gebhart/patrepeval huggingface dataset:
Inhibition of vascular adhesion protein‐1 suppresses endotoxin‐induced uveitis (2007)

Inflammatory leukocyte accumulation is a common feature of major ocular diseases, such as uveitis, diabetic retinopathy, and age-related macular degeneration. Vascular adhesion protein-1 (VAP-1), a cell surface and soluble molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity, is involved in leukocyte recruitment. However, the expression of VAP-1 in the eye and its contribution to ocular inflammation are unknown. Here, we investigated the role of VAP-1 in an established model of ocular inflammation, the endotoxin-induced uveitis (EIU), using a novel and specific inhibitor. Our inhibitor has a half-maximal inhibitory concentration (IC(50)) of 0.007 microM against human and 0.008 microM against rat SSAO, while its IC(50) against the functionally related monoamine oxidase (MAO) -A and MAO-B is >10 microM. In the retina, VAP-1 was exclusively expressed in the vasculature, and its expression level was elevated during EIU. VAP-1 inhibition in EIU animals significantly suppressed leukocyte recruitment to the anterior chamber, vitreous, and retina, as well as retinal endothelial P-selectin expression. Our data suggest an important role for VAP-1 in the recruitment of leukocytes to the immune-privileged ocular tissues during acute inflammation. VAP-1 inhibition may become a novel strategy in the treatment of ocular inflammatory diseases.
A Genetically Encoded Photocaged Amino Acid (2004)

We have developed a second orthogonal tRNA/synthetase pair for use in yeast based on the Escherichia coli tRNALeu/leucyl tRNA-synthetase pair. Using a novel genetic selection, we have identified a series of synthetase mutants that selectively charge the amber suppresor tRNA with the C8 amino acid, alpha-aminocaprylic acid, and the photocaged amino acid, o-nitrobenzyl cysteine, allowing them to be inserted into proteins in yeast in response to the amber nonsense codon, TAG.
Single-cell whole-genome analyses by Linear Amplification via Transposon Insertion (LIANTI) (2017)

Single-cell genomics is important for biology and medicine. However, current whole-genome amplification (WGA) methods are limited by low accuracy of copy-number variation (CNV) detection and low amplification fidelity. Here we report an improved single-cell WGA method, Linear Amplification via Transposon Insertion (LIANTI), which outperforms existing methods, enabling micro-CNV detection with kilobase resolution. This allowed direct observation of stochastic firing of DNA replication origins, which differs from cell to cell. We also show that the predominant cytosine-to-thymine mutations observed in single-cell genomics often arise from the artifact of cytosine deamination upon cell lysis. However, identifying single-nucleotide variations (SNVs) can be accomplished by sequencing kindred cells. We determined the spectrum of SNVs in a single human cell after ultraviolet radiation, revealing their nonrandom genome-wide distribution.
Invitro activation ofCPP32andMch3byMch4,anovelhuman apoptotic cysteine protease containing twoFADD-like domains (1996)

Emerging evidence suggests thatanampli- fiable protease cascade consisting ofmultiple aspartate- specific cysteine proteases (ASCPs) isresponsible forthe apoptotic changes observed inmammalian cells undergoing programmed cell death. Herewedescribe thecloning oftwo novel ASCPsfromhumanJurkat T-lymphocytes. Likeother ASCPs,thenewproteases, namedMch4andMch5,are derived fromsingle chainproenzymes. However, their puta- tive active sites contain aQACQGpentapeptide instead ofthe QACRGpresent inallknownASCPs.Also, their N termini contain FADD-like deatheffector domains, suggesting possi- bleinteraction withFADD.Expression ofMch4inEscherichia coli produced anactive protease that, like other ASCPs, was potently inhibited (Ki = 14nM)bythetetrapeptide aldehyde DEVD-CHO.Interestingly, bothMch4andtheserine protease granzyme Bcleave recombinant proCPP32 andproMch3 ata conserved IXXD-Ssequence toproduce thelarge andsmall subunits oftheactive proteases. Granzyme B alsocleaves proMch4 atahomologous IXXD-Aprocessing sequence to produce matureMch4.Theseobservations suggest that CPP32andMch3aretargets ofmatureMch4protease in apoptotic cells. Thepresence oftheFADD-like domains in Mch4andMch5suggests aroleforthese proteases inthe Fas-apoptotic pathway. Inaddition, these proteases could participate inthegranzyme B apoptotic pathway. Apoptosis isafundamental biochemical cell-death pathway es- sential fornormal tissue homeostasis, cellular differentiation, and development within amulticellular organism (for review, seerefs. 1-3). Members ofthegrowing family ofaspartate-specific cys-
A feasibility study for electrical impedance tomography as a means to monitor tissue electroporation for molecular medicine (2002)

