gebhart/patrepeval huggingface dataset:
SB-253514 and Analogues. Novel Inhibitors of Lipoprotein Associated Phospholipase A2 Produced by Pseudomonas fluorescens DSM 11579. II. Physico-chemical Properties and Structure Elucidation. (2000)

A series of novel inhibitors of lipoprotein associated phospholipase A2 were isolated from the culture broths of Pseudomonas fluorescens strain DSM11579. The inhibitors fall into two structurally isomeric classes each of which comprise compounds incorporating glycosylated hydrocarbon chains. The structure elucidation for the major member of each structural class is reported. The crystal structure of a non-glycosylated analogue of the 5,5-series, produced through biotransformation, is also reported.
Evaluation of Fern and Moss Protein‐Based Defenses Against Phytophagous Insects (2006)

Relatively little is known about insect defense mechanisms in the ferns and mosses. The current paradigm is that secondary metabolites and physical barriers are most important in conferring insect resistance in ferns, lycopods, and mosses. We investigated whether protein‐based resistance exists in representatives of these taxa. We screened a total of 23 plant species for protein‐based insecticidal activity against the two common lepidopteran pests: corn earworm (Helicoverpa zea) and fall armyworm (Spodoptera frugiperda). Protein extracts from fern and moss species were compared with those from a lepidopteran‐susceptible soybean (Glycine max) cultivar (Cobb) in bioassays for insect resistance. The ebony spleenwort (Asplenium platyneuron), sensitive fern (Onoclea sensibilis), glade fern (Anthyrium pycnocarpon), and the burned ground moss (Ceratodon purpureus) protein extracts caused the greatest decrease in damage in leaf‐disk assays and insect larval growth. These species are good candidates for follow‐up evaluation.
A New Method for the Quantification of Breathing (2007)

Quantification of the breath flow and nostril dominance reveals internal physiological cycles. There are very few existing methods for unobtrusive monitoring of the breath flow. In this paper we present a new method for the quantification of breath flow and evaluation of the symmetry of breathing through both nostrils. The system utilizes thermal film to visualize the flow of breath and implements image processing techniques to quantify the flow. We present system design and preliminary results from an experiment with 11 subjects. Preliminary results indicate a good correlation between subjective measure of the nostril dominance and two analyzed parameters - ratio of left/right area and average intensity. The proposed method can be used as a diagnostic tool, for stress monitoring, biofeedback techniques, and circadian rhythm analysis.
Tracking a driver's hands using computer vision (2002)

The paper describes a computer vision system for tracking a driver's hands. The applications of such a system are discussed with particular attention given to the control of a novel vehicle systems interface. This interface is controlled by pointing at the required function on a display mounted behind the top of the steering wheel. The vision system must detect and track the driver's hands to allow efficient recovery of a search space in which to look for a pointing finger. Cameras mounted above the driver provide images of the steering wheel area. The scene is segmented using adaptive background and foreground models. A distance transform is applied to the resulting contours. A geometric model is fitted to the resulting distance map by maximising an objective function over the model parameters in a local search space defined by the output of a Kalman filter. The appearance-based model fitting process can resolve ambiguous situations such as the hands touching or crossing, and parting again. The system is demonstrated running at 10 Hz on a standard PC.
Statistics of Single-Molecule Detection (1997)

A new mathematical approach for the calculation of the photon detection statistics in single-molecule detection experiments is presented. The approach is based on a path integral representation of the involved probability distributions. A numerical Monte Carlo sampling method for computing the involved path integrals is given. The general ideas are applied to the modeling of measured burst size distributions in single-molecule detection experiments with B-phycoerythrin.
Synthesis and Biological Evaluation of a Polyglutamic Acid–Dopamine Conjugate: A New Antiangiogenic Agent (2011)

Dopamine has previously been shown to inhibit angiogenesis in vitro and in vivo, but its clinical applications in this context are severely limited by its short half-life. Here we report the synthesis of a polyglutamic acid-dopamine conjugate and show that conjugation significantly extends (from 1 to 24 h) dopamine's antiangiogenic activity in vitro and in vivo. These findings form the basis for the development of a new class of agents for the treatment of angiogenesis-dependent diseases.
Biocatalysis in ionic liquids (2002)

