gebhart/patrepeval huggingface dataset:
Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole (2010)

Itraconazole is used clinically as an antifungal agent and has recently been shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers that give rise to eight stereoisomers. The complete role of stereochemistry in the two activities of itraconazole, however, has not been addressed adequately. For the first time, all eight stereoisomers of itraconazole (1a-1h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal activity against five fungal strains. Distinct antiangiogenic and antifungal activity profiles of the trans- stereoisomers, especially 1e and 1f, suggest different molecular mechanisms underlying the anti-angiogenic and anti-fungal activities of itraconazole.
Endothelial Progenitor Cells (2004)

Endothelial progenitor cells are a circulating, bone marrow-derived cell population that appears to participate in both vasculogenesis and vascular homeostasis. Questions persist regarding their functional characteristics, as well as the precise panel of cell surface markers that uniquely define this newly described progenitor cell population. We review experimental results obtained from both animal studies and recent clinical trials that suggest this cell type may have tremendous therapeutic potential for a wide range of human diseases.
Development of Mass Spectrometry-Based Shotgun Method for Proteome Analysis of 500 to 5000 Cancer Cells (2010)

A shotgun proteome analysis method and its performance for protein identification from 500 to 5000 cells are described. Sample preparation, which was done in one tube, involved the use of a surfactant (NP-40) for cell lysis, followed by acetone precipitation of the proteins. The resulting protein pellet was washed with cold acetone to remove remaining surfactant, and the pellet was then solubilized in NH(4)HCO(3). After trypsin digestion of the proteins, the digest was analyzed by the use of nanoflow liquid chromatography (LC) quadrupole time-of-flight mass spectrometry (QTOF MS). Sample injection and gradient speed in running LC QTOF MS were optimized. It was shown that this method could identify an average (n = 3) of 167 +/- 21, 237 +/- 30, 491 +/- 63, and 619 +/- 59 proteins from 500, 1000, 2500, and 5000 MCF-7 breast cancer cells, respectively. To demonstrate the potential use of this method for generating proteome profile from circulating tumor cells (CTCs) isolated from human blood, a healthy human blood sample was spiked with MCF-7 cells, and this mixture was processed and then subjected to antibody tagging of the MCF-7 cells. The tagged cells were sorted and collected using flow cytometry. The proteome profiles of small numbers of cells isolated in this way were found to be similar to those of the original MCF-7 cells, suggesting the possibility of the use of this method for cell typing of CTCs.
Critical role for Ets, AP-1 and GATA-like transcription factors in regulating mouse Toll-like receptor 4 (Tlr4) gene expression (2005)

TLR4 (Toll-like receptor 4) is essential for sensing the endotoxin of Gram-negative bacteria. Mutations or deletion of the TLR4 gene in humans or mice have been associated with altered predisposition to or outcome of Gram-negative sepsis. In the present work, we studied the expression and regulation of the Tlr4 gene of mouse. In vivo, TLR4 levels were higher in macrophages compared with B, T or natural killer cells. High basal TLR4 promoter activity was observed in RAW 264.7, J774 and P388D1 macrophages transfected with a TLR4 promoter reporter vector. Analysis of truncated and mutated promoter constructs identified several positive [two Ets (E twenty-six) and one AP-1 (activator protein-1) sites] and negative (a GATA-like site and an octamer site) regulatory elements within 350 bp upstream of the transcriptional start site. The myeloid and B-cell-specific transcription factor PU.1 bound to the proximal Ets site. In contrast, none among PU.1, Ets-1, Ets-2 and Elk-1, but possibly one member of the ESE (epithelium-specific Ets) subfamily of Ets transcription factors, bound to the distal Ets site, which was indispensable for Tlr4 gene transcription. Endotoxin did not affect macrophage TLR4 promoter activity, but it decreased TLR4 steady-state mRNA levels by increasing the turnover of TLR4 transcripts. TLR4 expression was modestly altered by other pro- and anti-inflammatory stimuli, except for PMA plus ionomycin which strongly increased promoter activity and TLR4 mRNA levels. The mouse and human TLR4 genes were highly conserved. Yet, notable differences exist with respect to the elements implicated in gene regulation, which may account for species differences in terms of tissue expression and modulation by microbial and inflammatory stimuli.
Methadone‐naloxone mixtures for use in methadone maintenance programs; I. An evaluation in man of their pharmacological feasibility; II. Demonstration of acute physical dependence (1974)