Molecular medicine involves the introduction of macromolecules, such as drugs or gene constructs, into specific cells of the body. Electroporation, which uses electric pulses to permeate cell membranes, is a method for achieving this. However, as with other molecular medicine procedures, it lacks a real-time mechanism to detect and control which cells have been affected. We propose and demonstrate, via computer simulation, that electrical impedance tomography has the potential for detecting and imaging electroporation of cells in tissue in real-time, thereby providing feedback for controlling electroporation.
Crystallographic Study of Steps along the Reaction Pathway of d-Amino Acid Aminotransferase, (1998)

The three-dimensional structures of two forms of the D-amino acid aminotransferase (D-aAT) from Bacillus sp. YM-1 have been determined crystallographically: the pyridoxal phosphate (PLP) form and a complex with the reduced analogue of the external aldimine, N-(5'-phosphopyridoxyl)-d-alanine (PPDA). Together with the previously reported pyridoxamine phosphate form of the enzyme [Sugio et al. (1995) Biochemistry 34, 9661], these structures allow us to describe the pathway of the enzymatic reaction in structural terms. A major determinant of the enzyme's stereospecificity for D-amino acids is a group of three residues (Tyr30, Arg98, and His100, with the latter two contributed by the neighboring subunit) forming four hydrogen bonds to the substrate alpha-carboxyl group. The replacement by hydrophobic groups of the homologous residues of the branched chain L-amino acid aminotransferase (which has a similar fold) could explain its opposite stereospecificity. As in L-aspartate aminotransferase (L-AspAT), the cofactor in D-aAT tilts (around its phosphate group and N1 as pivots) away from the catalytic lysine 145 and the protein face in the course of the reaction. Unlike L-AspAT, D-aAT shows no other significant conformational changes during the reaction.
CD1c as a target recognition structure for human T lymphocytes: Analysis with peripheral blood γ/δ cells (1990)

It has been shown recently that one gamma/delta cell line, termed IDP2, derived from a immunodeficient patient recognizes the CD1c molecule on the surface of target cells. In light of these data, we have tested 43 cloned and 11 polyclonal gamma/delta cell lines derived from peripheral blood of 19 donors following nonspecific mitogenic stimulation. In this panel, which included lymphocytes expressing various combinations of gamma and delta chains, only one clone, termed J2B7, was found to interact with target cells via a CD1c-dependent recognition pathway. These J2B7 lymphocytes have, like IDP2, a delta chain which results from the frequent V1/J1 rearrangement while they use a distinct V gamma gene segment. The data support the view that the CD1c major histocompatibility complex "class I-like" gene product does not have a pivotal contribution to the repertoire of peripheral blood gamma/delta cells in adult individuals.
Mice Expressing Activated CaMKII Lack Low Frequency LTP and Do Not Form Stable Place Cells in the CA1 Region of the Hippocampus (1996)

To relate different forms of synaptic plasticity to the formation and maintenance of place cells in the hippocampus, we have recorded place cells in freely behaving, transgenic mice that express a mutated Ca2+-independent form of CaM Kinase II. These mice have normal long-term potentiation (LTP) at 100 Hz, but they lack LTP in response to stimulation at 5-10 Hz and are impaired on spatial memory tasks. In these transgenic mice, the place cells in the CA1 region have three important differences from those of wild types: they are less common, less precise, and less stable. These findings suggest that LTP in the 5-10 Hz range may be important for the maintenance of place-field stability and that this stability may be essential for the storage of spatial memory.
SIMNETMAN: an expert workstation for designing rule-based network management systems (1988)