This review describes the recent developments of enzymatic catalysis in ionic liquids, reporting the use of different biocatalysts in organic synthesis. Several ionic liquids appear as an alternative to conventional organic solvents, providing comparable or higher rates and, in some cases, improved enantioselectivity.
Pilot Study: Absorption and Efficacy of Multiple Hormones Delivered in a Single Cream Applied to the Mucous Membranes of the Labia and Vagina (2008)

This study is the first documenting systemic absorption of multiple hormones by both saliva and blood as well as improvement of HRQoL. This therapy was generally well-tolerated with only 2 patients experiencing minor irritation, not necessitating discontinuation. Additional studies in larger numbers of patients will provide better knowledge for clinicians wanting to provide similar therapy at the lowest effective dose.
Query Optimization in KESS - An Ontology-Based KBMS. (2000)

This paper presents an approach for the implementation of query optimization techniques in Kess (the Knowledge Enhanced SQL Server). Kess is a Knowledge Database Management Systems (KBMS) that uses a semantic ontology-based data model. We have classified our query optimization techniques in two different categories: 1. semantic-based and 2. data access path related. These techniques use a compiler optimizationapproach to simplify query predicates and use caching to optimize memory hierarchy performance for the evaluation of ontology-related predicates. This work also presents the results of the implementation of such optimizations in Kess in the form of a performance analysis. 1 Introduction This paper presents an approach for the implementation of query optimization techniques in Kess (the Knowledge Enhanced SQL Server) whose main novel feature, when compared to conventional SQL servers, is its capability to store knowledge and to use this embedded knowledge in a manner that is analo...
Delivery of radionuclides to pretargeted monoclonal antibodies using dihydrofolate reductase and methotrexate in an affinity system. (1993)

A novel affinity system for a two-phase delivery of radionuclides to tumor cells has been developed. In the first phase, a nontoxic bivalent monoclonal antibody conjugated to an enzyme is targeted to the tumor cells. In the second phase, a radionuclide-derivatized enzyme inhibitor, specific for the enzyme conjugated to the antibody, is administered. The model system selected for this study is the recombinant human enzyme dihydrofolate reductase (rhDHFR) and its high-affinity competitive inhibitor methotrexate (MTX). MTX was labeled with a radionuclide by covalent attachment of diethylenetriaminepentaacetic acid (DTPA) complexed with 111In. Using the gamma-carboxyl residue of MTX for the attachment of DTPA, binding of the inhibitor to rhDHFR was not affected. The inhibitory activities of nonderivatized MTX and DTPA-MTX were indistinguishable. Human K562 erythroleukemia cells were used to evaluate under in vitro conditions the DHFR-MTX affinity system for the delivery of 111In-labeled DTPA-MTX to pretargeted alpha-transferrin receptor antibody-rhDHFR conjugates (alpha-TFR-DHFR). The data demonstrate that the delivery of 111In is dose dependent and highly specific. Under saturating conditions, binding of 111In-DTPA-MTX to alpha-TFR-DHFR-treated cells was 14-fold higher than to cells treated with nonconjugated alpha-TFR antibody. Further experiments indicated that the low level of nonspecific binding of 111In-DTPA-MTX was comparable to that of 111In-DTPA, known for its complete extracellular distribution and rapid clearance through the kidneys. Based on the data of this study, antibody-conjugated rhDHFR and radionuclide-labeled DTPA-MTX complexes provide components for an alternative radioimmunotherapeutic approach that can be expected to result in improved tumor tissue ratios of both the targeting moiety and the radionuclide-labeled derivative as compared to current approaches.
X rays induce interallelic homologous recombination at the human thymidine kinase gene. (1992)