It has been proposed that mixtures of methadone and the narcotic antagonist, naloxone, be substituted for the methadone dispensed in methadone maintenance programs to reduce methadone diversion. By the oral route in nondependent subjects methadone‐naloxone mixtures are indistinguishable from methadone alone. By the parenteral route, the mixtures have significantly less miotic, behavioral, and subjective effects than methadone alone. Administration of methadone with naloxone to morphine‐dependent subjects ameliorates but does not abolish the abstinence precipitated by the naloxone. Ten milligrams of naloxone administered orally does not precipitate abstinence in rrwrphine‐dependent subjects, and doses of 15 and 30 mg produce only mild signs of abstinence. It is concluded that methadone‐naloxone mixtures could be compounded that would be interchangeable with methadone intended for oral consumption, but have less parenteral abuse liability than methadone. The observation that 4 mg of parenterally administered naloxone precipitated signs of abstinence 1 week after a single dose of methadone indicated the development of acute physical dependence on methadone.
Synthesis, Crystal Structures, and Fungicidal Activity of Novel 1,5‐Diaryl‐3‐(glucopyranosyloxy)‐1H‐pyrazoles (2012)

Abstract Five novel pyrazole‐coupled glucosides, 1,5‐diaryl‐1 H ‐pyrazol‐3‐yl 2,3,4,6‐tetra‐ O ‐acetyl‐ β ‐ D ‐glucopyranosides 5a – 5e , were synthesized by the phase‐transfer catalytic reaction of 1,5‐diaryl‐1 H ‐pyrazol‐3‐ols 4a – 4e with acetobromo‐ α ‐ D ‐glucose in H 2 O/CHCl 3 under alkaline conditions, using Bu 4 N + Br − as catalyst. Then, glucosides 5a – 5c were deacetylated in a solution of Na 2 CO 3 /MeOH to yield the 1,5‐diaryl‐3‐( β ‐ D ‐glucopyranosyloxy)‐1 H ‐pyrazoles 6a – 6c . Their structures were characterized by 1 H, 1 H‐COSY, 1 H‐, 13 C‐, and 19 F‐NMR spectroscopy, as well as elemental analysis. The structures of 5d and 6c were also determined by single‐crystal X‐ray diffraction analysis. A preliminary in vitro bioassay indicated that compounds 4e and 5d exhibited excellent‐to‐medium fungicidal activity against Sclerotinia sclerotiorum at the dosage of 10 μg/ml.
Fast Local Laplacian Filters (2014)

Multiscale manipulations are central to image editing but also prone to halos. Achieving artifact-free results requires sophisticated edge-aware techniques and careful parameter tuning. These shortcomings were recently addressed by the local Laplacian filters, which can achieve a broad range of effects using standard Laplacian pyramids. However, these filters are slow to evaluate and their relationship to other approaches is unclear. In this article, we show that they are closely related to anisotropic diffusion and to bilateral filtering. Our study also leads to a variant of the bilateral filter that produces cleaner edges while retaining its speed. Building upon this result, we describe an acceleration scheme for local Laplacian filters on gray-scale images that yields speedups on the order of 50×. Finally, we demonstrate how to use local Laplacian filters to alter the distribution of gradients in an image. We illustrate this property with a robust algorithm for photographic style transfer.
Concerns of using sialidase fusion protein as an experimental drug to combat seasonal and pandemic influenza (2008)

Sialidase fusion protein is reported to have great potential to combat seasonal and pandemic influenza, because it may prevent influenza virus infection by removing all sialic acid receptors from host cells. Meanwhile, recent studies have demonstrated that absence of alpha2-6 sialic acid does not protect a cell from influenza infection, and influenza virus can infect desialylated cells, suggesting that accessible surface sialic acid is dispensable for influenza virus infection. In addition, studies using animal models have shown that neuraminidase promotes adherence and invasion of Streptococcus pneumoniae, because cleavage of sialic acid from host cells exposes cryptic receptors for S. pneumoniae. The purpose of this article is to comment on the benefits and potential risks of using sialidase fusion protein as an experimental drug to combat seasonal and pandemic influenza.
Optical design in a flow system for imaging cells. (1991)