The authors present SIMNETMAN, a network simulator, and discuss its role in exploring the utility of expert system technology for network management. SIMNETMANs companion system, NETMAN, is a collection of rule-based experts for network management. SIMNETMAN provides the user interface for NETMAN by allowing the experimenter to construct the network to be simulated, to specify the experiments, and also to modify the rules that comprise NETMAN, SIMNETMAN simulates a packet-switched network and actually conducts the experiments requested by the user. An overview of the system is presented, followed by a discussion of the implementation problems. The simulation capabilities of SIMNETMAN and preliminary performance results for the NETMAN/SIMNETMAN system are reported.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Oxidation Management of White Wines Using Cyclic Voltammetry and Multivariate Process Monitoring (2008)

The development of a fingerprinting strategy capable to evaluate the "oxidation status" of white wines based on cyclic voltammetry is proposed here. It is known that the levels of specific antioxidants and redox mechanisms may be evaluated by cyclic voltammetry. This electrochemical technique was applied on two sets of samples. One group was composed of normal aged white wines and a second group obtained from a white wine forced aging protocol with different oxygen, SO(2), pH, and temperature regimens. A study of antioxidant additions, namely ascorbic acid, was also made in order to establish a statistical link between voltammogram fingerprints and chemical antioxidant substances. It was observed that the oxidation curve presented typical features, which enables sample discrimination according to age, oxygen consumption, and antioxidant additions. In fact, it was possible to place the results into four significant orthogonal directions, compressing 99.8% of nonrandom features. Attempts were made to make voltammogram fingerprinting a tool for monitoring oxidation management. For this purpose, a supervised multivariate control chart was developed using a control sample as reference. When white wines are plotted onto the chart, it is possible to monitor the oxidation status and to diagnose the effects of oxygen regimes and antioxidant activity. Finally, quantification of substances implicated in the oxidation process as reagents (antioxidants) and products (off-flavors) was tried using a supervised algorithmic the partial least square regression analysis. Good correlations (r > 0.93) were observed for ascorbic acid, Folin-Ciocalteu index, total SO(2), methional, and phenylacetaldehyde. These results show that cyclic voltammetry fingerprinting can be used to monitor and diagnose the effects of wine oxidation.
Point Mutations and an Intragenic Deletion in LIS1, the Lissencephaly Causative Gene in Isolated Lissencephaly Sequence and Miller-Dieker Syndrome (1997)

Classical lissencephaly (smooth brain) or generalized agyria-pachygyria is a severe brain malformation which results from an arrest of neuronal migration at 9-13 weeks gestation. It has been observed in several malformation syndromes including Miller-Dieker syndrome (MDS) and isolated lissencephaly sequence (ILS). A gene containing beta-transducin like repeats, now known as LIS1, was previously mapped to the ILS/MDS chromosome region on 17p13.3. We recently localized the classical lissencephaly critical region to the LIS1 gene locus by molecular analysis of key ILS and MDS patients. We have now characterized the structure of LIS1, which consists of 11 exons, and have searched for the presence of subtle mutations in 19 ILS patients who showed no gross rearrangements of LIS1. Single strand conformational polymorphism (SSCP) analysis revealed band-shifts for three patients, each involving a different coding exon, which were not observed in their respective parental DNAs. Sequence analysis identified these de novo mutations as dA --> dG transition in exon VI at nucleotide 446, a dC --> dT transition in exon VIII at nucleotide 817, and a 22 bp deletion at the exon IX-intron 9 junction from nucleotide 988 to 1,002+7, which causes skipping of exon IX in the mature LIS1 transcript. These changes are predicted to result in an H149R amino acid substitution, an R273X premature translation termination, and abolition of amino acids 301-334, in the respective LIS1 proteins. These data thus confirm LIS1 as the gene responsible for classical lissencephaly in ILS and MDS.
Ionic Liquid High-Temperature Gas Sensor Array (2006)