We have developed a human lymphoblast cell line for the study of interchromosomal homologous recombination at the endogenous thymidine kinase (tk) gene on chromosome 17 (M. B. Benjamin, H. Potter, D. W. Yandell, and J. B. Little, Proc. Natl. Acad. Sci. USA 88:6652-6656, 1991). This cell line (designated 6:86) carries unique heterozygous frameshift mutations in exons 4 and 7 of its endogenous tk alleles and can revert to TK+ by frame-restoring mutations, gene conversion, or reciprocal recombination. Line 6:86 reverts spontaneously to TK+ at a frequency of 10(-7) to 10(-8), and exposures to X-irradiation or the frameshift mutagen ICR-191 induce increased reversion frequencies in a dose-dependent manner. Another cell line (designated 4:2) carries a homozygous exon 7 frameshift and is not expected to revert through mechanisms other than frame-restoring mutation. Line 4:2 reverts to TK+ at a lower spontaneous frequency than does 6:86 but can be induced with similar kinetics by ICR-191. In contrast to line 6:86, however, X rays did not induce detectable reversion of line 4:2. We have characterized a number of 6:86-derived revertants by means of restriction fragment length polymorphism analysis at tk and linked loci, single-strand conformation polymorphisms, and direct transcript sequencing. For X rays, most revertants retain both original mutations in the genomic DNA, and a subset of these frameshift-retaining revertants produce frameshift-free message, indicating that reversion is the result of reciprocal recombination within the tk gene. Frame-restoring point mutations, restoration of original sequences, and phenocopy reversion by acquisition of aminopterin resistance were also found among X-ray-induced revertants, whereas the ICR-191-induced revertants examined show only loss of the exon 7 frameshift.
Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711. (1992)

The ability of L-644,711 to limit brain injury in two related models of thromboembolic stroke suggests a potential therapeutic role for anion channel blockers in cerebral ischemia.
Fractionation of Isotopically Labeled Peptides in Quantitative Proteomics (2001)

The goal of quantitative proteomics is to examine the expression levels of all of the proteins in a biological system and recognize those that change as a function of some stimulus. Quantification is now frequently based on derivatization of peptides with isotopically distinguishable labeling agents. This study examines the extent to which isotopic forms of peptides having the same amino acid sequence are resolved by reversed-phase chromatography and assesses the degree to which resolution of these isotopically different forms of a peptide impact quantification. Three derivatizing agents were examined, the do and d3 forms of N-acetoxysuccinimide, the do and d4 forms of succinic anhydride, and the do and d8 forms of the commercial ICAT reagent Peptide mixtures from control and experimental samples were derivatized individually, mixed, subjected to reversed-phase chromatography, and analyzed by ESI-MS. When partial resolution of the isotopic forms of a peptide occurs, the largest error in assessing the true isotope ratio in a sample occurs when sampling at the extremes of a peak. Early in the elution of a peak, the sample will be enriched in the deuterated species, whereas the opposite is true at the tailing edge of a peak. Acetylated peptides showed the lowest degree of separation. Resolution of the deuterated and nondeuterated forms in this case was 0.023. This amounts to slightly over a 1-s difference in their peak maxima and can cause a typical error of +/- 6% at the leading and tailing edges of a peak. In contrast, resolution of the deuterated and nondeuterated forms of the ICAT reagent were calculated to be 0.45. This means that in a peak of 1-min width (W1/2), the peak maxima will vary by approximately 30 s, and measurement errors of -83 and +500% can occur at the leading and tailing edges of a peak. It is concluded that resolution of isotopic forms of a peptide can cause substantial quantification errors in quantitative proteomics.
Genomic Cloning and Promoter Analysis of Aortic Preferentially Expressed Gene-1 (1999)