The imaging flow cytometer is an instrument that acquires the images of cells in a flow system. These images are analyzed for real-time cell classification and sorting. The optical units in the system perform the functions of laser beam focusing, cell detection, and cell imaging. The glass nozzle in which the cell stream flows introduces air-glass optical interfaces, resulting in optical aberrations that impair performance. This report describes the analysis of the optical aberrations in nozzles fabricated from a cylindrical glass capillary tube. Flat surfaces could be machined on the originally cylindrical surface to reduce the severity of these aberrations. The analysis shows that a nozzle with three flat surfaces is a feasible low-cost solution.
Cortisol, Biochemical, and Galvanic Skin Responses to Music Stimuli of Different Preference Values by College Students in Biology and Music (1993)

The purpose of this study was to examine biochemical and galvanic skin responses to music stimuli. Specifically, 30 university biology and 30 music students' plasma levels of norepinephrine and cortisol and their galvanic skin responses were measured before and after listening to two different musical selections, one of which was preferred (liked) by the music students and not preferred (disliked) by the biology students. The music-listening sessions and the controlled silent sessions were done in an anechoic chamber. 30 biology majors and 30 music majors were in the experimental groups; 14 biology and 17 music majors comprised the control group. Analysis indicated that the cortisol levels and galvanic skin responses were significantly higher for the music majors than the biology majors. The data indicate that music majors listen more critically and analytically to music than biology majors, and cortisol levels are associated with this as increases in music majors and decreases in biology majors after the music.
<title>MultiVIS: a web-based interactive remote visualization environment and navigable volume imagemap system</title> (2000)

This work represents the convergent evolution of a number of technologies and research 'threads'. A project called MetaMAP, which developed early hypermedia imagemap technology, dates back to 1986. Work on creating a new paradigm for doing client-server visualization over the Internet began in 1992. Another major project began in 1993 to turn the Web into a platform for interactive applications. A project to develop multidimensional imagemap technology began in 1995. Finally, work on a scalable computational server architecture called 'Dark Iron' began in 1997. The MultiVIS project represents the intersection of these various research efforts to create a new kind of navigable knowledge space that leverages the advantages of each of its constituent technologies.
Nmycplays an essential role during lung development as a dosage-sensitive regulator of progenitor cell proliferation and differentiation (2005)

Understanding how lung progenitor cells balance proliferation against differentiation is relevant to clinical disorders such as bronchopulmonary dysplasia of premature babies and lung cancer. Previous studies have established that lung development is severely disrupted in mouse mutants with reduced levels of the proto-oncogene Nmyc, but the precise mechanisms involved have not been explored. We show here that Nmyc expression in the embryonic lung is normally restricted to a distal population of undifferentiated epithelial cells, a high proportion of which are in the S phase of the cell cycle. Overexpression of NmycEGFP in the epithelium under the control of surfactant protein C (Sftpc) regulatory elements expands the domain of S phase cells and upregulates numerous genes associated with growth and metabolism, as shown by transcriptional microarray. In addition, there is marked inhibition of differentiation, coupled with an expanded domain of expression of Sox9 protein, which is also normally restricted to the distal epithelial compartment. By contrast, conditional deletion of Nmyc leads to reduced proliferation, epithelial differentiation and high levels of apoptosis in both epithelium and mesenchyme. Unexpectedly, about 50% of embryos in which only one copy of Nmyc is deleted die perinatally, with similarly abnormal lungs. We propose a model in which Nmyc is essential in the developing lung for maintaining a distal population of undifferentiated, proliferating progenitor cells.
Studies on Chlamydomonas chloroplast transformation: foreign DNA can be stably maintained in the chromosome. (1989)