A novel sensor array using seven room-temperature ionic liquids (ILs) as sensing materials and a quartz crystal microbalance (QCM) as a transducer was developed for the detection of organic vapors at ambient and elevated temperatures. Ethanol, dichloromethane, benzene, and heptane were selected as representative gas analytes for various kinds of environmental pollutants and common industrial solvents. The QCM/IL sensors responded proportionately and reversibly to the organic vapor concentrations (i.e., ethanol, heptane, and benzene) in the gas phase from 0 to 100% saturation at room and elevated temperatures (e.g., 120 degrees C) but deviated from this linear relationship at high concentrations for dichloromethane, a highly volatile compound. Linear discriminant analysis was used to analyze the sensing patterns. Excellent classifications were obtained for both known and unknown concentrations of vapor samples. The correct classifications were 100% for known concentration samples and 96% for samples with unknown concentrations. Thermodynamics and ATR-FT-IR studies were conducted to understand specific molecular interactions, the strength of the interaction between ILs and organic vapors, and the degree of ordering that takes place upon dissolution of the vapors in ILs. The different response intensity of the QCM/IL sensors to the organic vapors depends on the different solubilities of organic vapors in ILs and varying molecular/ion interactions between each organic vapor and IL. The diverse set of IL studied showed selective responses due to structural differences. Therefore, a sensor array of ILs would be able to effectively differentiate different vapors in pattern recognitions, facilitating discrimination by their distinctive patterns in response to organic vapors in both room and high temperatures.
An expression-independent catalog of genes from human chromosome 22. (1995)

To accomplish large-scale identification of genes from a single human chromosome, exon amplification was applied to large pools of clones from a flow-sorted human chromosome 22 cosmid library. Sequence analysis of more than one-third of the 6400 cloned products identified 35% of the known genes previously localized to this chromosome, as well as several unmapped genes and randomly sequenced cDNAs. Among the more interesting sequence similarities are those that represent novel human genes that are related to others with known or putative functions, such as one exon from a gene that may represent the human homolog of Drosophila Polycomb. It is anticipated that sequences from at least half of the genes residing on chromosome 22 are contained within this exon library. This approach is expected to facilitate fine-structure physical and transcription mapping of human chromosomes, and accelerate the process of disease gene identification.
PRACTICAL p-VALUE ADJUSTMENT FOR OPTIMALLY SELECTED CUTPOINTS (1996)

This paper concerns a series of simulations undertaken to examine the effects of two data features – number of cutpoints and true marker prognostic effect size – on three methods of p-value adjustment (asymptotic, Pacor; improved Bonferroni, Pbon; and empirical permutation, Pemp). H0 rejection rates for Pemp and Pbon are almost indistinguishable from those for an independent validation sample (Pvld), while those of Pacor are somewhat conservative, especially when the number of cutpoints is small. Analysis of a new breast cancer prognostic marker, heat shock protein 70, illustrates the methods. These results underscore many of the problems associated with data-derived cutpoints in general, and the need for p-value adjustment.
Perspectives on the Optimal Genetically Engineered Pig in 2018 for Initial Clinical Trials of Kidney or Heart Xenotransplantation (2018)

For a clinical trial today, what might realistically be the optimal pig among those currently available? Deletion of expression of the 3 pig carbohydrate antigens, against which humans have natural (preformed) antibodies (triple-knockout pigs), should form the basis of any clinical trial. However, because both complement and coagulation can be activated in the absence of antibody, the expression of human complement- and coagulation-regulatory proteins is likely to be important in protecting the graft further. Any genetic manipulation that might reduce inflammation of the graft, for example, expression of hemeoxygenase-1 or A20, may also be beneficial to the long-term survival of the graft. The transgene for human CD47 is likely to have a suppressive effect on monocyte/macrophage and T-cell activity. Furthermore, deletion of xenoantigen expression and expression of a human complement-regulatory protein are both associated with a reduced T-cell response. Although there are several other genetic manipulations that may reduce the T-cell response further, it seems likely that exogenous immunosuppressive therapy, particularly if it includes costimulation blockade, will be sufficient. We would therefore suggest that, with our present knowledge and capabilities, the optimal pig might be a triple-knockout pig that expressed 1 or more human complement-regulatory proteins, 1 or more human coagulation-regulatory proteins, a human anti-inflammatory transgene, and CD47. Absent or minimal antibody binding is important, but we suggest that the additional insertion of protective human transgenes will be beneficial, and may be essential.
Simple Nanoimprint Lithography with 50 nm Resolution Using Vacuum Packing (2010)