Aortic preferentially expressed gene-1 (APEG-1) was originally identified as a 1.4-kilobase (kb) transcript preferentially expressed in differentiated vascular smooth muscle cells (VSMC). Its expression is markedly down-regulated in de-differentiated VSMC, suggesting a role for APEG-1 in VSMC differentiation. We have now determined that APEG-1 is a single-copy gene in the human, rat, and mouse genomes and have mapped human APEG-1 to chromosome 2q34. To study the molecular mechanisms regulating its expression, we characterized the genomic organization and promoter of mouse APEG-1. APEG-1 spans 4.5 kb in the mouse genome and is composed of five exons. Using reporter gene transfection analysis, we found that a 2. 7-kb APEG-1 5'-flanking sequence directed a high level of promoter activity only in VSMC. Its activity was minimal in five other cell types. A repressor region located within an upstream 685-base pair sequence suppressed the activity of this 2.7-kb promoter. Further deletion and mutation analyses identified an E box motif as a positive regulatory element, which was bound by nuclear protein prepared from VSMC. In conjunction with its flanking sequence, this E box motif confers VSMC-specific enhancer activity to a heterologous SV40 promoter. To our knowledge, this is the first demonstration of an E box motif that mediates gene expression restricted to VSMC.
Modifying the Release Properties of Eudragit® L30D (1991)

The influence of various additives, namely, PEG, mannitol, and HPMCP 50 incorporated with Eudragit® L30D on drug release from pellets was investigated. Cores of a water soluble drug were prepared by the powder layering technique using the CF Granulator (CF 360) and coating was accomplished utilizing the Glatt GPCG3 machine. Drug release from pellets coated with Eudragit® L30D was found to be influenced by the type and the level of the additive incorporated with the copolymer. At pH 1.5, PEG, regardless of the molecular weight, did not have any significant effect on drug release. At pH 5.5, however, PEG significantly decreased drug release from coated pellets, and the decrease was more pronounced as the molecular weight of PEG was increased. Release of the drug from pellets coated with Eudragit® L30D containing mannitol was found to be dependent on mannitol concentration at pH 1.5, 3.5 and 4.5 but independent of mannitol concentration at pH 5.5. The release of drug through Eudragit® L30D:HPMCP 50 films was found to be dependent on the ratio of the polymers.
Tumor-targeted salmonella as a novel anti-melanoma vector (1997)

1Departments of Dermatology and Pharmacology, therapeutic Radiology, and 3Internal Medicine, Yale University School of Medicine, New Haven, CT, USA and 3Vion Pharmaceuticals, New Haven, CT, USA
Proteolytic release of human angiotensin-converting enzyme. Localization of the cleavage site. (1993)

Angiotensin-converting enzyme (EC 3.4.15.1, ACE) is a transmembrane protein with a short carboxyl-terminal cytoplasmic domain, a 17-amino acid hydrophobic anchor domain, and a large N-terminal extracellular region containing two catalytically homologous domains. An active soluble form of ACE circulates in human plasma and is produced in culture medium of Chinese hamster ovary (CHO) cells transfected with the full-length human ACE cDNA. The mechanism of ACE release in CHO cells involves a post-translational proteolytic cleavage occurring in the carboxyl-terminal region. The carboxyl terminus of the secreted recombinant ACE, AGQR, was established by carboxyl-terminal microsequencing and corresponds to a cleavage site between Arg-1137 and Leu-1138. Two independent studies confirmed this proposed cleavage site: amino acid analysis of a carboxyl-terminal peptide derived from soluble ACE and immunocharacterization of membrane-bound and soluble ACE with antibodies raised against three peptides located along the carboxyl-terminal ACE sequence. In order to assess the importance of Arg-1137, this amino acid was mutated to a glutamine residue. This mutation did not prevent the secretion of ACE, suggesting that the solubilizing enzyme can accommodate this change or can use an alternative cleavage site. Finally, the production of soluble ACE in CHO cells appears to be proportional to the level of cellular ACE, implying that the solubilizing enzyme is not a limiting factor. In addition, the carboxyl-terminal sequence of the human plasma ACE was identified as AGQR, thus supporting the fact that a similar mechanism could operate in human vascular cells.
Flow-dependent expression of ectonucleotide tri(di)phosphohydrolase-1 and suppression of atherosclerosis (2015)