As shown originally by Boynton and co-workers (Boynton, J.E., Gillham, N.W., Harris, E.H., Hosler, J.P., Johnson, A.M., Jones, A.R., Randolph-Anderson, B.L., Robertson, D., Klein, T.M., Shark, K.B., and Sanford, J.C. [1988]. Science 240, 1534-1538), a nonphotosynthetic, acetate-requiring mutant strain of Chlamydomonas reinhardtii with a 2.5-kilobase pair deletion in the chloroplast Bam 10 restriction fragment region that removes the 3' half of the atpB gene and a portion of one inverted repeat can be transformed to photosynthetic competency following bombardment with microprojectiles coated with wild-type Bam 10 DNA. We have found that assorted other circular plasmids, single-strand DNA circles, or linear, duplex DNA molecules containing the wild-type atpB gene can also complement the same mutant. DNA gel blot hybridization analysis of all such transformants indicates that the complementing DNA has integrated into the chromosome at the atpB locus and suggests that a copy-correction mechanism operating between the inverted repeats maintains sequence identity in this region. Sequences from the intact inverted repeat may be recruited to restore the incomplete copy when exogenous DNA with only a portion of the deleted sequence is introduced. Furthermore, a foreign, unselected-for, chimeric gene flanked by chloroplast DNA sequences can be integrated and maintained stably in the chloroplast chromosome. The bacterial neomycin phosphotransferase structural gene fused to the maize chloroplast promoter for the large subunit gene of ribulose-1,5-biphosphate carboxylase (rbcL) has been integrated into the inverted repeat region of the Bam10 restriction fragment. RNA transcripts that hybridize to the introduced foreign gene have been identified.
Dramatic reduction of sidegating in MODFETs (1988)

The results of systematic materials and process modifications to implant-isolated MODFETs, aimed at the elimination of sidegating in MODFET ICs, are reported. Two different methods of ion-implant isolation and four different kinds of MBE buffer layer were studied. It was found that the sidegating is independent of the implantation type but depends on the type of buffer layer. MODFETs fabricated with a low-temperature buffer layer exhibited excellent sidegating characteristics and maintained less than 0.2% reduction in the MODFET channel current up to a sidegating voltage of -70 V at a distance of 3 mu m.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Development of Base Concrete Block for Quiet Pavement System (2010)

The rapid economic development induced the massive road constructions, becoming bigger and high-speed of the vehicles. However, it brings lots of social problems, such as air pollutions, traffic noise and vibration. Special concrete block for the base course of asphalt pavement is needed to decrease traffic noise such as tire's explosive and vehicles sound, applying Helmholtz Resonators theory to asphalt pavement. If it is applied to the area where it happens considerable noise such as a junction, the street of a housing complex and a residential street, it is one of considerable method to solve the social requirements of noise problem. This research examines couple of laboratory tests for the sound absorption effect of the concrete block and the base concrete block. There are specimens which is fixed hall-size, space, depth as the condition of this research, and these are analysed of noise decrease effect using different condition of the first noise of each vehicle. As a result of analysis data according to vehicle noise volume, measurement distance, a form and size of the hall using the base concrete block, the use of special concrete base showed a good alternative solution for decreasing traffic noise level, from 4 dB to 9 dB.
Taking Advantage of Basic Research: p63 Is a Reliable Myoepithelial and Stem Cell Marker (2002)

p63 is a recently characterized p53-homolog that is consistently expressed by basal/somatic stem cells of stratified epithelia, myoepithelial cells of the breast and salivary glands, and proliferative compartment of gastric mucosa. p63 is located on the long arm of chromosome 3 (3q27) and it encodes six isoforms, three transactivating (TA) and three DeltaN-isoforms. While the first three isoforms may act as tumor suppressor genes, the DeltaN-isoforms may inhibit the p53/TA-p63-driven cell cycle arrest and apoptosis. Recently, the putative applications of p63 in the identification of myoepithelial cells of the breast and basal cells of the prostate acini have been evaluated; however, no critical systematic analysis of its role in surgical pathology practice have hitherto been reported. We review the putative roles of p63 in surgical pathology practice and provide guidelines for future directions on p63 translational research.
Use of a Mycobacterium tuberculosis H37Rv Bacterial Artificial Chromosome Library for Genome Mapping, Sequencing, and Comparative Genomics (1998)

