for rational risk assessment. In conclusion, all of the tested in vitro systems were useful in the prediction of at least some aspects of in vivo pharmacokinetics and metabolism, but validation and refinement are still essential, as is also the need to keep in mind the limitations characteristic of each in vitro method.
A new era (2004)

The U.S. payments system has entered a new era — one that is witnessing a marked decline in the use of paper checks and a sharp increase in the use of electronic payments.
Retrodifferentiation--an alternative biological pathway in human leukemia cells. (1992)

Human myeloid leukemia cells (i.e., HL-60, U937, THP-1) which are induced to differentiate along the monocytic pathway by 12-O-tetradecanoylphorbol-13-acetate (TPA), revert back to the undifferentiated phenotype after 3 to 4 weeks. During this differentiation and retrodifferentiation process the cells obviously establish a distinct sequence of biological processes which is integrally regulated to simultaneously control differentiation and cell growth. Thus, induction of monocytic markers by TPA is associated with a down-regulation of cell cycle genes and cessation of proliferation. In particular, crosstalk between the TPA-induced translocation of protein kinase C (PKC) and the activation of transcription factors, especially AP-1, enhances the expression of genes associated with the monocytic phenotype. This is accompanied by induction of intermediate filament proteins, surface glycoproteins, changes in membrane properties and intracellular metabolism. In parallel, the cells cease to divide, and genes associated with cell cycle progression including cdc2, cyclins, cdc25, and histones are down-regulated. Although signals responsible for arrested cell growth remain unclear, there are several control mechanisms regarding cell cycle genes and differentiation parameters (for a review, see Nigg, E. A., Seminars in Cell Biol., 2, 262-270, 1991). For example, activated p34cdc2 kinase is involved in lamina disassembly by direct phosphorylation of lamin proteins which may contribute to nuclear envelope breakdown during mitosis (Enoch, T., M. Peter, P. Nurse, J. Cell Biol. 112, 797-807 (1991)). Moreover, endomembrane traffic is arrested by a cdc2-like kinase probably via phosphorylation of members of the rab protein family which contributes to vesiculation and membrane transport by hydrolyzing GTP (Tuomikoski, T., et al., Nature 342, 942-945 (1989)). Although there are several reports on a possible feedback control between differentiation and cell cycle, including phosphorylation of cyclins and activation of a ubiquitin-dependent proteolytic degradation, signaling pathways and possible mechanisms for retrodifferentiation and reentry into the cell cycle remain unclear. While some terminally differentiated cells are committed to die, the major part of the differentiated monocytic population undergoes retrodifferentiation. All cellular signals characterized so far are reverted during retrodifferentiation: Redistribution of PKC and down-regulation of c-fos and c-jun contribute to an interruption of the differentiation-associated transsignaling cascade. Thus, down-regulation of markers associated with monocytic differentiation in combination with metabolic changes restore the original cell phenotype. At the same time cell cycle genes are up-regulated, and the cells regain proliferative capacity. Finally, retrodifferentiated and untreated control cells demonstrate indistinguishable properties.
Heterocyclen aus Carbonsäurederivaten, II. Substituierte 4‐Hydroxy‐ und 4‐Amino‐pyrimidine (1967)

Abstract Essigsäure‐ und Arylessigsäurealkylester ( 2 ) sowie Acetonitril und Arylacetonitrile ( 6 ) reagieren mit Nitrilen ( 3 ) in Gegenwart von Alkoholaten zu 4‐Hydroxy‐pyrimidinen ( 4 ) bzw. 4‐Amino‐pyrimidinen ( 7 ).
The Human Gene FALL39 and Processing of the Cathelin Precursor to the Antibacterial Peptide LL‐37 in Granulocytes (1996)

The peptide FA-LL-37, previously termed FALL-39, was originally predicted from on ORF of a cDNA clone isolated from a human bone marrow library. This peptide was synthesized and found to have antibacterial activity. We have now characterized and sequenced the complete gene for FA-LL-37, termed FALL39. It is a compact gene of 1963 bp with four exons. Exons 1-3 code for a signal sequence and the cathelin region. Exon 4 contains the information for the mature antibacterial peptide. Our results indicate that FALL39 is the only member of the cathelin gene family present in the human genome. Potential binding sites for acute-phase-response factors are identified in the promoter and in intron 2. A possible role for the cytokine interleukin-6 in the regulation of FALL 39 is discussed. Anti-(FA-LL-37) IgG located the peptide in granulocytes and we isolated the mature peptide from these cells after degranulation. Structural analysis determined the mature peptide to be LL-37. To obtain LL-37 for antibacterial assays, synthetic FA-LL-37 was degraded with dipeptidyl-peptidase I. This analysis showed that mature LL-37 is a potent antibacterial peptide.
Effects of floating-gate interference on NAND flash memory cell operation (2002)

Introduced the concept of floating-gate interference in flash memory cells for the first time. The floating-gate interference causes V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> shift of a cell proportional to the V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> change of the adjacent cells. It results from capacitive coupling via parasitic capacitors around the floating gate. The coupling ratio defined in the previous works should be modified to include the floating-gate interference. In a 0.12-μm design-rule NAND flash cell, the floating-gate interference corresponds to about 0.2 V shift in multilevel cell operation. Furthermore, the adjacent word-line voltages affect the programming speed via parasitic capacitors.
Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice (2006)

MicroRNAs (miRNAs) represent a newly discovered class of posttranscriptional regulatory noncoding small RNAs that bind to targeted mRNAs and either block their translation or initiate their degradation. miRNA profiling of hematopoietic lineages in humans and mice showed that some miRNAs are differentially expressed during hematopoietic development, suggesting a role in hematopoietic cell differentiation. In addition, recent studies suggest the involvement of miRNAs in the initiation and progression of cancer. miR155 and BIC, its host gene, have been reported to accumulate in human B cell lymphomas, especially in diffuse large B cell lymphomas, Hodgkin lymphomas, and certain types of Burkitt lymphomas. Here, we show that E(mu)-mmu-miR155 transgenic mice exhibit initially a preleukemic pre-B cell proliferation evident in spleen and bone marrow, followed by frank B cell malignancy. These findings indicate that the role of miR155 is to induce polyclonal expansion, favoring the capture of secondary genetic changes for full transformation.
Measurement of Mouse and Human Interleukin 5 (1991)

Two fundamentally different types of assays are available for quantitating interleukin 5 in biological samples. One type, a bioassay, is based on the ability of IL-5 to enhance B cell proliferation and immunoglobulin secretion or eosinophil proliferation and differentiation. The other type of assay, an ELISA, uses antibodies against IL-5 to capture and quantitate IL-5 in samples. Advantages and disadvantages of each assay are discussed. The bioassay described in this unit, utilizing BCL(1) cells as the indicator line, has been designed primarily to assay murine IL-5; however, it can also be used to measure human IL-5. The IL-5 ELISA, while sensitive and specific, provides no information about biological activity.