We demonstrated a simple UV nanoimprint method using vacuum packing. A glass substrate and a Si mold dropped with a photo-curable resist were vacuum-packed together in a packing sheet. They were pressed by atmospheric pressure and easily fixed without a complicated apparatus. We obtained a successful nanoimprint result for 100 nm width lines with high aspect ratio of 3.2. Further fine pattern of about 50 nm line width was also replicated using our simple method. The remaining thickness of the resist after imprint decreased with increasing the pressing pressure whereas it saturated due to the viscosity of the resist. This saturation tendency is well explained by the balance between the pressing force and the viscous force of the resist.
Substrate specificity characterization of a cdc2-like protein kinase purified from bovine brain. (1993)

A serine/threonine kinase from bovine brain has been purified (Lew, J., Beaudette, K. N., Litwin, C. M. E., and Wang, J. H. (1992) J. Biol. Chem. 267, 13383-13390) and found to consist of a 33-kDa catalytic subunit having high sequence homology to p34cdc2 and cdk2 (Lew, J., Winkfein, R. J., Paudel, H., and Wang, J. H. (1992) J. Biol. Chem. 267, 25922-25926). Substrate specificity determinants for this cdc2-like kinase were examined using synthetic peptide substrates derived from the in vitro p34cdc2 phosphorylation sites of histone H1. The peptide P-K-T-P-K-K-A-K-K-L was found to be an excellent substrate for the bovine cdc2-like kinase, having a Km value in the micromolar range. Important determinants for efficient substrate phosphorylation of this peptide were found both within the proposed substrate consensus motif (S/T-P-X-K/R) of p34cdc2 kinase and outside of this sequence. In addition to the absolute requirement for a proline residue immediately COOH-terminal to the phosphorylatable residue (+1) and a basic residue at the +3 position, a basic amino acid at the +2 position was greatly preferred over an acidic amino acid. A proline residue at the -2 position and a cluster of basic amino acids further COOH-terminal to the consensus motif were also found to be important for substrate binding. HeLa cell p34cdc2 kinase displays similar specificity to that of the bovine cdc2-like kinase, as the additional determinants outside of the consensus motif that contribute to the efficient phosphorylation of the histone peptide by this novel enzyme also appear to be important for p34cdc2-catalyzed phosphorylation.
Acute renal failure: controversies, clinical trials, and future directions. (1998)

Acute renal failure (ARF) is an important clinical syndrome. Despite the frequent occurrence of ARF, nephrologists have not made major therapeutic inroads in the treatment or prevention of ARF. This article will speculate as to why it has been so difficult to gain a substantial foothold in the ongoing battle against ARF. First, some of the major controversies regarding the pathogenesis of ARF will be considered. Scientific debates regarding the mechanisms of ARF have greatly enriched the scientific literature, but may have slowed the development of clinically applicable therapies. Controversies regarding the treatment of ARF will then be discussed. Next, the fate of several recent clinical trials in ARF will be examined. Finally, the future directions that research in ARF may pursue will be contemplated.
Morphological and biochemical characterization of viral particles produced by the tsO45 mutant of vesicular stomatitis virus at restrictive temperature (1979)

The growth at restrictive temperature of tsO45, a group V (glycoprotein) conditional lethal mutant of vesicular stomatitis virus (VSV), was demonstrated to result in the production of large numbers of noninfectious viral particles. The infectivity of these tsO45 particles could be enhanced by procedures known to promote membrane fusion. Morphologically and biochemically these particles differed from wild-type VSV by their lack of viral glycoprotein. The other structural proteins of VSV were present and indistinguishable by size and relative proportion from those of virus grown at the permissive temperature. Examination of glycoprotein maturation at the restrictive temperature (39.5 degrees C) in tsO45-infected cells demonstrated the synthesis of normal viral glycoprotein but failed to demonstrate the presence of this glycoprotein in either the cell membrane or the envelope of free virions. The further absence of soluble viral glycoprotein from the supernatants of such cells strongly suggests that viral glycoprotein may not be necessary for the successful budding of VSV.
Highly efficient and linear level shifting digital LINC transmitter with a phase offset cancellation (2009)

In this paper, a novel level shifting digital linear amplifier with nonlinear components (LINC) transmitter for OFDM system is presented. By using a multi-level switched power supply, the final power added efficiency is significantly improved compared to a conventional LINC amplifier. Moreover, with digital phase offset cancellation scheme, the transmitter has a good linearity as well. This work was verified by ADS simulation with standard 0.18μm CMOS Technology.