The ability of cells to detect and respond to nucleotide signals in the local microenvironment is essential for vascular homeostasis. The enzyme ectonucleotide tri(di)phosphohydrolase-1 (ENTPD1, also known as CD39) on the surface of leukocytes and endothelial cells metabolizes locally released, intravascular ATP and ADP, thereby eliminating these prothrombotic and proinflammatory stimuli. Here, we evaluated the contribution of CD39 to atherogenesis in the apolipoprotein E-deficient (ApoE-deficient) mouse model of atherosclerosis. Compared with control ApoE-deficient animals, plaque burden was markedly increased along with circulating markers of platelet activation in Cd39+/-Apoe-/- mice fed a high-fat diet. Plaque analysis revealed stark regionalization of endothelial CD39 expression and function in Apoe-/- mice, with CD39 prominently expressed in atheroprotective, stable flow regions and diminished in atheroprone areas subject to disturbed flow. In mice, disturbed flow as the result of partial carotid artery ligation rapidly suppressed endothelial CD39 expression. Moreover, unidirectional laminar shear stress induced atheroprotective CD39 expression in human endothelial cells. CD39 induction was dependent upon the vascular transcription factor Krüppel-like factor 2 (KLF2) binding near the transcriptional start site of CD39. Together, these data establish CD39 as a regionalized regulator of atherogenesis that is driven by shear stress.
Carbon nanotube-based three-dimensional monolithic optoelectronic integrated system (2017)

Single material-based monolithic optoelectronic integration with complementary metal oxide semiconductor-compatible signal processing circuits is one of the most pursued approaches in the post-Moore era to realize rapid data communication and functional diversification in a limited three-dimensional space. Here, we report an electrically driven carbon nanotube-based on-chip three-dimensional optoelectronic integrated circuit. We demonstrate that photovoltaic receivers, electrically driven transmitters and on-chip electronic circuits can all be fabricated using carbon nanotubes via a complementary metal oxide semiconductor-compatible low-temperature process, providing a seamless integration platform for realizing monolithic three-dimensional optoelectronic integrated circuits with diversified functionality such as the heterogeneous AND gates. These circuits can be vertically scaled down to sub-30 nm and operates in photovoltaic mode at room temperature. Parallel optical communication between functional layers, for example, bottom-layer digital circuits and top-layer memory, has been demonstrated by mapping data using a 2 × 2 transmitter/receiver array, which could be extended as the next generation energy-efficient signal processing paradigm.
Anti–citrullinated protein antibodies bind surface‐expressed citrullinated Grp78 on monocyte/macrophages and stimulate tumor necrosis factor α production (2010)

We clearly demonstrated that ACPAs enhance NF-kappaB activity and TNFalpha production in monocyte/macrophages via binding to surface-expressed citrullinated Grp78.
Targeted Genome Modification via Triple Helix Formation (2005)

Triplex-forming oligonucleotides (TFOs) that can bind to duplex DNA in a sequence-specific manner are potential tools to achieve targeted gene modification. Initial studies demonstrated the ability of TFOs to deliver mutagenic agents in a DNA site-specific manner. It has also been found that TFOs can induce gene modification in chromosomal DNA via the effect of the triple helix itself. Gene modification with TFOs includes induced recombination between a DNA target and a donor DNA molecule, a process that allows a TFO to exert an effect at a distance from the third-strand binding site. Ongoing efforts to develop chemical modifications on the third strand have increased the number of target sites possible for gene correction and new techniques for TFO delivery are beginning to enhance the biologic effectiveness of these reagents.
NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes (2014)

Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most ligand screening cascades, NMR-based methods are applied to identify and structurally validate small molecule binding. These can be high-throughput and are often used synergistically with other biophysical assays. Here, we describe current state-of-the-art in the portfolio of available NMR-based experiments that are used to aid early-stage lead discovery. We then focus on multi-protein complexes as targets and how NMR spectroscopy allows studying of interactions within the high molecular weight assemblies that make up a vast fraction of the yet untargeted proteome. Finally, we give our perspective on how currently available methods could build an improved strategy for drug discovery against such challenging targets.
Stearoyl-CoA desaturase inhibitors: update on patented compounds (2009)

The rapid development of SCD1 inhibitors is evidenced by the increasing number of patent applications published and the number of promising preclinical compounds that have emerged in the past 5 years. Between January 2005 and February 2009, there were approximately 70 SCD1 inhibitor patent applications published.