The bacterial artificial chromosome (BAC) cloning system is capable of stably propagating large, complex DNA inserts in Escherichia coli. As part of the Mycobacterium tuberculosis H37Rv genome sequencing project, a BAC library was constructed in the pBeloBAC11 vector and used for genome mapping, confirmation of sequence assembly, and sequencing. The library contains about 5,000 BAC clones, with inserts ranging in size from 25 to 104 kb, representing theoretically a 70-fold coverage of the M. tuberculosis genome (4.4 Mb). A total of 840 sequences from the T7 and SP6 termini of 420 BACs were determined and compared to those of a partial genomic database. These sequences showed excellent correlation between the estimated sizes and positions of the BAC clones and the sizes and positions of previously sequenced cosmids and the resulting contigs. Many BAC clones represent linking clones between sequenced cosmids, allowing full coverage of the H37Rv chromosome, and they are now being shotgun sequenced in the framework of the H37Rv sequencing project. Also, no chimeric, deleted, or rearranged BAC clones were detected, which was of major importance for the correct mapping and assembly of the H37Rv sequence. The minimal overlapping set contains 68 unique BAC clones and spans the whole H37Rv chromosome with the exception of a single gap of approximately 150 kb. As a postgenomic application, the canonical BAC set was used in a comparative study to reveal chromosomal polymorphisms between M. tuberculosis, M. bovis, and M. bovis BCG Pasteur, and a novel 12.7-kb segment present in M. tuberculosis but absent from M. bovis and M. bovis BCG was characterized. This region contains a set of genes whose products show low similarity to proteins involved in polysaccharide biosynthesis. The H37Rv BAC library therefore provides us with a powerful tool both for the generation and confirmation of sequence data as well as for comparative genomics and other postgenomic applications. It represents a major resource for present and future M. tuberculosis research projects.
Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue (2002)

Angiopoietins (Ang) are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis. We have compared the distribution of the receptor tyrosine kinase (Tie) and the Ang ligands in synovial tissues from normal subjects and those with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemical analysis was used to determine the expression of Ang-1, Ang-2, Tie1 and Tie2 in synovial tissue of normal subjects and those with RA and OA. Ang-1, Ang-2, Tie1 and Tie2 mRNA and protein expression were quantified in synovial tissues and RA synovial tissue fibroblasts with real-time reverse transcription polymerase chain reaction and western blot analysis. In RA, Ang-1 positive immunostaining on lining cells, macrophages and endothelial cells was significantly higher than in OA and normal synovial tissue. The expression pattern of Ang-2 in synovial tissue was similar in RA and OA, whereas the Ang-2 expression was low in normal tissue. Synovial tissue from subjects with RA and OA showed a significant upregulation of Tie1 on lining cells, macrophages and endothelial cells compared to that from normal subjects. Tie2 was significantly upregulated in the RA and OA synovial tissue lining cells, macrophages and smooth muscle cells compared to normal synovial tissue. Generally Ang-1, Ang-2, Tie1 and Tie2 mRNA levels were higher in RA synovial tissue compared to normal and OA synovial tissues, and RA synovial tissue fibroblasts. Western blot analysis also demonstrated greater Tie1 and Tie2 protein expression in RA and OA synovial tissue compared to RA synovial tissue fibroblasts. In conclusion, the dominance of Ang-1 mRNA and protein expression over Ang-2 is in agreement with an active neovascularization in RA synovial tissue.
FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas (2009)

Different cell types interpret their distinct extracellular matrix (ECM) environments to bring about specific cell fate decisions, and can differentiate or undergo apoptosis depending on their local adhesive interactions. Apoptosis in response to an inappropriate ECM environment is termed ;anoikis', or homelessness. Several studies, utilising a variety of cell types, have indicated a common, crucial role for focal adhesion kinase (FAK) in suppressing anoikis. A wide range of different integrins can activate FAK, raising the question of how cell type specific effects are regulated. In this study, we have used a constitutively active form of FAK to examine the mechanism of FAK-mediated survival signalling in cell types from distinct embryonic lineages that show differing sensitivities to anoikis. We demonstrate that both fibroblasts and epithelial cells prevent anoikis through FAK activation. We show that FAK activates multiple downstream pathways in order to suppress anoikis. However FAK regulates survival through a more restricted set of pathways in the more anoikis-sensitive epithelial cells. Furthermore, we identify a novel role for paxillin in apoptosis suppression.